In 2013, when the journal was founded, no programmed death (PD)-1 inhibitors had yet been approved by the Food and Drug Administration (FDA); the first study of CD19 chimeric antigen receptor (CAR) T ...cells in ALL patients was just published, and cancer immunotherapy was named the ‘Breakthrough of the Year’ by Science magazine. With this new transition comes promising new opportunities and developments, both in terms of the scientific content of JITC and the logistical and publishing experiences for authors, reviewers, and readers alike. For their initial submission, authors will only need to provide part of the overall required submission information for section editors to evaluate their work and begin the review process, as applicable.
Abstract
A simple and scalable approach has been reported for V
2
O
5
encapsulation over interconnected multi-walled carbon nanotubes (MWCNTs) network using chemical bath deposition method. ...Chemically synthesized V
2
O
5
/MWCNTs electrode exhibited excellent charge-discharge capability with extraordinary cycling retention of 93% over 4000 cycles in liquid-electrolyte. Electrochemical investigations have been performed to evaluate the origin of capacitive behavior from dual contribution of surface-controlled and diffusion-controlled charge components. Furthermore, a complete flexible solid-state, flexible symmetric supercapacitor (FSS-SSC) device was assembled with V
2
O
5
/MWCNTs electrodes which yield remarkable values of specific power and energy densities along with enhanced cyclic stability over liquid configuration. As a practical demonstration, the constructed device was used to lit the ‘VNIT’ acronym assembled using 21 LED’s.
Tissue resident memory T cells (Trm) are a subset of memory T cells mainly described in inflammation and infection settings. Their location in peripheral tissues, such as lungs, gut, or skin, makes ...them the earliest T cell population to respond upon antigen recognition or under inflammatory conditions. The study of Trm cells in the field of cancer, and particularly in cancer immunotherapy, has recently gained considerable momentum. Different reports have shown that the vaccination route is critical to promote Trm generation in preclinical cancer models. Cancer vaccines administered directly at the mucosa, frequently result in enhanced Trm formation in mucosal cancers compared to vaccinations via intramuscular or subcutaneous routes. Moreover, the intratumoral presence of T cells expressing the integrin CD103 has been reported to strongly correlate with a favorable prognosis for cancer patients. In spite of recent progress, the full spectrum of Trm anti-tumoral functions still needs to be fully established, particularly in cancer patients, in different clinical contexts. In this mini-review we focus on the recent vaccination strategies aimed at generating Trm cells, as well as evidence supporting their association with patient survival in different cancer types. We believe that collectively, this information provides a strong rationale to target Trm for cancer immunotherapy.
Hybrid materials are very attractive for the fabrication of high‐performance supercapacitors. Here, we have explored organic–inorganic hybrid materials based on open‐end porous 1 D polypyrrole ...nanopipes (PPy‐NPipes) and heteropolyoxometalates (phosphotungstate (PW12O403−, PW12) or phosphomolybdate (PMo12O403−, PMo12)) that display excellent areal capacitances. Two different hybrid materials (PMo12@PPy and PW12@PPy) were effectively synthesized and used for symmetric supercapacitors. The anchoring of the inorganic nanoclusters onto the conducting polymer nanopipes led to electrodes that stood up to our best expectations exhibiting outstanding areal capacitances that are almost 1.5 to 2 fold higher than that of pristine PPy‐NPipes. In addition, symmetric cells based on PMo12@PPy and PW12@PPy hybrid electrodes were fabricated and showed significant improvement in cell performance with very high volumetric capacitances in the range of 6.3–6.8 F cm−3 (considering the volume of whole device). Indeed, they provide extended potential windows in acidic electrolytes (up to 1.5 V) which led to ultrahigh energy densities of 1.5 and 2.2 mWh cm−3 for PMo12@PPy and PW12@PPy cells, respectively. Thus, these unique organic‐inorganic hybrid symmetric cells displayed extraordinary electrochemical performances far exceeding those of more complex asymmetric systems.
POM‐Nanopipes: Redox‐active polyoxometalates (POMs) are used to functionalize polypyrrole nanopipes and obtain hybrid organic–inorganic materials (PMo12@PPy and PW12@PPy) with very high volumetric capacitances that can be used in supercapacitors.
The evolution of crocodylians as sea dwellers remains obscure because living representatives are basically freshwater inhabitants and fossil evidence lacks crucial aspects about crocodylian ...occupation of marine ecosystems. New fossils from marine deposits of Peru reveal that crocodylians were habitual coastal residents of the southeastern Pacific (SEP) for approximately 14 million years within the Miocene (
19 to 5 Ma), an epoch including the highest global peak of marine crocodylian diversity. The assemblage of the SEP comprised two long and slender-snouted (longirostrine) taxa of the Gavialidae: the giant
and a new early diverging species,
. Although living gavialids (
and
) are freshwater forms, this remarkable fossil record and a suite of evolutionary morphological analyses reveal that the whole evolution of marine crocodylians pertained to the gavialids and their stem relatives (Gavialoidea). This adaptive radiation produced two longirostrine ecomorphs with dissimilar trophic roles in seawaters and involved multiple transmarine dispersals to South America and most landmasses. Marine gavialoids were shallow sea dwellers, and their Cenozoic diversification was influenced by the availability of coastal habitats. Soon after the richness peak of the Miocene, gavialoid crocodylians disappeared from the sea, probably as part of the marine megafauna extinction of the Pliocene.
Advances in computation have been enabling many recent advances in biomolecular applications of NMR. Due to the wide diversity of applications of NMR, the number and variety of software packages for ...processing and analyzing NMR data is quite large, with labs relying on dozens, if not hundreds of software packages. Discovery, acquisition, installation, and maintenance of all these packages is a burdensome task. Because the majority of software packages originate in academic labs, persistence of the software is compromised when developers graduate, funding ceases, or investigators turn to other projects. To simplify access to and use of biomolecular NMR software, foster persistence, and enhance reproducibility of computational workflows, we have developed NMRbox, a shared resource for NMR software and computation. NMRbox employs virtualization to provide a comprehensive software environment preconfigured with hundreds of software packages, available as a downloadable virtual machine or as a Platform-as-a-Service supported by a dedicated compute cloud. Ongoing development includes a metadata harvester to regularize, annotate, and preserve workflows and facilitate and enhance data depositions to BioMagResBank, and tools for Bayesian inference to enhance the robustness and extensibility of computational analyses. In addition to facilitating use and preservation of the rich and dynamic software environment for biomolecular NMR, NMRbox fosters the development and deployment of a new class of metasoftware packages. NMRbox is freely available to not-for-profit users.
No clinical trials have compared osteoporosis drugs with incident fractures as the primary outcome. We compared the anti-fracture efficacy of teriparatide with risedronate in patients with severe ...osteoporosis.
In this double-blind, double-dummy trial, we enrolled post-menopausal women with at least two moderate or one severe vertebral fracture and a bone mineral density T score of less than or equal to −1·50. Participants were randomly assigned to receive 20 μg of teriparatide once daily plus oral weekly placebo or 35 mg of oral risedronate once weekly plus daily injections of placebo for 24 months. The primary outcome was new radiographic vertebral fractures. Secondary, gated outcomes included new and worsened radiographic vertebral fractures, clinical fractures (a composite of non-vertebral and symptomatic vertebral), and non-vertebral fractures. This study is registered with ClinicalTrials.gov (NCT01709110) and EudraCT (2012-000123-41).
We enrolled 680 patients in each group. At 24 months, new vertebral fractures occurred in 28 (5·4%) of 680 patients in the teriparatide group and 64 (12·0%) of 680 patients in the risedronate group (risk ratio 0·44, 95% CI 0·29–0·68; p<0·0001). Clinical fractures occurred in 30 (4·8%) of 680 patients in the teriparatide group compared with 61 (9·8%) of 680 in the risedronate group (hazard ratio 0·48, 95% CI 0·32–0·74; p=0·0009). Non-vertebral fragility fractures occurred in 25 (4·0%) patients in the teriparatide group and 38 (6·1%) in the risedronate group (hazard ratio 0·66; 95% CI 0·39–1·10; p=0·10).
Among post-menopausal women with severe osteoporosis, the risk of new vertebral and clinical fractures is significantly lower in patients receiving teriparatide than in those receiving risedronate.
Lilly.
Significance mAbs directed to inhibitory immune receptors represent a very promising class of immunotherapeutics. This study suggests a potential mechanism of action of ipilimumab (a fully human ...anti–cytotoxic T lymphocyte–associated antigen 4), by which FcγRIIIA (CD16)-expressing nonclassical monocytes kill regulatory T cells ex vivo via antibody-dependent cell-mediated cytotoxicity. Notably, at baseline, responder patients display significantly higher peripheral frequencies of nonclassical monocytes and a selective enrichment in tumor-infiltrating CD68 ⁺CD16 ⁺ macrophages compared with nonresponder patients. If further confirmed, these findings may contribute to the generation of predictive biomarker panels, antibody design, and the development of rational combination therapies to promote antitumor immunity.
Enhancing immune responses with immune-modulatory monoclonal antibodies directed to inhibitory immune receptors is a promising modality in cancer therapy. Clinical efficacy has been demonstrated with antibodies blocking inhibitory immune checkpoints such as cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) or PD-1/PD-L1. Treatment with ipilimumab, a fully human CTLA-4–specific mAb, showed durable clinical efficacy in metastatic melanoma; its mechanism of action is, however, only partially understood. This is a study of 29 patients with advanced cutaneous melanoma treated with ipilimumab. We analyzed peripheral blood mononuclear cells (PBMCs) and matched melanoma metastases from 15 patients responding and 14 not responding to ipilimumab by multicolor flow cytometry, antibody-dependent cell-mediated cytotoxicity (ADCC) assay, and immunohistochemistry. PBMCs and matched tumor biopsies were collected 24 h before (i.e., baseline) and up to 4 wk after ipilimumab. Our findings show, to our knowledge for the first time, that ipilimumab can engage ex vivo FcγRIIIA (CD16)-expressing, nonclassical monocytes resulting in ADCC-mediated lysis of regulatory T cells (Tregs). In contrast, classical CD14 ⁺⁺CD16 ⁻ monocytes are unable to do so. Moreover, we show that patients responding to ipilimumab display significantly higher baseline peripheral frequencies of nonclassical monocytes compared with nonresponder patients. In the tumor microenvironment, responders have higher CD68 ⁺/CD163 ⁺ macrophage ratios at baseline and show decreased Treg infiltration after treatment. Together, our results suggest that anti–CTLA-4 therapy may target Tregs in vivo. Larger translational studies are, however, warranted to substantiate this mechanism of action of ipilimumab in patients.
Electrochemical stability of energy storage devices is one of their major concerns. Polymeric binders are generally used to enhance the stability of the electrode, but the electrochemical performance ...of the device is compromised due to the poor conductivity of the binders. Herein, 3D binder-free electrode based on nickel oxide deposited on graphene (G-NiO) was fabricated by a simple two-step method. First, graphene was deposited on nickel foam via atmospheric pressure chemical vapour deposition followed by electrodeposition of NiO. The structural and morphological analyses of the fabricated G-NiO electrode were conducted through Raman spectroscopy, X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and energy dispersive X-ray spectroscopy (EDS). XRD and Raman results confirmed the successful growth of high-quality graphene on nickel foam. FESEM images revealed the sheet and urchin-like morphology of the graphene and NiO, respectively. The electrochemical performance of the fabricated electrode was evaluated through cyclic voltammetry (CV), galvanostatic charge-discharge (GCD), and electrochemical impedance spectroscopy (EIS) in aqueous solution at room temperature. The G-NiO binder-free electrode exhibited a specific capacity of ≈ 243 C g
at 3 mV s
in a three-electrode cell. A two-electrode configuration of G-NiO//activated charcoal was fabricated to form a hybrid device (supercapattery) that operated in a stable potential window of 1.4 V. The energy density and power density of the asymmetric device measured at a current density of 0.2 A g
were estimated to be 47.3 W h kg
and 140 W kg
, respectively. Additionally, the fabricated supercapattery showed high cyclic stability with 98.7% retention of specific capacity after 5,000 cycles. Thus, the proposed fabrication technique is highly suitable for large scale production of highly stable and binder-free electrodes for electrochemical energy storage devices.
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