Photocatalytic Activity of BaAl2O4 for Water Purification.

Degradation of dyes under natural light sources is one of the most active research areas in basic science for greener technology. In this context, the photocatalytic activity of semiconductors has received massive attention in solving water treatment-related issues as these possess enormous potential for degrading organic impurities. Here, we report that barium aluminate (BaAl2O4, BAO), which has been extensively studied for photoluminescence applications, is found to be a highly potent candidate for photocatalytic activities. We have explored the degradation of dyes (meant for water purification) by using the photocatalytic properties of pure and Dy- and Yb-codoped BAO. Crystal structure, electron microscopy, and Raman analysis of the autocombustion-synthesized pure and codoped BAO samples revealed significant morphological changes such as increased particle size and stabilization of rod-like structures. UV-vis absorbance measurements confirm the presence of multiple bandgaps in the BAO samples, which is substantiated by X-ray absorption spectroscopy measurements. Photocatalytic degradation studies of methylene blue (MB) dye (with different catalyst concentrations, dopings, and MB dye concentrations) have been carried out by using BAO. The kinetics of the photocatalytic degradation measurements has been explained by the Boltzmann distribution function, and the fastest (in less than 40 min), with more than 99% degradation of MB impurity, is reported here for the first time in BAO compounds. Synthesized BAO samples show excellent cyclic stability, which is essential for their potential applications in environmental remediation. The trade-off between the enhancement of surface area and increased particle size is considered the key parameter for controlling the photocatalytic performance of the BAO catalyst after Dy and Yb codopings.

Electronic correlations in epitaxial CrN thin film.

Chromium nitride (CrN) spurred enormous interest due to its coupled magnetostructural and unique metal-insulator transition. The underneath electronic structure of CrN remains elusive. Herein, the electronic structure of epitaxial CrN thin film has been explored by employing resonant photoemission spectroscopy (RPES) and X-ray absorption near edge spectroscopy study in combination with the first-principles calculations. The RPES study indicates the presence of a charge-transfer screened 3[Formula: see text] ([Formula: see text]: hole in the N-2[Formula: see text]) and 3[Formula: see text] final-states in the valence band regime. The combined experimental electronic structure along with the orbital resolved electronic density of states from the first-principles calculations reveals the presence of Cr(3[Formula: see text])-N(2[Formula: see text]) hybridized (3[Formula: see text]) states between lower Hubbard (3[Formula: see text]) and upper Hubbard (3[Formula: see text]) bands with onsite Coulomb repulsion energy (U) and charge-transfer energy ([Formula: see text]) estimated as [Formula: see text] 4.5 and 3.6 eV, respectively. It verifies the participation of ligand (N-2[Formula: see text]) states in low energy charge fluctuations and provides concrete evidence for the charge-transfer ([Formula: see text]U) insulating nature of CrN thin film.

Conventional DNA-Damaging Cancer Therapies and Emerging cGAS-STING Activation: A Review and Perspectives Regarding Immunotherapeutic Potential.

Many traditional cancer treatments such as radiation and chemotherapy are known to induce cellular DNA damage as part of their cytotoxic activity. The cGAS-STING signaling axis, a key member of the DNA damage response that acts as a sensor of foreign or aberrant cytosolic DNA, is helping to rationalize the DNA-damaging activity of these treatments and their emerging immunostimulatory capacity. Moreover, cGAS-STING, which is attracting considerable attention for its ability to promote antitumor immune responses, may fundamentally be able to address many of the barriers limiting the success of cancer immunotherapy strategies, including the immunosuppressive tumor microenvironment. Herein, we review the traditional cancer therapies that have been linked with cGAS-STING activation, highlighting their targets with respect to their role and function in the DNA damage response. As part of the review, an emerging "chemoimmunotherapy" concept whereby DNA-damaging agents are used for the indirect activation of STING is discussed as an alternative to the direct molecular agonism strategies that are in development, but have yet to achieve clinical approval. The potential of this approach to address some of the inherent and emerging limitations of cGAS-STING signaling in cancer immunotherapy is also discussed. Ultimately, it is becoming clear that in order to successfully employ the immunotherapeutic potential of the cGAS-STING axis, a balance between its contrasting antitumor and protumor/inflammatory activities will need to be achieved.

Purification of ursolic acid and ß-sitosterol from endophytic Alternaria alternata for their alpha-amylase inhibitory activity.

Fungal endophytes are a known warehouse of bioactive compounds with multifarious applications. In the present investigation two compounds, ß-Sitosterol (1) and ursolic acid (2), were isolated from Alternaria alternata, an endophytic fungus associated with Morus alba Linn for the first time. The structure of the compounds was elucidated on the basis of comprehensive spectral analysis (UV, IR, 1 H-, 13 C- and 2D-NMR, as well as HRESI-MS). In the in vitro alpha amylase inhibitory assay both compounds (1) and (2) show potent antidiabetic activity. In support, Docking studies indicate significant binding affinity of the isolated compounds. Hence from the present study, it can be concluded that endophytic fungi in Morus alba Linn can find use in antidiabetic drug development in the medicinal industry.Communicated by Ramaswamy H. Sarma.

Tunable electronic structure of heterosite FePO4: an in-depth structural study and polaron transport.

The development of better electrode materials for lithium-ion batteries has been intensively investigated both due to their fundamental scientific aspects as well as their usefulness in technological applications. The present technological development of rechargeable batteries is hindered by fundamental challenges, such as low energy and power density, short lifespan, and sluggish charge transport kinetics. Among the various anode materials proposed, heterosite FePO4 (h-FP) has been found to intercalate lithium and sodium ion hosts to obtain novel rechargeable batteries. The h-FP has been obtained via the delithiation of triphylite LiFePO4 (LFP), and its structural and electronic properties have been investigated with different crystallite sizes. The synchrotron XRD measurements followed by Rietveld refinement analysis reveal lattice expansion upon the reduction of crystallite size of h-FP. In addition, the decrease in the crystallite size enhances surface energy contributions, thereby creating more oxygen vacancies up to 2% for 21 nm crystallite size. The expansion in the lattice parameters is reflected in the vibrational properties of the h-FP structure, where the red-shift has been observed in the characteristic modes upon the reduction of crystallite size. The local environment of the transition metal ion and its bonding characteristics have been elucidated through soft X-ray absorption spectroscopy (XAS) with the effect of crystallite size. XAS unequivocally reveals the valence state of iron 3d electrons near the Fermi level, which is susceptible to local lattice distortion and uncovers the detailed information on the evolution of electronic states with crystallite size. The observed local lattice distortion has been considered to be as a result of the decrease in the level of covalency between the Fe-3d and O-2p states. Further, we demonstrate the structural advantages of nanosized h-FP on the transport properties, where an enhancement in the polaronic conductivity with decreasing crystallite size has been observed. The polaronic conduction mechanism has been analyzed and discussed on the basis of the Mott model of polaron conduction along with an insightful analysis on the role of the electronic structure. The present study provides spectroscopic results on the anode material that reveal the evolution of electronic states for fingerprinting, understanding, and optimizing it for advanced rechargeable battery operations.

Light-Controlled Magnetoelastic Effects in Ni/BaTiO3 Heterostructures.

Magnetoelastic and magnetoelectric coupling in the artificial multiferroic heterostructures facilitate valuable features for device applications such as magnetic field sensors and electric-write magnetic-read memory devices. In ferromagnetic/ferroelectric heterostructures, the intertwined physical properties can be manipulated by an external perturbation, such as an electric field, temperature, or a magnetic field. Here, we demonstrate the remote-controlled tunability of these effects under visible, coherent, and polarized light. The combined surface and bulk magnetic study of domain-correlated Ni/BaTiO3 heterostructures reveals that the system shows strong sensitivity to the light illumination via the combined effect of piezoelectricity, ferroelectric polarization, spin imbalance, magnetostriction, and magnetoelectric coupling. A well-defined ferroelastic domain structure is fully transferred from a ferroelectric substrate to the magnetostrictive layer via interface strain transfer. The visible light illumination is used to manipulate the original ferromagnetic microstructure by the light-induced domain wall motion in ferroelectric substrates and consequently the domain wall motion in the ferromagnetic layer. Our findings mimic the attractive remote-controlled ferroelectric random-access memory write and magnetic random-access memory read application scenarios, hence facilitating a perspective for room temperature spintronic device applications.

Aliovalent Ta-Doping-Engineered Oxygen Vacancy Configurations for Ultralow-Voltage Resistive Memory Devices: A DFT-Supported Experimental Study.

Alteration of transport properties of any material, especially metal oxides, by doping suitable impurities is not straightforward as it may introduce multiple defects like oxygen vacancies (Vo) in the system. It plays a decisive role in controlling the resistive switching (RS) performance of metal oxide-based memory devices. Therefore, a judicious choice of dopants and their atomic concentrations is crucial for achieving an optimum Vo configuration. Here, we show that the rational designing of RS memory devices with cationic dopants (Ta), in particular, Au/Ti1-xTaxO2-δ/Pt devices, is promising for the upcoming non-volatile memory technology. Indeed, a current window of ∼104 is realized at an ultralow voltage as low as 0.25 V with significant retention (∼104 s) and endurance (∼105 cycles) of the device by considering 1.11 at % Ta doping. The obtained device parameters are compared with those in the available literature to establish its excellent performance. Furthermore, using detailed experimental analyses and density functional theory (DFT)-based first-principles calculations, we comprehend that the meticulous presence of Vo configurations and the columnar-like dendritic structures is crucial for achieving ultralow-voltage bipolar RS characteristics. In fact, the dopant-mediated Vo interactions are found to be responsible for the enhancement in local current conduction, as evidenced from the DFT-simulated electron localization function plots, and these, in turn, augment the device performance. Overall, the present study on cationic-dopant-controlled defect engineering could pave a neoteric direction for future energy-efficient oxide memristors.

T cell-inflamed gene expression profile and PD-L1 expression and pembrolizumab efficacy in advanced esophageal cancer.

Aim: Investigate the relationship between response to pembrolizumab and expression of the 18-gene T cell-inflamed gene expression profile (TcellinfGEP) or PD-L1 combined positive score (CPS) in esophageal cancer. Materials & methods: This analysis included heavily pretreated patients with advanced/metastatic esophageal/gastroesophageal junction adenocarcinoma or squamous cell carcinoma who received pembrolizumab in the single-arm, phase II study KEYNOTE-180. PD-L1 CPS was evaluated with PD-L1 IHC 22C3 pharmDx. Results: In patients with squamous cell carcinoma, trends toward enrichment for responders were observed for patients with PD-L1 CPS ≥10 tumors. In patients with adenocarcinoma, a trend was observed for TcellinfGEP but not for PD-L1. Conclusion: TcellinfGEP and PD-L1 CPS may enrich for responders to pembrolizumab in patients with esophageal cancer. Clinical trial registration: NCT02559687 (ClinicalTrials.gov).

Stabilizing effects of Ag doping on structure and thermal stability of FeN thin films.

In this work, we investigated the effect of Ag doping (2-20 at.%) on the phase formation of iron mononitride (FeN) thin films. Together with deposition of FeN using reactive dc magnetron sputtering, Ag was also co-sputtered at various doping levels between 2-20 at.%. We found that doping of Ag around 5 at.% is optimum to not only improve the thermal stability of FeN but also to reduce intrinsic defects that are invariably present in (even in epitaxial) FeN. Conversion electron Mössbauer spectroscopy and N K-edge x-ray near edge absorption measurements clearly reveal a reduction of defects in Ag doped FeN samples. Moreover, Fe self-diffusion measurements carried out using secondary ion mass spectroscopy depth-profiling and polarized neutron reflectivity in57Fe enriched samples exhibit an appreciable reduction in Fe self-diffusion in Ag doped FeN samples. Ag being immiscible with Fe and non-reactive with N, occupies grain-boundary positions as nanoparticles and prohibits the fast Fe self-diffusion in FeN.

In situ N K-edge XANES study of iron, cobalt and nickel nitride thin films.

A prototype in situ X-ray absorption near-edge structure (XANES) system was developed to explore its sensitivity for ultra-thin films of iron-nitride (Fe-N), cobalt-nitride (Co-N) and nickel-nitride (Ni-N). They were grown using DC-magnetron sputtering in the presence of an N2 plasma atmosphere at the experimental station of the soft XAS beamline BL01 (Indus-2, RRCAT, India). XANES measurements were performed at the N K-edge in all three cases. It was found that the N K-edge spectral shape and intensity are greatly affected by increasing thickness and appear to be highly sensitive, especially in low-thickness regions. From a certain thickness of ∼1000 Å, however, samples exhibit a bulk-like behavior. On the basis of the obtained results, different growth stages were identified. Furthermore, the presence of a molecular N2 component in the ultra-thin regime (<100 Å) was also obtained in all three cases studied in this work. In essence, this prototype in situ system reveals that N K-edge XANES is a powerful technique for studying ultra-thin films, and the development of a dedicated in situ system can be effective in probing several phenomena that remain hitherto unexplored in such types of transition metal nitride thin films.

Effect of disorder on superconductivity of NbN thin films studied using x-ray absorption spectroscopy.

The superconducting transition temperature (TC) of rock-salt type niobium nitride (δ- NbN) typically varies between 9 to 17 K and the theoretically predicted value of 18 K has not been achieved hitherto. The lowTCinδ- NbN has been assigned to some structural disorder which is always present irrespective of the microstructure (polycrystalline or epitaxial), methods or conditions adopted during the growth of NbN thin films. In this work, we investigate the atomic origin of such suppression of theTCinδ- NbN thin films by employing combined methods of experiments andab initiosimulations. Sputteredδ- NbN thin films with different disorder were studied using the synchrotron-based N and Nb K-edge x-ray absorption spectroscopy techniques. A strong correlation between the superconductivity and the electronic structure reconstruction was observed. The theoretical analysis revealed that under N-rich growth conditions, atomic and molecular N-interstitial defects assisted by cation vacancies form spontaneously and results into a smeared electronic structure around Fermi-level. The role of electronic smearing on theTCis thoroughly discussed.

Studying the onset of galvanic steel corrosionin situusing thin films: film preparation, characterization and application to pitting.

This work reports about a novel approach for investigating surface processes during the early stages of galvanic corrosion of stainless steelin situby employing ultra-thin films and synchrotron x-radiation. Characterized by x-ray techniques and voltammetry, such films, sputter deposited from austenitic steel, were found representing useful replicas of the target material. Typical for stainless steel, the surface consists of a passivation layer of Fe- and Cr-oxides, a couple of nm thick, that is depleted of Ni. Films of ≈4 nm thickness were studiedin situin an electrochemical cell under potential control (-0.6 to +0.8 V vs Ag/AgCl) during exposure to 0.1 M KCl. Material transport was recorded with better than 1/10 monolayer sensitivity by x-ray spectroscopy. Leaching of Fe was observed in the cathodic range and the therefor necessary reduction of Fe-oxide appears to be accelerated by atomic hydrogen. Except for minor leaching, reduction of Ni, while expected from Pourbaix diagram, was not observed until at a potential of about +0.8 V Cr-oxide was removed from the steel film. After couple of minutes exposure at +0.8 V, the current in the electrochemical cell revealed a rapid pitting event that was simultaneously monitored by x-ray spectroscopy. Continuous loss of Cr and Ni was observed during the induction time leading to the pitting, suggesting a causal connection with the event. Finally, a spectroscopic image of a pit was recordedex situwith 50 nm lateral and 1 nm depth resolution by soft x-ray scanning absorption microscopy at the Fe L2,3-edges by using a 80 nm film on a SiN membrane, which is further demonstrating the usefulness of thin films for corrosion studies.

Mechanistic insights into defect generation and tuning of optical properties in Zn1-xFexAl2O4(0.01 ≤ x ≤ 0.40) nanocrystals.

The correlation of several defects and optical and magnetic properties with Fe content in Zn1-xFexAl2O4 (0.01 ≤ x ≤ 0.40) nanocrystals has been scrutinized through X-ray diffraction, O K-edge X-ray absorption near-edge structure, FT-IR, diffuse reflectance, photoluminescence and electron spin-resonance spectroscopies, and vibrating sample magnetometry. Increasing Fe content causes elongation in the octahedral units of the lattice, accompanied by distortion in the octahedral coordination. Fe introduces non-radiative centres in the forbidden gap, thereby tuning the band gap from 4.37 to 3.88 eV and eliminating emission in the visible region. Zn vacancies are found to tail off, while {\rm Fe}_i^{\bullet \bullet \bullet}, {\rm Al}_{\rm Zn}^\bullet and FeAl× antisite defects increase in concentration with increasing Fe content. Inhomogeneous broadening of spin-resonance signals infers strong spin-lattice interactions of Fe3+ ions at distorted octahedral and non-symmetric tetrahedral sites. A transition is observed from paramagnetism to superparamagnetism at higher Fe concentrations. A visual colour change from pearly white to orange-brown is observed in Zn1-xFexAl2O4 nanocrystals with increasing Fe content, revealing its potential candidature for pigments in the paint and dye industries.

Safety and Efficacy of Nivolumab in Patients With Advanced Non-Clear Cell Renal Cell Carcinoma: Results From the Phase IIIb/IV CheckMate 374 Study.

BACKGROUND: The open-label phase IIIb/IV CheckMate 374 study (NCT02596035) was conducted to validate the safety and efficacy of flat-dose nivolumab 240 mg every 2 weeks (Q2W) in previously treated advanced/metastatic renal cell carcinoma. Three cohorts included patients with predominantly clear cell histology, non-clear cell histologies, or brain metastases. We report safety and efficacy from the advanced non-clear cell RCC (nccRCC) cohort of CheckMate 374. METHODS: Eligible patients received 0 to 3 prior systemic therapies. Patients received nivolumab 240 mg Q2W for ≤24 months or until confirmed progression or unacceptable toxicity. The primary endpoint was incidence of high-grade (grade 3-5) immune-mediated adverse events (IMAEs). Exploratory endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: Forty-four patients had advanced nccRCC (papillary [n = 24], chromophobe [n = 7], unclassified [n = 8], other [n = 5]); 34.1% received ≥1 prior systemic regimen in the advanced/metastatic setting. With median follow-up of 11 (range, 0.4-27) months, no all-cause grade 3-5 IMAEs or treatment-related grade 5 adverse events were reported. ORR was 13.6% (95% confidence interval [CI], 5.2-27.4), with 1 complete response (chromophobe) and 5 partial responses (papillary [n = 2], chromophobe [n = 1], collecting duct [n = 1], and unclassified [n = 1] histology). Median PFS was 2.2 months (95% CI, 1.8-5.4). Median OS was 16.3 months (95% CI, 9.2-not estimable). CONCLUSIONS: Safety of flat-dose nivolumab 240 mg Q2W was consistent with previous results. Clinically meaningful efficacy was observed with responses in several histologies, supporting nivolumab as a treatment option for patients with advanced nccRCC, a patient population with high unmet need.

Insight into the photophysics of strong dual emission (blue & green) producing graphene quantum dot clusters and their application towards selective and sensitive detection of trace level Fe3+ and Cr6+ ions.

Graphene-nanostructured systems, such as graphene quantum dots (GQDs), are well known for their interesting light-emitting characteristics and are being applied to a variety of luminescence-based applications. The emission properties of GQDs are complex. Therefore, understanding the science of the photophysics of coupled quantum systems (like quantum clusters) is still challenging. In this regard, we have successfully prepared two different types of GQD clusters, and explored their photophysical properties in detail. By co-relating the structure and photophysics, it was possible to understand the emission behavior of the cluster in detail. This gave new insight into understanding the clustering effect on the emission behaviour. The results clearly indicated that although GQDs are well connected, the local discontinuity in the structure prohibits the dynamics of photoexcited charge carriers going from one domain to another. Therefore, an excitation-sensitive dual emission was possible. Emission yield values of about 18% each were recorded at the blue and green emission wavelengths at a particular excitation energy. This meant that the choice of emission color was decided by the excitation energy. Through systematic analysis, it was found that both intrinsic and extrinsic effects contributed to the blue emission, whereas only the intrinsic effect contributed to the green emission. These excitation-sensitive dual emissive GQD clusters were then used to sense Fe3+ and Cr6+ ions in the nanomolar range. While the Cr6+ ions were able to quench both blue and green emissions, the Fe3+ ions quenched blue emission only. The insensitivity of the Fe3+ ions in the quenching of the green emission was also understood through quantum chemical calculations.

Structural, optical and electronic properties of Ni1-x Co x O in the complete composition range.

Crystallographic and electronic structures of phase pure ternary solid solutions of Ni1-x Co x O (x = 0 to 1) have been studied using XRD, EXAFS and XAS measurements. The lattice parameter of the cubic rock-salt (RS) Ni1-x Co x O solid solutions increases linearly with increasing Co content and follows Vegard's law, in the complete composition range. A linear increase in the bond lengths (Ni/Co-O, Ni-Ni and Ni-Co) with "x", closely following the bond lengths determined from virtual crystal approximation (VCA), is observed, which implies that there is only a minimal local distortion of the lattice in the mixed crystal. The optical gap of the ternary solid solution determined from diffuse reflectivity measurements shows neither a linear variation with Co composition nor bowing, as observed in many ternary semiconductors. This trend in the variation of optical gaps is explained by probing the conduction band using XAS at the O K-edge. We have observed that the variation in the onset energy of the conduction band edge with "x" is very similar to the variation in the optical gap with "x", thus clearly indicating the dominant role played by the conduction band position in determining the optical gap. The variation in the intensities of the pre-edge peak in the XANES spectra measured at Ni and Co K-edges, and the L1/2 peak in XAS spectra measured at Ni and Co L-edges, is found to depend on the unoccupied O 2p-metal-(Ni/Co) 3d hybridized states and the bond lengths.

Size induced structural changes in maricite-NaFePO4: an in-depth study by experiment and simulations.

Rechargeable batteries based on the most abundant elements, such as sodium and iron, have a great potential in the development of cost effective sodium ion batteries for large scale energy storage devices. We report, for the first time, crystallite size dependent structural investigations on maricite-NaFePO4 through X-ray diffraction, X-ray absorption spectroscopy and theoretical simulations. Rietveld refinement analysis on the X-ray diffraction data reveals that a decrease in the unit cell parameters leads to volume contraction upon reduction in the crystallite size. Further, the atomic multiplet simulations on X-ray absorption spectra provide unequivocally a change in the site symmetry of transition metal ions. The high resolution oxygen K-edge spectra reveal a substantial change in the bonding character with the reduction of crystallite size, which is the fundamental cause for the change in the unit cell parameters of maricite-NaFePO4. In parallel, we performed first-principles density functional theory (DFT) calculations on maricite-NaFePO4 with different sodium ion vacancy concentrations. The obtained structural parameters are in excellent agreement with the experimental observations on the mesostructured maricite-NaFePO4. The volumetric changes with respect to crystallite size are related to the compressive strain, resulting in the improvement in the electronic diffusivity. The nano-crystalline maricite-NaFePO4 with improved kinetics will open a new avenue for its usage as a cathode material in sodium ion batteries.

Depth-resolved compositional analysis of W/B4C multilayers using resonant soft X-ray reflectivity.

W/B4C multilayers (MLs) consisting of ten layer pairs with varying boron carbide layer thicknesses have been investigated. The ML structures were characterized using grazing-incidence hard X-ray reflectivity (GIXR), resonant soft X-ray reflectivity (RSXR), hard X-ray photoelectron spectroscopy (HAXPES) and X-ray absorption near-edge spectroscopy (XANES). Depth-resolved spectroscopic information on the boron carbide layer in W/B4C MLs was extracted with sub-nanometre resolution using reflectivity performed in the vicinity of the B K-edge. Interestingly, these results show that the composition of boron carbide films is strongly dependent on layer thicknesses. HAXPES measurements suggest that most of the boron is in the chemical state of B4C in the multilayer structures. XANES measurements suggest an increase in boron content and C-B-C bonding with increase in boron carbide layer thickness.

In situ soft x-ray absorption spectroscopic study of polycrystalline Fe/MgO interfaces.

Interfacial interactions between a layer of iron and MgO hold the key to various phenomena like tunnel magnetoresistance, perpendicular magnetic anisotropy, interlayer exchange coupling, observed in the system. Interface structure has been studied in situ during deposition of iron on MgO surface, using soft x-ray absorption spectroscopy (SXAS). Sub-monolayer sensitivity of SXAS, combined with in situ measurements as a function of iron layer thickness, allowed one to study the evolution of interface with film thickness. Two different substrates namely MgO (0 0 1) single crystal, and a polycrystalline MgO film on Si substrate have been used in order to elucidate the role of the state of MgO surface in controlling the interface structure. It is found that at the interface of iron and MgO film, about two monolayers of Fe3O4 are formed. Fe3O4 being the oxide of iron with the highest heat of formation, the reaction appears to be controlled thermodynamically. On the other hand, on the interface with MgO (0 0 1) surface, FeO is formed, suggesting that the reaction is limited by the availability of oxygen atoms. Magnetic behavior of the FeO layer gets modified significantly due to proximity effect of the bulk ferromagnetic iron layer.

Efficacy and Safety of Pembrolizumab for Heavily Pretreated Patients With Advanced, Metastatic Adenocarcinoma or Squamous Cell Carcinoma of the Esophagus: The Phase 2 KEYNOTE-180 Study.

IMPORTANCE: Effective treatment options are limited for patients with advanced, metastatic esophageal cancer progressing after 2 or more lines of systemic therapy. OBJECTIVE: To evaluate the efficacy and safety of pembrolizumab for patients with advanced, metastatic esophageal squamous cell carcinoma (ESCC) or advanced, metastatic adenocarcinoma of the esophagus and gastroesophageal junction that progressed after 2 or more lines of systemic therapy. DESIGN, SETTING, AND PARTICIPANTS: This phase 2, open-label, interventional, single-arm study, KEYNOTE-180, enrolled 121 patients from January 12, 2016, to March 21, 2017, from 57 sites in 10 countries. Patients had advanced, metastatic esophageal cancer that progressed after 2 or more lines of therapy and had evaluable tumor samples for biomarkers. INTERVENTIONS: Pembrolizumab, 200 mg, was administered intravenously every 3 weeks until disease progression, unacceptable toxic effects, or study withdrawal, for up to 2 years. MAIN OUTCOMES AND MEASURES: Primary end point was objective response rate per the Response Evaluation Criteria in Solid Tumors by central imaging review for all patients. RESULTS: As of September 18, 2017, of 121 enrolled patients (100 men and 21 women; median age, 65 years [range, 33-87 years]), 18 (14.9%) had undergone 3 or more prior therapies, 63 (52.1%) had ESCC, and 58 (47.9%) had tumors positive for programmed death ligand-1 (PD-L1), defined as a combined positive score of 10 or higher assessed by immunohistochemistry. Median duration of follow-up was 5.8 months (range, 0.2-18.3 months). Objective response rate was 9.9% (95% CI, 5.2%-16.7%) among all patients (12 of 121), and median duration of response was not reached (range, 1.9-14.4 months). Objective response rate was 14.3% (95% CI, 6.7%-25.4%) among patients with ESCC (9 of 63), 5.2% (95% CI, 1.1%-14.4%) among patients with adenocarcinoma (3 of 58), 13.8% (95% CI, 6.1%-25.4%) among patients with PD-L1-positive tumors (8 of 58), and 6.3% (95% CI, 1.8%-15.5%) among patients with PD-L1-negative tumors (4 of 63). Overall, 15 patients (12.4%) had treatment-related grade 3 to 5 adverse events. Only 5 patients (4.1%) discontinued treatment because of adverse events. There was 1 treatment-related death from pneumonitis. CONCLUSIONS AND RELEVANCE: Where effective treatment options are an unmet need, pembrolizumab provided durable antitumor activity with manageable safety in patients with heavily pretreated esophageal cancer. Phase 3 studies evaluating pembrolizumab vs standard therapy for patients with esophageal cancer progressing after first-line therapy or in combination with chemotherapy as first-line therapy for patients with locally advanced unresectable or metastatic esophageal cancer are ongoing. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02559687.