Redefining Clinical Hyperprogression: The Incidence, Clinical Implications, and Risk Factors of Hyperprogression in Non-Small Cell Lung Cancer Treated with Immunotherapy.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) may be associated with hyperprogressive disease (HPD). However, there is currently no standardized definition of HPD, with its risk factors and clinical implications remaining unclear. We investigated HPD in lung cancer patients undergoing immunotherapy, aiming to redefine HPD, identify risk factors, and assess its impact on survival. METHODS: Clinical and radiologic data from 121 non-small cell lung cancer (NSCLC) patients with 136 immunotherapy cases were reviewed retrospectively. Three HPD definitions (Champiat et al., HPDc; Saâda-Bouzid et al., HPDs; and Ferrara et al., HPDf) were employed. Additionally, all new measurable lesions on the post-treatment CT scan were incorporated in measuring the sum of longest diameters (SLD) to define modified HPD (mHPD). RESULTS: Among the 121 patients, 4 (3.3%) had HPDc, 11 (9.1%) had HPDs, and none had HPDf. Adding all new measurable lesions increased HPD incidence by 5%-10% across definitions. Multivariate analysis revealed significantly lower progression-free survival (PFS) and overall survival (OS) for patients with HPDc (HR 5.25, P = .001; HR 3.75, P = .015) and HPDs (HR 3.74, P < .001; HR 3.46, P < .001) compared to those without. Patients with mHPD showed similarly poor survival outcomes as HPD patients. Liver metastasis at diagnosis was associated with HPDs, and a high tumor burden correlated with HPDc. CONCLUSIONS: The incidence and risk factors of HPD varied with different definitions, but mHPD identified more cases with poor outcomes. This comprehensive approach may enhance the identification of at-risk patients and lead to a better understanding of HPD in lung cancer during immunotherapy.

Reinforcement of Positive Electrode-Electrolyte Interface without Using Electrolyte Additives Through Thermoelectrochemical Oxidation of LiPF6 for Lithium Secondary Batteries.

Owing to the limited electrochemical stability window of carbonate electrolytes, the initial formation of a solid electrolyte interphase and surface film on the negative and positive electrode surfaces by the decomposition of the electrolyte component is inevitable for the operation of lithium secondary batteries. The deposited film on the surface of the active material is vital for reducing further electrochemical side reactions at the surface; hence, the manipulation of this formation process is necessary for the appropriate operation of the assembled battery system. In this study, the thermal decomposition of LiPF6 salt is used as a surface passivation agent, which is autocatalytically formed during high-temperature storage. The thermally formed difluorophosphoric acid is subsequently oxidized on the partially charged high-Ni positive electrode surface, which improves the cycleability of lithium metal cells via phosphorus- and fluorine-based surface film formation. Moreover, the improvement in the high-temperature cycleability is demonstrated by controlling the formation process in the lithium-ion pouch cell with a short period of high-temperature storage before battery usage.

Anion Engineering for Stabilizing Li Interstitial Sites in Halide Solid Electrolytes for All-Solid-State Li Batteries.

Halide solid electrolytes (SEs) have been highlighted for their high-voltage stability. Among the halide SEs, the ionic conductivity has been improved by aliovalent metal substitutions or choosing a ccp-like anion-arranged monoclinic structure (C2/m) over hcp- or bcc-like anion-arranged structures. Here, we present a new approach, hard-base substitution, and its underlying mechanism to increase the ionic conductivity of halide SEs. The oxygen substitution to Li2ZrCl6 (trigonal, hcp) increased the ionic conductivity from 0.33 to 1.3 mS cm-1 at Li3.1ZrCl4.9O1.1 (monoclinic, ccp), while the sulfur and fluorine substitutions were not effective. A systematic comparison study revealed that the energetic stabilization of interstitial sites for Li migration plays a key role in improving the ionic conductivity, and the ccp-like anion sublattice is not sufficient to achieve high ionic conductivity. We further examined the feasibility of the oxyhalide SE for practical and all-solid-state battery applications.

Survival Outcomes After Double-Lung Transplantation for Refractory Lung-Limited Cancers and Incidence of Post-Transplant Lung Cancer.

BACKGROUND To evaluate the role of double-lung transplantation (DLT) for lung cancer, the survival outcomes of patients who underwent DLT for lung cancer and the incidence of de novo lung cancer after DLT were assessed. MATERIAL AND METHODS Data from all cases reported in the literature were pooled for analysis and additional data were collected from the Organ Procurement Transplantation Network (OPTN) registry. Recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS) of patients who underwent DLT for lung cancer were determined. Moreover, the incidence of de novo lung cancer and associated OS in lung transplant recipients were examined. RESULTS Of the 20 cases series and 15 cases from the OPTN registry, the 5-year RFS was 55.0% and 66.7% and the 5-year OS was 55.0% and 26.7%, respectively, and the median CSS was 48.0 (range, 2.0-144.0) and 27.7 (range, 0.2-66.6) months, respectively. In the OPTN data, the incidence of post-transplant lung cancer in patients who underwent DLT for the non-cancerous disease was 0.8% and the 5-year OS was 47.3%. CONCLUSIONS In conclusion, our integrated analysis of the case series and the OPTN registry demonstrated promising survival outcomes for patients with refractory bilateral lung cancer who underwent DLT. Although there are limitations to consider, the results of this study underscore the potential benefits of DLT in managing refractory lung-limited lung cancer.

A Comprehensive Landscape of De Novo Malignancy After Double Lung Transplantation.

Although the association between post-transplant malignancy (PTM) and immunosuppressive therapy after organ transplantation has been studied, an integrated review of PTM after lung transplantation is lacking. We investigated the incidence and types of de novo PTM and its impact on survival following double lung transplantation (DLT). The incidence and type of PTM as well as the annual and cumulative risks of each malignancy after DLT were analyzed. The overall survival (OS) of recipients with or without PTM was compared by the Kaplan-Meier survival method and landmark analysis. There were 5,629 cases (23.52%) with 27 types of PTMs and incidences and OS varied according to the types of PTMs. The recipients with PTM showed a significantly longer OS than those without PTM (p < 0.001). However, while the recipients with PTM showed significantly better OS at 3, and 5 years (p < 0.001, p = 0.007), it was worse at the 10-year landmark time (p = 0.013). And the single PTM group showed a worse OS rate than the multiple PTM group (p < 0.001). This comprehensive report on PTM following DLT can help understand the risks and timing of PTM to improve the implementation of screening and treatment.

Dry-Electrode All-Solid-State Batteries Fortified with a Moisture Absorbent.

For realizing all-solid-state batteries (ASSBs), it is highly desirable to develop a robust solid electrolyte (SE) that has exceptional ionic conductivity and electrochemical stability at room temperature. While argyrodite-type Li6PS5Cl (LPSCl) SE has garnered attention for its relatively high ionic conductivity (∼3.19 × 10-3 S cm-1), it tends to emit hydrogen sulfide (H2S) in the presence of moisture, which can hinder the performance of ASSBs. To address this issue, researchers are exploring approaches that promote structural stability and moisture resistance through elemental doping or substitution. Herein, we suggest using zeolite imidazolate framework-8 as a moisture absorbent in LPSCl without modifying the structure of the SE or the electrode configuration. By incorporating highly ordered porous materials, we demonstrate that ASSBs configured with LPSCl SE display stable cyclability due to effective and long-lasting moisture absorption. This approach not only improves the overall quality of ASSBs but also lays the foundation for developing a moisture-resistant sulfide electrolyte.

Flattening of Lithium Plating in Carbonate Electrolytes Enabled by All-In-One Separator.

The uncontrollable dendritic growth of metallic lithium during repeated cycling in carbonate electrolytes is a crucial obstacle hindering the practical use of Li-metal batteries (LMBs). Among numerous approaches proposed to mitigate the intrinsic constraints of Li metal, the design of a functional separator is an attractive approach to effectively suppress the growth of Li dendrites because direct contact with both the Li metal surface and the electrolyte is maintained. Here, a newly designed all-in-one separator containing bifunctional CaCO3 nanoparticles (CPP separator) is proposed to achieve the flattening of Li deposits on the Li electrode. Strong interactions between the highly polar CaCO3 nanoparticles and the polar solvent reduces the ionic radius of the Li+ -solvent complex, thus increasing the Li+ transference number and leading to a reduced concentration overpotential in the electrolyte-filled separator. Furthermore, the integration of CaCO3 nanoparticles into the separator induces the spontaneous formation of mechanically-strong and lithiophilic CaLi2 at the Li/separator interface, which effectively decreases the nucleation overpotential toward Li plating. As a result, the Li deposits exhibit dendrite-free planar morphologies, thus enabling excellent cycling performance in LMBs configured with a high-Ni cathode in a carbonate electrolyte under practical operating conditions.

Beneficial Role of Inherently Formed Residual Lithium Compounds on the Surface of Ni-Rich Cathode Materials for All-Solid-State Batteries.

This study validates the beneficial role of residual Li compounds on the surface of Ni-rich cathode materials (LiNixCoyMnzO2, NCM). Residual Li compounds on Ni-rich NCM are naturally formed during the synthesis procedure, which degrades the initial Coulombic efficiency and generates slurry gelation during electrode fabrication in Li-ion batteries (LIBs) using liquid electrolytes. To solve this problem, washing pretreatment is usually introduced to remove residual Li compounds on the NCM surface. In contrast to LIBs, we found that residual Li compounds can serve as a functional layer that suppresses the interfacial side reactions of the NCM in all-solid-state batteries (ASSBs). The formation of resistive phosphate-based compounds from the undesirable side reaction during the initial charging step is suppressed by the residual Li compounds on the surface of the NCM, thereby reducing polarization growth in ASSBs and enhancing rate performances. The advantageous effects of the intrinsic residual Li compounds on the NCM surface suggest that the essential washing process of the NCM for the liquid-based LIB system should be reconsidered for ASSB systems.

Bi-Morphological Form of SiO2 on a Separator for Modulating Li-Ion Solvation and Self-Scavenging of Li Dendrites in Li Metal Batteries.

The lithium (Li) metal anode is highly desirable for high-energy density batteries. During prolonged Li plating-stripping, however, dendritic Li formation and growth are probabilistically high, allowing physical contact between the two electrodes, which results in a cell short-circuit. Engineering the separator is a promising and facile way to suppress dendritic growth. When a conventional coating approach is applied, it usually sacrifices the bare separator structure and severely increases the thickness, ultimately decreasing the volumetric density. Herein, we introduce dielectric silicon oxide with the feature of bi-morphological form, i.e., backbone-covered and backbone-anchored, onto the conventional polyethylene separator without any volumetric change. These functionally vary the Li+ transference number and the ionic conductivity so as to modulate Li-ion solvation and self-scavenging of Li dendrites. The proposed separator paves the way to maximizing the full cell performance of Li/NCM622 toward practical application.

Novel Strategy for the Formulation of High-Energy-Density Cathodes via Porous Carbon for Li-S Batteries.

Porous carbon is considered an attractive host material for high-energy sulfur electrodes. This study concerns the design of a porous carbon-based sulfur electrode for the formulation of high-energy Li-S batteries. The porous carbon is impregnated with up to 80 vol.% of sulfur and a reduction in both the conductive agent and binder content. Therefore, less solvent can be used during slurry casting to inhibit crack formation following electrode drying. In addition, the utilization of two distinct electrically conducting networks enables reduced battery polarization, resulting in a battery with a capacity of 690 mAh g-1 (even after 100 cycles). Finally, pouch cells are prepared to characterize the practical performance of the optimized cathode. This yields a capacity of 741 mAh and a cathode energy density of 1001 Wh kg-1 . These findings are expected to guide the further development of high-energy-density cathode materials for Li-S batteries.

Stable Li Metal-Electrolyte Interface Enabled by SEI Improvement and Cation Shield Functionality of the Azamacrocyclic Ligand in Carbonate Electrolytes.

To promote the reversible cycleability of Li metal negative electrodes, a Li-chelating azamacrocyclic ligand molecule is introduced into a carbonate-based electrolyte intended for lithium metal batteries. Reversible Li plating and stripping on the Cu electrode are found to be the outcomes of the bifunctional effects of adding the lithium nitrate-chelating azamacrocyclic ligand. The negatively shifted redox potential of the Li-chelating macrocyclic ligand, relative to that of the free Li-ion, acted as a cationic shielding molecule for smooth Li deposition, and the Li3N-based solid electrolyte interphase (SEI) film derived from the nitrate anion strengthened the interphasial characteristics of the Li metal negative electrode. Cationic shielding and Li3N-based SEI composition could help enhance the cycleability of the Li metal in a cascading manner. Consequently, the physicochemical characteristics of the lithium nitrate-chelated 1,4,8,11-tetramethyl-1,4,8,11-tetraazacylcotetradecane molecule exhibit stable Li/LiNi0.8Co0.1Mn0.1O2 cycleability.

Development of titanium 3D mesh interlayer for enhancing the electrochemical performance of zinc-bromine flow battery.

Zinc dendrite growth negatively affects zinc-bromine flow battery (ZBB) performance by causing membrane damage, inducing self-discharge. Herein, in a ZBB, a conventional polymer mesh was replaced with a titanium-based mesh interlayer; this provided additional abundant active sites for the Zn2+/Zn redox reaction and well-developed electrolyte flow channels, which resulted in improved reaction kinetics and suppressed Zn dendrite growth. Compared with a ZBB cell comprising a conventional polymer mesh and a carbon-based electrode, the ZBB cell using the titanium mesh interlayer and a carbon-based electrode showed significantly reduced frequency of the refreshing process, which occurs at regular cycling intervals during practical use for removing residual zinc dendrites in ZBB; also, the average energy efficiency at a current density of 40 mA cm-2 increased by 38.5%. Moreover, the modified ZBB cell exhibited higher energy efficiency at a high current density of 80 mA cm-2, which is an improvement of 14.7% than in case of the contemporary polymer mesh. Consequently, this study can provide helpful insights for new anode side structures including spacer mesh for developing high-performance ZBBs.

Sulfide-Compatible Conductive and Adhesive Glue-Like Interphase Engineering for Sheet-Type All-Solid-State Battery.

An all-solid-state lithium battery based on a sulfide electrolyte is one of the most promising next-generation energy storage systems. However, the high interfacial impedance, particularly due to the internal pores in the electrode or electrolyte layers, is the major limiting factor to the development of sheet-type all-solid-state batteries. In this study, a low-resistance integrated all-solid composite electrode is developed using a hybrid of a pyrrolidinium-based ionic liquid and a polyethylene oxide polymer with lithium salt as a multifunctional interphase material, which is engineered to be compatible with the sulfide electrolyte as well as the fabrication process of sheet-type composite electrode. The interphase material fills the pore in the composite sheet while binding the components together, which effectively increases the interfacial contact area and strengthens the physical network between the components, thereby enabling enhanced ion transport throughout the electrode. The interphase-engineered sheet-type LiNi0.8 Co0.1 Mn0.1 O2 /Li10 GeP2 S12 electrode shows a high reversible capacity of 166 mAh g-1 at 25 °C, corresponding to 92% of the observed capacity in a current liquid-based cathode system, as well as enhanced cycle and rate performances. This study proposes a novel and practical method for the development of high-performance sheet-type all-solid-state lithium batteries.

Using insurance data to quantify the multidimensional impacts of warming temperatures on yield risk.

Previous research predicts significant negative yield impacts from warming temperatures, but estimating the effects on yield risk and disentangling the relative causes of these losses remains challenging. Here we present new evidence on these issues by leveraging a unique publicly available dataset consisting of roughly 30,000 county-by-year observations on insurance-based measures of yield risk from 1989-2014 for U.S. corn and soybeans. Our results suggest that yield risk will increase in response to warmer temperatures, with a 1 °C increase associated with yield risk increases of approximately 32% and 11% for corn and soybeans, respectively. Using cause of loss information, we also find that additional losses under warming temperatures primarily result from additional reported occurrences of drought, with reported losses due to heat stress playing a smaller role. An implication of our findings is that the cost of purchasing crop insurance will increase for producers as a result of warming temperatures.

Estimating non-additive within-season temperature effects on maize yields using Bayesian approaches.

Detrimental impacts of extreme heats on the U.S. crop yields have been well-documented by a number of empirical studies. However, less have focused on within-growing season weather variation and the interaction between temperature and precipitation. The objective of this study is to emphasize the importance of disaggregating temperature exposures within growing season. To achieve our objective, we estimate the impact of within-season monthly temperature and precipitation variations on maize yields in the U.S. corn belt region. We provide a discussion on variable selection methods in the context of estimating crop yield responses to climate variables. We find that the models that utilize within-growing season monthly variations performs better compared to the models with growing season aggregated weather variables and show the strength of Bayesian estimations. We also find that the warming impacts predicted by the models that utilize within-growing season variations are smaller than the predicted impacts of the models with aggregated weather variables. The findings indicate that the temperature effects are not additive across months within growing season.

Rational Design of a Composite Electrode to Realize a High-Performance All-Solid-State Battery.

A potential solid electrolyte for realizing all-solid-state battery (ASB) technology has been discovered in the form of Li10 GeP2 S12 (LGPS), a lithium superionic conductor with a high ionic conductivity (≈12 mS cm-1 ). Unfortunately, the achievable Li+ conductivity of LGPS is limited in a sheet-type composite electrode owing to the porosity of this electrode structure. For the practical implementation of LGPS, it is crucial to control the pore structures of the composite electrode, as well as the interfaces between the active materials and solid- electrolyte particles. Herein, the addition of an ionic liquid, N-methyl-N-butylpyrrolidinium bis(trifluoromethylsulfonyl)imide ([Py14 ][TFSI]), is proposed as a pore filler for constructing a highly reliable electrode structure using LGPS. [Py14 ][TFSI] is coated onto the surface of LGPS powder through a wet process and a sheet-type composite electrode is prepared using a conventional casting procedure. The [Py14 ][TFSI]-embedded composite electrode exhibits significantly improved reversible capacity and power characteristics. It is suggested that pore-filling with [Py14 ][TFSI] is effective for increasing contact areas and building robust interfaces between the active materials and solid-electrolyte particles, leading to the generation of additional Li+ pathways in the composite electrode of ASBs.

Amide-Functionalized Porous Carbonaceous Anode Materials for Lithium-Ion Batteries.

Porous carbonaceous anode materials have received considerable attention as an alternative anode material, however, there is a critical bottleneck as it suffers from a large irreversible specific capacity loss over several initial cycles owing to undesired surface reactions. In order to suppress undesired surface reactions of porous carbonaceous anode material, here, we suggest a simple and convenient two-step surface modification approach that allows the embedding of an amide functional group on the surface of a porous carbonaceous anode, which effectively improves the surface stability. In this approach, the porous carbonaceous anode material is firstly activated by means of strong acid treatment comprising a combination of H2 SO4 and HNO3 , and it is subjected to further modification by means of an amide coupling reaction. Our additional systematic analyses confirm that the acid functional group effectively transforms into the amide functional group. The resulting amide-functionalized porous carbon exhibits an improved electrochemical performance: the initial discharge specific capacity is greatly reduced to less than 2,620 mA h g-1 and charge specific capacity is well still remained, indicating stabling cycling performance of the cell.

Facile Mn Surface Doping of Ni-Rich Layered Cathode Materials for Lithium Ion Batteries.

A facile Mn surface doping process is proposed to improve the thermal and structural stabilities of Ni-rich layered cathode materials (Ni ≥ 80%) for lithium-ion batteries in electric vehicles. Herein, we demonstrate that the surface structure of the Ni-rich layered cathode materials can be stabilized by the introduction of a thin Mn-rich surface layer. This layer effectively reduces the direct exposure of the highly reactive Ni on the surface of the cathode materials, thus enhancing thermal stability and mitigating side reactions associated with highly reactive Ni that causes the loss of reversible capacity. In practice, the Mn surface-doped Ni-rich layered cathode material exhibits a high specific capacity with an improved cycling stability even at a high temperature (60 °C). We believe that our simple approach offers more opportunities to upscale production without any extra caution.

Few-Layer Graphene Island Seeding for Dendrite-Free Li Metal Electrodes.

Li metal batteries such as Li-air and Li-S systems have increasingly attracted the attention of researchers because of their high energy densities, which are enhanced by the use of Li metal negative electrodes. However, poor cycle efficiency and safety concerns, which are mainly related to dendritic Li growth during cycling, need to be addressed. Here we propose a solution to the Li dendrite problems. We distributed chemically prepared nitrogen-doped few-layer graphene (N-FLG) sheets on Cu substrates to create island structures. The island-type FLG on the Cu electrode was prepared via spin-coating using slurries that included a polymer binder. When the electrode was used for Li deposition, Li ions were first inserted into the graphene layers. Then, Li metal nucleation occurred at the N-FLG sheets owing to their high electrical conductivity; meanwhile, an insulating polymer layer on the Cu prevented the growth of metallic Li there. Lastly, Li metal grew from the edges of N-FLG sheets in both the lateral and vertical direction, and Li metal deposits filled the gaps between the N-FLG islands as well as covering the remainder of the electrode surface. Thus, stable cycling with flat voltage profiles was demonstrated over 100 cycles at a current density of 2 mA cm-2. The materials and electrochemical characterization results highlight the effectiveness of this method, which paves the way for the development of robust, dendrite-free Li metal electrodes.

Mechanochemically Reduced SiO2 by Ti Incorporation as Lithium Storage Materials.

This study presents a simple and effective method of reducing amorphous silica (a-SiO2 ) with Ti metal through high-energy mechanical milling for improving its reactivity when used as an anode material in lithium-ion batteries. Through thermodynamic calculations, it is determined that Ti metal can easily take oxygen atoms from a-SiO2 by forming a thermodynamically stable SiO2-x /TiOx composite, meaning that electrochemically inactive a-SiO2 is partially reduced by the addition of Ti metal powder during milling. This mechanically reduced SiO2-x /TiOx composite anode exhibits a greatly improved electrochemical reactivity, with a reversible capacity of more than 700 mAh g(-1) and excellent cycle performance over 100 cycles. Furthermore, an enhancement in the mechanical and thermal stability of the composite during cycling can be mainly attributed to the in situ formation of the SiO2-x /TiOx phase. These findings provide new insight into the rational design of robust, high-capacity, Si-based anode materials, as well as their reaction mechanism.