Doublet or Triplet Antiemetic Prophylaxis for Nausea and Vomiting Induced by Trastuzumab Deruxtecan: an Open-Label, Randomized, and Multicenter Exploratory Phase 2 Study.

Background: Trastuzumab deruxtecan is classified as an anticancer agent that poses a moderate emetic risk in the international guidelines for antiemetic therapy. The guidelines recommend emesis prophylaxis using a two-drug combination therapy comprising a 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) and dexamethasone (DEX). However, the high incidence of nausea and vomiting associated with trastuzumab deruxtecan is problematic. The National Comprehensive Cancer Network guideline version 1.2023 classified trastuzumab deruxtecan as having a high risk of emesis and changed its recommendation to a triplet regimen including a neurokinin-1 receptor antagonist (NK1RA). However, the emetogenic potential of trastuzumab-deruxtecan and the optimal antiemetic prophylaxis are controversial. Hence, this exploratory phase 2 study aimed to assess the efficacy and safety of treatment comprising 5-HT3RA and DEX with or without a NK1RA in preventing trastuzumab deruxtecan-induced nausea and vomiting. Methods: We conducted an open-label and randomized exploratory phase 2 study at 14 centers in Japan. Patients with breast cancer who were scheduled to receive trastuzumab deruxtecan were enrolled in this study. The patients were randomly assigned to receive granisetron and DEX (arm GD) or granisetron, DEX, and aprepitant (fosaprepitant; arm GDA). The primary endpoint was complete response (CR; no emesis or no rescue therapy) during the overall phase (120 h after the start of trastuzumab deruxtecan). Results: Between September 2020 and March 2023, 40 patients were randomly assigned to the GD (n = 19) or GDA (n = 21) arm. In the GDA arm, one patient who did not complete the use of the rescue medication listed in the diary was excluded from the efficacy analysis, which included the use of rescue medication. The CR rates during the overall phase were 36.8% and 70.0% in the GD and GDA arms, respectively (odds ratio 0.1334; 95% confidence interval [CI]: 0.0232-0.7672; P = 0.0190), with a difference of 33.2%. No grade 3 or 4 toxicity related to antiemetic therapy was observed. Conclusions: Patients receiving trastuzumab deruxtecan require triple therapy, including mandatory NK1RA administration.

[Clinical Features of Endocrine Disorders with Immune Checkpoint Inhibitor in Patients with Non-Small Cell Lung Cancer].

Immune checkpoint inhibitors(ICIs)could cause immune-related adverse events(irAEs), of which endocrine disorders are relatively common. Symptoms include fatigue, anorexia, and shock, making diagnosis and treatment difficult. This study aimed to analyze the characteristics of patients with non-small cell lung cancer concomitant with endocrine disorders as irAEs. In total, 83 patients who were administered ICIs for advanced or postoperative recurrent non-small cell lung cancer between February 2016 and February 2021 were identified. We retrospectively studied the clinical course and findings of 7 patients who developed endocrine disorders after treatment. Four patients had hypopituitarism, and 3 patients had thyroid dysfunctions. There were 6 male patients and 1 female patient. Regarding anticancer agents, 5 patients received ICI alone, and 2 patients received ICI plus cytotoxic chemotherapies. The patients received treatment from the irAE treatment team in our hospital, and 5 of 7 patients could were able to be readministered ICIs. Endocrine disorders as irAEs require collaboration with specialized departments for early diagnosis and treatment.

Tunable Thermal Switch via Order-Order Transition in Liquid Crystalline Block Copolymer.

Organic material-based thermal switch is drawing much attention as one of the key thermal management devices in organic electronic devices. This study aims at tuning the switching temperature (TS) of thermal conductivity by using liquid crystalline block copolymers (BCs) with different order-order transition temperature (Ttr) related to the types of mesogens in the side chain. The BC films with low Ttr of 363 K and high Ttr of 395 K exhibit reversible thermal conductivity switching behaviors at TS of ∼360 K and ∼390 K, respectively. The BC films also exhibit thermal conductivity variation originating from the anisotropy of the internal structures: poly(ethylene oxide) domains and liquid crystals. These results demonstrate that the switching behavior is attributed to an order-order transition between BC films with vertically arranged cylinder domains and the ones with ordered sphere domains. This highlights that BCs become a promising thermal conductivity switching material with tailored TS.

Self-template-assisted micro-phase segregation in blended liquid-crystalline block copolymers films toward three-dimensional structures.

In-plane mesopatterns derived from block-copolymer (BCP) micro-phase segregation in thin films have attracted much interest in practical applications as well as fundamental research programs. However, phase segregation along the film-normal direction has been less studied. Here, we describe a strategy to concurrently, yet independently, control in-plane micro-phase and out-of-plane macro-phase segregation in multiblended films composed of liquid-crystalline BCPs (LCBCPs), affording spontaneously layered three-dimensional (3D) mesostructures. This strategy relies on sequential liquid crystallization during the cooling process in thermal annealing as follows. The constituent LCBCP with the highest isotropic-transition temperature (Tiso) first liquid-crystallizes and segregates from the other LCBCP mixture remaining in isotropic states to form a noncontaminated layer at the top surface. This preformed LCBCP layer preserves its inherent in-plane pattern and acts as a template guiding the subsequent micro-phase segregations of the other low-Tiso LCBCPs underneath. This self-template-assisted micro-phase segregation (STAMPS) readily provides 3D mesostructures, the potential toward rational material design of which is also demonstrated in water-separation applications.

Terahertz emission from gold nanorods irradiated by ultrashort laser pulses of different wavelengths.

Electron photoemission and ponderomotive acceleration by surface enhanced optical fields is considered as a plausible mechanism of terahertz radiation from metallic nanostructures under ultrafast laser excitation. To verify this mechanism, we studied experimentally terahertz emission from an array of gold nanorods illuminated by intense (~10-100 GW/cm2) femtosecond pulses of different central wavelengths (600, 720, 800, and 1500 nm). We found for the first time that the order of the dependence of the terahertz fluence on the laser intensity is, unexpectedly, almost the same (~4.5-4.8) for 720, 800, and 1500 nm and somewhat higher (~6.6) for 600 nm. The results are explained by tunneling currents driven by plasmonically enhanced laser field. In particular, the pump-intensity dependence of the terahertz fluence is more consistent with terahertz emission from the sub-cycle bursts of the tunneling current rather than with the ponderomotive mechanism.

Ice/Salt-Assisted Synthesis of Ultrathin Two-Dimensional Micro/Mesoporous Iron and Nitrogen Co-Doped Carbon as an Efficient Electrocatalyst for Oxygen Reduction.

An ice/salt-assisted strategy has been developed to achieve the green and efficient synthesis of ultrathin two-dimensional (2D) micro/mesoporous carbon nanosheets (CNS) with the dominant active moieties of Fe-N4 (Fe-N-CNS) as high-performance electrocatalysts for the oxygen reduction reaction (ORR). The strategy involves freeze-drying a mixture of iron porphyrin and KCl salt using ice as template followed by a confined pyrolysis with KCl as an independent sealed nanoreactor to facilitate the formation of 2D carbon nanosheets, N incorporation, and porosity creation. The well-defined assembly of ultrathin 2D carbon nanosheets ensures high utilization of D1 and D3 Fe-N4 active sites, and effectively promotes the mass transport of ORR reactants by virtue of the pronounced mesoporous structure. The resulting Fe-N-CNS electrocatalyst was shown to exhibit superior ORR activity, better electrochemical durability, and methanol tolerance towards ORR in alkaline electrolyte relative to the commercial Pt/C electrocatalyst.

Vibrational Cooling in Oligomeric Viologens of Different Sizes and Topologies.

Vibrational cooling was investigated in a set of homologous dimers and trimers with methyl viologen repeat units (MV2+). The rapid, <500 fs decay of the D1 excited state of monoreduced viologen (MV+•) via a conical intersection allows the preparation of a vibrationally hot D0 ground state with a large excess energy of 1.7 eV, which is equivalent to the initial effective temperature of ∼800 K. Pump-probe spectroscopy was used to monitor the disappearance of the characteristic D0 → D1 hot absorption band, which appears at longer wavelengths than the steady-state spectrum of "cold" MV+• in equilibrium with the solvent. It is assumed that the vibrational excitation of the ground is initially confined to the same monoreduced viologen repeat unit, which was optically excited to the localized electronic D1 state, although some degree of redistribution may occur already in the excited state. The observed cooling rates depend on the size and topology of the oligomer, with the linear trimer exhibiting significantly faster thermalization than the branched one. The experimental results were corroborated by molecular dynamics simulations carried out in the harmonic approximation. The dynamics of the thermal equilibration in these systems appears to be consistent with primarily ballistic initial propagation of the vibrational excess energy over distances as large as ∼4 nm and suggests the presence of interference between the equivalent pathways in the branched trimer.

Helical micromotor operating under stationary DC electrostatic field.

The direct current (DC) motor is a rotary device that converts DC electrical energy into mechanical energy. However, it is known that, in downsizing the currently available macromotor, rotary motion of DC micromotors cannot work well due to the larger viscous effect. Here, we report simple DC micromotors working under a new principle. We previously revealed that in an oil phase containing an ionic surfactant, non-spherical particles exhibit various types of regular motions such as spinning and circular orbital motions. In this study, we found that a microhelix exhibits a new type of periodic motion, namely, the cork-screw-type rotation, in a specific direction depending on the material of the helix, metal or non-metallic organics. The results show that a left-handed nickel helix rotates in the clockwise direction when viewed from the positive electrode, whereas an organic one rotates in the opposite direction (anti-clockwise) under the same electrode arrangement with stationary constant DC voltage. In addition, we demonstrate that the cork-screw rotation is switched to opposite direction by changing the handedness (chirality). It is to be noted that the micromotors reported here maintain their stable motion without any mechanical support such as rotational axes or electronic switching devices. The invented DC micromotor would be applicable for mechanical and fluidic devices, being useful as a smart device in microrobots and microfluidics.

Identification of Short- and Long-Wavelength Emitting Chlorophylls in Cyanobacterial Photosystem I by Plasmon-Enhanced Single-Particle Spectroscopy at Room Temperature.

A peculiarity of cyanobacterial Photosystem I (PSI) is the presence of so-called red chlorophylls absorbing at wavelengths longer than the reaction center P700. The origin and function of these chlorophylls have been debated in literature, but so far no consensus has been reached on either question. Here, we use plasmon-enhanced single-particle fluorescence spectroscopy to elucidate the origin of both short- and long-wavelength emitting species in monomeric PSI from Thermosynechococcus elongatus at room temperature. Polarized fluorescence spectra of single PSI complexes reveal a phase shift in the modulation of the short-wavelength (687 nm) and long-wavelength (717 nm) peaks. Numerical simulations show that this phase shift reflects a spatial angle of 15° between the transition dipole moments of the two forms. Quantum chemical calculations, together with reported X-ray structural and spectroscopic data, were used to assign the chlorophyll a monomer A3 as a candidate for the short-wavelength emitter and the B31-B32 chlorophyll dimer as a candidate for the long-wavelength emitter.

Electrostatic Repulsion-Induced Desorption of Dendritic Viologen-Arranged Molecules Anchored on a Gold Surface through a Gold-Thiolate Bond Leading to a Tunable Molecular Template.

We investigated the adsorption and desorption behavior of self-assembled monolayers (SAMs) on gold derived from dendritic viologen-arranged molecules with an ω-mercaptodecyl group (A n, n (dendritic generation) = 0-3) at the apex of the dendritic structure in polar solvents. The adsorption of the dendritic molecules occurred quickly and saturated within a few minutes in an acetonitrile/ethanol (1/1, v/v) mixture at a concentration of 2 mM. Atomic force microscopy images of the SAMs showed flat surfaces regardless of the dendritic generation because the peripheral viologen units were closely packed at the surface of the molecular layer. Individual A3 molecules immobilized on the substrate were observed by scanning tunneling microscopy measurements of a mixed SAM with decanethiol. The desorption behaviors of dendritic molecules from the A n-SAMs in several solvents such as water were also investigated. The spontaneous desorption of the A n-SAM occurred more rapidly than that of a conventional n-alkanethiol SAM. However, the desorption was inhibited by adding electrolytes such as NaNO3 due to the shielding effect on the electrostatic repulsion between the dendritic molecules. These results indicate that the surface density of the dendritic molecules can be controlled through the desorption.

Resolution of Infliximab-Refractory Nivolumab-Induced Acute Severe Enterocolitis After Cyclosporine Treatment in a Patient with Non-Small Cell Lung Cancer.

BACKGROUND Enterocolitis is an immune-related adverse event associated with nivolumab treatment. Although intravenous corticosteroids and infliximab are recommended as a first-line and second-line therapy, respectively, there is no established treatment for severe enterocolitis that is refractory to these drugs. CASE REPORT A 62-year-old male with non-small cell lung cancer, with multiple brain metastasis, received nivolumab as the eighth-line chemotherapy for his disease. A few days after nivolumab administration, grade 2-3 enterocolitis developed in the patient. The enterocolitis improved to grade 1 after careful observation; however, it was aggravated to grade 3 after resuming nivolumab treatment. After cessation of nivolumab, 3.3 mg of intravenous dexamethasone and 40 mg of methylprednisolone were administered for 16 days and subsequently 30-60 mg of oral prednisolone was administered for 50 days, with little improvement in the patient's colitis. A second-line treatment with 5 mg/kg of infliximab was twice attempted, but the patient had persistent diarrhea. Therefore, 50 mg of oral cyclosporine was started as a third-line therapy. Three days after the start of cyclosporine, the number of diarrhea events decreased, with resolution 2 weeks after cyclosporine administration. CONCLUSIONS Oral cyclosporine treatment can be a third-line therapy for enterocolitis associated with immune-related adverse events.

High-space resolution imaging plate analysis of extreme ultraviolet (EUV) light from tin laser-produced plasmas.

With the advent of high volume manufacturing capabilities by extreme ultraviolet lithography, constant improvements in light source design and cost-efficiency are required. Currently, light intensity and conversion efficiency (CE) measurments are obtained by charged couple devices, faraday cups etc, but also phoshpor imaging plates (IPs) (BaFBr:Eu). IPs are sensitive to light and high-energy species, which is ideal for studying extreme ultraviolet (EUV) light from laser produced plasmas (LPPs). In this work, we used IPs to observe a large angular distribution (10°-90°). We ablated a tin target by high-energy lasers (1064 nm Nd:YAG, 1010 and 1011 W/cm2) to generate the EUV light. The europium ions in the IP were trapped in a higher energy state from exposure to EUV light and high-energy species. The light intensity was angular dependent; therefore excitation of the IP depends on the angle, and so highly informative about the LPP. We obtained high-space resolution (345 µm, 0.2°) angular distribution and grazing spectrometer (5-20 nm grate) data simultaneously at different target to IP distances (103 mm and 200 mm). Two laser systems and IP types (BAS-TR and BAS-SR) were also compared. The cosine fitting values from the IP data were used to calculate the CE to be 1.6% (SD ± 0.2) at 13.5 nm 2% bandwidth. Finally, a practical assessment of IPs and a damage issue are disclosed.

Nanoporous Films with Sub-10 nm in Pore Size from Acid-Cleavable Block Copolymers.

Nanoporous thin films with pore size of sub-10 nm are fabricated using an acid-cleavable block copolymer (BCP), a benzoic imine junction between poly(ethylene oxide) (PEO) and poly(methacrylate) (PMAAz) bearing an azobenzene side chain (denoted as PEO-bei-PMAAz) as the precursor. After a thermal annealing, the block copolymers are self-assembled to form highly ordered PEO cylinders within a PMAAz matrix normal to the film, even in the case of low BCP molecular weight due to the existing of the liquid crystalline (LC) azobenzene rigid segment. Thus, PMAAz thin films with pore size of ≈7 nm and density of ≈1012 cm-2 are obtained after removal of the PEO minor phase by breaking the benzoic imine junction under mild acidic conditions. This work enriches the nanoporous polymer films from BCP precursors and introduces the LC property as a functionality which can further enhance the mechanical properties of the films and broaden their applications.

Water-Rich Fluid Material Containing Orderly Condensed Proteins.

A fluid material with high protein content (120-310 mg mL-1 ) was formed through the ordered self-assembly of native proteins segregated from water. This material is instantly prepared by the simple mixing of a protein solution with anionic and cationic surfactants. By changing the ratio of the surfactants based on the electrostatic characteristics of the target protein, we observed that the surfactants could function as a versatile molecular glue for protein assembly. Moreover, these protein assemblies could be disassembled back into an aqueous solution depending on the salt conditions. Owing to the water-retaining properties of the hydrophilic part of surfactants, the proteins in this material are in a water-rich environment, which maintains their native structure and function. The inclusion of water also provides functional extensibility to this material, as demonstrated by the preparation of an enzymatically active gel. We anticipate that the unique features of this material will permit the use of proteins not only in solution but also as elements of integrated functionalized materials.

Slowing the translocation of single-stranded DNA by using nano-cylindrical passage self-assembled by amphiphilic block copolymers.

We report a novel approach to slow the translocation of single-stranded DNA (ssDNA) by employing polyethylene oxide (PEO) filled nano-cylindrical domains as transportation channels. DNA strands were demonstrated to electrophoretically translocate through PEO filled cylindrical domains with diameters of 2 and 9 nm, which were self-assembled by amphiphilic liquid crystalline block copolymers. The average translocation rate of ssDNA strands was effectively reduced to an order of 10 µs per nucleotide, which was 1-2 orders slower than that attained by utilizing conventional solid-state nanopore devices.

[Comparison of the Cost-Effectiveness of the SOX and COX Regimens in Patients with Unresectable Advanced and Recurrent Colorectal Cancer Using a Clinical Decision Analysis Approach].

Phase III clinical trials have comfirmed that the S-1 plus oxaliplatin(SOX)is inferior to the capecitabine plus oxaliplatin (COX)regimen in the treatment of metastatic colorectal cancer.On the basis of these findings, we compared, using a clinical decision analysis-based approach, the cost-effectiveness of the SOX and COX regimens.Herein, we simulated the expected effects and costs of the SOX and COX regimens using the markov model.Clinical data were obtained from Hong's 2012 report.The cost data comprised the costs for pharmacist labor, material, inspection, and treatment for adverse event, as well as the total cost of care at the advanced stage.The result showed that the expected cost of the SOX and COX regimen was 1,538,330 yen, and 1,429,596 yen, respectively, with an expected survival rate of 29.18 months, and 28.63 months, respectively.The incremental cost-effectiveness ratio of the SOX regimen was 197,698 yen/month; thus, the SOX regimen was found to be more cost-effective that the COX regimen.

Generation Dependent Ultrafast Charge Separation and Recombination in a Pyrene-Viologen Family of Dendrons.

The ability of a dendritic network to intercept electrons and extend the lifetime of a short-lived photoinduced charge separated (CS) state was investigated in a homologous family of methyl viologen (MV(2+)) dendrons spanning four generations, G0 through G3. The CS state in the parent pyrene-methylene-viologen G0 system with a single acceptor exhibits an extremely short lifetime of τ = 0.72 ps. The expansion of the viologen network introduces slower components to the recombination kinetics by allowing the injected electron to migrate further away from the donor. The long-lived fraction of the population increases monotonically in the order G3 > G2 > G1 > G0, while the respective recombination rates decrease. In the highest generation of the dendron ∼14% of the CS state population experiences a 10-fold or greater lifetime extension. Long range tunneling across multiple viologen units and sequential site-to-site hopping both contribute to the overall effect. The large excess energy deposited in the apical viologen upon charge separation and the presence of an extended network of low lying π-orbitals likely facilitate shuttling the electron further down the dendron.

Engineered Asymmetric Composite Membranes with Rectifying Properties.

Asymmetric composite membranes with rectifying properties are developed by grafting pH-stimulus-responsive materials onto the top layer of the composite structure, which is prepared by two novel block copolymers using a phase-separation technique. This engineered asymmetric composite membrane shows potential applications in sensors, filtration, and nanofluidic devices.

Atelocollagen-templated fabrication of tangled fibrous silica.

Protein-templated structured silica and titania are fabricated via a biomimetic method based on the synergistic effect of amine/carboxyl complexes under ambient conditions. Atelocollagen-templated silica showed a tangled fibrous structure with a smooth surface. The number of carboxyl groups of a protein is an important factor for homogeneous silica growth.