Two-dimensional heavy fermion in a monoatomic-layer Kondo lattice YbCu2.

The Kondo effect between localized f-electrons and conductive carriers leads to exotic physical phenomena. Among them, heavy-fermion (HF) systems, in which massive effective carriers appear due to the Kondo effect, have fascinated many researchers. Dimensionality is also an important characteristic of the HF system, especially because it is strongly related to quantum criticality. However, the realization of the perfect two-dimensional (2D) HF materials is still a challenging topic. Here, we report the surface electronic structure of the monoatomic-layer Kondo lattice YbCu2 on a Cu(111) surface observed by synchrotron-based angle-resolved photoemission spectroscopy. The 2D conducting band and the Yb 4f state, located very close to the Fermi level, are observed. These bands are hybridized at low-temperature, forming the 2D HF state, with an evaluated coherence temperature of about 30 K. The effective mass of the 2D state is enhanced by a factor of 100 by the development of the HF state. Furthermore, clear evidence of the hybridization gap formation in the temperature dependence of the Kondo-resonance peak has been observed below the coherence temperature. Our study provides a new candidate as an ideal 2D HF material for understanding the Kondo effect at low dimensions.

Impact of increased plasma levels of calreticulin on prognosis of patients with advanced lung cancer undergoing combination treatment of chemotherapy and immune checkpoint inhibitors.

BACKGROUND: Damage-associated molecular pattern (DAMP)-related immunogenic cell death triggers secondary adaptive immune responses. The relationship between DAMP levels and prognosis in patients with non-small cell lung cancer (NSCLC) who undergo a combination therapy of immune checkpoint inhibitors (ICI) and chemotherapy remains unclear. METHODS: Serial plasma samples were prospectively collected from 45 patients treated with ICI combination therapy for advanced NSCLC. Plasma concentrations of high-mobility group box 1 (HMGB1), calreticulin (CRT), annexin A1, and heat shock protein 70 were measured. Associations between increases in plasma DAMP levels and the efficacy of the ICI combination therapy were evaluated. RESULTS: The maximum fold changes in plasma levels differed across individuals but demonstrated a marked increase, especially for CRT (mean ± SEM, 11.61 ± 46.15). Increased plasma DAMP levels were not clearly associated with clinical responses. There was a significant correlation between the maximum fold change in CRT levels and progression-free survival (PFS; r = 0.49, P < 0.001). Median PFS and overall survival (OS) rates were higher in patients with a ≥ 2-fold increase in plasma CRT levels than in those with a < 2-fold increase (PFS, 14.9 versus 6.0 months, hazard ratio (HR), 0.58; P = 0.17; OS, not reached versus 21.6 months, HR, 0.31, P = 0.02). CONCLUSIONS: Plasma CRT level monitoring has the potential to predict the efficacy of ICI combination therapy and shed light on the mechanisms underlying DAMP-related immunogenic cell death.

Trauma-associated left renal vein thrombosis with nutcracker syndrome.

Background: Nutcracker syndrome is a compression of the left renal vein between the superior mesenteric artery and aorta, resulting in thrombogenesis. While renal vein thrombosis caused by renal disease is more common, solitary left renal vein thrombosis with nutcracker syndrome is rare. Case Presentation: We present the case of a patient with trauma-associated left renal vein thrombosis with nutcracker syndrome. A 24-year-old woman with low body mass index taking oral contraceptives was admitted for trauma. She had multiple injuries, including thoracolumbar fractures, for which elective spinal fusion surgery was scheduled. As the D-dimer level elevated to 82.5 µg/dL preoperatively, enhanced computed tomography was performed, which revealed a solitary left renal vein thrombus. Conclusion: This is the report of solitary left renal vein thrombosis in a patient with nutcracker syndrome after trauma. Patients with low body mass index and coagulopathy might have solitary left renal vein thrombosis associated with nutcracker syndrome.

Breakdown of bulk-projected isotropy in surface electronic states of topological Kondo insulator SmB6(001).

The topology and spin-orbital polarization of two-dimensional (2D) surface electronic states have been extensively studied in this decade. One major interest in them is their close relationship with the parities of the bulk (3D) electronic states. In this context, the surface is often regarded as a simple truncation of the bulk crystal. Here we show breakdown of the bulk-related in-plane rotation symmetry in the topological surface states (TSSs) of the Kondo insulator SmB6. Angle-resolved photoelectron spectroscopy (ARPES) performed on the vicinal SmB6(001)-p(2 × 2) surface showed that TSSs are anisotropic and that the Fermi contour lacks the fourfold rotation symmetry maintained in the bulk. This result emphasizes the important role of the surface atomic structure even in TSSs. Moreover, it suggests that the engineering of surface atomic structure could provide a new pathway to tailor various properties among TSSs, such as anisotropic surface conductivity, nesting of surface Fermi contours, or the number and position of van Hove singularities in 2D reciprocal space.

Bulk-sensitive spin-resolved resonant electron energy-loss spectroscopy (SR-rEELS): Observation of element- and spin-selective bulk plasmons.

We have developed spin-resolved resonant electron energy-loss spectroscopy with the primary energy of 0.3-1.5 keV, which corresponds to the core excitations of 2p-3d absorption of transition metals and 3d-4f absorption of rare-earths, with the energy resolution of about 100 meV using a spin-polarized electron source as a GaAs/GaAsP strained superlattice photocathode. Element- and spin-selective carrier and valence plasmons can be observed using the resonance enhancement of core absorptions and electron spin polarization. Furthermore, bulk-sensitive electron energy-loss spectroscopy spectra can be obtained because the primary energy corresponds to the mean free path of 1-10 nm. The methodology is expected to provide us with novel information about elementary excitations by resonant inelastic x-ray scattering and resonant photoelectron spectroscopy.

Increased plasma levels of damage-associated molecular patterns during systemic anticancer therapy in patients with advanced lung cancer.

BACKGROUND: Immunogenic cell death (ICD) characterized by the release of damage-associated molecular patterns (DAMPs) from dying cancer cells may contribute to the synergistic antitumor effect of cytotoxic chemotherapy combined with an immune checkpoint inhibitor. The kinetics of circulating DAMP levels in cancer patients have remained largely uncharacterized, however. METHODS: We evaluated the possible effects of various systemic anticancer therapy modalities on the kinetics of plasma DAMP concentrations in a prospective observational study of patients with advanced lung cancer. The plasma concentrations of high-mobility group box 1 (HMGB1), calreticulin (CRT), heat shock protein 70 (HSP70), annexin A1, and histone H3 were thus determined in 121 such patients at four time points during the first cycle of treatment. RESULTS: The mean of the maximum fold change in HMGB1, HSP70, or annexin A1 concentration observed during treatment was significantly greater than the corresponding baseline value (P<0.005). The maximum fold changes in HMGB1 and CRT concentrations tended to be associated with clinical response as evaluated by RECIST criteria, although the changes in the levels of these two DAMPs were not correlated, suggestive of differential induction mechanisms. Among the various treatment modalities administered, platinum-based combination or single-agent chemotherapy tended to elicit robust increases in the concentrations of HMGB1 and CRT. CONCLUSIONS: Serial monitoring of plasma revealed that systemic anticancer therapy increased the circulating levels of HMGB1 and CRT and that these changes tended to be associated with clinical response, suggesting that agents capable of releasing these DAMPs into plasma might induce ICD in advanced lung cancer patients.

Correlation of 4-meter gait speed with clinical indicators of chronic obstructive pulmonary disease.

BACKGROUND: Measuring daily physical activity and exercise capacity is recommended in the routine care of patients with chronic obstructive pulmonary disease (COPD). The 4-m gait speed (4mGS) is simple and effective in stratifying patients according to exercise performance, dyspnea, health status, and prognosis. We assessed the reliability of the 4mGS as a clinical marker by examining its association with established clinical indicators among hospitalized patients with COPD. METHODS: This retrospective study included 78 patients hospitalized with COPD (mean age: 76.3 ± 0.9 years; males, n = 69) between January 2016 and June 2018 who were assessed using the 4mGS and divided into slow (<0.8 m/s) and normal (≥0.8 m/s) 4mGS groups. Clinical characteristics were compared, including death during the observation period, time to first exacerbation, and long-term oxygen therapy requirement. RESULTS: There were strong relationships between 4mGS performance, the 6-min walk test (R = 0.70; p < 0.0001), and the modified Medical Research Council dyspnea scale (R = 0.68; p < 0.0001) among the 78 patients. The slow 4mGS group had a higher frequency of death during the observation period (p = 0.0095) and a greater requirement for long-term oxygen therapy (p = 0.0063). The 4mGS correlated with inspiratory capacity (IC) and IC/total lung capacity ratios, which are respiratory failure indicators. CONCLUSIONS: The 4mGS is a simple and easy method of assessing the physical condition as well as estimating the prognosis of patients with COPD, and may serve as a useful marker in home medical treatment or clinical settings.

Relaxation dynamics of [Re(CO)2(bpy){P(OEt)3}2](PF6) in TEOA solvent measured by time-resolved attenuated total reflection terahertz spectroscopy.

To reveal highly efficient photocatalytic properties of an artificial photosynthesis material [Re(CO)2(bpy){P(OEt)3}2](PF6), we have directly observed the photo-induced relaxation dynamics and reductive quenching process of the photo-excited state on a photosynthesis material in Triethanolamine (TEOA) solvent as an electron donor by time-resolved attenuated total reflection spectroscopy in the terahertz (THz) region. The spectrum of the complex in TEOA has an intermolecular vibrational mode between the complex and TEOA molecules, which reflects the precursor of the reductive quenching process. The intermolecular vibrational mode has three-step relaxation process in a picosecond timescale after photo-excitation, where firstly the triplet metal-to-ligand charge transfer excited state is vibrationally cooled down, secondly the distance between Re and TEOA is reduced by the rotation of TEOA molecules due to dipole-dipole interaction accelerated by heat transfer, and finally electrons transfer from TEOA to Re. These observations provide us the detailed information of the electron transfer process of photocatalytic properties of [Re(CO)2(bpy){P(OEt)3}2](PF6) in TEOA solvent.

Non-trivial surface states of samarium hexaboride at the (111) surface.

The peculiar metallic electronic states observed in the Kondo insulator, samarium hexaboride (SmB6), has stimulated considerable attention among those studying non-trivial electronic phenomena. However, experimental studies of these states have led to controversial conclusions mainly due to the difficulty and inhomogeneity of the SmB6 crystal surface. Here, we show the detailed electronic structure of SmB6 with angle-resolved photoelectron spectroscopy measurements of the three-fold (111) surface where only two inequivalent time-reversal-invariant momenta (TRIM) exist. We observe the metallic two-dimensional state was dispersed across the bulk Kondo gap. Its helical in-plane spin polarisation around the surface TRIM indicates that SmB6 is topologically non-trivial, according to the topological classification theory for weakly correlated systems. Based on these results, we propose a simple picture of the controversial topological classification of SmB6.

Evidence for a preformed Cooper pair model in the pseudogap spectra of a Ca10(Pt4As8)(Fe2As2)5 single crystal with a nodal superconducting gap.

For high-Tc superconductors, clarifying the role and origin of the pseudogap is essential for understanding the pairing mechanism. Among the various models describing the pseudogap, the preformed Cooper pair model is a potential candidate. Therefore, we present experimental evidence for the preformed Cooper pair model by studying the pseudogap spectrum observed in the optical conductivity of a Ca10(Pt4As8)(Fe2As2)5 (Tc = 34.6 K) single crystal. We observed a clear pseudogap structure in the optical conductivity and observed its temperature dependence. In the superconducting (SC) state, one SC gap with a gap size of Δ = 26 cm-1, a scattering rate of 1/τ = 360 cm-1 and a low-frequency extra Drude component were observed. Spectral weight analysis revealed that the SC gap and pseudogap are formed from the same Drude band. This means that the pseudogap is a gap structure observed as a result of a continuous temperature evolution of the SC gap observed below Tc. This provides clear experimental evidence for the preformed Cooper pair model.

Sensitivity of epidermal growth factor receptor with single or double uncommon mutations to afatinib confirmed by a visual assay.

Patients with non-small cell lung cancer (NSCLC) harboring common mutations of the epidermal growth factor receptor (EGFR) are sensitive to EGFR-tyrosine kinase inhibitors (TKI). Although forms of EGFR harboring single uncommon mutations such as G719X or L861Q are thought to be less sensitive to EGFR-TKI, the efficacy of these drugs in patients with double uncommon mutations has remained unclear. We here present an NSCLC patient found to be positive for double uncommon EGFR mutations (G719X and L861Q) by clinical genomic sequencing analysis of a pleural effusion specimen who showed a durable response to the EGFR-TKI afatinib. The sensitivity of EGFR with single or double uncommon mutations to afatinib and the EGFR-TKI erlotinib was also evaluated in vitro with a visual assay based on HEK293 cells transiently transfected with expression plasmids for yellow fluorescent protein (YFP)-tagged fragments of the EGFR intracellular domain (ICD). Whereas forms of EGFR with double uncommon mutations were more sensitive to erlotinib than were those with single uncommon mutations, those with single or double uncommon mutations were similarly sensitive to afatinib, consistent with the patient's clinical outcome. Our data support the notion that afatinib is the most suitable EGFR-TKI for NSCLC harboring uncommon mutations of EGFR. Furthermore, the YFP-EGFR-ICD assay is potentially applicable to prediction of EGFR-TKI efficacy in patients with such mutations.

N-methyl-d-aspartate receptor dysfunction in the prefrontal cortex of stroke-prone spontaneously hypertensive rat/Ezo as a rat model of attention deficit/hyperactivity disorder.

AIM: We previously reported that stroke-prone spontaneously hypertensive rat/Ezo (SHRSP/Ezo) has high validity as an attention deficit/hyperactivity disorder (AD/HD) animal model, based on its behavioral phenotypes, such as inattention, hyperactivity, and impulsivity. Fronto-cortical dysfunction is implicated in the pathogenesis of AD/HD. In this study, we investigated prefrontal cortex (PFC) function in SHRSP/Ezo rats by electrophysiological methods and radioreceptor assay. METHODS: We recorded excitatory postsynaptic potential in layer V pyramidal neurons in the PFC by intracellular recording method to assess synaptic plasticity in the form of long-term potentiation (LTP). We also performed N-methyl-d-aspartate acid (NMDA) receptor binding assay in the PFC and hippocampus using radiolabeled NMDA receptor antagonist [3 H]MK-801. RESULTS: Theta-burst stimulation induced LTP in the PFC of genetic control, WKY/Ezo, whereas failed to induce LTP in that of SHRSP/Ezo. The Kd value of [3 H]MK-801 binding for NMDA receptors in the PFC of SHRSP/Ezo was higher than in the WKY/Ezo. Neither the Bmax nor Kd of [3 H]MK-801 binding in the SHRSP/Ezo hippocampus was significantly different to WKY/Ezo. CONCLUSION: These results suggest that the AD/HD animal model SHRSP/Ezo has NMDA receptor dysfunction in the PFC.

Temperature dependence of the superconducting energy gaps in Ca9.35La0.65(Pt3As8)(Fe2As2)5 single crystal.

We measured the optical reflectivity R(ω) for an underdoped (Ca0.935La0.065)10(Pt3As8)(Fe2As2)5 single crystal and obtained the optical conductivity [Formula: see text] using the K-K transformation. The normal state [Formula: see text] at 30 K is well fitted by a Drude-Lorentz model with two Drude components (ωp1 = 1446 cm-1 and ωp2 = 6322 cm-1) and seven Lorentz components. Relative reflectometry was used to accurately determine the temperature dependence of the superconducting gap at various temperatures below Tc. The results clearly show the opening of a superconducting gap with a weaker second gap structure; the magnitudes for the gaps are estimated from the generalized Mattis-Bardeen model to be Δ1 = 30 and Δ2 = 50 cm-1, respectively, at T = 8 K, which both decrease with increasing temperature. The temperature dependence of the gaps was not consistent with one-band BCS theory but was well described by a two-band (hence, two gap) BCS model with interband interactions. The temperature dependence of the superfluid density is flat at low temperatures, indicating an s-wave full-gap superconducting state.

Expression of brain-derived neurotrophic factor and its receptor TrkB is associated with poor prognosis and a malignant phenotype in small cell lung cancer.

OBJECTIVES: TrkB is a receptor for brain-derived neurotrophic factor (BDNF) and is highly expressed in various cancers, with BDNF-TrkB signaling having been implicated in tumor progression and metastasis. The role of the BDNF-TrkB system in small cell lung cancer (SCLC), a neuroendocrine cancer, has remained unclear, however. We examined BDNF and TrkB expression in SCLC patients as well as the function of BDNF-TrkB signaling in SCLC cell lines. MATERIALS AND METHODS: BDNF and TrkB expression in tumor specimens of 58 SCLC patients and 20 non-small cell lung cancer (NSCLC) patients was examined by immunohistochemistry and was scored on the basis of the distribution and intensity of staining. TrkB-overexpressing SCLC (SBC5TrkB) cells were established by retrovirus transduction and were examined for the effects of BDNF on intracellular signaling, cell proliferation, and cell migration in vitro. RESULTS: The staining score for TrkB in NSCLC and SCLC specimens was 2.80 ±â€¯0.19 and 3.60 ±â€¯0.15, respectively, whereas that for BDNF was 1.95 ±â€¯0.32 and 2.76 ±â€¯0.14, respectively. High levels of both TrkB and BDNF expression in SCLC tumors were significantly associated with poor overall survival in multivariate analysis (hazard ratio = 1.821, P = 0.036). BDNF activated AKT and ERK signaling pathways in and promoted the migration of SBC5TrkB cells, and these effects were attenuated by the pan-Trk inhibitor GNF-5837. GNF-5837 also inhibited the proliferation of SBC5TrkB cells in the presence of BDNF. CONCLUSION: Coexpression of BDNF and TrkB was associated with poor prognosis in SCLC patients, and BDNF promoted the migration of TrkB-overexpressing SCLC cells. TrkB is thus a potential therapeutic target for SCLC.

Infrared Evaluation of Enantiometric Amount and Application to Racemization at the Interface Between L- and D-Alanine.

Amino acids, except for glycine, have two types of molecular structures, L- and D-forms, which are enantiomers. As the L- and D-form molecules have identical chemical and physical properties, they cannot be easily identified by conventional methods. In this study, we found that the amount and the spatial distribution of D-enantiomers in an L-alanine (CH3CH(COOH)NH2) matrix in evaporated thin films, which is one of amino acid molecules, can be evaluated quantitatively using an infrared micro spectroscopy with synchrotron radiation. This method was applied to the evaluation of the volume fraction of a racemic component appearing at the interface between L- and D-alanine thin films.

Near-field spectroscopic investigation of dual-band heavy fermion metamaterials.

Broadband tunability is a central theme in contemporary nanophotonics and metamaterials research. Combining metamaterials with phase change media offers a promising approach to achieve such tunability, which requires a comprehensive investigation of the electromagnetic responses of novel materials at subwavelength scales. In this work, we demonstrate an innovative way to tailor band-selective electromagnetic responses at the surface of a heavy fermion compound, samarium sulfide (SmS). By utilizing the intrinsic, pressure sensitive, and multi-band electron responses of SmS, we create a proof-of-principle heavy fermion metamaterial, which is fabricated and characterized using scanning near-field microscopes with <50 nm spatial resolution. The optical responses at the infrared and visible frequency ranges can be selectively and separately tuned via modifying the occupation of the 4f and 5d band electrons. The unique pressure, doping, and temperature tunability demonstrated represents a paradigm shift for nanoscale metamaterial and metasurface design.

A case of disseminated cryptococcosis with necrotizing fasciitis in a non-HIV patient.

Case: Disseminated cryptococcosis is a well-recognized condition among HIV patients, but it also occurs in non-HIV patients. Necrotizing fasciitis caused by cryptococcus is rare. An 81-year-old man who had received steroid therapy presented with erythema and pain in his right thigh. After the rapid progression of symptoms and a failure to respond to antibiotic therapy, a clinical diagnosis of necrotizing fasciitis was made. We performed debridement, and yeasts were detected using a Gram stain of the fascia. We treated the patient with liposomal amphotericin B. On day 3, he developed meningitis. Cryptococcus neoformans was detected in the blood, fascia, and cerebrospinal fluid. Flucytosine was added to liposomal amphotericin B. Outcome: Despite the antifungal treatment, new regions of dissemination to the skin developed, and the patient died of multiple organ failure. Conclusion: A diagnosis of disseminated cryptococcosis should be considered in a differential diagnosis of necrotizing fasciitis among immunocompromised patients, regardless of their HIV status.

Large-Gap Magnetic Topological Heterostructure Formed by Subsurface Incorporation of a Ferromagnetic Layer.

Inducing magnetism into topological insulators is intriguing for utilizing exotic phenomena such as the quantum anomalous Hall effect (QAHE) for technological applications. While most studies have focused on doping magnetic impurities to open a gap at the surface-state Dirac point, many undesirable effects have been reported to appear in some cases that makes it difficult to determine whether the gap opening is due to the time-reversal symmetry breaking or not. Furthermore, the realization of the QAHE has been limited to low temperatures. Here we have succeeded in generating a massive Dirac cone in a MnBi2Se4/Bi2Se3 heterostructure, which was fabricated by self-assembling a MnBi2Se4 layer on top of the Bi2Se3 surface as a result of the codeposition of Mn and Se. Our experimental results, supported by relativistic ab initio calculations, demonstrate that the fabricated MnBi2Se4/Bi2Se3 heterostructure shows ferromagnetism up to room temperature and a clear Dirac cone gap opening of ∼100 meV without any other significant changes in the rest of the band structure. It can be considered as a result of the direct interaction of the surface Dirac cone and the magnetic layer rather than a magnetic proximity effect. This spontaneously formed self-assembled heterostructure with a massive Dirac spectrum, characterized by a nontrivial Chern number C = -1, has a potential to realize the QAHE at significantly higher temperatures than reported up to now and can serve as a platform for developing future "topotronics" devices.

Surface Kondo effect and non-trivial metallic state of the Kondo insulator YbB12.

A synergistic effect between strong electron correlation and spin-orbit interaction has been theoretically predicted to realize new topological states of quantum matter on Kondo insulators (KIs), so-called topological Kondo insulators (TKIs). One TKI candidate has been experimentally observed on the KI SmB6(001), and the origin of the surface states (SS) and the topological order of SmB6 has been actively discussed. Here, we show a metallic SS on the clean surface of another TKI candidate YbB12(001) using angle-resolved photoelectron spectroscopy. The SS shows temperature-dependent reconstruction corresponding to the Kondo effect observed for bulk states. Despite the low-temperature insulating bulk, the reconstructed SS with c-f hybridization is metallic, forming a closed Fermi contour surrounding on the surface Brillouin zone and agreeing with the theoretically expected behaviour for SS on TKIs. These results demonstrate the temperature-dependent holistic reconstruction of two-dimensional states localized on KIs surface driven by the Kondo effect.

Infected complex renal cysts during crizotinib therapy in a patient with non-small cell lung cancer positive for ALK rearrangement.

Crizotinib is the first clinically available tyrosine kinase inhibitor that targets anaplastic lymphoma kinase (ALK) and is associated with the development of complex renal cysts. We now describe a 39-year-old woman who developed infected complex renal cysts during crizotinib treatment. After 10 months of such treatment, she presented with a high fever and low back pain. Computed tomography findings were consistent with complex renal cysts and perilesional inflammation. Interventions including cyst drainage and antibiotic administration contributed to diagnosis and management of the infected cysts.