The Effect of Block Ratio and Structure on the Thermosensitivity of Double and Triple Betaine Block Copolymers.

AB-type and BAB-type betaine block copolymers composed of a carboxybetaine methacrylate and a sulfobetaine methacrylate, PGLBT-b-PSPE and PSPE-b-PGLBT-b-PSPE, respectively, were synthesized by one-pot RAFT polymerization. By optimizing the concentration of the monomer, initiator, and chain transfer agent, block extension with precise ratio control was enabled and a full conversion (~99%) of betaine monomers was achieved at each step. Two sets (total degree of polymerization: ~300 and ~600) of diblock copolymers having four different PGLBT:PSPE ratios were prepared to compare the influence of block ratio and molecular weight on the temperature-responsive behavior in aqueous solution. A turbidimetry and dynamic light scattering study revealed a shift to higher temperatures of the cloud point and micelle formation by increasing the ratio of PSPE, which exhibit upper critical solution temperature (UCST) behavior. PSPE-dominant diblocks created spherical micelles stabilized by PGLBT motifs, and the transition behavior diminished by decreasing the PSPE ratio. No particular change was found in the diblocks that had an identical AB ratio. This trend reappeared in the other set whose entire molecular weight approximately doubled, and each transition point was not recognizably impacted by the total molecular weight. For triblocks, the PSPE double ends provided a higher probability of interchain attractions and resulted in a more turbid solution at higher temperatures, compared to the diblocks which had similar block ratios and molecular weights. The intermediates assumed as network-like soft aggregates eventually rearranged to monodisperse flowerlike micelles. It is expected that the method for obtaining well-defined betaine block copolymers, as well as the relationship of the block ratio and the chain conformation to the temperature-responsive behavior, will be helpful for designing betaine-based polymeric applications.

Effect of Hydrophobicity and Salt on the Temperature Responsiveness of Polymeric Micelles Consisting of Hydrophobic and Sulfobetaine Chains.

The effect of the hydrophobicity of the core part and salt on the temperature responsiveness of polymeric micelles composed of sulfobetaine and hydrophobic blocks was investigated. Poly(sulfopropyl dimethylammonium propylacrylamide) (PSPP) was used as the sulfobetaine; poly(2-ethylhexyl acrylate) (PEHA), poly(n-butyl acrylate) (PnBA), poly(ethyl acrylate) (PEA), or poly(n-hexyl acrylate) (PnHA) was used as the hydrophobic polymer. Measurement of the transmittance revealed that the transition temperature of the sulfobetaine homopolymer could be controlled by adjusting the concentration, the degree of polymerization (DP), and the concentration of the added salt. The effect of the anionic species of the added salt due to the chemical structural properties of the sulfobetaine chain was consistent with the order of ionic species with strong structural destruction in the Hofmeister series. The temperature response and micelle formation behavior of the polymeric micelles according to the hydrophobicity of the core part and the preparation method were examined by static light scattering (SLS), fluorescence measurement with pyrene, dynamic light scattering (DLS), transmittance, and atomic force microscopy (AFM). Micelles that had EHA (solubility in water was 0.01 g/100 mL) as the core and did not show temperature responsiveness expressed temperature responsiveness at a lower hydrophobicity (solubility of nBA in water was 0.14 g/100 mL). nBA-b-SPP did not show temperature responsiveness due to the block ratio. However, when micelles were prepared by dialysis, smaller and more stable micelles could be formed in an equilibrium state, and temperature responsiveness was observed. Their transition temperature can be controlled by adjusting the ratio of the sulfobetaine blocks, the hydrophobicity of the core part, the concentration of the polymer aqueous solution, and the concentration of the added salt. Furthermore, like the sulfobetaine homopolymer, the effect depended on the anionic species of the added salt.

Preparation of Water-Soluble Polyion Complex (PIC) Micelles with Random Copolymers Containing Pendant Quaternary Ammonium and Sulfonate Groups.

Cationic random copolymers (PCm) consisting of 2-(methacryloyloxy)ethyl phosphorylcholine (MPC; P) with methacroylcholine chloride (MCC; C) and anionic random copolymers (PSn) consisting of MPC and potassium 3-(methacryloyloxy)propanesulfonate (MPS; S) were prepared via a reversible addition-fragmentation chain transfer method. "m" and "n" represent the compositions (mol %) of the MCC and MPS units in the copolymers, respectively. The degrees of polymerization for the copolymers were 93-99. Water-soluble MPC unit contains a pendant zwitterionic phosphorylcholine group whose charges are neutralized in pendant groups. MCC and MPS units contain the cationic quaternary ammonium and anionic sulfonate groups, respectively. The stoichiometrically charge-neutralized mixture of a matched pair of PCm and PSn aqueous solutions resulted in the spontaneous formation of water-soluble PCm/PSn polyion complex (PIC) micelles. These PIC micelles have the MPC-rich surface and MCC/MPS core. These PIC micelles were characterized using 1H NMR, dynamic and static light scattering, and transmission electron microscopic measurements. The hydrodynamic radius of these PIC micelles depends on the mixing ratio of the oppositely charged random copolymers. The charge-neutralized mixture formed maximum-size PIC micelles.

Layer-Number-Independent Two-Dimensional Ferromagnetism in Cr3Te4.

In a conventional magnetic material, a long-range magnetic order develops in three dimensions, and reducing a layer number weakens its magnetism. Here we demonstrate anomalous layer-number-independent ferromagnetism down to the two-dimensional (2D) limit in a metastable phase of Cr3Te4. We fabricated Cr3Te4 thin films by molecular-beam epitaxy and found that Cr3Te4 could host two distinct ferromagnetic phases characterized with different Curie temperatures (TC). One is the bulk-like "high-TC phase" showing room-temperature ferromagnetism, which is consistent with previous studies. The other is the metastable "low-TC phase" with TC ≈ 160 K, which exhibits a layer-number-independent TC down to the 2D limit in marked contrast with the conventional high-TC phase, demonstrating a purely 2D nature of its ferromagnetism. Such significant differences between two distinct phases could be attributed to a small variation in the doping level, making this material attractive for future ultracompact spintronics applications with potential gate-tunable room-temperature 2D ferromagnetism.

Spin-Orbit-Induced Ising Ferromagnetism at a van der Waals Interface.

Magnetocrystalline anisotropy, a key ingredient for establishing long-range order in a magnetic material down to the two-dimensional (2D) limit, is generally associated with spin-orbit interaction (SOI) involving a finite orbital angular momentum. Here we report strong out-of-plane magnetic anisotropy without orbital angular momentum, emerging at the interface between two different van der Waals (vdW) materials, an archetypal metallic vdW material NbSe2 possessing Zeeman-type SOI and an isotropic vdW ferromagnet V5Se8. We found that the Zeeman SOI in NbSe2 induces robust out-of-plane magnetic anisotropy in V5Se8 down to the 2D limit with a more than 2-fold enhancement of the transition temperature. We propose a simple model that takes into account the energy gain in NbSe2 in contact with a ferromagnet, which naturally explains our observations. Our results demonstrate a conceptually new magnetic proximity effect at the vdW interface, expanding the horizons of emergent phenomena achievable in vdW heterostructures.

Complex Formation in the Sulfobetaine-Containing Entirely Ionic Block Copolymer/Ionic Homopolymer System and Their Temperature Responsivity.

The behavior of micelle formation in the sulfobetaine-containing entirely ionic block copolymer/ionic homopolymer system and its functional expression (temperature responsivity) were investigated. Poly(sulfopropyl dimethylammonium propylacrylamide) was used as the sulfobetaine, poly[3-(methacrylamido)propyl trimethylammonium chloride] was used as the cationic polymer, and poly(p-styrenesulfonic acid sodium salt) was used as the anionic polymer. The changes in transition temperature with the concentration and the behavior of micelle formation in the block-/cationic homopolymer and block-/anionic homopolymer system were compared and examined by transmittance, dynamic light scattering, atomic force microscopy, and 1H nuclear magnetic resonance. Only block-/cationic homopolymer systems with a core-shell (polyion complex-sulfobetaine) structure showed temperature responsivity of upper critical solution temperature type, and the responsiveness was dependent on the concentration. On the other hand, the block-/anionic homopolymer system had a core-shell structure at a concentration of 0.05 wt %, but temperature responsiveness was not observed at this concentration. At higher concentrations, electrostatic attraction caused the anionic homopolymer and block copolymer to interact as a whole, resulting in a loss of responsiveness. When the ionic homopolymer had a higher degree of polymerization than the sulfobetaine, it could not form a core-shell structure by interacting with the sulfobetaine and ionic polymer moieties of the block copolymer, thus resulting in the loss of responsiveness. The block-/ionic homopolymer system prepared by the reforming method through dialysis formed uniform and small micelles but lost responsiveness due to morphological stability and electrostatic interaction between the block copolymer and ionic homopolymer.

Edinburgh Postnatal Depression Scale scores at 2-week post-partum may reflect those at 4-week post-partum: A single-center retrospective observational study.

AIM: Most Japanese institutions screen for post-partum depression (PPD) using the Edinburgh Postnatal Depression Scale (EPDS) at outpatient visits conducted at 2- and 4-week post-partum, but there are no published data on the usefulness of EPDS scores 2-week post-partum. In the present study, relationships between 2-week post-partum EPDS scores and 4-week post-partum EPDS scores were investigated to determine whether 2-week scores may facilitate early intervention in high-risk mothers. METHODS: A retrospective analysis of 451 deliveries from 2017 to 2019 was conducted at a single institution. EPDS scores were obtained using the Japanese EPDS 2- and 4-week post-partum, in conjunction with other perinatal data from medical records. RESULTS: In total, 334 of 451 mothers (74.1%) completed the EPDS at both 2- and 4-week post-partum and were included in the analysis. Of 48 who had higher scores 2-week post-partum, 21 (43.8%) continued to be at high risk of PPD. Of 284 who had lower scores 2-week post-partum, 9 (3.2%) transitioned to scores indicating high risk. Women considered high-risk 4-week post-partum tended to have exhibited higher scores 2-week post-partum. Women who had experienced more deliveries tended to exhibit lower scores, and psychiatric illness was strongly associated with higher EPDS scores (odds ratio 11.2, 95% confidence interval 3.7-33.8, P < 0.01). CONCLUSION: Two-week EPDS scores closely reflected 4-week scores, and may facilitate early intervention to prevent PPD. Primiparous mothers and those with a history of psychiatric illness should be followed-up closely.

Superconducting 3R-Ta1+xSe2 with Giant In-Plane Upper Critical Fields.

Molecular-beam epitaxy (MBE) enables the stabilization of a nonequilibrium material phase, providing a powerful approach to the exploration of emergent phenomena in condensed-matter research. Here we demonstrate that one of the metallic two-dimensional (2D) materials, TaSe2, grown by MBE crystallizes into the pure 3R phase with the self-intercalated Ta atoms, 3R-Ta1+xSe2, which is thermodynamically metastable and does not exist in nature as a pure material phase. Interestingly, the thick-enough 3R-Ta1+xSe2 film exhibits a superconducting (SC) critical temperature (Tc) of 3.0 K, which is the highest among all of the polymorphs in TaSe2. Thickness-dependence measurements reveal that Tc decreases with decreasing thickness, accompanied by the development of the charge-density wave phase. The 3R-Ta1+xSe2 films exhibit large in-plane upper critical fields (Hc2) in their SC states even in the thick-enough regime, most likely due to the suppression of the interlayer hopping associated with the unique 3R stacking. Moreover, the temperature dependence of the in-plane Hc2 evolves from linear to square-root behavior with decreasing thickness, indicating crossover behavior from anisotropic three-dimensional superconductivity to 2D superconductivity. Our results unveil intriguing SC properties of metastable 3R-Ta1+xSe2 distinct from those of thermodynamically stable 2H-TaSe2, demonstrating the essential importance of the MBE-based approach to the exploration of novel quantum phenomena in 2D materials research.

Cilostazol Addition to Aspirin could not Reduce the Neurological Deterioration in TOAST Subtypes: ADS Post-Hoc Analysis.

BACKGROUND: Our previous trial acute dual study (ADS) reported that dual antiplatelet therapy (DAPT) using cilostazol and aspirin did not reduce the rate of short-term neurological worsening in non-cardioembolic stroke patients. Present post-hoc analysis investigated whether the impact of combined cilostazol and aspirin differed among stroke subtypes and factors associated with neurological deterioration and/or stroke recurrence. METHODS: Using the ADS registry, the rate of neurological deterioration, defined as clinical worsening and/or recurrent stroke, including transient ischemic attack was calculated. Stroke subtypes included large-artery atherosclerosis (LAA), small vessel occlusion (SVO), other determined etiology (Others), and undetermined etiology of stroke (Undetermined). RESULTS: Data of 1022 patients were analyzed. Deterioration was seen in 104 (10%) patients, and the rates were not markedly different between patients treated with DAPT vs. aspirin in any stroke subtypes: LAA, 19% vs. 11%, (p=0.192); SVO, 10% vs. 10% (p=1.000); Others, 6% vs. 6% (p=1.000); Undetermined, 11% vs. 8% (p=0.590). Diabetes mellitus was the independent factor associated with deterioration (odds ratio 4.360, 95% confidence interval 1.139-16.691, p=0.032) in the LAA group. Age (1.030 [1.004-1.057], p=0.026), systolic blood pressure (1.012 [1.003-1.022], p=0.010), and infarct size (2.550 [1.488-4.371], p=0.001) were associated with deterioration in SVO group, and intracranial stenosis/occlusion was associated with it in the Undetermined group (3.744 [1.138-12.318], p=0.030). CONCLUSIONS: Combined cilostazol and aspirin did not reduce the rate of short-term neurological deterioration in any clinical stroke subtype. The characteristics of patients whose condition deteriorates in the acute period may differ based on the stroke subtypes.

UGT1A1 polymorphism has a prognostic effect in patients with stage IB or II uterine cervical cancer and one or no metastatic pelvic nodes receiving irinotecan chemotherapy: a retrospective study.

BACKGROUND: Uridine diphosphate glucuronosyltransferase 1 family polypeptide A1 (UGT1A1) is a predictive biomarker for the side-effects of irinotecan chemotherapy, which reduces the volume of tumors harboring UGT1A1 polymorphisms. We aimed to determine whether UGT1A1 polymorphisms can predict progression-free survival in patients with local cervical cancer treated with irinotecan chemotherapy. METHODS: We retrospectively analyzed the data of 51 patients with cervical cancer treated at a single institution between 2010 and 2015. All patients were diagnosed with 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IB1, IB2, IIA, or IIB squamous cell carcinoma, underwent radical hysterectomy, and received irinotecan chemotherapy as neoadjuvant and/or adjuvant treatment. All patients were examined for irinotecan side effects using UGT1A1 tests. Conditional inference tree and survival analyses were performed considering the FIGO stage, age, the UGT1A1 status, and the number of metastatic lymph nodes to determine primary factors associated with progression-free survival. RESULTS: The tree-structured survival model determined high recurrence-risk factors related to progression-free survival. The most relevant factor was ≥2 metastatic lymph nodes (p = 0.004). The second most relevant factor was UGT1A1 genotype (p = 0.024). Among patients with ≤1 metastatic lymph node, those with UGT1A1 polymorphisms benefited from irinotecan chemotherapy and demonstrated significantly longer progression-free survival (p = 0.020) than those with wild-type UGT1A1. CONCLUSIONS: Irinotecan chemotherapy might be beneficial in patients with cervical cancer, UGT1A1 polymorphisms, and ≤ 1 metastatic lymph nodes.

Effects of Halide Anions on the Solution Behavior of Double Hydrophilic Carboxy-Sulfobetaine Block Copolymers.

The solution behavior of the double polybetaine block copolymer poly(2-((2-(methacryloyloxy)ethyl)dimethylammonio)acetate)-block-poly(3-((2-(methacryloyloxy)ethyl)dimethylammonio)propane-1-sulfonate (PGLBT-b-PSPE) in sodium halide aqueous solutions was investigated. In the presence of salt ions, the unimer-to-micelle transition of PGLBT-b-PSPE that originated by Coulombic attraction between PSPE motifs was suppressed and shifted to much lower temperatures. The transition was hindered more by increases in the salt concentration because of additional counterion binding on the ionized site of PGLBT-b-PSPE chains, which screens the dipole-dipole attractions. The specific ion effect was investigated on four different halides, Cl-, Br-, I-, and F-. Cl- and two chaotropes (Br- and I-) apparently prevented micelle formation, and the hindering effectiveness on the PSPE pairing followed the general Hofmeister series of anions: I- > Br- > Cl-. More chaotropic anions strongly maintained the polymer chains in a fully hydrated state when the same amount of salts was incorporated. However, F-, which is classified as a kosmotrope, only made a small contribution to lowering the transition point and led to abrupt transition without showing a gradual phase change prior to the transition. The variations of hydrodynamic radius and zeta potentials of unimers and micelles gave hints of the solvation state of salt-incorporated PGLBT-b-PSPEs in each state. These results suggest that chaotropic halides tend to exist in the vicinity of the diblock polybetaine chain surface and thus prominently influenced the thermoresponsive solution behavior, whereas kosmotropic F- prefers water molecules and causes minor changes in the PGLBT-b-PSPE aqueous solution.

Effects of pH on the Stimuli-Responsive Characteristics of Double Betaine Hydrophilic Block Copolymer PGLBT-b-PSPE.

We investigated the pH-responsive behavior of the carboxybetaine-sulfobetaine diblock copolymer poly(2-(2-(methacryloyloxy)ethyl)dimethylammonio)acetate-block-3-((2-(methacryloyloxy)ethyl)dimethylammonio)propane-1-sulfonate (PGLBT-b-PSPE) in aqueous solution under varying temperatures. Alongside the temperature-responsive PSPE block which induces self-assembly of polymer micelles under the upper critical solution temperature, the PGLBT motifs having protonation sites caused additional changes in the phase behaviors. In acidic conditions where the pH is lower than the pKa of PGLBT-b-PSPE, the transmittance of polymer solutions more abruptly dropped and became cloudy at higher temperatures compared to the case of salt-free solutions. There were two simultaneous diffusive modes in the turbid solutions equivalent to unimers or micelles and large aggregates over a few hundred nanometers. Unlike in neutral and basic conditions, those large aggregates did not disappear after the emergence of the polymer micelles. The trend of the temperature-responsive behavior hardly changed in the alkaline solutions; however, the critical temperature significantly decreased. The surface charge of the unimers and self-assembled objects determined by zeta potential measurement varied from neutral or negative to positive with proton addition and further positively increased below the micelle formation temperature. This indicates the cationization of PGLBT moieties and their arrangement in the outer layer of the polymer micelle surface. In spite of the positively charged outer surface, two fast and slow diffusive modes representing micelles and large clusters were repeatedly observed in acidic solutions, and to some extent, size-grown particles eventually precipitated.

Formation of Sulfobetaine-Containing Entirely Ionic PIC (Polyion Complex) Micelles and Their Temperature Responsivity.

Sulfobetaine, a type of zwitterionic polymer, is highly biocompatible with temperature responsiveness of the upper critical solution temperature (UCST) type. The objective of this research was to construct polyion complex (PIC) micelles in the shell of sulfobetaine that had these properties. We used poly(sulfopropyl dimethylammonium propylacrylamide) (PSPP) as sulfobetaine, poly(sodium styrenesulfonate) (PSSNa) as the anionic polymer, and poly[3-(methacrylamido)propyl trimethylammonium chloride] (PMAPTAC) as the cationic polymer. The fundamental properties of the sulfobetaine-containing polymer and the complex were investigated to construct micelles in which the corona expands and contracts in response to temperature changes. Changes in the cloud point were observed from the transmittance for sulfobetaine homopolymers with different degrees of polymerization and concentration and aqueous solution of temperature-responsive diblock copolymers with different concentrations. The concentration and degree of polymerization dependencies on temperature responsivity were determined. Then we mixed two diblock copolymer aqueous solutions that did not have temperature responsivity so that the charge number of anions and cations became equal, and the temperature responsivity and the formation of micelles were confirmed from 1H NMR, DLS, and transmittance. This confirmed the formation of PIC micelles with temperature responsivity. The diblock copolymer did not have temperature responsivity due to the influence of the block ratio by introduction of the ionic chain. However, it is considered to have temperature responsivity because the ionic chain becomes the core when PIC micelles are formed. Furthermore, the PIC micelles with temperature responsivity also had a degree of polymerization and concentration dependencies.

Complex Formation of Sulfobetaine Surfactant and Ionic Polymers and Their Stimuli Responsivity.

We investigated the kinds of complexes sulfobetaine surfactant and ionic polymer formed using lauramidopropyl hydroxysultane (LAPHS) as a sulfobetaine surfactant, poly(sodium styrenesulfonate) (PSSNa) as the anionic polymer and poly[3-(methacrylamido)propyl trimethylammonium chloride] (PMAPTAC) as the cationic polymer. The fundamental properties of LAPHS at various salt concentrations were estimated by various measurements, and it was confirmed that the LAPHS micelles alone did not show temperature responsiveness. The presence of large aggregates in addition to LAPHS micelles was confirmed in the aggregates prepared by adding PSSNa to LAPHS at a charge ratio of 1:0.5, 1:1, and 1:2. However, the aggregates could not be formed when the salt concentration was high or when a monomer was added instead of the polymer. This revealed that the cation part of sulfobetaine, which is the shell of LAPHS micelles, and the anion part of PSSNa electrostatically interacted with each other to form a large aggregate. On the other hand, unlike the case of LAPHS micelles alone and the aggregate consisting of LAPHS micelles and PSSNa, the aggregate of LAPHS micelles and PMAPTAC showed an unprecedented phenomenon of "clear → opaque → clear" with increasing concentration in the concentration range above CMC. The change in the transition temperature due to the change of concentration was a factor. Additionally, we confirmed that the transition temperature was lowered when the concentration was higher than CMC or the salt concentration was increased, and the transition temperature was increased when the PMAPTAC with a high degree of polymerization was added. These results suggested that the LAPHS micelles and the ionic polymer form an aggregate, and the temperature responsivity can be expressed by the interaction with the cationic polymer.

Collapse Behavior of Polyion Complex (PIC) Micelles upon Salt Addition and Reforming Behavior by Dialysis and Its Temperature Responsivity.

Temperature-responsive polyion complex (PIC) micelles were prepared by using two diblock copolymers composed of a sulfobetaine chain (poly(sulfopropyldimethylammonium propylacrylamide), PSPP) and ionic chains (poly(sodium styrenesulfonate), PSSNa, or poly(3-(methacrylamido)propyltrimethylammonium chloride), PMAPTAC). Because the core is PIC and the shell is sulfobetaine with UCST-type temperature response, the corona expands and contracts in response to temperature. To control the size and uniformity of the PIC micelles, the collapse of PIC micelles by salt addition and the reforming behavior by dialysis were investigated by transmittance, DLS, TEM, AFM, and 1H NMR measurements. Investigation of the ionic species dependence of the added salt in the collapse behavior of PIC micelles revealed that it was dependent on the anionic species, although no dependence on the cationic species was observed. Its effectiveness was in the order of I- > Br- > Cl- > F-, which is in agreement with the order of ionic species with strong structural destruction in the Hofmeister series. Heterogeneous and large PIC micelles were formed by the simple mixing method. They collapsed by salt addition and were reformed by the dialysis method to form uniform and smaller PIC micelles. This is considered to be because a uniform and smaller micelle is formed to reform in equilibrium state by dialysis. The temperature response of PIC micelles formed by the simple mixing method and PIC micelles reformed by dialysis showed nearly the same temperature-transmittance curves. These results indicate that the temperature response of PIC micelles is affected by the concentration rather than the hydrodynamic radius. Furthermore, the stability of PIC micelles was found to be affected by the concentration temperature (the temperature at the time of concentration).

Left Atrial Size and Ischemic Events after Ischemic Stroke or Transient Ischemic Attack in Patients with Nonvalvular Atrial Fibrillation.

BACKGROUND: The present study aimed to clarify the association between left atrial (LA) size and ischemic events after ischemic stroke or transient ischemic attack (TIA) in patients with nonvalvular atrial fibrillation (NVAF). METHODS: Acute ischemic stroke or TIA patients with NVAF were enrolled. LA size was classified into normal LA size, mild LA enlargement (LAE), moderate LAE, and severe LAE. The ischemic event was defined as ischemic stroke, TIA, carotid endarterectomy, carotid artery stenting, acute coronary syndrome or percutaneous coronary intervention, systemic embolism, aortic aneurysm rupture or dissection, peripheral artery disease requiring hospitalization, or venous thromboembolism. RESULTS: A total of 1,043 patients (mean age, 78 years; 450 women) including 1,002 ischemic stroke and 41 TIA were analyzed. Of these, 351 patients (34%) had normal LA size, 298 (29%) had mild LAE, 198 (19%) had moderate LAE, and the remaining 196 (19%) had severe LAE. The median follow-up duration was 2.0 years (interquartile range, 0.9-2.1). During follow-up, 117 patients (11%) developed at least one ischemic event. The incidence rate of total ischemic events increased with increasing LA size. Severe LAE was independently associated with increased risk of ischemic events compared with normal LA size (multivariable-adjusted hazard ratio, 1.75; 95% confidence interval, 1.02-3.00). CONCLUSION: Severe LAE was associated with increased risk of ischemic events after ischemic stroke or TIA in patients with NVAF.

Intrinsic 2D Ferromagnetism in V5Se8 Epitaxial Thin Films.

The discoveries of intrinsic ferromagnetism in atomically thin van der Waals crystals have opened a new research field enabling fundamental studies on magnetism at two-dimensional (2D) limit as well as development of magnetic van der Waals heterostructures. Currently, a variety of 2D ferromagnetism has been explored mainly by mechanically exfoliating "originally ferromagnetic (FM)" van der Waals crystals, while a bottom-up approach by thin-film growth technique has demonstrated emergent 2D ferromagnetism in a variety of "originally non-FM" van der Waals materials. Here we demonstrate that V5Se8 epitaxial thin films grown by molecular-beam epitaxy exhibit emergent 2D ferromagnetism with intrinsic spin polarization of the V 3d electrons despite that the bulk counterpart is "originally antiferromagnetic". Moreover, thickness-dependence measurements reveal that this newly developed 2D ferromagnet could be classified as an itinerant 2D Heisenberg ferromagnet with weak magnetic anisotropy, broadening a lineup of 2D magnets to those potentially beneficial for future spintronics applications.

Synthesis and Stimuli Responsivity of Diblock Copolymers Composed of Sulfobetaine and Ionic Blocks: Influence of the Block Ratio.

Ionic diblock copolymers having sulfobetaine, poly(sodium styrenesulfonate)- b- poly(sulfopropyl dimethylammonium propylacrylamide) (PSSNa- b-PSPP), and poly[3-(methacrylamido)propyl trimethylammonium chloride])- b-poly(sulfobetaine) (PMAPTAC- b-PSPP) were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. Polysulfobetaine has the temperature responsivity of the upper critical solution temperature (UCST) type. However, sulfobetaine/PSSNa and sulfobetaine/PMAPTAC with block ratios of 1:1.8 (36- b-66) and 1:1.3 (50- b-66), respectively, did not show any temperature responsivity. This is probably due to the interaction between sulfobetaine and ionic polymer (anionic or cationic) to form some complex. Therefore, we investigated the effect of the block ratio on the temperature response and interaction between sulfobetaine and ionic polymers. The UCST behavior of the block copolymer composed of a sulfobetaine chain and ionic chain was investigated by changing the block ratio by turbidimetry. PSSNa- b-PSPP and PMAPTAC- b-PSPP with block ratios of 1:42.5 (6:255) and 1:4 (16:61), respectively, showed temperature responsivity. The expression of temperature responsivity was found to be very sensitive to the chain length of the ionic chain block. The temperature responsivity was considered to disappear because of the interaction between the sulfobetaine chain and the ionic chain. The interaction was investigated by adding the ionic polymer to the sulfobetaine homopolymer. UCST behavior was confirmed by adding 0.1% PSSNa and 1% PMAPTAC, respectively. The results suggested that the sulfobetaine chain and the ionic chain interacted with each other and that PSSNa was more sensitive than PMAPTAC. In addition, it was confirmed by a 1H NMR measurement that the sulfobetaine chain and ionic chain in the homopolymer mixture system and a block copolymer interact with each other.

Temperature-Responsive Behavior of Double Hydrophilic Carboxy-Sulfobetaine Block Copolymers and Their Self-Assemblies in Water.

The block copolymer poly(2-((2-(methacryloyloxy)ethyl)dimethylammonio)acetate)- b-poly(3-( N-(2-metharyloylethyl)- N, N-dimethylammonio)propanesulfonate) (PGLBT- b-PSPE) was synthesized by reversible addition-fragmentation chain transfer (RAFT) technique under precise control. The PGLBT- b-PSPE block copolymers showed upper critical solution temperature (UCST) behavior originating from PSPE moieties. Unlike PSPE homopolymers, the transmittance change with temperature was gradual, and unexpected retardation or slight changes in a reverse direction were found at the intermediate stage. Light scattering and 1H NMR studies proved that the block copolymers formed spherical micelles that were composed of a PSPE core and PGLBT shell around room temperature and lower temperatures, and slowly disassociated with temperature increase. During the transition, fast (small particle) and slow (large particle) diffusive modes were detected by dynamic light scattering (DLS), which implied that the unimers were escaping from the self-assembled structure and swollen micelles, respectively. At sufficiently high temperatures where the solutions became almost transparent, the slow mode eventually disappeared, and only the fast mode remained. In addition, once the polymeric particles are formed, the size did not vary much with additional cooling. The transition point and the pattern of transmittance alteration were dependent on the degree of polymerization and the [PGLBT]:[PSPE] ratios; more PGLBT made the block copolymer less responsive to temperature and led the cloud point to lower degrees. However, random copolymers PGLBT- r-PSPE did not show any temperature-responsivity, and even small amount of GLBTs (10%) distributed in a PSPE chain significantly suppressed the transition.

Associations between Pre-Admission Risk Scores and Two-Year Clinical Outcomes in Ischemic Stroke or Transient Ischemic Attack Patients with Non-Valvular Atrial Fibrillation.

BACKGROUND: We aimed to clarify associations between pre-admission risk scores (CHADS2, CHA2DS2-VASc, and HAS-BLED) and 2-year clinical outcomes in ischemic stroke or transient ischemic attack (TIA) patients with non-valvular atrial fibrillation (NVAF) using a prospective, multicenter, observational registry. METHODS: From 18 Japanese stroke centers, ischemic stroke or TIA patients with NVAF hospitalized within 7 days after onset were enrolled. Outcome measures were defined as death/disability (modified Rankin Scale score ≥3) at 2 years, 2-year mortality, and ischemic or hemorrhagic events within 2 years. RESULTS: A total of 1,192 patients with NVAF (527 women; mean age, 78 ± 10 years), including 1,141 ischemic stroke and 51 TIA, were analyzed. Rates of death/disability, mortality, and ischemic or hemorrhagic events increased significantly with increasing pre-admission CHADS2 (p for trend <0.001 for death/disability and mortality, p for trend = 0.024 for events), CHA2DS2-VASc (p for trend <0.001 for all), and HAS-BLED (p for trend = 0.004 for death/disability, p for trend <0.001 for mortality, p for trend = 0.024 for events) scores. Pre-admission CHADS2 (OR per 1 point, 1.52; 95% CI 1.35-1.71; p <0.001 for death/disability; hazard ratio (HR) per 1 point, 1.23; 95% CI 1.12-1.35; p <0.001 for mortality; HR per 1 point, 1.14; 95% CI 1.02-1.26; p = 0.016 for events), CHA2DS2-VASc (1.55, 1.41-1.72, p < 0.001; 1.21, 1.12-1.30, p < 0.001; 1.17, 1.07-1.27, p < 0.001; respectively), and HAS-BLED (1.33, 1.17-1.52, p < 0.001; 1.23, 1.10-1.38, p < 0.001; 1.18, 1.05-1.34, p = 0.008; respectively) scores were independently associated with all outcome measures. CONCLUSIONS: In ischemic stroke or TIA patients with NVAF, all pre-admission risk scores were independently associated with death/disability at 2 years and 2-year mortality, as well as ischemic or hemorrhagic events within 2 years.