Quantum spin nematic phase in a square-lattice iridate.

Spin nematic is a magnetic analogue of classical liquid crystals, a fourth state of matter exhibiting characteristics of both liquid and solid1,2. Particularly intriguing is a valence-bond spin nematic3-5, in which spins are quantum entangled to form a multipolar order without breaking time-reversal symmetry, but its unambiguous experimental realization remains elusive. Here we establish a spin nematic phase in the square-lattice iridate Sr2IrO4, which approximately realizes a pseudospin one-half Heisenberg antiferromagnet in the strong spin-orbit coupling limit6-9. Upon cooling, the transition into the spin nematic phase at TC ≈ 263 K is marked by a divergence in the static spin quadrupole susceptibility extracted from our Raman spectra and concomitant emergence of a collective mode associated with the spontaneous breaking of rotational symmetries. The quadrupolar order persists in the antiferromagnetic phase below TN ≈ 230 K and becomes directly observable through its interference with the antiferromagnetic order in resonant X-ray diffraction, which allows us to uniquely determine its spatial structure. Further, we find using resonant inelastic X-ray scattering a complete breakdown of coherent magnon excitations at short-wavelength scales, suggesting a many-body quantum entanglement in the antiferromagnetic state10,11. Taken together, our results reveal a quantum order underlying the Néel antiferromagnet that is widely believed to be intimately connected to the mechanism of high-temperature superconductivity12,13.

Dephasing Dynamics Accessed by High Harmonic Generation: Determination of Electron-Hole Decoherence of Dirac Fermions.

We reveal the critical effect of ultrashort dephasing on the polarization of high harmonic generation in Dirac fermions. As the elliptically polarized laser pulse falls in or slightly beyond the multiphoton regime, the elliptically polarized high harmonic generation is produced and exhibits a characteristic polarimetry of the polarization ellipse, which is found to depend on the decoherence time T2. T2 could then be determined to be a few femtoseconds directly from the experimentally observed polarimetry of high harmonics. This shows a sharp contrast with the semimetal regime of higher pump intensity, where the polarimetry is irrelevant to T2. An access to the dephasing dynamics would extend the prospect of high harmonic generation into the metrology of a femtosecond dynamic process in the coherent quantum control.

Metabolomic profiles of ovariectomized mice and their associations with body composition and frailty-related parameters in postmenopausal women.

BACKGROUND: Menopause, a dramatical estrogen-deficient condition, is considered the most significant milestone in women's health. PURPOSE: To investigate the metabolite changes attributed to estrogen deficiency using random forest (RF)-based machine learning (ML) modeling strategy in ovariectomized (OVX) mice as well as determine the clinical relevance of selected metabolites in older women. METHODS AND RESULTS: Untargeted and targeted metabolomic analyses revealed that metabolites related to TCA cycle, sphingolipids, phospholipids, fatty acids, and amino acids, were significantly changed in the plasma and/or muscle of OVX mice. Subsequent ML classifiers based on RF algorithm selected alpha-ketoglutarate (AKG), arginine, carnosine, ceramide C24, phosphatidylcholine (PC) aa C36:6, and PC ae C42:3 in plasma as well as PC aa 34:1, PC aa C34:3, PC aa C36:5, PC aa C32:1, PC aa C36:2, and sphingosine in muscle as top featured metabolites that differentiate the OVX mice from the sham-operated group. When circulating levels of AKG, arginine, and carnosine, which showed the most significant changes in OVX mice blood, were measured in postmenopausal women, higher plasma AKG levels were associated with lower bone mass, weak grip strength, poor physical performance, and increased frailty risk. CONCLUSIONS: Metabolomics- and ML-based methods identified the key metabolites of blood and muscle that were significantly changed after ovariectomy in mice, and the clinical implication of several metabolites was investigated by looking at their correlation with body composition and frailty-related parameters in postmenopausal women. These findings provide crucial context for understanding the diverse physiological alterations caused by estrogen deficiency in women.

Use of oxygen therapy for pneumocephalus: a systematic review.

Pneumocephalus is the pathologic collection of air in the intracranial cavity. In sufficient volumes, it can contribute to symptoms ranging from headaches to death. For conservative treatment, oxygen use is commonplace. Although this is an accepted tenet of clinical practice, it is not necessarily founded on robust trials. An electronic search of databases EMBASE and MEDLINE and the Cochrane Library was undertaken as per the 2020 Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) statement. Three articles were included. Although the modes of oxygen delivery were heterogenous (non-rebreather versus endotracheal versus hyperbaric chamber), all studies concluded favorably on the use of oxygen therapy for increased reabsorption of pneumocephalus.

Resonant inelastic X-ray scattering endstation at the 1C beamline of Pohang Light Source II.

An endstation for resonant inelastic X-ray scattering (RIXS), dedicated to operations in the hard X-ray regime, has been constructed at the 1C beamline of Pohang Light Source II. At the Ir L3-edge, a total energy resolution of 34.2 meV was achieved, close to the theoretical estimation of 34.0 meV, which considers factors such as the incident energy bandpass, intrinsic analyzer resolution, geometrical broadening of the spectrometer, finite beam-size effect and Johann aberration. The performance of the RIXS instrument is demonstrated by measuring the RIXS spectra of Sr2IrO4. The endstation can be easily reconfigured to measure energy-integrated intensities with very low background for diffuse scattering and diffraction experiments.

Time-resolved assessment of cortical venous drainage on multiphase CT angiography in patients with acute ischemic stroke.

PURPOSE: Cortical vein opacification is not routinely assessed in patients presenting with acute ischemic stroke (AIS), and the value of temporal assessment of venous outflow is not known. We evaluated the utility of assessing cortical venous drainage over time using multiphase CT angiography (mCTA). METHODS: Cortical venous drainage was assessed in patients from the Precise and Rapid Assessment of Collaterals Using Multi-Phase CTA in the Triage of Patients With Acute Ischemic Stroke for IA Therapy prospective multicenter cohort study of patients with symptoms of AIS with ICA and/or middle cerebral artery occlusion on baseline mCTA. Opacification of vein of Labbe, sphenoparietal sinus, superficial middle cerebral vein, and vein of Trolard of the affected hemisphere was graded as no (0), partial (1), or full (2) opacification in each mCTA phase. The venous opacification scores for each phase were added to generate a total venous score (TVS) (range 0-24). Primary outcome was 90-day modified Rankin score. Repeated measures analysis was used to assess the effect of phase timing on venous score on outcome. RESULTS: Of 432 patients, 284 (65.7%) had proximal arterial occlusions. Median venous opacification score per phase (range 0-8) was 3 (IQR 1-6) in the first phase and increased in the second and third phases [median (IQR): 6 (5-8) and 8 (6-8), respectively] of the mCTA. In a multivariable analysis adjusting for age, baseline National Institutes of Health Stroke Scale, and Alberta stroke program early CT score, a significant association between TVS and 90-day mRS was noted ([adjusted cOR for TVS 6-11: 0.16 (95% CI 0.05-0.51); TVS 12-17: 0.18 (95% CI 0.06-0.57); TVS 18-24: 0.20 (0.06-0.63)]. Repeated measures analysis of venous scores from all three phases showed a significant effect of time/phase on TVS (p < 0.001). CONCLUSION: This study concludes that venous opacification over time on multiphase CTA is associated with 90-day clinical outcome. There was however no added benefit of venous scoring vis-a-vis arterial collateral assessment in predicting outcome.

Diagnosis and treatment of nail melanoma: a review of the clinicopathologic, dermoscopic, and genetic characteristics.

Nail melanoma (NM) is an important differential diagnosis in patients with longitudinal melanonychia. However, diagnosis is often challenging as it is difficult to differentiate from other pigmented nail disorders. The main challenge for diagnosis is obtaining adequate nail matrix biopsy specimens for histopathological assessment. Furthermore, the histopathological changes in the early stages of NM are subtle and contribute to a delay in diagnosis and care. Therefore, the integration of clinical and histopathological analyses is essential. Clinical and dermoscopic features, such as a broadened width of asymmetric bands in an irregular pattern, with multicolour pigmentation, periungual pigmentation, and continuous growth, are features that support the diagnosis of NM. The essential histological features that must be assessed are cellular morphology, architectural features, melanocyte density, and inflammatory changes. The reported mutations in NMs were BRAF (0-43%), NRAS (0-31%), KIT (0-50%), NF1 (0-50%), and GNAQ (0-25%). Surgery is the primary treatment for NM. The recommended treatment for in situ or minimally invasive NM is functional surgery, but cases with suspected bone invasion should be treated with amputation. Targeted therapy and immunotherapy are indicated for advanced stages of NM. This review summarizes the updated guidelines for the diagnosis and treatment of NM.

Evidence of higher-order topology in multilayer WTe2 from Josephson coupling through anisotropic hinge states.

Td-WTe2 (non-centrosymmetric and orthorhombic), a type-II Weyl semimetal, is expected to have higher-order topological phases with topologically protected, helical one-dimensional hinge states when its Weyl points are annihilated. However, the detection of these hinge states is difficult due to the semimetallic behaviour of the bulk. In this study, we have spatially resolved the hinge states by analysing the magnetic field interference of the supercurrent in Nb-WTe2-Nb proximity Josephson junctions. The Josephson current along the a axis of the WTe2 crystal, but not along the b axis, showed a sharp enhancement at the edges of the junction, and the amount of enhanced Josephson current was comparable to the upper limits of a single one-dimensional helical channel. Our experimental observations suggest a higher-order topological phase in WTe2 and its corresponding anisotropic topological hinge states, in agreement with theoretical calculations. Our work paves the way for the study of hinge states in topological transition-metal dichalcogenides and analogous phases.

Author Correction: Evidence of higher-order topology in multilayer WTe2 from Josephson coupling through anisotropic hinge states.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A study of the microbiological profile of filler-induced skin necrosis.

Skin necrosis is one of the most severe complications following filler injections, and can result in permanent aesthetic defects. Although an increasing number of studies have addressed the management of dermal filler complications, no study has described the spectrum of microbial pathogens. The aim of this study was to delineate the bacterial profile and prognostic factors of filler-related skin necrosis by reviewing the clinical and microbiological features of these patients. A retrospective medical record review of patients undergoing treatment for skin necrosis induced by fillers was conducted. In total, 10 cases were identified, with injection sites being the nasolabial fold (70%; n = 7), nasal dorsum (20%; n = 2) and nasal tip (10%; n = 1). Reviewing the culture results, the true culture-positive rate was found to be 50% after cases of contamination were excluded. To avoid permanent sequelae, all physicians should be aware of possible secondary infections when treating filler-induced skin necrosis.

Systemic contact dermatitis induced by Rhus allergens in Korea: exercising caution in the consumption of this nutritious food.

Systemic contact dermatitis (SCD) develops when a person who was previously sensitized to an allergen is exposed to the same allergen via the systemic route. In East Asia, the use of lacquer for polishing furniture is common and a part of the traditional culture. Contact exposure to tableware polished with Rhus lacquer may lead to sensitization. In Korea, SCD is commonly observed after systemic exposure to Rhus, a nutritious food item consumed because of the common belief of it improving the immune system. In this study, we reviewed the medical records of 21 Korean patients with SCD caused by Rhus ingestion. We found that the most significant epidemiological factor for SCD was the season of the year. Furthermore, 66.67% of the patients presented with leucocytosis and 23.81% showed increased liver enzyme levels. It is important to educate people on the risks associated with the systemic ingestion of Rhus.

Randomized, double-blind, active-controlled, multicentre, phase III clinical trial with two stages to assess the safety and efficacy of letibotulinum toxin a vs. onabotulinum toxin a for subjects with moderate to severe crow's feet.

BACKGROUND: Letibotulinum toxin A (LeBA) was approved by the Ministry of Food and Drug Safety (known as the Korea Food & Drug Administration) for cosmetic indications in 2012. However, the efficacy and safety of this newly introduced LeBA have not been investigated in crow's feet lines (CFL) treatment and standardization before its universal use. OBJECTIVE: The aim of this multicentre, double-blind, randomized, parallel, active-controlled Phase III clinical trial with two stages (ClinicalTrials.gov identifier: NCT03408236) was to investigate the non-inferiority of LeBA vs. the existing onabotulinum toxin A (OnBA) for the treatment of CFL. METHODS: A total of 240 subjects were randomized to either the test (LeBA) or control (OnBA) group. At the baseline and at weeks 4 while maximum smiling (primary efficacy assessment), 8, 12 and 16, investigator's on-site evaluation, independent evaluator, evaluation by the subjects, subjects' satisfaction assessment and safety assessment were performed. RESULTS: At week 4, the response rate of primary efficacy assessment was 69.75% and 68.33% in the test (LeBA) and control (OnBA) groups, respectively, without a significant difference. Other minor secondary evaluation results showed significant differences suggesting that LeBA offered better improvement than OnBA, but the overall results did not show significant differences between the two groups. CONCLUSION: This study showed that LeBA was as effective and safe as OnBA for the treatment of CFL at the same doses.

Montel mirror based collimating analyzer system for high-pressure resonant inelastic X-ray scattering experiments.

Resonant inelastic X-ray scattering (RIXS) is increasingly playing a significant role in studying highly correlated systems, especially since it was proven capable of measuring low-energy magnetic excitations. However, despite high expectations for experimental evidence of novel magnetic phases at high pressure, unequivocal low-energy spectral signatures remain obscured by extrinsic scattering from material surrounding the sample in a diamond anvil cell (DAC): pressure media, Be gasket and the diamond anvils themselves. A scattered X-ray collimation based medium-energy resolution (∼100 meV) analyzer system for a RIXS spectrometer at the Ir L3-absorption edge has been designed and built to remediate these difficulties. Due to the confocal nature of the analyzer system, the majority of extrinsic scattering is rejected, yielding a clean low-energy excitation spectrum of an iridate Sr2IrO4 sample in a DAC cell. Furthermore, the energy resolution of different configurations of the collimating and analyzing optics are discussed.

Spin waves and spin-state transitions in a ruthenate high-temperature antiferromagnet.

Ruthenium compounds serve as a platform for fundamental concepts such as spin-triplet superconductivity1, Kitaev spin liquids2-5 and solid-state analogues of the Higgs mode in particle physics6,7. However, basic questions about the electronic structure of ruthenates remain unanswered, because several key parameters (including Hund's coupling, spin-orbit coupling and exchange interactions) are comparable in magnitude and their interplay is poorly understood, partly due to difficulties in synthesizing large single crystals for spectroscopic experiments. Here we introduce a resonant inelastic X-ray scattering (RIXS)8,9 technique capable of probing collective modes in microcrystals of 4d electron materials. We observe spin waves and spin-state transitions in the honeycomb antiferromagnet SrRu2O6 (ref. 10) and use the extracted exchange interactions and measured magnon gap to explain its high Néel temperature11-16. We expect that the RIXS method presented here will enable momentum-resolved spectroscopy of a large class of 4d transition-metal compounds.

Possible Quantum Paramagnetism in Compressed Sr_{2}IrO_{4}.

The effect of compression on the magnetic ground state of Sr_{2}IrO_{4} is studied with x-ray resonant techniques in the diamond anvil cell. The weak interlayer exchange coupling between square-planar 2D IrO_{2} layers is readily modified upon compression, with a crossover between magnetic structures around 7 GPa mimicking the effect of an applied magnetic field at ambient pressure. Higher pressures drive an order-disorder magnetic phase transition with no magnetic order detected above 17-20 GPa. The persistence of strong exchange interactions between J_{eff}=1/2 magnetic moments within the insulating IrO_{2} layers up to at least 35 GPa points to a highly frustrated magnetic state in compressed Sr_{2}IrO_{4}, opening the door for realization of novel quantum paramagnetic phases driven by extended 5d orbitals with entangled spin and orbital degrees of freedom.

Incidence of oral anticoagulant interruption among stroke patients with atrial fibrillation and subsequent stroke.

BACKGROUND AND PURPOSE: We analyzed the incidence and causes of oral anticoagulant (OAC) cessation and subsequent stroke after OAC withdrawal in a cohort of Korean stroke patients with atrial fibrillation. METHODS: The Korean Atrial Fibrillation Evaluation Registry in Ischemic Stroke patients (K-ATTENTION) is a multicenter cohort study, merging stroke registries from 11 tertiary centers in Korea. The number of OAC interruption episodes and the reasons were reviewed from hospital records. Stroke after OAC withdrawal was defined when a patient experienced ischaemic stroke within 31 days after OAC withdrawal. Clinical variables were compared between patients who experienced stroke recurrence during OAC interruption and those who did not experience recurrence. RESULTS: Among 3213 stroke patients with atrial fibrillation, a total of 329 episodes of OAC interruption were detected in 229 patients after index stroke (mean age 72.9 ± 8.3 years, 113 female patients). The most frequent reason for OAC withdrawal was poor compliance [103 episodes (31.3%)] followed by extracranial bleeding [96 episodes (29.2%)]. Stroke after OAC withdrawal was noted in 13 patients. Mean age, vascular risk factor profile and mean CHA2 DS2 -VASc score were not significantly different between patients with and without recurrent stroke. CONCLUSIONS: A considerable number of stroke patients with atrial fibrillation experienced temporary interruption of OAC after index stroke, which was associated with stroke recurrence of 4.0 cases per 100 interruption episodes.

Association between time to treatment and functional outcomes according to the Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score in endovascular stroke therapy.

BACKGROUND AND PURPOSE: The rate at which the chance of a good outcome of endovascular stroke therapy (EVT) decays with time when eligible patients are selected by baseline diffusion-weighted magnetic resonance imaging (DWI-MRI) and whether ischaemic core size affects this rate remain to be investigated. METHODS: This study analyses a prospective multicentre registry of stroke patients treated with EVT based on pretreatment DWI-MRI that was categorized into three groups: small [Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS)] (8-10), moderate (5-7) and large (<5) cores. The main outcome was a good outcome at 90 days (modified Rankin Scale 0-2). The interaction between onset-to-groin puncture time (OTP) and DWI-ASPECTS categories regarding functional outcomes was investigated. RESULTS: Ultimately, 985 patients (age 69 ± 11 years; male 55%) were analysed. Potential interaction effects between the DWI-ASPECTS categories and OTP on a good outcome at 90 days were observed (Pinteraction  = 0.06). Every 60-min delay in OTP was associated with a 16% reduced likelihood of a good outcome at 90 days amongst patients with large cores, although no associations were observed amongst patients with small to moderate cores. Interestingly, the adjusted rates of a good outcome at 90 days steeply declined between 65 and 213 min of OTP and then remained smooth throughout 24 h of OTP (Pnonlinearity  = 0.15). CONCLUSIONS: Our study showed that the probability of a good outcome after EVT nonlinearly decreased, with a steeper decline at earlier OTP than at later OTP. Discrepant effects of OTP on functional outcomes by baseline DWI-ASPECTS categories were observed. Thus, different strategies for EVT based on time and ischaemic core size are warranted.

RHEB gene therapy maintains the chondrogenic characteristics and protects cartilage tissue from degenerative damage during experimental murine osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is characterized by cartilage degeneration resulting from hypertrophic changes in chondrocytes caused by altered gene expression. The involvement of Ras homolog enriched in brain (RHEB) in OA regulation is unclear. METHODS: Human knee articular cartilage samples - were analyzed for structural and biological changes by histology, immunohistochemistry, real time PCR and western blotting. OA-mouse model developed by surgical destabilization of the medial meniscus (DMM) were treated with adenovirus harboring Rheb gene to analyze onset and progression of OA. Histological scoring, immunohistochemistry, and TUNEL assay was performed to assess cartilage damage across the entire joint. RESULTS: Human and mouse OA cartilage is degenerated and has markedly reduced levels of RHEB. Human OA-degenerated chondrocytes (DC) exhibited a fibroblastic phenotype and 80 % of degenerative cartilage were senescent, with higher levels of reactive oxygen species (ROS). Gene expression analysis of DC revealed almost no COL2A1 expression and reduced SOX9 and RHEB expression. Transient transfection of RHEB rescued the DC phenotype and reduced senescence and ROS levels markedly. RHEB overexpression also increased COL2A1 and SOX9 expression. In an OA-mouse model, the Rheb protein level decreased as the severity of OA increased. Ectopic expression of Rheb using adenovirus in mouse-OA cartilage suppressed surgically-induced OA pathogenesis accompanied by modulation of Adamts5, Mmp 13, Col 10, and Col2a1 expression. Rheb induction significantly reduced apoptosis in OA-cartilage. CONCLUSION: RHEB plays an important role in maintaining the chondrogenic characteristics of chondrocytes, and has potential in preventing progression of OA in the destabilize the medial meniscus (DMM) mouse model of OA.

Correction to: CD4 T cell count is positively associated with lumbar spine bone mass in HIV-infected men under the age of 50 years.

Two sentences in the Discussion section were incorrect.

CD4 T cell count is inversely associated with lumbar spine bone mass in HIV-infected men under the age of 50 years.

HIV-infected men under the age of 50 years had a lower bone mass compared to that of HIV-uninfected men. Lower CD4 T cell counts, independent of whether antiretroviral therapy (ART) was used, were associated with lower BMD. HIV-infected patients with low CD4 T cell counts may need follow-up and intervention regarding bone health, including younger patients. INTRODUCTION: HIV-infected patients have a low bone mineral density (BMD) owing to multifactorial interaction between common osteoporosis risk factors and HIV-related factors, including chronic inflammation and ART. Although HIV infection and ART might affect bone metabolism, little data is available for patients aged under 50 years. We aimed to investigate the association of HIV infection-induced low CD4 T cell counts and ART with BMD in men aged under 50 years. METHODS: We performed an age- and body mass index-matched case-control study. BMD values of HIV-infected and HIV-uninfected men (< 50 years) were compared, and HIV-infected men were stratified by CD4 T cell counts and ART use. RESULTS: After adjusting confounders, HIV-infected men with CD4 T cell counts ≥ 500 cells/µL (n = 28) and < 500 cells/µL (n = 139) had lower BMD at the femoral neck (FN, p < 0.001) and total hip (TH, p < 0.001) than HIV-uninfected men (n = 167). HIV-infected men with CD4 T cell counts < 500/µL had lower BMD at the lumbar spine (LS, p = 0.034) than those with counts of ≥ 500 cells/µL, but not at FN and TH. The CD4 T cell count (γ = 0.169, p = 0.031) was positively correlated with BMD at LS. There was no significant difference in the BMD (p = 0.499-> 0.999) between the ART-naïve (n = 75) and ART-user group (n = 92). CONCLUSIONS: Despite their relatively younger age, HIV-infected men had a lower BMD than HIV-uninfected men. Lower CD4 T cell counts, irrespective of ART, might result in lower bone mass.