Objective
There is no scale for rating the severity of autoimmune encephalitis (AE). In this study, we aimed to develop a novel scale for rating severity in patients with diverse AE syndromes and to ...verify the reliability and validity of the developed scale.
Methods
The key items were generated by a panel of experts and selected according to content validity ratios. The developed scale was initially applied to 50 patients with AE (development cohort) to evaluate its acceptability, reproducibility, internal consistency, and construct validity. Then, the scale was applied to another independent cohort (validation cohort, n = 38).
Results
A new scale consisting of 9 items (seizure, memory dysfunction, psychiatric symptoms, consciousness, language problems, dyskinesia/dystonia, gait instability and ataxia, brainstem dysfunction, and weakness) was developed. Each item was assigned a value of up to 3 points. The total score could therefore range from 0 to 27. We named the scale the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). The new scale showed excellent interobserver (intraclass correlation coefficient ICC = 0.97) and intraobserver (ICC = 0.96) reliability for total scores, was highly correlated with modified Rankin scale (r = 0.86, p < 0.001), and had acceptable internal consistency (Cronbach α = 0.88). Additionally, in the validation cohort, the scale showed high interobserver reliability (ICC = 0.99) and internal consistency (Cronbach α = 0.92).
Interpretation
CASE is a novel clinical scale for AE with a high level of clinimetric properties. It would be suitable for application in clinical practice and might help overcome the limitations of current outcome scales for AE. ANN NEUROL 2019;85:352–358.
Human pluripotent stem cell (hPSC)-derived intestinal organoids (hIOs) form 3D structures organized into crypt and villus domains, making them an excellent in vitro model system for studying human ...intestinal development and disease. However, hPSC-derived hIOs still require in vivo maturation to fully recapitulate adult intestine, with the mechanism of maturation remaining elusive. Here, we show that the co-culture with human T lymphocytes induce the in vitro maturation of hIOs, and identify STAT3-activating interleukin-2 (IL-2) as the major factor inducing maturation. hIOs exposed to IL-2 closely mimic the adult intestinal epithelium and have comparable expression levels of mature intestinal markers, as well as increased intestine-specific functional activities. Even after in vivo engraftment, in vitro-matured hIOs retain their maturation status. The results of our study demonstrate that STAT3 signaling can induce the maturation of hIOs in vitro, thereby circumventing the need for animal models and in vivo maturation.
Lithium metal batteries using solid electrolytes are considered to be the next-generation lithium batteries due to their enhanced energy density and safety. However, interfacial instabilities between ...Li-metal and solid electrolytes limit their implementation in practical batteries. Herein, Li-metal batteries using tailored garnet-type Li
La
Zr
O
(LLZO) solid electrolytes is reported, which shows remarkable stability and energy density, meeting the lifespan requirements of commercial applications. We demonstrate that the compatibility between LLZO and lithium metal is crucial for long-term stability, which is accomplished by bulk dopant regulating and dopant-specific interfacial treatment using protonation/etching. An all-solid-state with 5 mAh cm
cathode delivers a cumulative capacity of over 4000 mAh cm
at 3 mA cm
, which to the best of our knowledge, is the highest cycling parameter reported for Li-metal batteries with LLZOs. These findings are expected to promote the development of solid-state Li-metal batteries by highlighting the efficacy of the coupled bulk and interface doping of solid electrolytes.
Molecular classifications of breast cancer (BRC), such as human epidermal growth factor receptor 2 (HER2), luminal A and luminal B, have been developed to reduce unnecessary treatment by dividing ...patients with BRC into low- and high-risk progression groups. However, these methods do not cover all of the pathological characteristics of BRC, and investigations into novel prognostic/therapeutic markers are thus continually required. In this study, we identified the overexpression of the histone methyltransferase, euchromatic histone-lysine N-methyltransferase 2 (EHMT2) in BRC samples (n=1,222) and normal samples (n=113) derived from the TCGA portal by performing a BRC tissue microarray. EHMT2 overexpression was clearly associated with a poor prognosis in multiple cohorts of patients with BRC (total, n=1,644). Furthermore, the knockdown of EHMT2 expression affected cell apoptosis via the downregulation and re-localization of heat shock protein family D (Hsp60) member 1 (HSPD1). In addition, a statistically significant positive correlation between EHMT2 and HSPD1 expression was revealed in the clinical cohorts. On the whole, the findings of this study may assist the development of novel therapeutic strategies and provide a prognostic marker (EHMT2) for patients with BRC.
Recent data suggested a causative role of uric acid (UA) in the development of renal disease, in which endothelial dysfunction is regarded as the key mechanism. Endothelial‐to‐mesenchymal transition ...(EndoMT) and shedding of the glycocalyx are early changes of endothelial dysfunction. We investigated whether UA induced EndoMT in HUVECs and an animal model of hyperuricemia fed with 2% oxonic acid for 4 wk. UA induced EndoMT in HUVECs with a generation of reactive oxygen species via the activation of membranous NADPH oxidase (from 15 min) and mitochondria (from 6 h) along with glycocalyx shedding (from 6 h), which were blocked by probenecid. GM6001, an inhibitor of matrix metalloproteinase, alleviated UA‐induced glycocalyx shedding and EndoMT. Antioxidants including N‐acetyl cysteine, apocynin, and mitotempo ameliorated EndoMT; however, they did not change glycocalyx shedding in HUVECs. In the kidney of hyperuricemic rats, endothelial staining in peritubular capillaries (PTCs) was substantially decreased with a de novo expression of α‐smooth muscle actin in PTCs. Plasma level of syndecan‐1 was increased in hyperuricemic rats, which was ameliorated by allopurinol. UA caused a phenotypic transition of endothelial cells via induction of oxidative stress with glycocalyx shedding, which could be one of the mechanisms of UA‐induced endothelial dysfunction and kidney disease.—Ko, J., Kang, H.‐J., Kim, D.‐A., Kim, M.‐J., Ryu, E.‐S., Lee, S., Ryu, J.‐H., Roncal, C., Johnson, R. J., Kang, D.‐H. Uric acid induced the phenotype transition of vascular endothelial cells via induction of oxidative stress and glycocalyx shedding. FASEB J. 33, 13334–13345 (2019). www.fasebj.org
Abstract
Human pluripotent stem cell (hPSC)-derived organoids and cells have similar characteristics to human organs and tissues. Thus, in vitro human organoids and cells serve as a superior ...alternative to conventional cell lines and animal models in drug development and regenerative medicine. For a simple and reproducible analysis of the quality of organoids and cells to compensate for the shortcomings of existing experimental validation studies, a quantitative evaluation method should be developed. Here, using the GTEx database, we construct a quantitative calculation system to assess similarity to the human organs. To evaluate our system, we generate hPSC-derived organoids and cells, and detected organ similarity. To facilitate the access of our system by researchers, we develop a web-based user interface presenting similarity to the appropriate organs as percentages. Thus, this program could provide valuable information for the generation of high-quality organoids and cells and a strategy to guide proper lineage-oriented differentiation.
Focal cortical dysplasia (FCD) is a major cause of the sporadic form of intractable focal epilepsies that require surgical treatment. It has recently been reported that brain somatic mutations in ...MTOR account for 15%–25% of FCD type II (FCDII), characterized by cortical dyslamination and dysmorphic neurons. However, the genetic etiologies of FCDII-affected individuals who lack the MTOR mutation remain unclear. Here, we performed deep hybrid capture and amplicon sequencing (read depth of 100×–20,012×) of five important mTOR pathway genes—PIK3CA, PIK3R2, AKT3, TSC1, and TSC2—by using paired brain and saliva samples from 40 FCDII individuals negative for MTOR mutations. We found that 5 of 40 individuals (12.5%) had brain somatic mutations in TSC1 (c.64C>T p.Arg22Trp and c.610C>T p.Arg204Cys) and TSC2 (c.4639G>A p.Val1547Ile), and these results were reproducible on two different sequencing platforms. All identified mutations induced hyperactivation of the mTOR pathway by disrupting the formation or function of the TSC1-TSC2 complex. Furthermore, in utero CRISPR-Cas9-mediated genome editing of Tsc1 or Tsc2 induced the development of spontaneous behavioral seizures, as well as cytomegalic neurons and cortical dyslamination. These results show that brain somatic mutations in TSC1 and TSC2 cause FCD and that in utero application of the CRISPR-Cas9 system is useful for generating neurodevelopmental disease models of somatic mutations in the brain.
Because the digital workflow can begin directly in the oral cavity, intraoral scanners are being adopted in dental treatments. However, studies of the relationship between the experience of the ...practitioner and the accuracy of impression data are needed.
The purpose of this clinical study was to investigate the effect of the experience curve on changes in trueness when a patient’s complete dental arch is scanned.
Twenty dental hygienists with more than 3 years of experience in dental clinical practice (group 1 had 3 to 5 years; group 2 had >6 years) were recruited to learn to operate 2 intraoral scanner systems. All learners scanned the assigned patient’s oral cavity 10 times during the experience sessions. Precision was calculated as the mean deviation among all superimposition combinations from the 10 scanned data sets of each learner n=10C2=45. Trueness was evaluated by superimposing the 10 consecutive intraoral scan data onto the impression scan data from each patient’s rubber impression body (n=10). The acquired images were processed and analyzed using a 3-dimensional analysis software. For statistical analysis, the independent 2-sample t test and repeated measures ANOVA were performed (α=.05).
The mean precision of the Trios scanner was greater than that of the iTero (Trios, 52.30 μm; iTero, 60.46 μm; P<.01). The iTero group showed an improvement in trueness upon repeated experience (P<.05), whereas the Trios group did not (P>.05). In the iTero group but not in the Trios group, the length of clinical experience influenced the change of trueness as a result of repeated experience (P<.05). In terms of the scanned region, the results for trueness were better for the maxillary arch than the mandibular arch with repeated scanning in the iTero group (P<.05).
The single-image based system required repeated learning sessions for effective clinical application. The newer system offered better trueness and precision and was less likely to be influenced by the length of clinical career or the region being scanned.
We report on a molecularly tailored 1:1 donor–acceptor (D‐A) charge‐transfer (CT) cocrystal that manifests strongly red‐shifted CT luminescence characteristics, as well as noteworthy reconfigurable ...self‐assembling behaviors. A loosely packed molecular organization is obtained as a consequence of the noncentrosymmetric chemical structure of molecule A1, which gives rise to considerable free volume and weak intermolecular interactions. The stacking features of the CT complex result in an external stimuli‐responsive molecular stacking reorganization between the mixed and demixed phases of the D‐A pair. Accordingly, high‐contrast fluorescence switching (red↔blue) is realized on the basis of the strong alternation of the electronic properties between the mixed and demixed phases. A combination of structural, spectroscopic, and computational studies reveal the underlying mechanism of this stimuli‐responsive behavior.
To mix or not to mix: A donor–acceptor (D‐A) charge‐transfer (CT) crystalline film was designed to realize stimuli‐responsive reversible fluorescence switching media. Owing to the loosely packed CT state, reorganization between the red‐emissive mixed CT phase and blue‐emissive demixed self‐sorted phase can be demonstrated by external triggers such as solvent, thermal, and piezomechanical stimuli.
Non‐toxic InP‐based nanocrystals have been developed for promising candidates for commercial optoelectronic applications and they still require further improvement on photophysical properties, ...compared to Cd‐based quantum dots (QDs), for better device efficiency and long‐term stability. It is, therefore, essential to understand the precise mechanism of carrier trapping even in the state‐of‐the‐art InP‐based QD with near‐unity luminescence. Here, it is shown that using time‐resolved spectroscopic measurements of systematically size‐controlled InP/ZnSe/ZnS core/shell/shell QDs with the quantum yield close to one, carrier trapping decreases with increasing the energy difference between band‐edge and trap states, indicating that the process follows the energy gap law, well known in molecular photochemistry for nonradiative internal conversion between two electronic states. Similar to the molecular view of the energy gap law, it is found that the energy gap between the band‐edge and trap states is closely associated with ZnSe phonons that assist carrier trapping into defects in highly luminescent InP/ZnSe/ZnS QDs. These findings represent a striking departure from the generally accepted view of carrier trapping mechanism in QDs in the Marcus normal region, providing a step forward understanding how excitons in nanocrystals interact with traps, and offering valuable guidance for making highly efficient and stable InP‐based QDs.
In InP/ZnSe/ZnS quantum dots with near‐unity luminescence, carrier trapping into shallow defects at a picosecond timescale is a key mechanism to reduce the quantum yield. The carrier trapping assisted by ZnSe phonons can slow down with increasing the energy gap between the band‐edge and shallow trap states.
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