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Backgrounds Alzheimer’s disease is the most common cause of dementia, and currently, there is no disease-modifying treatment. Favorable functional outcomes and reduction of amyloid levels were observed following transplantation of mesenchymal stem cells (MSCs) in animal studies. Objectives We conducted a phase I clinical trial in nine patients with mild-to-moderate Alzheimer’s disease dementia to evaluate the safety and dose-limiting toxicity of three repeated intracerebroventricular injections of human umbilical cord blood–derived MSCs (hUCB-MSCs). Methods We recruited nine mild-to-moderate Alzheimer’s disease dementia patients from Samsung Medical Center, Seoul, Republic of Korea. Four weeks prior to MSC administration, the Ommaya reservoir was implanted into the right lateral ventricle of the patients. Three patients received a low dose (1.0 × 107 cells/2 mL), and six patients received a high dose (3.0 × 107 cells/2 mL) of hUCB-MSCs. Three repeated injections of MSCs were performed (4-week intervals) in all nine patients. These patients were followed up to 12 weeks after the first hUCB-MSC injection and an additional 36 months in the extended observation study. Results After hUCB-MSC injection, the most common adverse event was fever (n = 9) followed by headache (n = 7), nausea (n = 5), and vomiting (n = 4), which all subsided within 36 h. There were three serious adverse events in two participants that were considered to have arisen from the investigational product. Fever in a low dose participant and nausea with vomiting in another low dose participant each required extended hospitalization by a day. There were no dose-limiting toxicities. Five participants completed the 36-month extended observation study, and no further serious adverse events were observed. Conclusions Three repeated administrations of hUCB-MSCs into the lateral ventricle via an Ommaya reservoir were feasible, relatively and sufficiently safe, and well-tolerated. Currently, we are undergoing an extended follow-up study for those who participated in a phase IIa trial where upon completion, we hope to gain a deeper understanding of the clinical efficacy of MSC AD therapy. Trial registration ClinicalTrials.gov NCT02054208. Registered on 4 February 2014. ClinicalTrials.gov NCT03172117. Registered on 1 June 2017

Although van der Waals-layered transition metal dichalcogenides from transient absorption spectroscopy have successfully demonstrated an ideal carrier multiplication (CM) performance with an onset of nearly 2E

This paper presents a multi-functional strand capable of introducing prestressing force in prestressed concrete (PSC) girders and sensing their static and dynamic behavior as well. This innovative strand is developed by replacing the core steel wire of the strand used in PSC structures with a carbon fiber-reinforced polymer (CFRP) wire with a built-in optical Fiber Bragg Grating (FBG) sensor. A full-scale girder specimen was fabricated by applying this multi-function strand to check the possibility of tracking the change of prestressing force at each construction stage. Moreover, dynamic data could be secured during dynamic loading tests without installing accelerometers and made it possible to obtain the natural frequencies of the structure. The results verified the capability to effectively manage the prestressing force in the PSC bridge structure by applying the PC strand with a built-in optical sensor known for its outstanding practicability and durability.

To assess the utility of three-dimensional double-echo steady-state with water excitation (3D-DESS-WE) imaging for localizing deep-seated parotid tumors in relation to the facial nerve. A prospective study comparing the surgical outcomes of parotidectomy with or without 3D-DESS-WE sequence is currently enrolling the patients. Magnetic resonance imaging data from the first 25 patients with 3D-DESS-WE sequence were reviewed. Visibility of the intraparotid facial nerve was independently assessed by two neuroradiologists. The diagnostic performance of the 3D-DESS-WE sequence for prediction of deep lobe involvement was compared with that of two conventional methods based on the retromandibular vein line (RMVL) and facial nerve line (FNL). The relationship between the tumor and the main trunk of the facial nerve was also evaluated on the 3D-DESS-WE sequence. On 3D-DESS-WE images, the main trunk, temporofacial division, and cervicofacial division of the intraparotid facial nerve were visualized in 100% (25/25), 48% (12/25), and 36% (9/25) of patients, respectively. The diagnostic accuracy of the 3D-DESS-WE sequence for prediction of deep lobe involvement was 92% (23/25), which was significantly superior to that of the RMVL (68% [17/25]; p = 0.008) and FNL (64% [16/25]; p = 0.004) methods. The relationship between the tumor and the main trunk of the facial nerve was correctly predicted in 92% (23/25) of 3D-DESS-WE images. By direct visualization of the facial nerve, the 3D-DESS-WE sequence improved the preoperative localization of the intraparotid facial nerve in deep-seated parotid tumors. This information may help better surgical planning for deep-seated parotid tumors.

This study intends to verify analytically and experimentally the performance of a new type of prestressed concrete (PSC) I-girder for its application as railway bridge. Since the girder-type railway bridge develops relatively low torsional rigidity, there is risk for the dynamic responses to amplify due to the superposition of the torsional mode and flexural mode. The superposition of the torsional and flexural modes as well as the dynamic stability of the railway bridge were examined through dynamic analysis. Three-dimensional modelling was built to be suitable for carrying out moving load analysis. Four different span lengths of 30, 35, 40 and 45 m adopted considering the most applied span length currently and future lengthening of the span length. Moreover, a full-scale girder specimen with span length of 35 m was fabricated and subjected to dynamic loading. The measured dynamic responses were then compared to the analytic values. Finally, the ultimate bearing capacity of the specimen was verified by static loading test.

Background Diffuse midline glioma H3 K27M-mutant (DMG) are reported to show heterogeneous radiologic imaging features in children. We hypothesized that other genetic mutations may contribute to this heterogeneity. Purpose To describe the magnetic resonance imaging (MRI) findings of DMG in adult patients and to correlate the imaging findings with the molecular expression profile. Material and Methods Eighteen patients with pathologically proven DMG were enrolled. On preoperative MRI, the following were evaluated: location; size of the lesion; ratio of non-enhancing (NE) and contrast-enhancing (CE) area; presence of cortical invasion and necrotic component; maximum relative cerebral blood volume ratio (rCBV ratio) of NE and CE portions; and minimum apparent diffusion coefficient (ADC) of NE and CE portions, among others. Molecular profiles including ATRX expression and p53 mutation were reviewed to find correlation with imaging features. Results Thalamus was the most commonly involved location, followed by pons and tectum. Five patients showed loss of normal ATRX expression. p53 mutation was positive in 12 patients. 40% of normal ATRX expression patients had cortical involvement and 20% had leptomeningeal seeding; none of the patients with ATRX loss had cortical involvement or leptomeningeal seeding. Patients with normal ATRX expression showed significantly higher rCBV ratio and lower ADC value in the NE area than patients with ATRX loss ( P=0.04, 0.016). p53 mutation status did not correlate with any imaging finding. Conclusion Cortical invasion, leptomeningeal tumor spread, lower ADC value and higher rCBV ratio in NE areas of DMG may be related to normal expression of ATRX.

It is well‐known that the alkali doping of polycrystalline Cu2ZnSn(S,Se)4 (CZTSSe) and Cu(In,Ga)(Se,S)2 has a beneficial influence on the device performance and there are various hypotheses about the principles of performance improvement. This work clearly explains the effect of Na doping on the fill factor (FF) rather than on all of the solar cell parameters (open‐circuit voltage, FF, and sometimes short circuit current) for overall performance improvement. When doping is optimized, the fabricated device shows sufficient built‐in potential and selects a better carrier transport path by the high potential difference between the intragrains and the grain boundaries. On the other hand, when doping is excessive, the device shows low contact potential difference and FF and selects a worse carrier transport path even though the built‐in potential becomes stronger. The fabricated CZTSSe solar cell on a flexible metal foil optimized with a 25 nm thick NaF doping layer achieves an FF of 62.63%, thereby clearly showing the enhancing effect of Na doping.

One key to improve the performance of advanced optoelectronic devices and energy harvesting in graphene is to understand the predominant carrier scattering

We purposed to compare diagnostic accuracy of contrast-enhanced (CE) 3D T1-weighted fast field echo (3D T1-WI), CE 2D spin echo T1-weighted image (2D T1-WI), and CE 2D T2 FLAIR on evaluation of leptomeningeal metastasis(LM) using detailed features suggested in RANO proposal in a homogeneous group with cytology-proven LM. Thirty-five lung adenocarcinoma patients with CSF cytology-proven leptomeningeal metastasis were enrolled in this retrospective analysis, who were enrolled in the prospective study (NCT03257124). MR images including CE 3D T1-WI, CE 2D T1-WI, and CE 2D FLAIR were reviewed. Presence of leptomeningeal nodule, leptomeningeal enhancement, and cranial nerve enhancement was evaluated according to the RANO proposal. Diagnostic accuracy of each sequence was compared and added value of CE 2D FLAIR to CE 3D T1-WI was evaluated. Two patients had unmeasurable small nodules recognized on 3D T1-WI only. Leptomeningeal enhancement was positive in 60%, 60%, and 77.1%, cranial nerve enhancement was positive in 51.4%, 45.7%, and 68.6% of the patients on 3D T1-WI, 2D T1-WI, and 2D FLAIR, respectively. Overall sensitivity for detection of LM was 71.4%, 71.4%, and 82.9% on 3D T1-WI, 2D T1-WI, and 2D FLAIR. When adding 2D FLAIR to 3D T1-WI, overall sensitivity for detection of LM was 82.9%. 3D T1-WI is the best for identifying leptomeningeal nodules. The sensitivity of 2D FLAIR is the highest for both LNE and CNE. Since both sequences are complementary, it can be helpful to take both sequences. Checking each feature according to the RANO proposal, especially CNE, may help you not to miss LM.

Objective Microsurgical treatment could be a good alternative for the treatment of recurrent cerebral aneurysm after coil embolization. The purpose of this study was to present our experience of microsurgical treatment for recurrent cerebral aneurysm previously treated using coil embolization. Methods From June 2012 to May 2019, 34 patients consecutively received microsurgical treatment for a recurrent cerebral aneurysm previously treated using coil embolization after it ruptured. Results Of the 34 patients with aneurysm, 33 had the aneurysm located in the anterior circulation. The most common location was the anterior communicating artery (13 cases). Immediate radiologic outcome at coil embolization was completed (n=6), residual neck (n=26), and residual sac (n=2). The reason for microsurgical treatment included rebleeding (n=12), persistent residual sac (n=1), and recurrence on follow-up study (n=21). Rebleeding occurred within 10 days after coil embolization in 10 cases, and the other 2 were due to regrowth. In the 20 recurred and saccular aneurysms, coil compaction was present in 11 aneurysms and regrowth in 9 aneurysms. Simple neck clipping (n=29) and clipping with coil mass extraction (n=3) was possible in the saccular aneurysms. The blood blister like aneurysm (n=2) were treated using bypass and endovascular internal carotid artery trapping. In the follow-up study group after microsurgical treatment there were no severe complications due to the treatment. Age, cause of retreatment, and modified Rankin Scale before microsurgery were associated with good outcome (pl0.001). Conclusions Microsurgical treatment may be a viable and effective option for treating recurrent aneurysms previously treated by endovascular techniques.

Backside contact technology has been employed for increasing the efficiency of the solar cells by minimizing the reflectance caused by the metal electrodes. Via-hole etching is one of the key processes for realizing the backside contacts in the inverted InGaP/GaAs double heterojunction solar cells. The via-holes were fabricated by using three-step dry etching process. It involved three different plasma chemistries such BCl 3 /Cl 2 , CH 4 /H 2 and CH 4 /H 2 /Ar to achieve smooth and tapered sidewall profile of the via-holes. After the dielectric insulating layer was deposited on the etched via-holes, the metal contact to reach the front side ohmic contact layer was successfully deposited.

Whether M1 occlusions proximal (pM1) and distal (dM1) to the lenticulostriate perforators result in different clinical outcomes after mechanical thrombectomy (MT) is unknown. We retrospectively compared the clinical outcomes and baseline characteristics of patients with these two types of occlusions.From March 2010 to May 2019, we performed MT for 141 M1 occlusions, including pM1 occlusions (n = 58) and dM1 occlusions (n = 83).Good clinical outcomes (modified Rankin Scale score 0 to 2) were achieved in 28 out of 58 (48.3%) patients with pM1 occlusions and 46 out of 83 (55.4%) patients with dM1 occlusions without significance (p = 0.493). Cardioembolic occlusions represented 19 out of 58 (32.6%) pM1 occlusions and 53 out of 83 (63.9%) dM1 occlusions, and atherosclerotic occlusions represented 37 out of 58 (63.8%) pM1 occlusions and 27 out of 83 (32.5%) dM1 occlusions, with significance (p = 0.001). Rescue treatments, such as balloon angioplasty or stenting, were needed more for pM1 occlusions than dM1 occlusions (21 out of 58 (36.2%) vs. 8 out of 83 (9.8%), p 0.001). The multivariable logistic regression analysis demonstrated that the need for rescue treatment was associated with pM1 occlusions (adjusted odds ratio; 3.804, 95% confidence interval; 1.306-11.082, p = 0.014).In our series, pM1 and dM1 occlusions did not significantly differ in good clinical outcomes. Our study also showed that pM1 occlusions were more strongly associated with atherosclerotic occlusions, while dM1 occlusions were more strongly associated with cardioembolic occlusions, and rescue treatments were needed more often for pM1 occlusions than dM1 occlusions.

A micro-prism array (MPA) realized on a flexible polymer substrate was integrated on the top of flexible Cu(In,Ga)Se 2 (CIGS) solar cells to overcome the optical reflection loss caused by the metal grids used with these cells. The integrated MPA refracts light normally incident to the metal grids into an active area not covered by the metal grid. This reduces the optical reflection loss, which increases the photocurrent. The original MPA structure was fabricated on a Si substrate by a combined process of dry and wet etching. The MPA structure on the Si template was transferred to soft-polydimethylsiloxane (S-PDMS) by using a stamping method. The short-current density and the power conversion efficiency of the flexible CIGS solar cell integrated with the MPA based on S-PDMS were improved by 4.9 and 5.2%, respectively, when compared with those of conventional flexible CIGS solar cell without MPA.

In recent years, clock speed and power density have increased rapidly, improving the performance of mobile devices, and thus, thermal management issues for local hot spots of chips are increasing. Dynamic thermal management (DTM) through frequency modulation and passive cooling components such as heat pipes is currently being used as a cooling strategy for mobile devices. However, DTM has an inverse relationship with chip performance, and passive cooler occupy too much space for local hot spot cooling. From the point of view of local hot spot cooling, a solid-state thermoelectric cooler (TEC) has the advantage of enabling on/off control and site-specific cooling. However, most of the research on TECs focuses on the material or interfacial properties of TECs, not the design rule or structure of TECs for practical applications. This study proposes an active cooling device using a TEC with a unique planar-radial structure that can selectively cool only locally generated hot spots and minimize form factor designs with 2D structures, making this cooling device highly applicable to mobile devices. A 5-pair TEC using the optimized TE leg thickness (n-Bi2Te3 5.05 μm and p-Sb2Te3 5.45 μm) and radial structure enhanced the Peltier effect and confirmed the maximum junction temperature difference of 2.4 °C. By adopting a hybrid cooling system combining active and passive coolers in a mobile device, we obtained an effective cooling area ratio of 4 and a cooling effect (~3.87 °C).

The purpose of this study is to identify the effects of a stabilizer and matrix former in the development of a celecoxib dried nanosuspension (DNS) for high dissolution rate and drug loading. Tween 80 and Hydroxypropyl Methylcellulose (HPMC) were used as stabilizers in the bead-milling process and dextrin was used as the matrix former in the spray-drying. Various nanosuspensions (NS) were prepared by varying the ratio of HPMC and dextrin, and the physicochemical properties of each formulation were evaluated for particle size, morphology, drug loading, crystallinity, redispersibility, physical stability and dissolution rate. HPMC efficiently stabilized the NS system and reduced the particle size of NS. The mean particle size of the NS with 0.5% HPMC (w/v) was the smallest (248 nm) of all formulations. Dextrin has been shown to inhibit the increase of particle size efficiently, which is known to occur frequently when NS is being solidified. As the dextrin increased in DNS, the dissolution rates of reconstituted NS were significantly improved. However, it was confirmed that more than the necessary amount of dextrin in DNS reduced the dissolution and drug loading. The dissolution of celecoxib in DNS prepared at the ratio (drug:dextrin, 1:2.5) was almost the highest. The dissolution of optimal formulation was 95.8% at 120 min, which was 2.0-fold higher than that of NS dried without dextrin. In conclusion, these results suggest that the formulation based on Tween 80, HPMC and dextrin may be an effective option for DNS to enhance its in vitro dissolution and in vivo oral absorption.

Tenofovir disoproxil (TD) has narrow absorption site mostly in upper intestinal tract where tenofovir rapidly decomposes. The aim of this work was to prepare and evaluate tenofovir disoproxil-loaded enteric microparticles (TDEMs) for the enhanced duodenal delivery. TDEMs were composed of TD, eudragit L-100 (EL) and ethyl cellulose (EC) as release-controlling polymers. For the physicochemical characterization, TDEMs were evaluated in terms of encapsulation efficiency (EE%), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR). The dissolution test was also performed while continuously changing the medium pH. The EE% of TD in TDEMs was good and more than 90%. The EC and EL formed a physically mixed structure and maintained their respective properties in TDEMs as confirmed by SEM image and FT-IR analysis. Combination of EL and EC gave higher enteric properties to TDEMs than the single use of EL or EC. The optimized TDEM (TD/EL/EC = 0.2/1/1, w/w/w ratio) yielded mean dissolution rate less than 10% in 1 h at pH 1.2, but completed dissolution with a dissolution more than 85% within 1 h at pH 6.5. Thus, the suggested TDEM would be promising enteric microparticles for the intensive delivery of TD to the duodenum.

Among mild cognitive impairment (MCI) patients, those with memory impairment (amnestic MCI, aMCI) are at a high risk of dementia. However, the precise cognitive domain, beside memory, that predicts dementia conversion is unclear. Therefore, we investigated the cognitive domain that predicts dementia conversion in a longitudinal aMCI cohort. We collected data of 482 aMCI patients who underwent neuropsychological tests and magnetic resonance imaging at baseline and were followed for at least 1 year. The patients were categorized according to number (1–4) and type of impaired cognitive domains (memory, language, visuospatial, and frontal-executive function). We evaluated dementia conversion risk in each group when compared to single-domain aMCI after controlling for age, education, diabetes and dyslipidemia. Baseline cortical thickness of each group was compared to that of 410 cognitively normal controls (NCs) after controlling for age, intracranial volume, diabetes and dyslipidemia. Compared to single-domain aMCI, aMCI patients with frontal-executive dysfunction at baseline had a higher risk of dementia conversion than aMCI patients with visuospatial or language dysfunction. Compared to NCs, aMCI patients with frontal-executive dysfunction had overall cortical thinning including frontal areas. Our findings suggest that aMCI patients with frontal-executive dysfunction have poor prognosis and,thus, should be considered for intervention therapy with a higher priority among aMCI patients.

Proximal middle cerebral artery (M1 segment) aneurysms are relatively deeply located in neighboring lenticulostriate arteries, which make them unsuitable for microsurgery. We aimed to investigate the clinical and radiological outcomes of endovascular coiling of M1 segment aneurysms. Between January 2003 and December 2014, we retrospectively reviewed the medical records of 52 patients (52 aneurysms) from four institutions who underwent endovascular coiling of M1 segment aneurysms. Patients who underwent clinical and radiologic follow-up for more than a year after the procedure were evaluated. The aneurysms were located in the early frontal branch, early temporal branch, and lenticulostriate artery in 28, 15, and nine patients, respectively. Endovascular coiling was achieved in 51 cases and failed in one case. Of these 51 cases, 46 (90.2%) and five (9.8%) were non-ruptured and ruptured aneurysms, respectively. Initial angiographic results revealed complete occlusion in 26 (51.0%), residual neck in 16 (31.4%), and residual sac in nine (17.6%) cases. One failed case had a symptomatic procedural complication of thromboembolism. However, there was no permanent morbidity or mortality. Two major recanalization cases (3.9%) were retreated by endovascular coiling. On multivariable logistic regression analysis, aneurysmal recurrence was significantly related to aneurysm height (OR, 1.887; 95% CI, 1.107 to 3.217; p = 0.020), width (OR, 1.836; CI, 1.127 to 2.992; p = 0.015), and neck (OR, 4.017; CI, 1.220 to 13.232, p = 0.022). Endovascular coiling of M1 segment aneurysms appeared to be a feasible treatment option with a relatively low-retreatment rate. Aneurysm size was statistically significantly associated with recurrence.

To determine the feasibility of using high dimensional computer-extracted features, known as radiomics features, in differentiating primary central nervous system lymphoma (PCNSL) from glioblastoma on multi-parametric MR imaging including diffusion-weighted imaging. Retrospective evaluation of data was approved by the local ethics committee and informed consent was waived. A total of 143 patients (two independent cohorts for discovery [n = 86; glioblastoma = 49, PCNSL = 37] and validation [n = 57; glioblastoma = 29, PCNSL = 28]) with newly diagnosed glioblastoma and PCNSL were subjected to radiomics analysis using the multi-parametric MRI (contrast-enhanced T1-weighted imaging, T2-weighted imaging, and diffusion-weighted imaging). Radiomics analyses were performed for two types of regions of interest (ROI) covering contrast-enhancing tumor and whole (enhancing or non-enhancing) tumor plus peritumoral edema. A total of 127 radiomics features were calculated. Feature selection was performed to identify the most discriminating features for every MR image in the discovery cohort. The identified features were used to calculate radiomics scores, which were later used in logistic regression to distinguish between PCNSL and glioblastoma. The classification model was further tested on the independent validation cohort. Fifteen features were selected as significant features in the discovery cohort. Using the identified features and calculated radiomics scores, the logistic regression-based classifier yielded an area under the curve (AUC) of 0.979, sensitivity of 0.938, and specificity of 0.944 in the discovery cohort to distinguish between glioblastoma and PCNSL. A similarly high rate of performance was observed in the validation cohort (AUC = 0.956). Radiomics features derived from multi-parametric MRI can be used to differentiate PCNSL from glioblastoma effectively.

Carrier multiplication (CM) is the amplification of the excited carrier density by two times or more when the incident photon energy is larger than twice the bandgap of semiconductors. A practical approach to demonstrate the CM involves the direct measurement of photocurrent in the device. Specifically, photocurrent measurement in quantum dots (QDs) is typically limited by high contact resistance and long carrier-transfer length, which yields a low CM conversion efficiency and high CM threshold energy. Here, the local photocurrent is measured to evaluate the CM quantum efficiency from a QD-attached Au tip of a conductive atomic force microscope (CAFM) system. The photocurrent is efficiently measured between the PbS QDs anchored on a Au tip and a graphene layer on a SiO2 /Si substrate as a counter electrode, yielding an extremely short channel length that reduces the contact resistance. The quantum efficiency extracted from the local photocurrent data with an incident photon energy exhibits a step-like behavior. More importantly, the CM threshold energy is as low as twice the bandgap, which is the lowest threshold energy of optically observed QDs to date. This enables the CAFM-based photocurrent technique to directly evaluate the CM conversion efficiency in low-dimensional materials.

Background Sex effects on the progression of Alzheimer's disease (AD) have received less attention than other demographic factors, including onset age and education. Objective The aim of this study was to investigate whether sex affected cortical thinning in the disease progression of AD. Methods We prospectively recruited 36 patients with early-stage AD and 14 people with normal cognition. All subjects were assessed with magnetic resonance imaging at baseline, Year 1, Year 3, and Year 5. We performed cortical thickness analyses using surface-based morphometry on magnetic resonance imaging. Results Women with AD showed more rapid cortical thinning in the left dorsolateral frontal cortex, left superior temporal gyrus, bilateral temporo-parietal association cortices, bilateral anterior cingulate gyri, bilateral medial frontal cortices, and bilateral occipital cortices over 5 years than men with AD, even though there was no difference in cortical thickness at baseline. In contrast, there were no regions of significantly more rapid atrophy in men with AD. Conclusions Our findings suggest that women deteriorate faster than men in the progression of AD.

Background Despite extensive efforts on the genomic characterization of gliomas, very few studies have reported the genetic alterations of cerebellar glioblastoma (C-GBM), a rare and lethal disease. Here, we provide a systematic study of C-GBM to better understand its specific genomic features. Methods We collected a cohort of C-GBM patients and compared patient demographics and tumor pathologies with supratentorial glioblastoma (S-GBM). To uncover the molecular characteristics, we performed DNA and mRNA sequencing and DNA methylation arrays on 19, 6, and 4 C-GBM cases, respectively. Moreover, chemical drug screening was conducted to identify potential therapeutic options for C-GBMs. Results Despite differing anatomical origins of C-GBM and S-GBM, neither histological, cytological, nor patient demographics appeared significantly different between the 2 types. However, we observed striking differences in mutational patterns, including frequent alterations of ATRX, PDGFRA, NF1, and RAS and absence of EGFR alterations in C-GBM. These results show a distinct evolutionary path in C-GBM, suggesting specific therapeutic targeted options. Targeted-drug screening revealed that C-GBMs were more responsive to mitogen-activated protein kinase kinase (MEK) inhibitor and resistant to epidermal growth factor receptor inhibitors than S-GBMs. Also, differential expression analysis indicated that C-GBMs may have originated from oligodendrocyte progenitor cells, suggesting that different types of cells can undergo malignant transformation according to their location in brain. Master regulator analysis with differentially expressed genes between C-GBM and proneural S-GBM revealed NR4A1 as a potential therapeutic target. Conclusions Our results imply that unique gliomagenesis mechanisms occur in adult cerebellum and new treatment strategies are needed to provide greater therapeutic benefits for C-GBM patients. Key points 1. Distinct genomic profiles of 19 adult cerebellar GBMs were characterized. 2. MEK inhibitor was highly sensitive to cerebellar GBM compared with supratentorial GBM. 3. Master regulator analysis revealed NR4A1 as a potential therapeutic target in cerebellar GBM.

BACKGROUND: Recent evidence suggests that combining individual imaging markers of cerebral small vessel disease (SVD) may more accurately reflect its overall burden and better correlate with clinical measures. OBJECTIVE: We wished to establish the clinical relevance of the total SVD score in a memory clinic population by investigating the association with SVD score and cognitive performance, cortical atrophy, and structural network measures, after adjusting for amyloid-β burden. METHODS: We included 243 patients with amnestic mild cognitive impairment (MCI), Alzheimer’s disease dementia, subcortical vascular MCI, or subcortical vascular dementia. All underwent MR and [11C] PiB-PET scanning and had standardized cognitive testing. Multiple linear regression was used to evaluate the relationships between SVD score and cognition, cortical thickness, and structural network measures. Path analyses were performed to evaluate whether network disruption mediates the effects of SVD score on cortical thickness and cognition. RESULTS: Total SVD score was associated with the performance of frontal (β – 4.31, SE 2.09, p = 0.040) and visuospatial (β – 0.95, SE 0.44, p = 0.032) tasks, and with reduced cortical thickness in widespread brain regions. Total SVD score was negatively correlated with nodal efficiency, as well as changes in brain network organization, with evidence of reduced integration and increasing segregation. Path analyses showed that the associations between SVD score and frontal and visuospatial scores were partially mediated by decreases in their corresponding nodal efficiency and cortical thickness. CONCLUSION: Total SVD burden has clinical relevance in a memory clinic population and correlates with cognition, and cortical atrophy, as well as structural network disruption.

Purpose Lower urinary tract symptoms (LUTS) can be distressing and socially isolating, and the economic impact can be substantial. Further data to characterize the epidemiology and effects of LUTS in South Korea would be beneficial. Materials and methods In an international, internet-based survey, the prevalence and impact of LUTS was evaluated in adults aged ≥40 years. Questions related to International Continence Society (ICS) symptom definitions and the bother associated with each symptom. The international prostate symptom score (IPSS) and the overactive bladder symptom score (OABSS) were assessed. Results Of the 2,080 participants from South Korea, 1,090 (52.4%) were women and 740 (35.6%) were aged ≥60 years. The prevalence of LUTS according to ICS criteria was 68.2% (men, 70.6%; women, 66.0%). LUTS prevalence increased significantly with age (p=0.01 in men and women). Storage symptoms only were reported in 16.2% of men and 30.5% of women, making this the most common ICS symptom group overall. Individual symptoms with the highest prevalence in the overall population were nocturia, frequency, and weak stream (36%, 30%, and 29%, respectively). IPSS results showed that 40.1% of participants had at least moderate symptoms. The prevalence of OABSS-defined overactive bladder was 19.7% (men, 19.5%; women, 19.9%). Fourteen percent of individuals with any LUTS visited healthcare professionals regarding urinary symptoms. Conclusions LUTS affect the majority of adults aged ≥40 years in South Korea. The low percentage of individuals with LUTS consulting healthcare professionals regarding urinary symptoms indicates a need to improve rates of diagnosis and treatment.

BACKGROUND: Radiomics is a rapidly growing field in neuro-oncology, but studies have been limited to conventional MRI, and external validation is critically lacking. We evaluated technical feasibility, diagnostic performance, and generalizability of a diffusion radiomics model for identifying atypical primary central nervous system lymphoma (PCNSL) mimicking glioblastoma. METHODS: A total of 1618 radiomics features were extracted from diffusion and conventional MRI from 112 patients (training set, 70 glioblastomas and 42 PCNSLs). Feature selection and classification were optimized using a machine-learning algorithm. The diagnostic performance was tested in 42 patients of internal and external validation sets. The performance was compared with that of human readers (2 neuroimaging experts), cerebral blood volume (90% histogram cutoff, CBV90), and apparent diffusion coefficient (10% histogram, ADC10) using the area under the receiver operating characteristic curve (AUC). RESULTS: The diffusion radiomics was optimized with the combination of recursive feature elimination and a random forest classifier (AUC 0.983, stability 2.52%). In internal validation, the diffusion model (AUC 0.984) showed similar performance with conventional (AUC 0.968) or combined diffusion and conventional radiomics (AUC 0.984) and better than human readers (AUC 0.825–0.908), CBV90 (AUC 0.905), or ADC10 (AUC 0.787) in atypical PCNSL diagnosis. In external validation, the diffusion radiomics showed robustness (AUC 0.944) and performed better than conventional radiomics (AUC 0.819) and similar to combined radiomics (AUC 0.946) or human readers (AUC 0.896–0.930). CONCLUSION: The diffusion radiomics model had good generalizability and yielded a better diagnostic performance than conventional radiomics or single advanced MRI in identifying atypical PCNSL mimicking glioblastoma.

We evaluated how the impact of apolipoprotein E4 (APOE4) differs according to age in Alzheimer's disease (AD) patients. We recruited 846 AD patients and 815 cognitively normal controls and categorized into three groups with respect to their age (

A novel combination of machine learning algorithms is proposed for the differentiation of distinct spectra in a large electron energy loss spectroscopy spectrum image (EELS-SI) dataset. For clustering of the EEL spectra including similar fine structures in an efficient space, linear and nonlinear dimensionality reduction methods are used to project the EEL spectra onto a low-dimensional space. Then, a density-based clustering algorithm is applied to distinguish the meaningful data clusters. By applying this strategy to various experimental EELS-SI datasets, differentiation of several groups of EEL spectra representing specific fine structures was achieved. It is possible to investigate particular fine structures by averaging all of the spectra in each cluster. Also, the spatial distributions of each cluster in the scanning regions can be observed, which enables investigation of the locations of different fine structures in materials. This method does not require any prior knowledge, i.e., it is a data-driven analysis; therefore, it can be applied to any hyperspectral image.

Background and purpose Biomarker changes in cognitively impaired patients with small vessel disease are largely unknown. The rate of amyloid/lacune progression, cortical thinning and cognitive decline were evaluated in subcortical vascular mild cognitive impairment (svMCI) patients. Methods Seventy-two svMCI patients were divided into early stage (ES-svMCI, n = 39) and late stage (LS-svMCI, n = 33) according to their Clinical Dementia Rating Sum of Boxes score. Patients were annually followed up with neuropsychological tests and brain magnetic resonance imaging for 3 years, and underwent a second [11 C] Pittsburgh compound B (PiB) positron emission tomography scan within a mean interval of 32.4 months. Results There was no difference in the rate of increase in PiB uptake or lacune number between the ES-svMCI and LS-svMCI. However, LS-svMCI showed more rapid cortical thinning and cognitive decline than did the ES-svMCI. Conclusions We suggest that, whilst the rate of change in pathological burden did not differ between ES-svMCI and LS-svMCI, cortical thinning and cognitive decline progressed more rapidly in the LS-svMCI.

Docetaxel is a taxane chemotherapeutic agent used in the treatment of breast cancer, prostate cancer and gastric cancer, but several side effects such as peripheral neurotoxicity could occur. The present study was designed to investigate the therapeutic potential of phosphatidylcholine (PC) on docetaxel-induced peripheral neurotoxicity. Rats were randomly divided into three groups and treated for 4 weeks. Behavioral tests were conducted to measure the effects of PC on docetaxel-induced decreases in mechanical & thermal nociceptive threshold. Biochemical tests were conducted to measure the level of oxidative stress on sciatic nerve. Histopathological and immunohistochemical experiments were also conducted to assess neuronal damage and glial activation. PC treatment significantly attenuated docetaxel-induced changes in mechanical & thermal nociceptive response latencies. PC decreased oxidative stress in sciatic nerve by increasing antioxidant levels (glutathione, glutathione peroxidase and superoxide dismutase activity). In immunohistochemical evaluation, PC treatment ameliorated docetaxel-induced neuronal damage and microglial activation in the sciatic nerve and spinal cord. Thus, PC showed protective effects against docetaxel-induced peripheral neurotoxicity. These effects may be attributed to its antioxidant properties and modulation of microglia.

A nanostructured micro-prism array (MPA) was integrated onto a solar module consisting of multiple perovskite solar cells (PeSCs) to minimize optical losses from surface reflection and the inactive areas reserved for interconnection. The MPA structure redirects light that is incident on inactive areas onto active sub-cell areas to improve the light harvesting efficiency. The nanoscale sub-wavelength structures (SWSs) minimize the surface reflection at the surface of the PeSC module. Combining the technical advantages of these two structures, the MPA decorated with nanoscale SWSs improves the performance of the PeSC module. The short circuit current of the PeSC module employing the MPA decorated with nanoscale SWSs was improved by 1.4 mA/cm2 compared to a conventional PeSC module covered with bare glass.

A phosphatidylcholine (PPC) formulation has been used to treat cellulite; however, its underlying mechanism of action remains unclear. In this study, we demonstrated that PPC induces lipolysis and apoptosis in adipocytes, and evaluated a possible tumor necrosis factor alpha (TNFα)-dependent pathway, whereby PPC exerts these effects. For in vitro study, fully differentiated 3T3-L1 cells, mouse adipocytes were treated with various concentrations of PPC and cell apoptosis and lipolysis were assayed. For in vivo experiments, mice fed on a high-fat diet for 8 weeks were injected twice to abdominal subcutaneous fat tissues of either vehicle or PPC. We found that PPC induced lipolysis and apoptosis dose-dependently in fully differentiated 3T3-L1 cells. In addition, PPC augmented both expression and release of TNFα in a dose-dependent fashion. Induction of TNFα by PPC was associated with the stimulation of nuclear factor kappa B (NFκB)-mediated transcriptional activity. Small interfering RNA (siRNA)-mediated suppression of NFκB abrogated the effect of PPC on TNFα secretion. Suppression of TNFα with specific siRNA abrogated the effects of PPC on lipolysis and apoptosis. Through in vivo experiments, we demonstrated that PPC injection not only stimulated the local lipolysis and apoptosis, resulting in weight loss, but also induced TNFα mRNA expression and neutrophil infiltration. Furthermore, PPC injection prevented lipogenesis and suppressed the mRNA ­expression of adipokines (such as adiponectin and leptin), due to the down-sizing of adipocytes. In conclusion, we suggest that PPC induces lipolysis and apoptosis in adipocytes through TNFα-dependent pathways.

Amyloid positron emission tomography ([18F] florbetaben (FBB) PET) can be used to determine concomitant Alzheimer's disease (AD) in idiopathic normal pressure hydrocephalus (iNPH) patients. FBB PET scans and the tap test were performed in 31 patients with clinically suspected iNPH, and amyloid positive (iNPH/FBB+) and negative (iNPH/FBB-) groups were compared with respect to clinical characteristics. We evaluated prognostic value of FBB PET scans by analyzing the response to the tap test using a linear mixed model. We also performed a multivariable regression analysis to investigate whether amyloid PET positivity can predict the positive tap test response independent of other AD biomarkers. The results showed that the iNPH/FBB+ group (7/31, 22.6%) had a higher percentage of APOE4 carriers, lower Aβ42, higher CSF t-tau, and p-tau/Aβ42 ratio than the iNPH/FBB- group (24/31, 77.4%), while the two groups did not differ in imaging characteristics. The iNPH/FBB- group had a higher percentage of tap responders and showed a greater improvement in gait scores after the tap test than the iNPH/FBB+ group (group-tap test effect interaction, p = 0.035). A multivariable logistic regression analysis showed that amyloid positivity on PET scans (OR 0.03, p = 0.029) and CSF p-tau (OR 0.87, p = 0.044) were independently associated with the positive tap test response. Among 21 tap responders in the iNPH/FBB- group, 14 patients received shunt surgery and 12/14 (85.7%) patients showed symptom improvement. Our findings suggest that amyloid PET scans can help determine which iNPH patients will benefit from shunt surgery by discriminating concomitant AD.

본 논문은 토픽 모델링(Topic Modeling)의 latent Dirichlet allocation(LDA) 분석 방법을 적용하여 박근혜 정부 4년간 관련 신문 사설을 분석한 연구이다. 수집된 사설은 LDA를 적용하여 토픽(Topic)으로 분류하고 토픽별 보도량을 살펴봄으로써 박근혜 관련 사설에 나타난 국내의 보수와 진보성향을 대표하는 조선일보와 한겨레의 이슈소유권을 비교 분석하였다. 빅데이터 분석 결과, 총 23개의 주요 토픽이 도출되었는데, 토픽의 점유율 특성으로 볼 때 조선일보는 국회, 정당, 북핵, 경제, 지명직 인사 등과 관련하여 지속적으로 점유율 우위를 점하고 있었고, 정치와 경제 및 북핵 관련 공안 이슈를 지속적으로 제기했다. 이에 반해 한겨레는 폭로 저널리즘 성향이 강하게 나타났는데, 우리사회의 주요 정치, 사회, 경제 부문의 문제가 있는 상황을 꾸준히 제기하면서 새로운 토픽을 지속 발굴, 보도하는 성향을 확인했다. 연구진은 커뮤니케이션 연구에서 토픽 모델링이라는 빅데이터 분석 방법을 차용함으로써 기존에 정성적으로 많이 진행해왔던 내용분석에 대한 보완적 방법으로 대규모 텍스트 분석을 위한 의미 있는 접근이기를 기대해본다.