Search

Rationale: The optimal duration of dual antiplatelet therapy (DAPT) with clopidogrel-aspirin for the large artery atherosclerotic (LAA) stroke subtype has been debated. Aims: To determine whether the 1-year risk of recurrent vascular events could be reduced by a longer duration of DAPT in patients with the LAA stroke subtype. Methods and study design: A total of 4806 participants will be recruited to detect a statistically significant relative risk reduction of 22% with 80% power and a two-sided alpha error of 0.05, including a 10% loss to follow-up. This is a registry-based, multicenter, prospective, randomized, open-label, blinded end point study designed to evaluate the efficacy and safety of a 12-month duration of DAPT compared with a 3-month duration of DAPT in the LAA stroke subtype. Patients will be randomized (1:1) to either DAPT for 12 months or DAPT for 3 months, followed by monotherapy (either aspirin or clopidogrel) for the remaining 9 months. Study outcomes: The primary efficacy outcome of the study is a composite of stroke (ischemic or hemorrhagic), myocardial infarction, and all-cause mortality for 1 year after the index stroke. The secondary efficacy outcomes are (1) stroke, (2) ischemic stroke or transient ischemic attack, (3) hemorrhagic stroke, and (4) all-cause mortality. The primary safety outcome is major bleeding. Discussion: This study will help stroke physicians determine the appropriate duration of dual therapy with clopidogrel-aspirin for patients with the LAA stroke subtype. Trial registration: URL: https://cris.nih.go.kr/cris. CRIS Registration Number: KCT0004407 [ABSTRACT FROM AUTHOR]

[Display omitted] Excellent color purity and high external quantum efficiency (EQE) are major requirements in the development of deep-blue organic light-emitting diodes (OLEDs). To achieve this, multiple-resonance (MR)–thermally activated delayed fluorescence (TADF) emitters have been considered as promising options. Herein, we suggest a novel expanded MR design strategy to fabricate deep-blue MR–TADF emitters derived from a fused indolo[3,2,1- jk ]carbazole framework. The expanded MR structure managed a triplet excited state for the accelerated spin–vibronic coupling-assisted reverse intersystem crossing and increased the emission dipole orientation while maintaining the high efficiency and deep-blue emission color. The rigid and planar structure of the MR core yielded a small full-width at half-maximum (FWHM; less than 16 nm), high photoluminescence quantum yield (over 97%), and high horizontal emitting dipole orientation (over 90%), and facilitated a second-order spin–vibronic coupling-assisted triplet-to-singlet spin crossover. The fabricated MR–TADF OLEDs recorded a high EQE of 24.3% and FWHM of 21 nm at a CIE y of 0.044, thereby satisfying the BT.2020 blue standard. Additionally, further optimized device architecture provided an EQE of 26.8%. [ABSTRACT FROM AUTHOR]

The development of highly efficient and deep blue emitters satisfying the color specification of the commercial products has been a challenging hurdle in the organic light‐emitting diodes (OLEDs). Here, deep blue OLEDs with a narrow emission spectrum with good color stability and spin‐vibronic coupling assisted thermally activated delayed fluorescence are reported using a novel multi‐resonance (MR) emitter built on a pure organic‐based molecular platform of fused indolo[3,2,1‐jk]carbazole structure. Two emitters derived from 2,5,11,14‐tetrakis(1,1‐dimethylethyl)indolo[3,2,1‐jk]indolo[1′,2′,3′:1,7]indolo[3,2‐b]carbazole (tBisICz) core are synthesized as the MR type thermally activated delayed fluorescence emitters realizing a very narrow emission spectrum with a full‐width‐at‐half‐maximum (FWHM) of 16 nm with suppressed broadening at high doping concentration. The tBisICz core is substituted with a diphenylamine or 9‐phenylcarbazole blocking group to manage the intermolecular interaction for high efficiency and narrow emission. The deep blue OLEDs achieve high external quantum efficiency (EQE) of 24.9%, small FWHM of 19 nm, and deep blue color coordinate of (0.16, 0.04) with good color stability with increase in doping concentration. To the authors' knowledge, the EQE in this work is one of the highest values reported for the deep blue OLEDs that achieve the BT.2020 standard. [ABSTRACT FROM AUTHOR]

Background: Clinical decision-making of invasive high-intensity care for critically ill stage IV cancer patients in the emergency department (ED) is challenging. A reliable and clinically available prognostic score for advanced cancer patients with septic shock presented at ED is essential to improve the quality of intensive care unit care. This study aimed to develop a new prognostic score for advanced solid cancer patients with septic shock available early in the ED and to compare the performance to the previous severity scores.Methods: This multi-center, prospective cohort study included consecutive adult septic shock patients with stage IV solid cancer. A new scoring system for 28-day mortality was developed and validated using the data of development (January 2016 to December 2017; n = 469) and validation sets (January 2018 to June 2019; n = 428). The developed score's performance was compared to that of the previous severity scores.Results: New scoring system for 28-day mortality was based on six variables (score range, 0-8): vital signs at ED presentation (respiratory rate, body temperature, and altered mentation), lung cancer type, and two laboratory values (lactate and albumin) in septic shock (VitaL CLASS). The C-statistic of the VitaL CLASS score was 0.808 in the development set and 0.736 in the validation set, that is superior to that of the Sequential Organ Failure Assessment score (0.656, p = 0.01) and similar to that of the Acute Physiology and Chronic Health Evaluation II score (0.682, p = 0.08). This score could identify 41% of patients with a low-risk group (observed 28-day mortality, 10.3%) and 7% of patients with a high-risk group (observed 28-day mortality, 73.3%).Conclusions: The VitaL CLASS score could be used for both risk stratification and as part of a shared clinical decision-making strategy for stage IV solid cancer patients with septic shock admitting at ED within several hours. [ABSTRACT FROM AUTHOR]

Pyruvate dehydrogenase kinase (PDK) controls the activity of pyruvate decarboxylase complex (PDC) by phosphorylating key serine residues on the E1 subunit, which leads to a decreased oxidative phosphorylation in mitochondria. Inhibition of PDK activity by natural/synthetic compounds has been shown to reverse the Warburg effect, a characteristic metabolism in cancer cells. PDK-PDC axis also has been associated with diabetes and heart disease. Therefore, regulation of PDK activity has been considered as a promising strategy to treat related diseases. Here we present the X-ray crystal structure of PDK2 complexed with a recently identified PDK4 inhibitor, compound 8c, which has been predicted to bind at the lipoyl-binding site and interrupt intermolecular interactions with the E2-E3bp subunits of PDC. The co-crystal structure confirmed the specific binding location of compound 8c and revealed the remote conformational change in the ATP-binding pocket. In addition, two novel 4,5-diarylisoxazole derivatives, GM10030 and GM67520, were synthesized and used for structural studies, which target the ATP-binding site of PDK2. These compounds bind to PDK2 with a sub-100nM affinity as determined by isothermal titration calorimetry experiments. Notably, the crystal structure of the PDK2-GM10030 complex displays unprecedented asymmetric conformation of human PDK2 dimer, especially in the ATP-lids and C-terminal tails. Image 1 • A crystal structure of human PDK2 with a novel allosteric inhibitor at the lipoyl-binding site. • Crystal structures of human PDK2 with the 4,5-diarylisoxazole-derived compounds. • These inhibitors are first to be found in the crystal structure of any PDK isoform. • First structures showing the asymmetric composition of PDK2 dimer from human. Scientific Summary: We describe the structural, biophysical, and mechanistic characterization of human PDK2, which is responsible for modulating the activity of pyruvate dehydrogenase complex (PDH) through phosphorylating key serine residues of the E1 subunit. Overexpression of PDK isoforms results in the inhibition of OXPHOS in mitochondria, which at least partly contribute to the Warburg effect, a characteristic feature of cancer metabolism. PDK activities are also known to be closely related to diabetes and heart failure, hence have been extensively studied. We have determined a crystal structure of human PDK2, the most abundant isoform among four, in the presence of an allosteric inhibitor to 1.93 Å resolution. The chemical structure of this compound is based on a novel anthraquinone-scaffold, and the co-crystal structure provides a unique binding mode of the inhibitor in the lipoyl-binding pocket of the protein. Moreover, we have determined two crystal structures bound with ATP-competitive inhibitors, which are derived from 4,5-diarylisoxazole core. These structures are also the first to demonstrate detailed molecular interactions of PDK with a 4,5-diarylisoxazole derivative. We interrogated in vitro binding affinities of these compounds in solution through biophysical approaches including isothermal calorimetry (ITC) and saturation transfer difference (STD) experiments. Lastly, the anticancer activities of these inhibitors were examined via cell viability assays against HeLa cells. Highlights and significance of this manuscript include 1) co-crystal structures of PDK2 provide valuable insights into the mechanism underlying the structural basis for the inhibition of PDK by compounds targeting the ATP- and lipoyl-binding sites, 2) the asymmetric composition of conformational states within dimeric PDK2, which has not previously identified in human PDK2 structures, and 3) a potential structural-guide for designing enhanced therapeutic agents to control related diseases including diabetes, obesity, and cancer. [ABSTRACT FROM AUTHOR]

Objective: This study investigated the effect of residual stenosis after carotid artery stenting (CAS) on periprocedural and long-term outcomes. Methods: Patients treated with CAS for symptomatic or asymptomatic carotid arterial stenosis were consecutively enrolled. Residual stenosis was estimated from post-procedure angiography findings. The effects of residual stenosis on 30-day periprocedural outcome and times to restenosis and clinical outcome were analyzed using logistic regression models and Wei-Lin-Weissfeld models, respectively. Results: A total of 412 patients (age, 64.7 ± 17.0 years; male, 82.0%) were enrolled. The median baseline stenosis was 80% (interquartile range [IQR], 70–90%), which improved to 10% (0–30%) for residual stenosis. Residual stenosis was significantly associated with periprocedural outcome (adjusted odds ratio, 0.983; 95% confidence interval [CI], 0.965–0.999, P = 0.01) after adjustment for baseline stenosis, age, hypertension, symptomaticity, and statin use. Over the 5-year observation period, residual stenosis did not increase the global hazard for restenosis and clinical outcome (adjusted hazard ratio, 1.011; 95% CI, 0.997–1.025. In the event-specific model, residual stenosis increased the hazard for restenosis (adjusted hazard ratio, 1.041; 1.012–1.072) but not for clinical outcome (adjusted hazard ratio, 1.011; 0.997–1.025). Conclusions: Residual stenosis after carotid artery stenting may be useful to predict periprocedural outcome and restenosis. [ABSTRACT FROM AUTHOR]

In organic light-emitting diodes (OLEDs), host engineering is important in improving the device performance. however, it remains as a big challenge in blue phosphorescent OLEDs because of the high triplet energy of blue phosphors. In this work, we develop a sterically modulated thermally activated delayed fluorescence-type host based on an ortho -linked carbazole–triazine backbone structure. An additional π -spacer spatially twisting the two moieties delivers a short delayed decay time of 5.0 μs without any loss of the photoluminescence quantum yield while realizing high triplet and small singlet-triplet energy splitting. The photophysical modulation enables a more efficient utilization of the triplet excitons of the two blue phosphorescent emitters in OLEDs. The fabricated blue phosphorescent OLEDs exhibit a significantly improved device performance in all efficiency parameters compared to reference devices with a maximum external quantum efficiency of 23.6%. This work demonstrates a simple and powerful thermally activated delayed fluorescence host design strategy to realize high efficiency blue-phosphorescence OLEDs. [Display omitted] • Steric modulation of blue host for thermally activated delayed fluorescence characteristics. • Ortho-linked carbazole-triazine backbone structure for high triplet energy. • High external quantum efficiency over 20% in the blue phosphorescent organic light-emitting diodes. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the correlation between the pharmacokinetics and pharmacodynamics of granulocyte colony-stimulating factor (lenograstim) and the impact of initiation time of apheresis on stem cell mobilization in patients with multiple myeloma.Study Design and Methods: Twenty-four patients with multiple myeloma were randomized into one of the two groups (early vs. late). Lenograstim at 10 μg/kg/day once daily was injected for at least 4 consecutive days. Apheresis was initiated 2 hours after the fourth dose of lenograstim in the early collection group and 16 hours after the fourth dose of lenograstim in the late collection group. Blood sampling for pharmacokinetics was performed within 30 minutes before, and 1, 2, 6, and 24 hours after the fourth dose of lenograstim.Results: Overall, the two groups (early vs. late, n = 10 vs. 14) exhibited similar baseline characteristics including age, sex, subtype of myeloma, stage distribution, and myeloma-associated symptoms. No correlation was found between plasma lenograstim concentration and peripheral blood (PB) CD34+ cell counts or hematopoietic progenitor cells. In the late collection group, the median number of apheresis procedures for minimal collection was significantly lower (early vs. late: 2 vs. 1; p = 0.04) and there was a higher number of total collected PB CD34+ cells in a single session of apheresis (1.4 vs. 3.1; p = 0.06). There were no differences in median overall PB stem cell collection efficiency.Conclusion: Late collection positively impacted the number of apheresis procedures for minimal collection, with numerically improved PB stem cell collection efficiency at first apheresis in patients with multiple myeloma. [ABSTRACT FROM AUTHOR]

Recently, One-class classification algorithms have been successfully used for outlier detection problems in several industrial fields. However, in case of that the target class has complex structures, single outlier detection model with one-class classifier often poorly performs because it cannot appropriately reflect intrinsic data structures. To address this limitation, we propose a clustering ensemble-based novelty score algorithm. The proposed algorithm calculates novelty score from the mixture of multiple clustering solutions generated by both random subspace and random- K ensemble approaches. Then, final ensemble novelty score is defined by summarizing multiple novelty scores obtained from individual clustering results. Because these multiple novelty scores are computed from many possible characteristics of target class information, the proposed ensemble novelty score can appropriately reflect the inherent structures of target class. Experiments were conducted on various benchmark datasets to compared with existing methods and investigate the properties of the proposed algorithm. The experimental results confirm that the proposed algorithm outperforms existing one-class classification methods in various cases. [ABSTRACT FROM AUTHOR]

Background: Immunoglobulin D multiple myeloma (IgD MM) is characterized by a poor prognosis. Data are lacking on the survival benefits associated with the use of novel agents followed by autologous stem cell transplantation (ASCT) in IgD MM patients. We evaluated the clinical outcomes of induction treatment with novel agents followed by ASCT. Methods: This was a single-center, retrospective study of 22 IgD MM patients who underwent ASCT between 1995 and 2016. Of these, 10 (45.4%) received novel agents and 12 (54.6%) received nonnovel agents. Clinical features and survival outcomes were examined. Results: Median overall survival (OS) was 37.7 months in the 22 patients. Those in the novel-agents group received bortezomib or thalidomide-based regimens, whereas 91.7% of the nonnovel-agents group received a vincristine-based regimen. The median progression-free survival and OS in the novel-agent/nonnovel-agent groups were 8.3/7.4 and 38.6/12.5 months, respectively. The median OS of patients receiving maintenance therapy was not reached. Conclusion: This study showed improved survival outcomes compared to our previous study (37.7 vs. 12 months), suggesting that the use of a novel agent as induction and maintenance therapy may be beneficial in patients with IgD MM who undergo ASCT. [ABSTRACT FROM AUTHOR]

Background: How short-term blood pressure variability (BPV) is affected in the acute stage of ischemic stroke and whether BPV is associated with early neurologic outcomes remains unclear. Methods: Patients who admitted for ischemic stroke within 24 h of symptom onset were consecutively identified between January 2010 and January 2015. BP profiles measured in real-time were summarized into short-term, 24-h time intervals, based on standard deviation (SD) and mean of systolic BP (SBPSD) during the first 3 days. The primary outcome was daily assessment of early neurological deterioration (END). The associations between short-term SBPSD values and the secular trend for primary outcome were examined. Results: A total of 2,545 subjects (mean age, 67.1 ± 13.5 years old and median baseline National Institutes of Health Stroke Scale score, 3) arrived at the hospital an average of 6.1 ± 6.6 h after symptom onset. SBPSD values at day 1 (SD#D1), SD#D2, and SD#D3 were 14.4 ± 5.0, 12.5 ± 4.5, and 12.2 ± 4.6 mmHg, respectively. Multivariable analyses showed that SD#D2 was independently associated with onset of END at day 2 (adjusted odds ratio, 1.08; 95% confidence interval, 1.03–1.13), and SD#D3 was independently associated with END#D3 (1.07, 1.01–1.14), with adjustments for predetermined covariates, SBPmean, and interactions with daily SBPSD. Conclusion: Short-term BPV changed and stabilized from the first day of ischemic stroke. Daily high BPV may be associated with neurological deterioration independent of BPV on the previous day. [ABSTRACT FROM AUTHOR]

Traditional control charts, such as Hotelling’s T 2 , are effective in detecting abnormal patterns. However, most control charts do not take into account a time-varying property in a process. In the present study, we propose a parameter-less self-organizing map-based control chart that can handle a situation in which changes occur in the distribution or parameter of the target observations. The control limits of the proposed chart are determined by estimating the empirical level of significance on the percentile using the bootstrap method. Experimental results obtained by using simulated data and actual process data from the manufacturing process for a thin-film transistor-liquid crystal display demonstrate the effectiveness and usefulness of the proposed algorithm. [ABSTRACT FROM AUTHOR]

Pumping sediment-laden water from excavations is often necessary on construction sites. This water is often treated by pumping it through geotextile dewatering bags. The bags are not designed to filter the fine sediments that create high turbidity, but dosing with a flocculant prior to the bag could result in greater turbidity control. This study compared two systems for introducing flocculant: passive dosing of commercial solid biopolymer (chitosan) and injection of dissolved polyacrylamide (PAM) in a length of corrugated pipe connected to the bag. The biopolymer system consisted of sequential porous socks containing a “charging agent” followed by chitosan in the corrugated pipe with two levels of dosing. The dissolved PAM was injected into turbid water at a flow-weighted concentration at 1 mg L −1 . For each treatment, sediment-laden turbid water in the range of 2000 to 3500 nephelometric turbidity units (NTU) was pumped into the upstream of corrugated pipe and samples were taken from pipe entrance, pipe exit, and dewatering bag exit. Without flocculant treatment, the dewatering bag reduced turbidity by 70% but the addition of flocculant increased the turbidity reduction up to 97% relative to influent. At the pipe exit, the low-dose biopolymer was less effective in reducing turbidity (37%) but it was equally effective as the high-dose biopolymer or PAM injection after the bag. Our results suggest that a relatively simple treatment with flocculants, either passively or actively, can be very effective in reducing turbidity for pumped water on construction sites. [ABSTRACT FROM AUTHOR]

Background and Objectives Light sharing PET detector configuration coupled with thick light guide and Geiger-mode avalanche photodiode (GAPD) with large-area microcells was proposed to overcome the energy non-linearity problem and to obtain high light collection efficiency (LCE). Methods A Monte-Carlo simulation was conducted for the three types of LSO block, 4 × 4 array of 3 × 3 × 20 mm 3 discrete crystals, 6 × 6 array of 2 × 2 × 20 mm 3 discrete crystals, and 12 × 12 array of 1 × 1 × 20 mm 3 discrete crystals, to investigate the scintillation light distribution after conversion of the γ-rays in LSO. The incident photons were read out by three types of 4 × 4 array photosensors, which were PSPMT of 25% quantum efficiency (QE), GAPD1 with 50 × 50 µm 2 microcells of 30% photon detection efficiency (PDE) and GAPD2 with 100 × 100 µm 2 of 45% PDE. The number of counted photons in each photosensor was analytically calculated. The LCE, linearity and flood histogram were examined for each PET detector module having 99 different configurations as a function of light guide thickness ranging from 0 to 10 mm. Results The performance of PET detector modules based on GAPDs was considerably improved by using the thick light guide. The LCE was increased from 24 to 30% and from 14 to 41%, and the linearity was also improved from 0.97 to 0.99 and from 0.75 to 0.99, for GAPD1 and GAPD2, respectively. As expected, the performance of PSPMT based detector did not change. The flood histogram of 12 × 12 array PET detector modules using 3 mm light guide coupled with GAPDs was obtained by simulation, and all crystals of 1 × 1 × 20 mm 3 size were clearly identified. PET detector module coupled with thick light guide and GAPD array with large-area microcells was proposed to obtain high QE and high spatial resolution, and its feasibility was verified. Conclusions This study demonstrated that the overall PET performance of the proposed design was considerably improved, and this approach will provide opportunities to develop GAPD based PET detector with a high LCE. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) cancer cell culture models mimic the complex 3D organization and microenvironment of human solid tumor tissue and are thus considered as highly predictive models representing avascular tumor regions. Confocal laser scanning microscopy is useful for monitoring drug penetration and therapeutic responses in 3D tumor models; however, photonic attenuation at increasing imaging depths and limited penetration of common fluorescence tracers are significant technical challenges to imaging. Immunohistological staining would be a good alternative, but the preparation of tissue sections from rather fragile spheroids through fixing and embedding procedures is challenging. Here we introduce a novel 3 × 3 mini-pillar array chip that can be utilized for 3D cell culturing and sectioning for high-content histologic analysis. The mini-pillar array chip facilitated the generation of 3D spheroids of human cancer cells within hydrogels such as alginate, collagen, and Matrigel. As expected, visualization of the 3D distribution of calcein AM and doxorubicin by optical sectioning was limited by photonic attenuation and dye penetration. The integrity of the 3D microtissue section was confirmed by immunostaining on paraffin sections and cryo-sections. The applicability of the mini-pillar array for drug activity evaluation was tested by measuring viability changes in spheroids exposed to anti-cancer agents, 5-fluorouracil and tirapazamine. Thus, our novel mini-pillar array platform can potentially promote high-content histologic analysis of 3D cultures and can be further optimized for field-specific needs. [ABSTRACT FROM AUTHOR]

Due to stringent water quality regulations on stormwater discharges, there is increasing interest in chemically-assisted settling of suspended sediments at construction sites. This study investigated settling characteristics of flocculated sediment by polyacrylamide (PAM) in a top-loading settling tube. Studied sediment materials were obtained from construction sites in North Carolina, USA: Coastal Plain loamy sand (CPLS), Piedmont sandy clay loam (PSCL), Piedmont silt loam (PSL), and Mountain clay loam (MCL). The four different sediment suspensions mixed with and without dissolved PAM were introduced to the top of the column individually. During a 1-h settling period, samples were taken at 1-m depth from surface at various times and analyzed for total suspended solids (TSS). Flocculated sediment by PAM greatly increased its settled TSS fraction up to 95–97% only in 1-min settling period compared to those of unflocculated sediment (16–72%). The settling improvement by PAM was profound in the finer-textured soils (PSL and MCL) by increasing their median particle settling velocity (>2 cm s −1 ) compared to unflocculated counterparts (<1.1 cm s −1 ). Estimated surface area requirement of sediment basin suggested that the basins receiving flocculated sediment could be reduced in size (surface area) by 2- to 4-times compared to those receiving unflocculated sediment. Our results suggests that current sediment basin design could be modified when chemically-assisted settling is implemented, taking up less space and cost in construction sites. [ABSTRACT FROM AUTHOR]

Background: To evaluate whether topographical characteristics of insular involvement in ischemic stroke are associated with cardioembolism. Methods and Findings: A consecutive series of patients hospitalized for ischemic stroke within 7 days of symptom onset were identified. Based on diffusion-weighted imaging, we included those who had ischemic lesions in the middle cerebral artery (MCA) territory. Each patient was assigned to one of two groups based on the presence or absence of insular involvement. The primary outcome was the frequency of cardioembolism, which was compared based on insular involvement. Of 1,311 patients with ischemic stroke in the MCA territory, 112 had insular involvement (8.5%). The frequency of cardioembolism in patients with insular involvement (52.7%) was significantly higher than that in patients without insular involvement (30.4%, P < 0.001). Although insular involvement was associated with a severe baseline National Institutes of Health Stroke Scale score (13 vs. 4), it did not independently affect the 3-month functional outcome. Conclusions: In cases of stroke in the MCA territory, involvement of the insular cortex may be associated with a risk of cardioembolism. [ABSTRACT FROM AUTHOR]

Polyacrylamide (PAM) is becoming a widely used soil conditioning and erosion control agent, and a better understanding of its transport is required to improve its use. In this study vertical PAM transport through a clay loam soil was investigated using thin soil columns (7.62-cm diameter × 2-cm thick) under saturated condition. The columns received a water-soluble, anionic PAM solution (16 Mg mol − 1 with 50 mol% charge density) under pulse and step (continuous) inputs using a constant-head method. The pulse input was 500 mg L − 1 PAM solution applied for 0.6 pore volume ( PV ), after which the input was switched to deionized (DI) water for 25 PVs . The step input was 25 mg L − 1 PAM solution applied continuously for 129 PVs . Saturated hydraulic conductivity ( K sat ) was measured prior to PAM application and was monitored during PAM and DI water leaching. Leachate samples were collected frequently with time from each column and analyzed for the dissolved PAM concentration. The PAM applications reduced K sat to 1% of the initial K sat (4 cm h − 1 ) under the pulse input and to 0.3% of the initial K sat under the step input. Transport of PAM was best-fitted with a two-region (dual-porosity) model. The fitted retardation factor ( R ) was more than two-fold greater for the step input ( R = 2695) than for the pulse input ( R = 1242). The results from transport modeling and pore size distribution analysis suggested that viscous PAM solution contributes to a mechanical entrapment of the PAM molecules, clogging most water-conducting pores smaller than 225–274 μm in diameter. Under saturated condition, either the pulse or step input of dissolved PAM could reduce seepage with limited mobility in the soil profile. [ABSTRACT FROM AUTHOR]

Glioma is the most common primary malignant brain tumor in adults and accounts for approximately 80% of brain and central nervous system tumors. In 2021, the World Health Organization (WHO) published a new taxonomy for glioma based on its histological features and molecular alterations. Isocitrate dehydrogenase (IDH) catalyzes the decarboxylation of isocitrate, a critical metabolic reaction in energy generation in cells. Mutations in the IDH genes interrupt cell differentiation and serve as molecular biomarkers that can be used to classify gliomas. For example, the mutant IDH is widely detected in low-grade gliomas, whereas the wild type is in high-grade ones, including glioblastomas. Long non-coding RNAs (lncRNAs) are epigenetically involved in gene expression and contribute to glioma development. To investigate the potential use of lncRNAs as biomarkers, we examined lncRNA dysregulation dependent on the IDH mutation status. We found that several lncRNAs, namely, AL606760.2, H19, MALAT1, PVT1 and SBF2-AS1 may function as glioma risk factors, whereas AC068643.1, AC079228.1, DGCR5, FAM13A-AS1, HAR1A and WDFY3-AS2 may have protective effects. Notably, H19, MALAT1, PVT1, and SBF2-AS1 have been associated with temozolomide resistance in glioma patients. This review study suggests that targeting glioma-associated lncRNAs might aid the treatment of glioma. [ABSTRACT FROM AUTHOR]

This study introduces a depth-encoding PET detector inserting a glass plate between the pixilated scintillation crystal layers. The principle of the proposed design was that the relative amount of light received by each photosensor will be altered by using the glass plate. This change in the light distribution can generate a pattern diagram of the 2D flood histogram that identifies depth position as well as X-Y position of \gamma–ray interaction. A Monte Carlo simulation was conducted for the assessment of the DOI-PET detector of 4 \times 4 array photosensor coupled with 2-layers of LSO arrays which consist of 4 \times 4 arrays of 3 \times 3 \times 10~\mm^3 discrete crystals. The traced light distribution for each event was converted by the modified resistive charge division networks into the 2D flood histogram. Optical glass plates with 11 different thicknesses that range from 0 to 10 mm with a 1 mm step were modeled. This was done, to estimate the thickness which allows the extraction of the depth information from the 2D flood histogram. An experimental study was performed to acquire the flood histograms of the DOI-PET detectors with 3 and 5 mm thick glass plate. The effect of glass plate on light loss and count rate loss were assessed for two detector configurations with and without glass plate. The simulation results showed that the flood histogram without overlapping of each crystal position can be generated for the detectors by inserting the glass plates with thickness of 3\sim 10~\mm. They were also demonstrated in the acquired representative flood histograms which were obtained by the experimental study. The light and count rate losses measured from DOI-PET detector with 3 mm thick glass plate was \sim 5\% and \sim 2\%, respectively. This study demonstrated that the proposed DOI-PET detector can extract the 3D \gamma -ray interaction position without considerable performance degradations of PET detector from the 2D flood histogram. [ABSTRACT FROM AUTHOR]

Abstract: High levels of turbidity and fine suspended sediments are often found in stormwater discharges from construction sites even when best management practices (BMPs) for sediment control are in place. This study evaluated turbidity reduction by three check dam types: 1) rock check dam representing a standard BMP, 2) excelsior wattle representing a fiber check dam (FCD), and 3) rock check dam wrapped with excelsior erosion control blanket (rock + excelsior ECB) representing an alternative FCD. Three check dams (all same type) were installed in a lined, 24-m ditch on a 5–7% slope and three consecutive simulated stormwater flows were run in the ditch. Additional tests were performed by adding granular polyacrylamide (PAM) on the check dams in the same manner using two sediment sources differing in clay content. Without PAM treatment, significantly higher effluent turbidity (>900 nephelometric turbidity units (NTU)) exited the ditch with rock check dams than with excelsior wattles or rock + excelsior ECBs (<440 NTU). The extent of sediment deposition between the check dam types was in the order of excelsior wattle > rock + excelsior ECB > rock check dam, indicating better water pooling behind the wattle. The PAM treatment reduced turbidity substantially (>75% relative to no PAM treatment) for all check dam types and it was very effective in excelsior wattles (<57 NTU) and rock + excelsior ECBs (<90 NTU) even during the third storm event. This study demonstrates that the passive treatment of runoff with PAM on FCDs (or rock + excelsior ECB) in construction site ditches can be very effective for sediment retention and turbidity reduction. [Copyright &y& Elsevier]

Highlights: [•] We estimated green energy production in a municipal wastewater treatment plant. [•] Engineered approaches in mining multiple green energy resources were presented. [•] The estimated green energy production accounted for 6.5% of energy independence in the plant. [•] We presented practical information regarding green energy projects in water infrastructures. [Copyright &y& Elsevier]

A comprehensive structure and performance study of thin blend films of the small-molecule semiconductor, 2,8-difluoro-5,11-bis(triethylsilylethynyl)anthradithiophene (diF-TESADT), with various insulating binder polymers in organic thin-film transistors is reported. The vertically segregated composition profile and nanostructure in the blend films are characterized by a combination of complementary experimental methods including grazing incidence X-ray diffraction, neutron reflectivity, variable angle spectroscopic ellipsometry, and near edge X-ray absorption fine structure spectroscopy. Three polymer binders are considered: atactic poly(α-methylstyrene), atactic poly(methylmethacrylate), and syndiotactic polystyrene. The choice of polymer can strongly affect the vertical composition profile and the extent of crystalline order in blend films due to the competing effects of confinement entropy, interaction energy with substrate surfaces, and solidification kinetics. The variations in the vertically segregated composition profile and crystalline order in thin blend films explain the significant impacts of binder polymer choice on the charge carrier mobility of these films in the solution-processed bottom-gate/bottom-contact thin-film transistors. [ABSTRACT FROM AUTHOR]

Andisols derived from volcanic ash minerals are characterized by a high P retention capacity (PRC). The PRC of soil is often correlated with various soil properties, and a simple correlation analysis alone may not necessarily explain the direct cause and effect relationships between soil properties and PRC values. The objectives of this study were to determine which soil properties best explain the variability in the PRC of allophanic and non-allophanic Andisols using path analysis. A total of 671 Japanese Andisols were used in this study. The PRC values were determined for allophanic and non-allophanic soil samples, along with pH, organic matter (OM) contents, acid ammonium oxalate extractable AI (Alox) and Fe (Feox) and pyrophosphate-extractable AI (Alp) and Fe (Fep). The PRC value of allophanic soils was correlated with Alox (r = 0.72) and Feox(r = 0.56). Path analysis revealed, however, that Alox was the single most important direct effect on PRC, and the correlation between PRC and Feox was mostly partitioned to an indirect effect through Alox. According to path analysis on non-allophanic soils, Alp was the single most important causal factor in predicting PRC, and the correlation between Alox and PRC (r = 0.77) was mostly partitioned to an indirect effect through Alp. The correlation between OM and PRC was attributable to organically bound Al in allophanic soils by the indirect effect of Alp on PRC through OM. Pyrophosphate extraction may be a better indicator than oxalate extraction for predicting PRC in non-allophanic Andisols. [ABSTRACT FROM AUTHOR]

Abstract: Long-term application of phosphorus (P) to soils as fertilizer or manure can increase the potential for P loss to ground and surface waters. Vertical P transport was investigated in a sandy soil material receiving seven different P fertilizer sources: poultry compost, poultry litter, triple superphosphate [Ca(H2PO4)2·H2O], dairy lagoon liquid, swine lagoon liquid, swine lagoon sludge, and dissolved potassium dihydrogen phosphate (KH2PO4). The P sources were surface-applied to soil columns (6.35-cm diameter, 10-cm long) at two rates equivalent to 75 and 150kg total P ha−1, and columns were intermittently leached with deionized (DI) water. Column effluents were collected for up to 23 pore volumes and analyzed for dissolved reactive phosphorus (DRP) and dissolved organic carbon (DOC). In addition, a P retardation factor was determined for the soil from a P adsorption isotherm. Transport of P through soil columns receiving liquid P sources was simulated by a one-dimensional equilibrium convective–dispersive equation (CDE) based on water-extractable P (WEP) concentrations. Cumulative amounts of DRP leached were linearly related to the amounts of WEP in P source materials (r2 =0.87***). The recovery of DRP in the column effluents relative to WEP in the applied materials was 126±15% (mean ± standard error) for organic P sources and 66±2% for inorganic P sources. The use of WEP in the CDE model underpredicted P transport in the columns amended with lagoon liquids compared with dissolved KH2PO4. Results indicated that leaching losses of P from land-applied manures exceed the amounts of WEP in source materials because of organic P mineralization and competitive sorption of DOC. [Copyright &y& Elsevier]

Purpose: A new positron emission tomography (PET) detector signal processing method, the charge signal transmission approach, is proposed for the development of a hybrid PET-magnetic resonance imaging (MRI). A number of experiments were performed to demonstrate that the Geiger-mode avalanche photodiode (GAPD) charge output could be transmitted to a preamplifier using a long cable without degrading the PET signal performance. Methods: A PET module consisted of LYSO and a GAPD with a 4×4 array. The GAPD output was transmitted to the preamplifier through flexible flat cables. The effect of the cable length on the PET performance was examined using seven different lengths ranging from 10 to 300 cm outside and inside the 7 T animal MRI. Four parameters (rise time, fall time, amplitude, and area of the preamplifier output) were measured as a function of the cable length using a 10 GS/s oscilloscope and three parameters (photopeak position, energy resolution, and time resolution) were measured using a 100 MS/s DAQ unit. The effect of the cable length on the MR phantom images was investigated. In addition, the effect of the PET module configuration on its temperature stability was assessed by acquiring the energy and time spectra. Results: There were no significant changes in the PET module performance as a function of the cable length, both outside and inside MRI. The performance changes in energy information, such as the amplitude, area, photopeak position, and energy resolution, were <3% with cable lengths ranging from 10 to 300 cm and the change in the time resolution was <6%. There were no obvious artifacts or changes in the line profile in the MR phantom images. Moreover, no manifest changes in the photopeak position and coincidence counting rate were observed in the PET modules employing the charge signal transmission approach, whereas considerable degradation of the PET module performance was observed in the voltage signal transmission approach. Conclusions: This study demonstrated that it is feasible to design a hybrid PET-MRI using the charge signal transmission approach, which is expected to have more advantages than other approaches. [ABSTRACT FROM AUTHOR]

Abstract: We report time-resolved photoluminescence (PL) spectroscopy study of solutions and thin films of pure penta-fluorenes with varying alkyl side-chain structures. While no low-energy green emissions were observed in solutions, spin-cast and vacuum dried initial films exhibited low-energy emission in time-delayed PL spectra, centered at 490nm, whose intensity varied strongly with the side-chain structure. In comparison, the films annealed at 170°C in air showed nearly identical low-energy emission in time-delayed PL spectra, centered at 520nm, regardless of the side-chain structures. Therefore, our experimental results obtained for pure penta-fluorenes provided clear evidence that the mechanism of the green emission of oligofluorene and polyfluorene films includes both the intermolecular aggregate/excimer formation, emitted around 490nm, and fluorenone-type chemical defects, emitted around 520nm. [Copyright &y& Elsevier]

The operational efficacy of lane departure warning systems (LDWS) in autonomous vehicles is critically influenced by the retro-reflectivity of road markings, which varies with environmental wear and weather conditions. This study investigated how changes in road marking retro-reflectivity, due to factors such as weather and physical wear, impact the performance of LDWS. The study was conducted at the Yeoncheon SOC Demonstration Research Center, where various weather scenarios, including rainfall and transitions between day and night lighting, were simulated. We applied controlled wear to white, yellow, and blue road markings and measured their retro-reflectivity at multiple stages of degradation. Our methods included rigorous testing of the LDWS's recognition rates under these diverse environmental conditions. Our results showed that higher retro-reflectivity levels significantly improve the detection capability of LDWS, particularly in adverse weather conditions. Additionally, the study led to the development of a simulation framework for analyzing the cost-effectiveness of road marking maintenance strategies. This framework aims to align maintenance costs with the safety requirements of autonomous vehicles. The findings highlight the need for revising current road marking guidelines to accommodate the advanced sensor-based needs of autonomous driving systems. By enhancing retro-reflectivity standards, the study suggests a path towards optimizing road safety in the age of autonomous vehicles. [ABSTRACT FROM AUTHOR]

The article discusses the approach to solve poor performance stability and limited charge carrier mobility of the organic thin film transistor (OTFT) due to low crystallinity and high resultant permeability of moisture and oxidizing compounds. Semiconducting small molecules and an insulating polymer is combined to create a stable field-effect mobility. The neutron reflectivity (NR) experiment is also done to obtain the structural information of its electrical properties.

Virtual metrology (VM) in semiconductor manufacturing is to predict product physical quality measurements using the processing information at a wafer fabrication process. The process state parameters from various sensors on production equipment are used for the accurate and reliable prediction of process outcomes, and several deep learning methods have been considered, including convolutional neural network (CNN). Recent studies in the literature have demonstrated the successful VM modeling with CNN for univariate-response prediction. Multivariate process outputs, however, are overlooked in deep learning-based VM modeling although the joint information among the process outputs can be used to improve the prediction performance. In this work, we propose a CNN-based multivariate VM model using multi-sensors process sensor data. We evaluate the proposed model on a real-life case for VM modeling at an etching process in wafer fabrication. [ABSTRACT FROM AUTHOR]

The "oxygen effect" improves radiation efficacy; thus, tumor cell oxygen concentration is a crucial factor for improving lung cancer treatment. In the current study, we aimed to identify aerobic exercise-induced changes in oxygen concentrations in non-small cell lung cancer (NSCLC) cells. To this end, an NSCLC xenograft mouse model was established using human A549 cells. Animals were subsequently subjected to aerobic exercise and radiation three times per week for 2 weeks. Aerobic exercise was performed at a speed of 8.0 m/m for 30 min, and the tumor was irradiated with 2 Gy of 6 MV X-rays (total radiation dose 12 Gy). Combined aerobic exercise and radiation reduced NSCLC cell growth. In addition, the positive effect of aerobic exercise on radiation efficacy through oxygenation of tumor cells was confirmed based on hypoxia-inducible factor-1 and carbonic anhydrase IX expression. Finally, whole-transcriptome analysis revealed the key factors that induce oxygenation in NSCLC cells when aerobic exercise was combined with radiation. Taken together, these results indicate that aerobic exercise improves the effectiveness of radiation in the treatment of NSCLC. This preclinical study provides a basis for the clinical application of aerobic exercise to patients with NSCLC undergoing radiation therapy. [ABSTRACT FROM AUTHOR]

Preterm birth prediction is essential for improving neonatal outcomes. While many machine learning techniques have been applied to predict preterm birth using health records, inflammatory markers, and vaginal microbiome data, the role of prenatal oral microbiome remains unclear. This study aimed to compare oral microbiome compositions between a preterm and a full-term birth group, identify oral microbiome associated with preterm birth, and develop a preterm birth prediction model using machine learning of oral microbiome compositions. Participants included singleton pregnant women admitted to Jeonbuk National University Hospital between 2019 and 2021. Subjects were divided into a preterm and a full-term birth group based on pregnancy outcomes. Oral microbiome samples were collected using mouthwash within 24 h before delivery and 16S ribosomal RNA sequencing was performed to analyze taxonomy. Differentially abundant taxa were identified using DESeq2. A random forest classifier was applied to predict preterm birth based on the oral microbiome. A total of 59 women participated in this study, with 30 in the preterm birth group and 29 in the full-term birth group. There was no significant difference in maternal clinical characteristics between the preterm and the full-birth group. Twenty-five differentially abundant taxa were identified, including 22 full-term birth-enriched taxa and 3 preterm birth-enriched taxa. The random forest classifier achieved high balanced accuracies (0.765 ± 0.071) using the 9 most important taxa. Our study identified 25 differentially abundant taxa that could differentiate preterm and full-term birth groups. A preterm birth prediction model was developed using machine learning of oral microbiome compositions in mouthwash samples. Findings of this study suggest the potential of using oral microbiome for predicting preterm birth. Further multi-center and larger studies are required to validate our results before clinical applications. [ABSTRACT FROM AUTHOR]

Background: Identifying acute ischemic stroke (AIS) among potential stroke cases is crucial for stroke research based on claims data. However, the accuracy of using the diagnostic codes of the International Classification of Diseases 10th revision was less than expected. Methods: From the National Health Insurance Service (NHIS) claims data, stroke cases admitted to the hospitals participating in the multicenter stroke registry (Clinical Research Collaboration for Stroke in Korea, CRCS-K) during the study period with principal or additional diagnosis codes of I60-I64 on the 10th revision of International Classification of Diseases were extracted. The datasets were randomly divided into development and validation sets with a ratio of 7:3. A stroke identification algorithm using the claims data was developed and validated through the linkage between the extracted datasets and the registry database. Results: Altogether, 40,443 potential cases were extracted from the NHIS claims data, of which 31.7% were certified as AIS through linkage with the CRCS-K database. We selected 17 key identifiers from the claims data and developed 37 conditions through combinations of those key identifiers. The key identifiers comprised brain CT, MRI, use of tissue plasminogen activator, endovascular treatment, carotid endarterectomy or stenting, antithrombotics, anticoagulants, etc. The sensitivity, specificity, and diagnostic accuracy of the algorithm were 81.2%, 82.9%, and 82.4% in the development set, and 80.2%, 82.0%, and 81.4% in the validation set, respectively. Conclusions: Our stroke identification algorithm may be useful to grasp stroke burden in Korea. However, further efforts to refine the algorithm are necessary. [ABSTRACT FROM AUTHOR]

Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and has a poor prognosis. Identifying biomarkers based on molecular mechanisms is critical for early diagnosis, timely treatment, and improved prognosis of lung cancer. MALAT1 has been reported to have overexpressed and tumor-promoting functions in NSCLC. It has been proposed as a potential biomarker for the diagnosis and prognosis of cancer. Therefore, this study was conducted to profile the changes in gene expression according to the regulation of expression of MALAT1 in NSCLC cell lines and to investigate the correlation through bioinformatic analysis of differentially expressed genes (DEGs). Methods: MALAT1 expression levels were measured using RT-qPCR. The biological functions of MALAT1 in NSCLC were analyzed by cell counting, colony forming, wound-healing, and Transwell invasion assays. In addition, gene expression profiling in response to the knockdown of MALAT1 was analyzed by transcriptome sequencing, and differentially expressed genes regulated by MALAT1 were performed by GO and KEGG pathway enrichment analyses. Bioinformatic databases were used for gene expression analysis and overall survival analysis. Results: Comparative analysis versus MALAT1 expression in MRC5 cells (a normal lung cell line) and the three NSCLC cell lines showed that MALAT1 expression was significantly higher in the NSCLC cells. MALAT1 knockdown decreased cell survival, proliferation, migration, and invasion in all three NSCLC cell lines. RNA-seq analysis of DEGs in NSCLC cells showed 198 DEGs were upregulated and 266 DEGs downregulated by MALAT1 knockdown in all three NSCLC cell lines. Survival analysis on these common DEGs performed using the OncoLnc database resulted in the selection of five DEGs, phosphoglycerate mutase 1 (PGAM1), phosphoglycerate mutase 4 (PGAM4), nucleolar protein 6 (NOL6), nucleosome assembly protein 1 like 5 (NAP1L5), and sestrin1 (SESN1). The gene expression levels of these selected DEGs were proved to gene expression analysis using the TNMplot database. Conclusion: MALAT1 might function as an oncogene that enhances NSCLC cell survival, proliferation, colony formation, and invasion. RNA-seq and bioinformatic analyses resulted in the selection of five DEGs, PGAM1, PGAM4, NOL6, NAP1L5, and SESN1, which were found to be closely related to patient survival and tumorigenesis. We believe that further investigation of these five DEGs will provide valuable information on the oncogenic role of MALAT1 in NSCLC. [ABSTRACT FROM AUTHOR]

We hypothesized that the association between BP and endovascular treatment (EVT) outcomes would differ by baseline perfusion and recanalization status. We identified 388 ICA or M1 occlusion patients who underwent EVT ≤ 24 h from onset with successful recanalization (TICI ≥ 2b). BP was measured at 5-min intervals from arrival and during the procedure. Systolic BPs (SBP) were summarized as dropmax (the maximal decrease over two consecutive measurements), incmax (the maximal increase), mean, coefficient of variation (cv), and standard deviation. Adequate baseline perfusion was defined as hypoperfusion intensity ratio (HIR) ≤ 0.5; infarct proportion as the volume ratio of final infarcts within the Tmax > 6 s region. In the adequate perfusion group, infarct proportion was closely associated with SBPdropmax (β ± SE (P-value); 1.22 ± 0.48, (< 0.01)), SBPincmax (1.12 ± 0.33, (< 0.01)), SBPcv (0.61 ± 0.15 (< 0.01)), SBPsd (0.66 ± 0.08 (< 0.01)), and SBPmean (0.71 ± 0.37 (0.053) before recanalization. The associations remained significant only in SBPdropmax, SBPincmax, and SBPmean after recanalization. SBPincmax, SBPcv and SBPsd showed significant associations with modified Rankin Scale score at 3 months in the pre-recanalization period. In the poor perfusion group, none of the SBP indices was associated with any stroke outcomes regardless of recanalization status. BP may show differential associations with stroke outcomes by the recanalization and baseline perfusion status. [ABSTRACT FROM AUTHOR]

Background and purpose: The temporal characteristics of stroke risks were evaluated in emergency department patients who had a diagnosis of peripheral vertigo. It was also attempted to reveal the stroke risk factor amongst those with peripheral vertigo. Methods: This is a parallel‐group cohort study in a tertiary referral hospital. After assigning each of 4367 matched patients to the comparative set of peripheral vertigo and appendicitis‐ureterolithiasis groups and each of 4911 matched patients to the comparative set of peripheral vertigo and ischaemic stroke groups, the relative stroke risk was evaluated. In addition, to predict the individual stroke risk in patients with peripheral vertigo, any association between the demographic factors and stroke events was evaluated in the peripheral vertigo group. Results: The peripheral vertigo group had a higher stroke risk than the appendicitis‐ureterolithiasis group (hazard ratio 1.73, 95% confidence interval 1.18–2.55) but a lower risk than the ischaemic stroke group (hazard ratio 0.30, 95% confidence interval 0.24–0.37). The stroke risk of the peripheral vertigo group was just below that of small vessel stroke. The stroke risk of the peripheral vertigo group differed markedly by time: higher within 7 days, moderate between 7 days and 1 year, and diminished thereafter. Old age (>65 years), male gender and diabetes mellitus were the risk factors for stroke in the peripheral vertigo group. Conclusion: Patients with a diagnosis of peripheral vertigo in the emergency department showed a moderate future stroke risk and so a stroke preventive strategy tailored to the timing of symptom onset and individual risk is required. [ABSTRACT FROM AUTHOR]

Objective: Anemia of chronic disease (ACD) refers to hypoproliferative anemia in the context of acute or chronic activation of the immune system. There is a paucity of prospective data addressing the risk factors for ACD development. An association between common chronic diseases and ACD was examined cross-sectionally and longitudinally. Method: A cohort of 265,459 healthy participants without ACD at baseline were prospectively followed annually or biennially. Results: During average follow-up period of 62 months, 4,906 participants developed ACD (incidence rate 3.58 per 1000 person-years). Multivariable-adjusted hazard ratio (HR) [95% confidence interval (CI)] for incident ACD comparing estimated glomerular filtration rate 30–60 and < 30 vs. ≥ 60 ml/min/1.73 m2 were 3.93 [3.18–4.85] and 39.11 [18.50–82.69]; HRs [95% CI] for ACD comparing prediabetes and diabetes vs. normal were 1.19 [1.12–1.27] and 2.46 [2.14–2.84], respectively. HRs [95% CI] for incident ACD comparing body-mass-index (BMI) of < 18.5, 23–24.9 and ≥ 25 vs. 18.5–22.9 kg/m2 were 0.89 [0.78–1.00], 0.89 [0.80–0.99] and 0.78 [0.66–0.91], respectively. HRs [95% CI] for incident ACD comparing prehypertension and hypertension vs. normal were 0.79 [0.73–0.86] and 1.10 [0.99–1.23], respectively. Metabolic syndrome, hypertension, chronic liver disease, and chronic obstructive pulmonary disease were not associated with incident ACD. Conclusions: The severity of chronic kidney disease and diabetic status were independently associated with an increased incidence of ACD, whereas prehypertension and an increasing BMI were significantly associated with decreased risk of ACD. [ABSTRACT FROM AUTHOR]

Objective: Heritability of stroke is assumed not to be low, especially in the young stroke population. However, most genetic studies have been performed in highly selected patients with typical clinical or neuroimaging characteristics. We investigated the prevalence of 15 Mendelian stroke genes and explored the relationships between variants and the clinical and neuroimaging characteristics in a large, unselected, young stroke population. Methods: We enrolled patients aged ≤55 years with stroke or transient ischemic attack from a prospective, nationwide, multicenter stroke registry. We identified clinically relevant genetic variants (CRGVs) in 15 Mendelian stroke genes (GLA, NOTCH3, HTRA1, RNF213, ACVRL1, ENG, CBS, TREX1, ABCC6, COL4A1, FBN1, NF1, COL3A1, MT‐TL1, and APP) using a customized, targeted next generation sequencing panel. Results: Among 1,033 patients, 131 (12.7%) had 28 CRGVs, most frequently in RNF213 (n = 59), followed by ABCC6 (n = 53) and NOTCH3 (n = 15). The frequency of CRGVs differed by ischemic stroke subtypes (p < 0.01): the highest in other determined etiology (20.1%), followed by large artery atherosclerosis (13.6%). It also differed between patients aged ≤35 years and those aged 51 to 55 years (17.1% vs 9.3%, p = 0.02). Only 27.1% and 26.7% of patients with RNF213 and NOTCH3 variants had typical neuroimaging features of the corresponding disorders, respectively. Variants of uncertain significance (VUSs) were found in 15.4% patients. Interpretation: CRGVs in 15 Mendelian stroke genes may not be uncommon in the young stroke population. The majority of patients with CRGVs did not have typical features of the corresponding monogenic disorders. Clinical implications of having CRGVs or VUSs should be explored. ANN NEUROL 2023;93:768–782 [ABSTRACT FROM AUTHOR]

Background/Aims: Radiotherapy is applied to patients with inoperable cancer types including advanced stage non-small cell lung cancer (NSCLC) and radioresistance functions as a critical obstacle in radiotherapy. This study was aimed to investigate the mechanism of radioresistance regulated by surfactant protein B (SP-B). Methods: To investigate the role of SP-B in radioresistance, ΔSFTPB A549 cell line was established and SP-B expression was analyzed. In response to ionizing radiation (IR), the change of SP-B expression was analyzed in A549 and NCI-H441 cell lines. Conditioned media (CM) from NSCLC cells were utilized to evaluate the downstream signaling pathway. The in vivo effects of SP-B were assessed through mouse xenograft model with intratumoral injection of CM. Results: In response to IR, NSCLC cell lines showed decreased SP-B regulated by the TGF-β signaling and decreased SP-B stimulated cell survival and epithelial-mesenchymal transition. Treatment with CM from irradiated cells activated sPLA2, enhanced protein kinase Cδ-MAPKs signaling pathway, and increased arachidonic acid production. We confirmed the in vivo roles of SP-B through mouse xenograft model. Conclusion: Our results revealed that down-regulation of SP-B was involved in the radiation-induced metastatic conversion of NSCLC and provided evidence that SP-B acted as a suppressor of NSCLC progression. [ABSTRACT FROM AUTHOR]

The Hippo signaling pathway is a conserved signaling pathway that regulates cell proliferation, apoptosis, and differentiation and plays essential roles in the maintenance of organ size and tissue homeostasis. Also, this signaling pathway is a critical regulator of malignant progression in a wide range of cancers. Furthermore, it has been established that YAP and TAZ are major effectors of the Hippo signaling pathway and transcription co-activators that regulate the expressions of genes involved in cell growth and differentiation. Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides involved in several biological processes, including chromatin remodeling, transcriptional regulation, and post-transcriptional processing. Evidence suggests that the aberrant expression and dysregulation of lncRNAs contribute to the development and progression of various malignancies by acting as oncogenes or tumor suppressors. In addition, many studies have shown that lncRNAs can directly or indirectly regulate the Hippo-YAP/TAZ signaling pathway in cancer. Here, we overview the roles played by lncRNAs in tumor progression with focus on their regulation of the Hippo-YAP/TAZ signaling pathway and discuss their potential usages as clinical biomarkers and therapeutic targets. [ABSTRACT FROM AUTHOR]

Detector signals for positron emission tomography (PET) are commonly multiplexed to reduce the number of digital processing channels so that the system can remain cost effective while also maintaining imaging performance. In this work, a multiplexed readout combining Anger position estimation algorithm and position decoder circuit (PDC) was developed to reduce the number of readout channels by a factor of 24, 96-to-4. The data acquisition module consisted of a TDC (50 ps resolution), 4-channel ADCs (12 bit, 105 MHz sampling rate), 2 GB SDRAM and USB3.0. The performance of the multiplexed readout was assessed with a high-resolution PET detector block composed of 2×3 detector modules, each consisting of an 8×8 array of 1.52×1.52×6 mm 3 LYSO, a 4×4 array of 3×3 mm 2 silicon photomultiplier (SiPM) and 13.4×13.4 mm 2 light guide with 0.7 mm thickness. The acquired flood histogram showed that all 384 crystals could be resolved. The average energy resolution at 511 keV was 13.7±1.6% full-width-at-half-maximum (FWHM) and the peak-to-valley ratios of the flood histogram on the horizontal and vertical lines were 18.8±0.8 and 22.8±1.3, respectively. The coincidence resolving time of a pair of detector blocks was 6.2 ns FWHM. The reconstructed phantom image showed that rods down to a diameter of 1.6 mm could be resolved. The results of this study indicate that the multiplexed readout would be useful in developing a PET with a spatial resolution less than the pixel size of the photosensor, such as a SiPM array. [ABSTRACT FROM AUTHOR]

We developed a depth of interaction (DOI) positron emission tomography (PET) detector using depth-dependent reflector patterns in a discrete crystal array. Due to the different reflector patterns at depth, light distribution was changed relative to depth. As a preliminary experiment, we measured DOI detector module crystal identification performance. The crystal consisted of a 9×9 array of 2 mmx2 mmx20 mm lutetium-yttrium oxyorthosilicate (LYSO) crystals. The crystal array was optically coupled to a 64-channel position-sensitive photomultiplier tube with a 2 mmx2 mm anode size and an 18.1 mmx18.1 mm effective area. We obtained the flood image with an Anger-type calculation. DOI layers and 9×9 pixels were well distinguished in the obtained images. Preclinical PET scanners based on this detector design offer the prospect of high and uniform spatial resolution. [ABSTRACT FROM AUTHOR]

Background: There has been no large-scale trial comparing endovascular treatment (add-on EVT) after intravenous tissue plasminogen activator (IV tPA) and IV tPA alone in acute ischemic stroke (AIS) caused by internal carotid artery occlusion (ICAO). We aimed at investigating the effectiveness and safety of add-on EVT after IV tPA in AIS patients with ICAO. Methods: Between March 2010 and March 2013, 3,689 consecutive ischemic stroke patients who were hospitalized within 4.5 h of onset were identified using a prospective stroke registry at 11 centers in Korea. Among them, patients with persistent ICAO after receiving IV tPA and whose 3-month modified Rankin Scale (mRS) was available were finally enrolled. A propensity score analysis with inverse-probability of treatment weighting was used to eliminate baseline imbalances between those receiving add-on EVT and IV tPA alone. Results: Among 264 patients enrolled in this study (mean age 71.4; male 56.4%; median National Institute of Health Stroke Scale score 15), 117 (44.3%) received add-on EVT. The add-on EVT group had a higher frequency of favorable outcome on the mRS ≤ 2 (35.0 vs. 18.4%; adjusted OR (aOR) 2.79; 95% CI 1.66-4.67) and lower mortality (17.9 vs. 35.4%; aOR 0.24; 95% CI 0.13-0.42) at 3 months, when compared to the IV tPA-alone group. Add-on EVT did not significantly increase the risk of symptomatic hemorrhage (5.1 vs. 4.1%; aOR 1.01; 95% CI 0.37-2.70). The rate of successful recanalization (thrombolysis in cerebral infarction grade ≥ 2b) in the add-on EVT group was 69.2%. Conclusions: Compared to an IV tPA alone, add-on EVT can improve clinical outcomes in patients with symptomatic ICAO within 4.5 h of onset without a significant increase of symptomatic hemorrhage. [ABSTRACT FROM AUTHOR]

Metabolic alterations that support the supply of biosynthetic molecules necessary for rapid and sustained proliferation are characteristic of cancer. Some cancer cells rely on glutamine to maintain their energy requirements for growth. Glutamine is an important metabolite in cells because it not only links to the tricarboxylic acid cycle by producing α-ketoglutarate by glutaminase and glutamate dehydrogenase but also supplies other non-essential amino acids, fatty acids, and components of nucleotide synthesis. Altered glutamine metabolism is associated with cancer cell survival, proliferation, metastasis, and aggression. Furthermore, altered glutamine metabolism is known to be involved in therapeutic resistance. In recent studies, lncRNAs were shown to act on amino acid transporters and glutamine-metabolic enzymes, resulting in the regulation of glutamine metabolism. The lncRNAs involved in the expression of the transporters include the abhydrolase domain containing 11 antisense RNA 1, LINC00857, plasmacytoma variant translocation 1, Myc-induced long non-coding RNA, and opa interacting protein 5 antisense RNA 1, all of which play oncogenic roles. When it comes to the regulation of glutamine-metabolic enzymes, several lncRNAs, including nuclear paraspeckle assembly transcript 1, XLOC_006390, urothelial cancer associated 1, and thymopoietin antisense RNA 1, show oncogenic activities, and others such as antisense lncRNA of glutaminase, lincRNA-p21, and ataxin 8 opposite strand serve as tumor suppressors. In addition, glutamine-dependent cancer cells with lncRNA dysregulation promote cell survival, proliferation, and metastasis by increasing chemo- and radio-resistance. Therefore, understanding the roles of lncRNAs in glutamine metabolism will be helpful for the establishment of therapeutic strategies for glutamine-dependent cancer patients. [ABSTRACT FROM AUTHOR]

The manufacturing process of semiconductors has become complex due to the ultra-fine chemical process technologies, and a large amount of testing process is also needed to find out yield-reducing defects of wafers. In order to utilize the cost of visual inspection, several artificial intelligence techniques have been proposed to detect systematic defects. Despite these efforts, semiconductor process still relies on time-consuming manual inspections carried out by quality engineers to detect and classify defects because of lack of efficiency and reliability for AI technologies. In this paper, we propose a morphological feature transformation for 3D wafer bin maps and an automatic embedding technique based on simultaneous optimization. Since proposed technique removes unnecessary features and embeds them into feature vectors related to more meaningful WBM patterns, high cluster quality can be obtained only with the similarity of feature vectors, enabling classification without labels. Proposed idea provides a solution for open set recognition problems and a quicker and more efficient method of the detection and classification of wafer defects in commercial manufacturing processes. [ABSTRACT FROM AUTHOR]

Recently, we reported a hybrid positron emission tomography-magnetic resonance imaging (PET-MRI) approach involving the transmission of a photo-sensor charge signal to a preamplifier using a long cable. However, in this application, pulse distortions may degrade the performance of the PET detector. The purpose of this study is to further extend the charge signal transmission (CST) approach and to design a PET detector module capable of transmitting the photo-sensor charge signal to PET electronics remotely located outside the MRI room for the hybrid PET-MRI. To achieve this, we developed a pulse restoration circuit (PRC) compensating the performance degradations caused by using the long cable from Geiger-mode avalanche photodiode (GAPD) to PET electronics. The effect of the cable length on the PET detector performance was examined using different lengths of flexible flat cable ranging from 0 to 21 m. Rise time, fall time and amplitude of the GAPD output were measured as a function of the cable length. Photopeak position, energy resolution and time resolution were also measured using a 100 MS/s data acquisition unit. PRC based on the filtering and shaping networks consisted of amplitude, and rise and fall restorations. The amplitude restoration was designed using op-amp and resistors. The rise time-fall time restoration was designed using RC shaping filter. The measured pulse shapes passing through the long cable with PRC were similar to the output of GAPD with the cable length of 0 m (amplitude 169 mV, rise time 35 ns and fall time 210 ns), and the degrading PET detector performance caused by long cable were restored (energy resolution 16%, photopeak position 400 ch and time resolution 1.3 ns). There were no significant changes in the PET detector module performance using the CST approach with PRC as a function of the cable length, both outside and inside the MRI room. There were no obvious artifacts or changes in the MR phantom images. These results show that the proposed approach using extended charge signal transmission method with long cable and simple pulse restoration circuit is reliable and useful for the development of a hybrid PET-MRI system. [ABSTRACT FROM AUTHOR]

Background: Noncontrast computed tomography (NCCT) markers for hematoma expansion (HE) in intracerebral hemorrhage (ICH) are difficult to be found in small ICHs, of which can also expand. We aimed to investigate whether there were size-related differences in the prevalence of NCCT markers and their association with HE. Methods: This retrospective analysis of prospectively collected stroke registry included 267 consecutive patients with ICH who underwent baseline NCCT within 12 h of onset. Qualitative NCCT markers, including heterogeneous density and irregular shape, were assessed. Hematoma density, defined as mean Hounsfield unit of hematoma, and hematoma volume were measured by semiautomated planimetry. Hematoma volume was categorized as small (≤ 10 ml) and large (> 10 ml). Associations of NCCT markers with HE were analyzed using multivariable logistic regression analyses. The model performances of NCCT markers and hematoma density were compared using receiver operating characteristic curves. Results: Hematoma expansion occurred in 29.9% of small ICHs and 35.5% of large ICHs. Qualitative NCCT markers were less frequently observed in small ICHs. Heterogeneous density, irregular shape, and hematoma density were associated with HE in small ICH (adjusted odds ratios [95% confidence interval] 3.94 [1.50–10.81], 4.23 [1.73–10.81], and 0.72 [0.60–0.84], respectively), and hematoma density was also related to HE in large ICH (0.84 [0.73–0.97). The model performance was significantly improved in small ICHs when hematoma density was added to the baseline model (DeLong's test, p = 0.02). Conclusions: The prevalence of NCCT markers and their association with HE differed according to hematoma volume. Quantitative hematoma density was associated with HE, regardless of hematoma size. [ABSTRACT FROM AUTHOR]

DOI-PET detector with multiple spatial resolutions to provide high versatility for both clinical and research applications using a single camera was proposed and examined. Two layers of pixelated LYSO crystal arrays with different pixel pitches were stacked in the depth direction. The top layer was a 6 × 6 array of 2.1 × 2.1 × 10 mm3 crystals, arranged with a 2.2-mm fine pitch. The bottom layer was a 4 × 4 array of 3.2 × 3.2 × 10 mm3 crystals, arranged with a coarse 3.3-mm pitch. A Monte-Carlo simulation was conducted to estimate the glass plate thickness which allows the discrimination of each crystal position from the 2D flood histogram. In experimental measurement, we inserted 4-mm, 5-mm, and 6-mm thick glass plates between the crystal layers. These generated a unique light response for each discrete scintillator position. Light was shared more relatively when the top layer interacted with the gamma rays, whereas light sharing was reduced when the bottom layer interacted with the gamma rays. These light spreading methods allow us to extract 3D information from a 2D flood histogram. Sixteen output signals from a 4 × 4 GAPD array were multiplexed by resistive charge division networks. These were fed into the preamplifiers. The four amplified signals were digitized and were recorded into the DAQ system. By inserting the glass plates into the detectors, we acquired 2D flood histograms without the overlapping of each crystal position. The average peak-to-valley ratios of selected line profiles of a DOI-PET detector with 4-mm thick glass plate were 12.5 for the top layer and 30.8 for bottom layer. The mean energy resolution of the top layer providing high spatial resolution (the bottom layer providing moderate spatial resolution) were 14.4 ± 1.0% (13.4 ± 1.4%), 13.3 ± 1.7% (13.8 ± 0.8%), and 13.7 ± 1.6% (13.8 ± 0.9%) for the DOI-PET detector using 4-mm-, 5-mm-, and 6-mm-thick glass plates, respectively. Our results demonstrated that it is feasible to provide multiple spatial resolutions and 2-layer depth positions for the proposed DOI-PET detector using fine- and coarse-pitch crystals and inserting a glass plate between the crystal layers. [ABSTRACT FROM AUTHOR]