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Objective To evaluate the efficacy and safety of mesenchymal stem cells (MSCs) therapy in patients with tendon disorders enrolled in prospective clinical studies.Methods We systematically searched prospective clinical studies that investigated the effects of MSC administration on human tendon disorders with at least a 6-month follow-up period in the PubMed-MEDLINE, EMBASE, and Cochrane Library databases. The primary outcome of interest was the change in pain on motion related to tendon disorders. Meta-regression analyses were performed to assess the relationship between MSC dose and pooled effect sizes in each cell dose.Results Four prospective clinical trials that investigated the effect of MSCs on tendon disorders were retrieved. MSCs showed a significant pooled effect size (overall Hedges’ g pooled standardized mean difference=1.868; 95% confidence interval, 1.274–2.462; p

Pretransplant crossmatch (XM) testing is widely used for detecting preformed donor-specific antibodies (DSAs) against human leukocyte antigen (HLA). However, in some cases, there is a positive XM result in the absence of HLA-DSAs, the cause of which was rarely identified. We reviewed the causes of sequential positive XM results at a single center and analyzed the presence of non-HLA antibodies in patients with an unexplained positive pretransplant XM result. Among 251 patients with T-cell/B-cell complement-dependent cytotoxicity (CDC) or flow cytometric crossmatch (FCXM) positivity, HLA-DSAs were confirmed in 88 (35.1%) by a single antigen bead (SAB) assay, 150 (59.8%) used rituximab (anti-CD20), and 13 (5.2%) had neither HLA-DSAs nor a desensitization history. Anti-angiotensin II type 1 receptor IgG and 33 non-HLA antibodies were tested in the 13 patients with an unexplained positive pretransplant XM result, and more than one non-HLA antibody were revealed in all these patients; 11 patients had non-HLA antibodies reported to be associated with graft rejection, and two patients experienced rejection episode after kidney transplantation. Our study suggests considering non-HLA antibodies testing when a CDC or FCXM test is positive without a definite cause. Assessing non-HLA antibodies might be useful for interpreting XM results and evaluating immunologic risk in transplant recipients.

We were able to diversify blood substitutes that emphasized the existing physical characteristics by adding the synthetic DNA, which was designed and produced in this study, to developed blood substitute. By doing so, we could improve the availability of developed blood substitute to the point where it can be identified similarly as in DNA analysis from the human blood.

Nuclear receptor are major regulators of hepatic drug metabolizing enzymes and antioxidants enzymes. Nuclear receptor humanized mice were used for overcome species differences between experimental animals and human. The present study was performed to investigate the hepatic regulation of antioxidant enzymes in pregnane X receptor (PXR) and constitutive androstane receptor (CAR) double humanized mice treated with the human PXR ligand, rifampicin (RIF; 10 mg/kg for 4 days). RIF decreased the hepatic protein levels of superoxide dismutase-1, thioredoxin-1, and γ-glutamylcysteine ligase catalytic subunit in wild-type (WT) mice, but not in the double humanized mice. Catalase protein levels were decreased by RIF in both WT and double humanized mice. The hepatic protein level and activity of glutathione reductase (GR) were increased in the humanized mice treated with RIF, but decreased in WT mice. Glutathione S-transferase (GST) alpha-class (GSTA) and mu-class (GSTM) but not pi-class were induced by RIF in the humanized mice, but not in WT mice. The activities of total GST, GSTA and GSTM were also increased only in humanized mice treated with RIF. These results suggest that PXR and CAR may play roles in xenobiotic-induced hepatic regulation of GSTA, GSTM, and GR. The PXR/CAR double humanized mouse can be used as a suitable predictive model of the regulation of human antioxidant enzymes by xenobiotics.

Introduction Flow cytometric crossmatch assay (FCXM) is a sensitive cell-based method for evaluating the presence of donor-specific antibodies (DSA) before transplantation. Recently, 96-well tray FCXM protocol (Halifax FCXM) with improved test efficiency has been introduced. The objective of the present study was to assess the performance of Halifax FCXM by correlating with DSA results based on single antigen bead (SAB) assays (virtual crossmatch, VXM). Methods A total of 341 FCXMs were evaluated for the detection of HLA-DSA. A positive VXM was defined as having at least one HLA - DSA (HLA-A, B, Cw, DR, DQB1) with ≥ 1000 MFI (mean fluorescence intensity) identified by SAB assay. Results Of a total 341 cases, 113 showed class I VXM (+) with class I DSA MFI ≥ 1000 exclusively against one or more donor HLA class I antigens (HLA-A, B, Cw), 72 had class I-/II + DSA, and 156 had VXM(-). Halifax T-FCXM showed a sensitivity of 87.6% (99/113) and a specificity of 98.2% (224/228) for detecting class I VXM (+). The concordance between T-FCXM and class I VXM was 94.7% (323/341). Halifax B-FCXM showed a sensitivity of 58.3% (42/72) and a specificity of 98.7% (154/156) for detecting class I-/II + DSAs. The concordance between B-FCXM and class I-/II + VXM was 86.0% (196/228). When we separately analyzed data, B-FCXM detected HLA-DR (+) (68.8%) and HLA-DQ (+) DSAs (71.0%) similarly (P > 0.05). T-FCXM detected 87.6%, 97.2%, and 98.2% of class I DSA-positive cases with MFI values (sumDSA) ≥ 1000, ≥ 3000, and ≥ 5000, respectively. B-FCXM detected 58.3% of class I-II + DSA -positive (≥1000) cases, but detected 76.7% (33/43) and 89.2% (33/37) of class I-II + DSAs if MFI values of sumDSA and immunodominant DSA (iDSA) were above 5000, respectively. Halifax FCXM had sensitivities of 91.5% and 96.2% for detecting VXM (+) having MFI values above 5000 for class I or class II sumDSA and iDSA, respectively. Conclusion Halifax FCXM showed a good correlation, especially with SAB assay-based high MFI DSA or sumDSA. Concurrent application of FCXM with VXM can improve pre-transplant risk assessment and progress organ allocation efficiency.

AIM We aimed to determine whether both hands should be tested for handgrip strength and whether it is necessary to perform repeated measurements in each hand. METHODS The data were obtained from the Korea National Health and Nutrition Examination Survey conducted from 2014 to 2018. The participants performed three trials of handgrip strength measurement for each hand alternately, with 60-s rest between the trials. From this pool of data, we included 23 901 participants aged ≥19 years who had completed surveys on the handgrip strength test, and obtained their medical history. RESULTS The dominant hand had a significantly stronger handgrip strength than the non-dominant hand (32.75 ± 0.10 vs. 30.95 ± 0.09 kg, P

Background Vasculitis, a systemic disorder with inflammation of blood vessel walls, can develop broad spectrum of signs and symptoms according to involvement of various organs, and therefore, early diagnosis of vasculitis is challenging. We herein describe a patient who developed a special case of systemic vasculitis with mononeuropathy multiplex, rectal perforation and antiphospholipid syndrome (APS) presented with pulmonary embolism. Case summary A 61-year-old woman visited hospital with complaints of myalgia and occasional fever. She was initially diagnosed as proctitis and treated with antibiotics, however, there was no improvement. In addition, she also complained right foot drop with hypesthesia, and left 2nd and 3rd finger tingling sensation. She underwent nerve conduction study for evaluation, and it revealed sensorimotor polyneuropathy in the left arm and bilateral legs. Subsequent sural nerve biopsy strongly suggested vasculitic neuropathy. Based on nerve biopsy and clinical manifestation, she was diagnosed with vasculitis and treated with immuno-suppressive therapy. During treatment, sudden rectal perforation and pulmonary thromboembolism occurred, and further laboratory study suggested probable concomitant APS. Emergency Hartmann operation was performed for rectal perforation, and anti-coagulation therapy was started for APS. After few cycles of immunosuppressive therapy, tingling sensation and weakness in her hand and foot had been partially recovered and vasculitis was considered to be stationary. Conclusion Vasculitis can be presented with a variety of signs and symptoms, therefore, clinicians should always consider the possibility of diagnosis.

We investigated the associations between retinal vascular geometric measurements and idiopathic epiretinal membrane (ERM). Whether changes in retinal vascular geometry are independent of systemic cardiovascular risk factors was also evaluated. This retrospective, cross sectional study included 98 patients with idiopathic ERM, and 99 healthy age-matched controls. Quantitative retinal vascular parameters were measured from digital retinal fundus photographs using a semi-automated computer-assisted program. Multivariate logistic regression analyses were performed to evaluate associations between retinal vascular geometric parameters and the presence of idiopathic ERM after adjusting for systemic cardiovascular risk factors. There was no significant difference in the baseline characteristics of the two groups, except that the ERM group had a higher proportion of females than the control group. In multivariate regression analyses, after adjusting for age, sex, hypertension, diabetes, hypertriglyceridemia, hypercholesterolemia, and body mass index, wider retinal venular caliber (odds ratio [OR] = 1.058, P P = 0.001) were associated with idiopathic ERM. Idiopathic ERM was associated with alterations in global retinal microvascular geometric parameters, wider retinal venules, and less complex vascular branching patterns, independent of cardiovascular risk factors. These changes may reflect hemodynamic disturbances in the microcirculation of eyes with idiopathic ERM.

The development of alternative meat, such as cultured meat, is of current interest due to its potential to solve various problems common to the livestock industry. Cultured meat is defined as in vitro, lab-grown, or synthetic meat, and is produced through the differentiation and culture of animal cells. To increase the efficiency of this culture veterinary drugs are commonly employed. It is therefore necessary to develop a method that allows the amounts of veterinary drugs, growth-promoting hormones, and antibiotics to be determined in cultured meat, to ultimately ensure an adequate safety profile. In this study, we report the development of an analytical method based on liquid chromatography–tandem mass spectrometry for the simultaneous analysis of various veterinary drugs. Validation of the developed method indicated a high accuracy and precision, in addition to a linearity of 0.9868–0.9999. Using this method, the veterinary drugs present in samples of culture media were analyzed. Importantly, penicillin was detected in the range of 2 to 44,259 mg/L, and no other veterinary drugs were detected. It is therefore expected the implementation of this method will improve the safety profile of the cultured meat market, in addition to securing the safety of new food technologies.

The dynamics and stability of premixed hydrogen-air flames in square microchannels with heated walls were investigated through three-dimensional direct numerical simulations. The inlet velocity and equivalence ratio were 1.5 m/s and 0.5. The effect of the wall temperature gradient characteristics on the flame dynamics and stability was examined varying the width and location of the wall temperature gradient for a channel height of 1.5 mm. Five distinct flame modes were observed at different wall temperature profiles: flame with repetitive extinction-ignition (FREI), pulsating flame, laterally oscillating flame, spinning flame, and steady flame modes. Furthermore, transitions between these flame modes were observed for specific inflow and boundary conditions. The effect of the channel height on the flame stability was investigated by varying the channel height from 1.0 mm to 1.677 mm for a fixed wall temperature gradient. As the channel height was increased, four of the flame modes, namely, FREI, laterally oscillating flame, spinning flame, and steady flame modes appeared sequentially. To determine whether this sequential appearance was associated with the variation of the wall heat loss, the maximum wall temperature was changed by small amounts. For a lower wall temperature, the laterally oscillating flame mode transitioned to the FREI mode, and for a higher wall temperature, unstable flame modes such as the FREI and laterally oscillating flame modes disappeared, resulting in stable flame.

Background To evaluate subclinical liver fibrosis after Fontan procedure using a comprehensive method that reflects the overall liver status rather than the focal biopsy lesion. Method This cross-sectional study included 66 patients without symptoms of liver disease who had at least 5 years of elapsed time since the Fontan procedure (time since Fontan procedure 17.5 ± 7.3 years). Serum enhanced liver fibrosis (ELF) scores and 2D shear wave elastography (SWE), which are expected to detect liver fibrosis earlier than liver enzyme tests and ultrasonography, were evaluated along with general examinations. Results Liver cirrhosis diagnosed by ultrasonography showed a marked increase 16 years after surgery (elapsed time: 6–15 years since Fontan, 43.8%; 16–25 years, 70.8%; 26–35 years, 90.0%). The age-adjusted ELF score and liver stiffness according to SWE were elevated during the early postoperative period (6–15 years since Fontan). In adulthood (elapsed time > 16 years), the adjusted ELF score was correlated with liver stiffness (r = 0.514, p = .009) and liver enzyme levels. There was no correlation between liver fibrosis and the Fontan palliation type. AST to platelet count ratio and FIB-4, which are non-invasive fibrosis markers, presumed absence of fibrosis in approximately 90% of patients. Conclusions In the evaluation of early liver fibrosis after the Fontan procedure, abnormal findings of 2D SWE and ELF scores were observed before abnormal ultrasound and liver enzyme results. Therefore, these indicators may be helpful for the diagnosis of early liver fibrosis, and further longitudinal study might be needed.

Fluorescent graphene quantum dots (GQDs) have a significant potential in the application to bio-fields. However, most of the GQDs synthesized by existing methods face limitations due to the harmful chemicals involved in their synthesis and the presence of various oxygen functional groups, both of which affect the biocompatibility of the GQDs. Here, we present a simple approach to fabricating fluorescent and biocompatible high-quality GQDs with low oxygen content without the involvement of harmful chemicals. High-quality GQDs are synthesized by hydrogen-assisted pyrolysis of silicon carbide and this dry synthesis process allows the GQDs to possess high crystallinity with no unwanted chemicals on the surface. Subsequently, the high-quality GQDs are slightly oxidized through sonication in ethanol, but the treated GQDs (t-GQDs) still retain their high crystallinity. The t-GQDs exhibit strong ultraviolet/blue light emission with a high yield of 30.9%, a phenomenon that can be attributed to intrinsic emission resulting from the low oxygen content of the t-GQDs. Furthermore, the t-GQDs show low cytotoxicity even at a high concentration of 200 μg/mL due to the absence of harmful chemicals during their synthesis and the low oxygen content of the t-GQDs. These results demonstrate the excellence of the t-GQDs and their applicability in bio-fields.

Purpose To investigate 24-hour nyctohemeral intraocular pressure (IOP)-related patterns with contact lens sensors (CLSs) in eyes with primary open-angle glaucoma (POAG) with normal baseline IOP (i.e., normal-tension glaucoma [NTG]) and healthy controls. Design Prospective, case-control study. Participants Thirty eyes of 30 patients with NTG, who had had a wash-out period for their IOP-lowering treatment, and 20 eyes of 20 healthy volunteer subjects. Methods Patients and subjects were hospitalized for the purposes of 24-hour CLS (SENSIMED Triggerfish; Sensimed AG, Lausanne, Switzerland) measurement. The IOP-related patterns during wake and sleep times over the course of the 24 hours were compared between the 2 groups. The 24-hour ambulatory blood pressure and posture were monitored simultaneously. A generalized linear model was used to find the factors associated with NTG. Main Outcome Measures The IOP-related patterns, including mean and standard deviation (SD) of measurements, amplitude of cosine-fit curve, acrophase (signal peak), and bathyphase (signal trough) values (millivolt equivalents [mVEq]). Results The SDs of the 24-hour CLS measurements were significantly greater in NTG eyes than in healthy controls (112.51±26.90 vs. 85.18±29.61 mVEq, P = 0.002). The amplitudes of cosine-fit curve (141.88±39.96 vs. 106.08±41.49 mVEq, P = 0.004) and acrophase values (277.74±129.80 vs. 190.58±127.88 mVEq, P = 0.024), mostly measured during nocturnal period, were significantly greater in NTG eyes than in healthy controls. The NTG subjects slept longer in the lateral decubitus posture than the healthy controls (199.1±137.8 vs. 113.2±86.2 minutes, P = 0.009). In the multivariable generalized linear model, the greater amplitude of cosine-fit curve (β = 0.218, P = 0.012) and greater time of decubitus posture during sleep (β = 0.180, P = 0.004) were found to be significantly associated with NTG. Conclusions Continuous monitoring of 24-hour IOP-related values with CLS can be useful for assessment of glaucoma risk, especially for patients with NTG whose IOP appears to be in the normal range. Fluctuation of 24-hour IOP-related values and posture during sleep time might be associated with NTG.

Introduction Sarcopenia is known as a risk factor for falls and hip fracture, and understanding fall characteristics is important for the fall-prevention programs. The aim of this study is to investigate whether sarcopenia is associated with fall characteristics in older adults with fragility hip fracture. Methods A cross-sectional study was conducted in 147 patients over 65 years of age who had undergone a two-week postoperative rehabilitation for hip fracture. Fall characteristics included the fall type, direction and location. Fall types were categorized into two groups: fragile falls, leg weakness during walking, changing positions or standing; non-fragile falls, slipping or tripping while walking. Correlations between sarcopenia and fall characteristics, and of fall type with sarcopenia and fall characteristics were analyzed. Logistic regression analyzes were used to identify independent risk factors for fragile falls. Results Sarcopenia was significantly correlated with fragile falls (r = .222, p = .007) and was more prevalent in the fragile fall group than the non-fragile fall group (53.5% vs. 32.9%). Sarcopenia (OR = 2.354, 95% CI 1.177–4.709, p = .016), moderate comorbidities (OR = 3.572, 95% CI 1.109–11.501, p = .033) and severe comorbidities (OR = 5.396, 95% CI 1.476–19.729, p = .011) by the Charlson Comorbidity Index were significant independent risk factors for fragile falls. Conclusions Sarcopenia was correlated with fragile falls; moreover, it was a risk factor for all of these fall types in older adults with fragility hip fracture. Based on these associations, targeted fall-prevention programs for older adults with sarcopenia, a high risk factor of falls and fractures, could help reduce the incidence rates of falls and fragility hip fracture.

This brief presents a power- and area-efficient forwarded-clock (FC) receiver with a delay-locked loop (DLL)-based self-tracking loop for unmatched memory interfaces. In the proposed FC receiver, the self-tracking loop is composed of two-stage cascaded DLLs to support a burst mode. The proposed scheme compensates for a delay drift neither by relying on data (DQ) transitions nor by re-training but with a write training of the memory controller to fine-tune a data strobe (DQS) path delay through DLLs. The proposed FC receiver is fabricated in the 65-nm CMOS technology and the active area including 4 DQ lanes is 0.0329 mm2. After the write training is completed at supply voltage of 1 V, the measured timing margin remains larger than 0.31 UI when the supply voltage drifts in the range of 0.94 V and 1.06 V from the training voltage, 1 V. At the data rate of 6.4 Gb/s, the proposed FC receiver achieves an energy efficiency of 0.45 pJ/bit.

Skews between data and strobe signals can occur in HBM transceivers due to process and voltage variations across the base die. Skew compensation is introduced into the deserializers of our quarter-rate single-ended receiver for next-generation unmatched source-synchronous HBM interfaces. Data and strobe signals are energy-efficiently realigned by using a 45° strobe phase DQS45. This phase, which is equidistant between quadrature strobe phases DQS0 and DQS90, is generated by a digital type phase interpolator of our receiver. The transceiver, including the proposed receiver, was designed and fabricated in a 65nm CMOS process. The receiver corrects skews to within 7.8ps at a data-rate of 6.4Gb/s, with an energy cost of 0.83pJ/bit per pin.

Purpose: To assess if alternate treatment with intravitreal anti-vascular endothelial growth factor (VEGF) and corticosteroid injections can improve visual and anatomical outcomes of treatment-naiv...

Alpha-fetoprotein (AFP) is a well-established serum biomarker for hepatocellular carcinoma (HCC) in clinical laboratories. However, AFP levels can often be high in benign liver diseases such as liver cirrhosis. For this reason, specifically, the level of the aberrant N-glycosylation of AFP has been proposed as a HCC biomarker to improve diagnostic performance using targeted mass spectrometry (MS). In this study, we developed an endoglycosidase-assisted absolute quantification (AQUA) method by which to measure N-glycosylated AFP levels in serum using liquid chromatography-parallel reaction monitoring with immunoprecipitation. Especially, an isotopically labeled synthetic N-glycopeptide with N-acetylhexosamine (HexNAc) attached to asparagine (N) was used as an internal standard. The efficacy of this method was demonstrated by quantifying the N-glycosylation of AFP in human serum. As a result, we showed that the lower limit of the quantification of a stable isotope-labeled N-glycopeptide reached an attomolar level. Our method also had a linear dynamic range from 2 to 6000 ng/mL for N-glycosylated AFP levels. Finally, the N-glycosylation levels of AFP were measured in HCC patients and in healthy donors with the coefficient of variation in both cases (

Oculocutaneous albinism (OCA) is a group of rare genetically heterogeneous disorders, characterized by hypopigmentation of the eyes, skin, and hair, which result in ocular abnormalities and a risk of developing skin cancer. Currently, there is no ophthalmologic procedure or drug that prevents the clinical features of OCA. Here, we report a new type of OCA in two, unrelated Korean families with the same OCA2 mutation. Affected individuals in this study are different from those of previous reports in two aspects: an inheritance pattern and clinical presentation. All reported patients with OCA have shown an autosomal recessive inheritance pattern, while our patients showed an autosomal dominant inheritance pattern. Small amounts of pigment can be acquired with age in OCA, but there is no substantial variation from adolescence to adulthood in this regard. A case where the patient attained normal pigmentation levels has never been reported. However, our patients displayed completely normal pigmentation in their late twenties. Whole exome sequencing and in-silico analysis revealed a novel mutation, OCA2 c.2338G>A p.(G780S) (NM_000275) with a high likelihood of pathogenicity. Sanger sequencing of p.G780S identified the same mutation in the affected individuals, which was not found in the family members with normal phenotype. We hypothesize that OCA2 G780S not only acts as a pathogenic variant of OCA but also induces pigmentation by enhancing the melanogenesis gene expression of other modifier genes, such as SLC45A2 and TPC2. These findings may provide further understanding of melanin biosynthesis and new treatment methods for OCA.

Studies have demonstrated that chronic kidney disease (CKD) is significantly associated with the increased risk of functional difficulty in daily activity and mobility. However, data are less available for association between CKD and functional disability in Asians. Using a data from Korea National Health and Nutrition Examination Survey III, we investigated the association of CKD with functional disability in 882 subjects over the age of 65. Disability was identified in activity of daily living (ADL), instrumental ADL (IADL), and visual, hearing, and walking function. The prevalence of disability was evaluated according to the stage of CKD, and multivariate logistic regression analysis was used to calculate the adjusted odds ratios (ORs) and 95% confidence interval (CI) [adjusted ORs (95% CI)] of CKD stage 3a for disability in ADL, IADL, visual, hearing, and walking function. Individuals with CKD stage 3–4 had the higher prevalence of disability ADL, IADL, visual, hearing, and walking function than individuals without CKD. CKD stage 3a was significantly associated with abnormal ADL [1.63 (1.04–2.54)] and visual impairment [1.39 (1.01–1.93)] even after adjusting for DM, hypertension, education, income, marital status, age, and sex. The presence of mild CKD was significantly associated with disability in daily activity and multiple function.

Excitatory corticofugal projections in the subcortical white matter (WM) convey signals arising from local neuronal activity in the gray matter (GM). We hypothesized that metabotropic glutamate receptor-5 (mGluR5) availability in GM, as a surrogate marker for local glutamatergic neuronal activity, correlates with WM properties in healthy brain. We examined the relationship in healthy individuals between GM mGluR5 availability measured in vivo using [11C]ABP688 positron emission tomography (PET) and WM properties measured as fractional anisotropy (FA) using diffusion tensor imaging (DTI). Twenty-three healthy volunteers underwent this multimodal imaging. We calculated mGluR5 availability, [11C]ABP688 binding potential (BPND), using the simplified reference tissue model, and generated DTI FA maps using FMRIB’s Diffusion Toolbox (FDT) along with Tract-Based Spatial Statistics (TBSS). To investigate the relationship between mGluR5 availability and FA, we performed voxel-wise and region of interest (ROI)-based analyses. The voxel-wise analysis showed significant positive correlations between the whole cerebral GM [11C]ABP688 BPND and the FA in widespread WM regions including the corpus callosum body, internal capsule, and corona radiata (FWE corrected p

The coronavirus disease 2019 (COVID-19) pandemic has casted a huge impact on global public health and the economy. In this challenging situation, older people are vulnerable to the infection and the secondary effects of the pandemic and need special attention. To evaluate the impacts of COVID-19 on older people, it is important to balance the successful pandemic control and active management of secondary consequences. These considerations are particularly salient in the Asian context, with its diversity among countries in terms of sociocultural heritage, healthcare setup and availability of resources. Thus, the Asian Working Group for Sarcopenia summarized the considerations of Asian countries focusing on responses and difficulties in each country, impacts of health inequity related to the COVID-19 pandemic and proposed recommendations for older people, which are germane to the Asian context. More innovative services should be developed to address the increasing demands for new approaches to deliver healthcare in these difficult times and to establish resilient healthcare systems for older people. Geriatr Gerontol Int 2020; 9999: n/a-n/a.

In this paper, we derive a closed-form solution and an explicit characterization of the worst-case distribution for the data-driven distributionally robust newsvendor model with an ambiguity set ba...

We synthesised cesium lead bromide and formamidinium lead bromide perovskite colloidal nanocrystals by ligand-assisted reprecipitation method for the wide-colour gamut low-cost displays. The prepared perovskite colloidal nanocrystal solutions were formulated into the ink-jet printable homogeneous inks and uniformly coated as the colour conversion layers of the quantum dot organic light-emitting diode displays. The silica capped CsPbBr3 nanocrystals were very stable in high temperature observation while the FAPbBr3 showed the excellent long-term stability at room temperature even without the silica passivation. The ink-jet printed colour conversion films had very narrow full-width-at-half-maximums of around 20 nm and high photoluminescence quantum yields of 73.0% and 76.9%, respectively. Particularly, the FAPbBr3 thin film had an excellent cut-off ratio of blue emission and exhibited external quantum efficiency of 5.39% when fabricated as the hybrid display devices.

This study examined whether leucine-rich protein supplements improve muscle strength, mass, and performance in sarcopenic older adults.We searched PubMed-Medline, Embase, and Cochrane Library databases for randomized controlled trials comparing leucine-rich protein supplements with a control intervention in sarcopenic older adults. A pairwise meta-analysis using a fixed-effects model was performed. The primary outcome of interest was muscle strength regardless of the measures used. Effect sizes were computed as standardized mean differences (SMDs) with 95% confidence intervals (CIs).Six randomized controlled trials including a total of 699 participants were retrieved. Leucine-rich protein supplements improved participants' overall muscle strength, mass, and performance compared to the control group (SMD = 0.939; 95% CI, 0.440-1.438; P 0.001). As the primary outcome, muscle strength improved significantly in the leucine group (SMD = 0.794; 95% CI, 0.104-1.485; P = 0.024).Leucine-rich protein supplements improve muscle strength in sarcopenic older adults. They may be suggested in nutritional treatment of sarcopenia.

Alzheimer’s disease (AD) is characterized by the deposition of extracellular amyloid plaques and intracellular accumulation of neurofibrillary tangles (NFT). Amyloid beta (Aβ) and tau imaging are widely used for diagnosing and monitoring AD in clinical settings. We evaluated the pathology of a recently developed 6 × Tg − AD (6 × Tg) mouse model by crossbreeding 5 × FAD mice with mice expressing mutant (P301L) tau protein using micro-positron emission tomography (PET) image analysis. PET studies were performed in these 6 × Tg mice using [18F]Flutemetamol, which is an amyloid PET radiotracer; [18F]THK5351 and [18F]MK6240, which are tau PET radiotracers; moreover, [18F]DPA714, which is a translocator protein (TSPO) radiotracer, and comparisons were made with age-matched mice of their respective parental strains. We compared group differences in standardized uptake value ratio (SUVR), kinetic parameters, biodistribution, and histopathology. [18F]Flutemetamol images showed prominent cortical uptake and matched well with 6E10 staining images from 2-month-old 6 × Tg mice. [18F]Flutemetamol images showed a significant correlation with [18F]DPA714 in the cortex and hippocampus. [18F]THK5351 images revealed prominent hippocampal uptake and matched well with AT8 immunostaining images in 4-month-old 6 × Tg mice. Moreover, [18F]THK5351 images were confirmed using [18F]MK6240, which revealed significant correlations in the cortex and hippocampus. Uptake of [18F]THK5351 or [18F]MK6240 was highly correlated with [18F]Flutemetamol in 4-month-old 6 × Tg mice. In conclusion, PET imaging revealed significant age-related uptake of Aβ, tau, and TSPO in 6 × Tg mice, which was highly correlated with age-dependent pathology.

Alzheimer’s disease (AD) is characterized by the deposition of extracellular amyloid plaques and intracellular accumulation of neurofibrillary tangles (NFT). Amyloid beta (Aβ) and tau imaging are widely used for diagnosing and monitoring AD in clinical settings. We evaluated the pathology of a recently developed 6 × Tg − AD (6 × Tg) mouse model by crossbreeding 5 × FAD mice with mice expressing mutant (P301L) tau protein using micro-positron emission tomography (PET) image analysis. PET studies were performed in these 6 × Tg mice using [18F]Flutemetamol, which is an amyloid PET radiotracer; [18F]THK5351 and [18F]MK6240, which are tau PET radiotracers; moreover, [18F]DPA714, which is a translocator protein (TSPO) radiotracer, and comparisons were made with age-matched mice of their respective parental strains. We compared group differences in standardized uptake value ratio (SUVR), kinetic parameters, biodistribution, and histopathology. [18F]Flutemetamol images showed prominent cortical uptake and matched well with 6E10 staining images from 2-month-old 6 × Tg mice. [18F]Flutemetamol images showed a significant correlation with [18F]DPA714 in the cortex and hippocampus. [18F]THK5351 images revealed prominent hippocampal uptake and matched well with AT8 immunostaining images in 4-month-old 6 × Tg mice. Moreover, [18F]THK5351 images were confirmed using [18F]MK6240, which revealed significant correlations in the cortex and hippocampus. Uptake of [18F]THK5351 or [18F]MK6240 was highly correlated with [18F]Flutemetamol in 4-month-old 6 × Tg mice. In conclusion, PET imaging revealed significant age-related uptake of Aβ, tau, and TSPO in 6 × Tg mice, which was highly correlated with age-dependent pathology.

Background: EGFR mutation in non-small cell lung cancer (NSCLC) presents a viable therapeutic target for which tyrosine kinase inhibitor (TKI) therapy has shown impressive clinical benefit over the past 20 years. Unfortunately, most patients inevitably progress on earlier-generation EGFR TKIs due to various mechanisms after a period of therapy. The most commonly acquired on-target resistance mutations are T790M and C797S, often appearing after progression on 1st-, 2nd-generation, and 3rd-generation EGFR TKIs, respectively. To prevent the emergence of drug-resistant subclones, a next-generation EGFR TKI must have activity against both treatment-emergent and drug-naïve mutants. Further preclinical studies were conducted to evaluate the activity of BBT-207 in delaying tumor regrowth or prolonging survival in NSCLC tumor models driven by the EGFR T790M and C797S mutation. Method: We evaluated the inhibitory potency of BBT-207 against wild-type (WT) and mutated EGFR proteins. In vivo anti-tumor activity was evaluated in Ba/F3 EGFR ex19del/T790M (DT), L858R/T790M (LT), ex19del/C797S (DC), L858R/C797S (LC), ex19del/T790M/C797S (DTC) or L858R/T790M/C797S (LTC), H1975 EGFR LTC cell line-derived xenograft (CDX), and EGFR DTC-patient-derived xenograft (PDX) models. In vivo inhibition of brain metastases (BM) was evaluated in a luciferase-expressing PC-9 EGFR DTC BM model through direct intracranial implantation. Results: BBT-207 is broadly active against activating and acquired resistance EGFR mutants and displayed potent anti-proliferation activity against Ba/F3 EGFR DT, LT, DC, LC, DTC, LTC with 4, 4, 1, 16, 5 and 8nM, respectively while being highly selective against Ba/F3 EGFR WT (184 nM). BBT-207 also showed IC50 values Conclusion: BBT-207 is a reversible, mutant-specific, broad-spectrum TKI, active to clinically observed mutations of EGFR and is expected to be compatible with monotherapy of QD schedule in humans. BBT-207 is well-positioned to augment the treatment of EGFR mutated NSCLC, either for acquired drug resistance or in earlier line, with potential to treat or prevent CNS metastasis. PK/TK evaluation justify exploration in humans. First-in-human study in patients harboring EGFRm and previously treated with EGFR TKI, is to begin enrollment in USA 1H 2023. Citation Format: Chulwon Kim, Youn Hee Jung, Naeun Jeon, Yong-Hee Lee, Sang-Yoon Lee, Jimmy Taiguang Jin. BBT-207 is a broad-spectrum, highly potent, 4th generation EGFR TKI with enhanced activity to both sensitizing and treatment-emergent EGFR mutations including T790M and C797S. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4018.