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Osteoarthritis (OA) is the most common form of arthritis associated with ageing. Vitamin D has diverse biological effect on bone and cartilage, and observational studies have suggested it potential benefit in OA progression and inflammation process. However, the effect of vitamin D on OA is still contradictory. Here, we investigated the therapeutic potential of vitamin D in OA. Six-week-old male Wistar rats were injected with monosodium iodoacetate (MIA) to induce OA. Pain severity, cartilage destruction, and inflammation were measured in MIA-induced OA rats. Autophagy activity and mitochondrial function were also measured. Vitamin-D (1,25(OH)

The bus driver's comfort is crucial. The location of the driver's seat, which is correlated with the seat support design, is one of the elements supporting his comfort. The bus business chosen as a representative is PT Selamet Trans Abadi, which has its headquarters in Pati City, Central Java. By considering the Safety Factor, House of Quality (HOQ), weight, shape, and seat support dimensions, this study intends to ascertain how the characteristics of the bus seat support form after receiving a load or force. Conducting a field visit to gather the necessary data is the initial step in this research. The following stage is to decide on the design criteria based on the collected data. Next, use Solidwork to model the design. Using the Finite Element Method (FEM), this program can investigate design characteristics. The loading simulation under consideration includes clutch engagement, bus brake application, and clutch engagement, whether the support is static or stationary. The validation with two supporting journals is then run as the following step to validate the findings. The constant chair support fulfills the typical value, according to the study's findings, whereas support 1 is the most fracture-prone. The outcomes of supports 2 and 3 demonstrate that the support strength is weak since it is subjected to an unequal load.

With advances in nanotechnology, nanoparticles have come to be regarded as carriers of therapeutic agents and have been widely studied to overcome various diseases in the biomedical field. Among these particles, mesoporous silica nanoparticles (MSNs) have been investigated as potential nanocarriers to deliver drug molecules to various target sites in the body. This review introduces the physicochemical properties of MSNs and synthesis procedures of MSN-based nanoplatforms. Moreover, we focus on updating biomedical applications of MSNs as a carrier of therapeutic or diagnostic cargo and review clinical trials using silica-nanoparticle-based systems. Herein, on the one hand, we pay attention to the pharmaceutical advantages of MSNs, including nanometer particle size, high surface area, and porous structures, thus enabling efficient delivery of high drug-loading content. On the other hand, we look through biosafety and toxicity issues associated with MSN-based platforms. Based on many reports so far, MSNs have been widely applied to construct tissue engineering platforms as well as treat various diseases, including cancer, by surface functionalization or incorporation of stimuli-responsive components. However, even with the advantageous aspects that MSNs possess, there are still considerations, such as optimizing physicochemical properties or dosage regimens, regarding use of MSNs in clinics. Progress in synthesis procedures and scale-up production as well as a thorough investigation into the biosafety of MSNs would enable design of innovative and safe MSN-based platforms in biomedical fields.

Cannabis belongs to the family Cannabaceae, and phytocannabinoids are produced by the Cannabis sativa L. plant. A long-standing debate regarding the plant is whether it contains one or more species. Phytocannabinoids are bioactive natural products found in flowers, seeds, and fruits. They can be beneficial for treating human diseases (such as multiple sclerosis, neurodegenerative diseases, epilepsy, and pain), the cellular metabolic process, and regulating biological function systems. In addition, several phytocannabinoids are used in various therapeutic and pharmaceutical applications. This study provides an overview of the different sources of phytocannabinoids; further, the biosynthesis of bioactive compounds involving various pathways is elucidated. The structural classification of phytocannabinoids is based on their decorated resorcinol core and the bioactivities of naturally occurring cannabinoids. Furthermore, phytocannabinoids have been studied in terms of their role in animal models and antimicrobial activity against bacteria and fungi; further, they show potential for therapeutic applications and are used in treating various human diseases. Overall, this review can help deepen the current understanding of the role of biotechnological approaches and the importance of phytocannabinoids in different industrial applications.

This study aimed to develop electrolyte complexes of paliperidone (PPD) with various particle sizes using cation-exchange resins (CERs) to enable controlled release (both immediate and sustained release). CERs of specific particle size ranges were obtained by sieving commercial products. PPD–CER complexes (PCCs) were prepared in an acidic solution of pH 1.2 and demonstrated a high binding efficiency (>99.0%). PCCs were prepared with CERs of various particle sizes (on average, 100, 150, and 400 μm) at the weight ratio of PPD to CER (1:2 and 1:4). Physicochemical characterization studies such as Fourier-transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy between PCCs (1:4) and physical mixtures confirmed PCC formation. In the drug release test, PPD alone experienced a complete drug release from PCC of >85% within 60 min and 120 min in pH 1.2 and pH 6.8 buffer solutions, respectively. Alternatively, PCC (1:4) prepared with CER (150 μm) formed spherical particles and showed an almost negligible release of PPD in pH 1.2 buffer (75%, 24 h). The release rate of PPD from PCCs was reduced with the increase in CER particle size and CER ratio. The PCCs explored in this study could be a promising technology for controlling the release of PPD in a variety of methods.

We performed simultaneous monitoring observations of the 22.2 GHz H2O and 43.1/42.8/86.2/129.3 GHz SiO masers toward the red supergiant VX Sagittarii using the Korean VLBI Network single-dish telescopes. The observations were conducted about every 2 months from 2013 May to 2019 January (30 epochs in total). They included four optical maxima in the active phase of the optical pulsation cycles. The line profile of a H2O maser always comprised various velocity components with a wider velocity range and varied from highly redshifted to blueshifted velocities with respect to the stellar velocity, in contrast to those of the SiO masers. We examined the relation between peak intensities and velocities of 11 detailed components in the line profile of the H2O maser and the pulsation phases. The peak intensity of each component generally exhibited a better correlation with the pulsation phases than that of total intensity. The peak velocities of several components gradually decreased or increased with respect to the stellar velocity, implying an accelerating motion and the development of asymmetries in the H2O maser region. The characteristics of four transition SiO maser properties were compared according to the stellar pulsation phases. The intensity and velocity variation trend of the 43.1 GHz SiO maser was similar to that of the 42.8 GHz SiO maser. However, the variation trend of the 43.1 and 42.8 GHz SiO masers was different from that of the 86.2 and 129.3 GHz SiO masers. This difference stems from the different location of each maser reflecting a different excitation condition.

Description, Ultrafast laser–excited nanoparticle images reveal nonequilibrium kinetics–driven unusual surface ordering at high temperature., Ultrafast light-matter interactions enable inducing exotic material phases by promoting access to kinetic processes blocked in equilibrium. Despite potential opportunities, actively using nonequilibrium kinetics for material discovery is limited by the poor understanding on intermediate states of driven systems. Here, using single-pulse time-resolved imaging with x-ray free-electron lasers, we found intermediate states of photoexcited bismuth nanoparticles that showed kinetically reversed surface ordering during ultrafast melting. This entropy-lowering reaction was further investigated by molecular dynamics simulations to reveal that observed kinetics were thermodynamically buried in equilibrium, which emphasized the critical role of electron-mediated ultrafast free-energy modification in inducing exotic material phases. This study demonstrated that ultrafast photoexcitations of electrons provide an efficient strategy to induce hidden material phases by overcoming thermodynamic barriers via nonequilibrium reaction pathways.

We aimed to compare the success rate, adverse drug events, and cost-effectiveness of tailoredThe diagnosis ofBetween the TT (n = 141) and PAM-B groups (n = 141),PAM-B therapy exhibits similar efficacy and improved cost-effectiveness compared to TT based on the results of DPO-PCR tests.www.clinicaltrials.gov identifier is NCT05002595.

Colloidal gels under constant moderate stress flow only after a prolonged solid-like deformation. Predicting the time-dependent yielding of the gels would facilitate control of their mechanical stability and transport, but early detectable signs of such delayed solid-to-fluid transition remain unknown. We show that the shear rate of colloidal gels under constant stress can forecast an eventual yielding during the earliest stage of deformation known as primary creep. The shear rate before failure exhibits a characteristic power-law decrease as a function of time, distinct from the linear viscoelastic response. We model this early-stage behavior as a series of uncorrelated local plastic events that are thermally activated, which illuminates the exponential dependence of the yield time on the applied stress. By revealing underlying viscoplasticity, this precursor to yield in the macroscopic shear rate provides a convenient tool to predict the yielding of a gel well in advance of its actual occurrence.

Background We assessed the prognostic accuracy of the standardized electroencephalography (EEG) patterns (“highly malignant,” “malignant,” and “benign”) according to the EEG timing (early vs. late) and investigated the EEG features to enhance the predictive power for poor neurologic outcome at 1 month after cardiac arrest. Methods This prospective, multicenter, observational, cohort study using data from Korean Hypothermia Network prospective registry included adult patients with out-of-hospital cardiac arrest (OHCA) treated with targeted temperature management (TTM) and underwent standard EEG within 7 days after cardiac arrest from 14 university-affiliated teaching hospitals in South Korea between October 2015 and December 2018. Early EEG was defined as EEG performed within 72 h after cardiac arrest. The primary outcome was poor neurological outcome (Cerebral Performance Category score 3–5) at 1 month. Results Among 489 comatose OHCA survivors with a median EEG time of 46.6 h, the “highly malignant” pattern (40.7%) was most prevalent, followed by the “benign” (33.9%) and “malignant” (25.4%) patterns. All patients with the highly malignant EEG pattern had poor neurologic outcomes, with 100% specificity in both groups but 59.3% and 56.1% sensitivity in the early and late EEG groups, respectively. However, for patients with “malignant” patterns, 84.8% sensitivity, 77.0% specificity, and 89.5% positive predictive value for poor neurologic outcome were observed. Only 3.5% (9/256) of patients with background EEG frequency of predominant delta waves or undetermined had good neurologic survival. The combination of “highly malignant” or “malignant” EEG pattern with background frequency of delta waves or undetermined increased specificity and positive predictive value, respectively, to up to 98.0% and 98.7%. Conclusions The “highly malignant” patterns predicted poor neurologic outcome with a high specificity regardless of EEG measurement time. The assessment of predominant background frequency in addition to EEG patterns can increase the prognostic value of OHCA survivors. Trial registration KORHN-PRO, NCT02827422. Registered 11 September 2016—Retrospectively registered.

The potential therapeutic effects of probiotic bacteria in rheumatoid arthritis (RA) remain controversial. Thus, this study aimed to discover potential therapeutic bacteria based on the relationship between the gut microbiome and rheumatoid factor (RF) in RA. Bacterial genomic DNA was extracted from the fecal samples of 93 RA patients and 16 healthy subjects. Microbiota profiling was conducted through 16S rRNA sequencing and bioinformatics analyses. The effects of Bifidobacterium strains on human peripheral blood mononuclear cells and collagen-induced arthritis (CIA) mice were assessed. Significant differences in gut microbiota composition were observed in patients with different RF levels. The relative abundance of Bifidobacterium and Collinsella was lower in RF-high than in RF-low and RF-negative RA patients, while the relative abundance of Clostridium of Ruminococcaceae family was higher in RF-high than in RF-low and RF-negative patients. Among 10 differentially abundant Bifidobacterium, B. longum RAPO exhibited the strongest ability to inhibit IL-17 secretion. Oral administration of B. longum RAPO in CIA mice, obese CIA, and humanized avatar model significantly reduced RA incidence, arthritis score, inflammation, bone damage, cartilage damage, Th17 cells, and inflammatory cytokine secretion. Additionally, B. longum RAPO significantly inhibited Th17 cells and Th17-related genes—IL-17A, IRF4, RORC, IL-21, and IL-23R—in the PBMCs of rheumatoid arthritis patients. Our findings suggest that B. longum RAPO may alleviate RA by inhibiting the production of IL-17 and other proinflammatory mediators. The safety and efficacy of B. longum RAPO in patients with RA and other autoimmune disorders merit further investigation.

Phase recovery is a well-known inverse problem prevalent across science disciplines and attracts active research interests to develop a number of theoretical and experimental methods. Recent developments in artificial intelligence have further prompted research activities in processing the experimentally collected imperfect data, but applications have been limited to slow-varying data such as real images. Experimental noise present in largely fluctuating diffraction data, in particular, adds practical challenges to hamper consistent phase recovery. Here, we introduce a convolutional neural-network assisted $k$-space denoising method that can directly manage noisy diffraction signals. It showed superior performance on denoising the diffraction data, which promote improved phase recovery from noise-buried single-pulse diffraction signals obtained by the x-ray free-electron laser. Adapting our method to general diffraction data can expand boundaries of interpretable data and enhance observability of faint objects with weak signals.

We carried out KF postdeposition treatment (PDT) on a Cu(In,Ga)Se

RNA polymerase II (Pol II)-dependent transcription in stimulus-inducible genes requires topoisomerase IIβ (TOP2B)-mediated DNA strand break and the activation of DNA damage response signalling in humans. Here, we report a novel function of the breast cancer 1 (BRCA1)-BRCA1-associated ring domain 1 (BARD1) complex in this process. We found that BRCA1 is phosphorylated at S1524 by the kinases ataxia-telangiectasia mutated and ATR during gene activation, and that this event is important for productive transcription. Our biochemical and genomic analyses showed that the BRCA1-BARD1 complex interacts with TOP2B in the EGR1 transcription start site and in a large number of protein-coding genes. Intriguingly, the BRCA1-BARD1 complex ubiquitinates TOP2B, which stabilizes TOP2B binding to DNA while BRCA1 phosphorylation at S1524 controls the TOP2B ubiquitination by the complex. Together, these findings suggest the novel function of the BRCA1-BARD1 complex in the regulation of TOP2B and Pol II-mediated gene expression.

DNA molecules are atomic-scale information storage molecules that promote reliable information transfer via fault-free repetitions of replications and transcriptions. Remarkable accuracy of compacting a few-meters-long DNA into a micrometer-scale object, and the reverse, makes the chromosome one of the most intriguing structures from both physical and biological viewpoints. However, its three-dimensional (3D) structure remains elusive with challenges in observing native structures of specimens at tens-of-nanometers resolution. Here, using cryogenic coherent X-ray diffraction imaging, we succeeded in obtaining nanoscale 3D structures of metaphase chromosomes that exhibited a random distribution of electron density without characteristics of high-order folding structures. Scaling analysis of the chromosomes, compared with a model structure having the same density profile as the experimental results, has discovered the fractal nature of density distributions. Quantitative 3D density maps, corroborated by molecular dynamics simulations, reveal that internal structures of chromosomes conform to diffusion-limited aggregation behavior, which indicates that 3D chromatin packing occurs via stochastic processes.

Particulate matters (PMs) increase oxidative stress and inflammatory response in different tissues. PMs disrupt the formation of primary cilia in various skin cells, including keratinocytes and melanocytes. In this study, we found that 2-isopropylmalic acid (2-IPMA) promoted primary ciliogenesis and restored the PM2.5-induced dysgenesis of primary cilia in dermal fibroblasts. Moreover, 2-IPMA inhibited the generation of excessive reactive oxygen species and the activation of stress kinase in PM2.5-treated dermal fibroblasts. Further, 2-IPMA inhibited the production of pro-inflammatory cytokines, including IL-6 and TNF-α, which were upregulated by PM2.5. However, the inhibition of primary ciliogenesis by IFT88 depletion reversed the downregulated cytokines by 2-IPMA. Moreover, we found that PM2.5 treatment increased the MMP-1 expression in dermal fibroblasts and a human 3-D-skin model. The reduced MMP-1 expression by 2-IPMA was further reversed by IFT88 depletion in PM2.5-treated dermal fibroblasts. These findings suggest that 2-IPMA ameliorates PM2.5-induced inflammation by promoting primary ciliogenesis in dermal fibroblasts.

The high security of optical phased array (OPA) signals is an important requirement for OPA-based optical wireless communication (OWC). We propose a method for improving the security of OPA-based OWC systems using optically injection-locked (OIL) semiconductor lasers. We theoretically demonstrate the amplitude and phase modulation of OIL-OPA elements by controlling the injection-locking parameters of the OIL lasers. When a Taylor window function is applied as the amplitude profile of the OPA transmitter, the sidelobe level decreases by 22 dB and the unsecured distance reduces 10 times compared to the case without the Taylor window function. In addition, the unsecured area factor becomes 0.8%.

Glutathione peroxidase 1 (Gpx1) and peroxiredoxin 2 (Prdx2) belong to the thiol peroxidase family of antioxidants, and have been studied for their antioxidant functions and roles in cancers. However, the physiological significance of Gpx1 and Prdx2 during vertebrate embryogenesis are lacking. Currently, we investigated the functional roles of Gpx1 and Prdx2 during vertebrate embryogenesis using Xenopus laevis as a vertebrate model. Our investigations revealed the zygotic nature of gpx1 having its localization in the eye region of developing embryos, whereas prdx2 exhibited a maternal nature and were localized in embryonic ventral blood islands. Furthermore, the gpx1-morphants exhibited malformed eyes with incompletely detached lenses. However, the depletion of prdx2 has not established its involvement with embryogenesis. A molecular analysis of gpx1-depleted embryos revealed the perturbed expression of a cryba1-lens-specific marker and also exhibited reactive oxygen species (ROS) accumulation in the eye regions of gpx1-morphants. Additionally, transcriptomics analysis of gpx1-knockout embryos demonstrated the involvement of Wnt, cadherin, and integrin signaling pathways in the development of malformed eyes. Conclusively, our findings indicate the association of gpx1 with a complex network of embryonic developmental pathways and ROS responses, but detailed investigation is a prerequisite in order to pinpoint the mechanistic details of these interactions.

Public transit has a significant impact on minimising traffic congestion and reducing the cost of travelling in urban areas. It is necessary to evaluate the efficiency of the public transit operation in response to the individual traveller's demands for transit. This study aims to analyse the demand for transit with overlapping origin-destination (OD) pairs to enhance the efficiency of transit operations. To achieve this, disaggregated-level travel demand data, i.e. individual traveller's data are collected from an automatic fare collection system called smart card. The Kneedle algorithm is used to calculate the knee point of travel demand. The overlapping OD pairs, which are higher than the knee point value, are calculated and displayed in a map format. On the basis of the overlapping OD pairs, the demand-based overlap index for each bus route is defined to evaluate the efficiency of bus operations. The proposed method is applied to six districts with higher transit demands than other districts in Seoul. On the basis of the results, discussion on the action plans to enhance the efficiency of bus operations are presented. The method proposed in this study contributes to improving the efficiency of the bus system by reflecting individual users' travel demands.

A 25-year-old runner received a single-lead, VDD pacemaker after ablation of AV nodal reentrant tachycardia complicated by intermittent AV block. The rate-adaptive AV delay algorithm (RAAV), which shortens the sensed AV interval (SAV) at faster atrial rates, was programmed to provide a physiologic SAV with exercise. She developed repetitive, atypical, long-RP pacemaker-mediated tachycardia (PMT) because the RAAV shortened the antegrade SAV and retrograde conduction occurred over the slow AV nodal pathway. PMT was refractory to usual programming solutions. Using high-density electroanatomic mapping, we were able to ablate the retrograde limb of PMT without further damaging AV conduction.

Backgrounds/aims As the development of surgical video recording technologies, educational videos have become widely utilized for trainee education. However, the current forms of surgical video are limited because they do not show all the roles of the participants. Aim of this study is to make optimal training material about living donor liver transplantation for residents and fellows using wearable recording system. Methods Three video clips about procedure of liver transplantation were made. A head mount was used to fix the camera on the surgeon or assistant's head. Anastomosis of vessels, bench operation and trocar insertion for laparoscopic donor hepatectomy were recorded. Each video clips were edited including indicators, subtitles, and narration. The edited videos were shown to 20 General Surgery trainees (18 residents, 2 fellows) and we received feedback. The results of the questionnaire were quantitatively analyzed to show how efficient and informative it is compared to existing educational materials. Results Sixteen of the 20 trainees (80%) responded that this video helped them improve their surgical skills. Eighteen trainees (90%) responded that they gained new knowledge through this video. Sixteen trainees (80%) responded that the action camera image material was more educational than existing text-based and video-based materials, with an average score of 8.5 and 6.5 (action camera materials vs. text-based materials, respectively). Conclusions A head-mounted action camera video recording system is a good model for making high-quality educational video modules and can be a useful teaching tool for living donor liver transplantation.

Quality control of peroxisomes is essential for cellular homeostasis. However, the mechanism underlying pexophagy is largely unknown. In this study, we identified HSPA9 as a novel pexophagy regulator. Downregulation of HSPA9 increased macroautophagy/autophagy but decreased the number of peroxisomes in vitro and in vivo. The loss of peroxisomes by HSPA9 depletion was attenuated in SQSTM1-deficient cells. In HSPA9-deficient cells, the level of peroxisomal reactive oxygen species (ROS) increased, while inhibition of ROS blocked pexophagy in HeLa and SH-SY5Y cells. Importantly, reconstitution of HSPA9 mutants found in Parkinson disease failed to rescue the loss of peroxisomes, whereas reconstitution with wild type inhibited pexophagy in HSPA9-depleted cells. Knockdown of Hsc70-5 decreased peroxisomes in Drosophila, and the HSPA9 mutants failed to rescue the loss of peroxisomes in Hsc70-5-depleted flies. Taken together, our findings suggest that the loss of HSPA9 enhances peroxisomal degradation by pexophagy.

The frequency of PIK3CA mutation and amplification was various and their clinical significances have not been clarified in Korean patients with invasive breast carcinoma (IBC). The study aimed to investigate the clinical and prognostic significances of PIK3CA mutation and amplification in IBC patients. DNA was isolated from paired normal and tumoral tissues in 128 IBC patients and the mutation and expression of PIK3CA gene were analyzed. PIK3CA mutation and expression was detected in 14.3% and 21.9% of IBC patients, respectively. And the level of PIK3CA expression was not different according to the presence of PIK3CA mutation (p = 0.775). PIK3CA mutation and expression were significantly associated with Luminal A type (p = 0.017 and p = 0.011, respectively). However, they did not have any clinical and prognostic values for IBC patients. This result suggested that alterations of PIK3CA pathway contribute to the pathogenesis of specific type of IBC.

The hardness-checking tools are essential tools in engineering study, especially in the mechanical and manufacturing process. The field problem in Akebono Brake Astra Indonesia is the utilization of more manual tools to achieve product demands. Considering those issues, the development of a modified hardness checking tool from manual operation to automatic operation. For more effectively, it uses automatic operation in time and savings for other manual tools. The automated tool applies the 3-axes system mechanism using Festo linear actuator with the servo motor. The testing capacity of automatic devices is equal to more manual devices. The frame of the auto-checking hardness machine is assessed by applying load variations. This paper provides a comparison of various aluminum frame types based on different tensile strength and cross-sectional area values. The value of displacement and maximum stress depends on the ultimate tensile strength properties and cross-sectional area of the frame.

The long stagnation of the photo-conversion efficiency of kesterites below 13% is a source of frustration in the scientific community. In this study, we investigated the effects of sodium on the passivation of grain boundaries and defects in Cu2ZnSnSe4 (CZTSe) grown on a soda-lime glass (SLG) and borosilicate (BS) glass. Because BS glass does not inherently contain sodium, we placed a thin layer of NaF between CZTSe and Mo. The composition of the samples is Cu-poor and Zn-rich. The distribution of sodium and its contributions to phase formation and defects were examined by cross-sectional energy-dispersive X-ray profiling, Raman scattering spectroscopy and imaging, surface potential and photoluminescence. From the experimental results, it can be strongly claimed that sodium ions segregate predominantly near the grain boundaries and reduce CuZn-related defects. These local surface imaging analyses provided the exact locations of the secondary phases. In particular, the photo-assisted scanning probe method enabled us to observe the changes in the optoelectrical properties of the thin films and the carrier behavior within the materials. Further studies with distinct alkali ions and optimal processing conditions will pave a way to improve the performance of kesterite solar cells.

Self-microemulsifying drug delivery systems represent a stable formulation for enhancing the solubility and absorption efficacy of poorly soluble drugs. In this study, a self-microemulsifying drug delivery system (SMEDDS) was designed and applied for oral administration of poorly water-soluble pazopanib, a Biopharmaceutical Classification Class II anticancer drug. The solubility of pazopanib was first evaluated using various oils, surfactants, and co-surfactants. Pseudoternary phase diagrams were plotted to identify the selfemulsifying region and the phase behavior of optimized vehicle selected after screening of oils, surfactants, and co-surfactants. The SMEDDS comprising Capmul MCM NF, Tween 80, and PEG 400 was fabricated for incorporating pazopanib. It exhibited spherical droplets with size of 86.9 ± 0.8 nm and zeta potential value of –14.7 ± 0.1 mV. In vitro dissolution profiles of the SMEDDS were 2.40-fold (pH 4.0) and 6.45-fold (pH 6.8) higher than that of pazopanib powder. In particular, pazopanib-SMEDDS showed pH-independent dissolution profiles. In vivo pharmacokinetic parameters of the SMEDDS revealed enhanced bioavailability of pazopanib, which was 3.32-fold higher than that of pazopanib powder when administered orally. Taken together, the SMEDDS is effective as an oral delivery vehicle for pazopanib. In addition, our findings demonstrate that self-microemulsifying drug delivery systems could be a potential tool for improving bioavailability of other poorly water-soluble drugs.

With each single X-ray pulse having its own characteristics, understanding the individual property of each X-ray free-electron laser (XFEL) pulse is essential for its applications in probing and manipulating specimens as well as in diagnosing the lasing performance. Intensive research using XFEL radiation over the last several years has introduced techniques to characterize the femtosecond XFEL pulses, but a simple characterization scheme, while not requiring ad hoc assumptions, to address multiple aspects of XFEL radiation via a single data collection process is scant. Here, it is shown that single-particle diffraction patterns collected using single XFEL pulses can provide information about the incident photon flux and coherence property simultaneously, and the X-ray beam profile is inferred. The proposed scheme is highly adaptable to most experimental configurations, and will become an essential approach to understanding single X-ray pulses.

Background Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is commonly diagnosed as hepatocellular carcinoma (HCC) preoperatively. Therefore, unexpected recurrence occurs in some patients after liver transplantation (LT). The aim of this study was to identify the risk factors of recurrence. Methods We retrospectively reviewed the data of 20 patients who underwent LT for cHCC-CC from January 2005 to December 2015. Results Of the 20 patients, 11 (55%) had concurrent HCC and 10 (50%) had multiple cHCC-CCs. Before LT, 13 patients had undergone transarterial chemoembolization (TACE, n = 9), radiofrequency ablation, and TACE (n = 3) or surgical resection (n = 1). Four of the patients (20%) had the classical type, whereas 16 (80%) had subtypes with stem cell features. Six of the 16 patients (37.5%) with subtypes with stem cell features and 3 of the 4 patients (75%) with the classical type showed recurrence after LT. In multivariate analysis, the classical type was significantly associated with poorer recurrence-free survival (RFS) (hazard ratio [HR]: 8.65, confidence interval [CI]: 1.25–60.05, P = .03) and poorer overall survival (HR: 8.89, CI: 1.37–57.84, P = .02). Spontaneous tumor necrosis also showed significance on RFS (P = .03) among 11 patients with nontreated lesions. Conclusion In cHCC-CC, the classical type and spontaneous tumor necrosis were associated with recurrence. If these risk factors are found after LT, short-interval follow-up and strategies such as chemotherapy and/or use of mammalian target of rapamycin inhibitors to prevent recurrence are needed.

Introduction While sleep is critical for health, the hospital is not conducive to patient sleep and few efforts have been made to improve. The current practices to promote hospitalized inpatient sleep at highly-ranked hospitals are unknown. Methods A mixed-methods study of Hospital Medicine Section Chiefs at the 2020 US News and World Report Honor Roll pediatric and adult hospitals was conducted to understand the current practices and attitudes towards inpatient sleep between June and August 2021. An anonymous, quantitative survey was disseminated to quantify current practices and satisfaction with sleep-friendly institutional efforts. Survey participants were invited to share their institutions’ progress and potential ways to further improve inpatient sleep during structured, qualitative interviews. Results Pediatric (n=10) and adult (n=20) section chiefs were queried. Survey response rate was 77% (n=23/30; pediatric n=8/10; adult n=15/20). While 96% (n=22) of hospitalist leaders rated sleep as important, only 43% (n=10) were satisfied with their institution’s efforts to improve patient sleep. Although 91% (n=21) of hospitalist leaders rated sleep equity as important, one institution (4%) had practices in place to address the issue. Less than half (n=11) of institutions reported having sleep-friendly practices. Among these institutions, the most common practices included: reducing overnight vital sign monitoring (91%, n=10), decreasing ambient light in the wards (91%, n=10), adjusting lab and medication schedules (73%, n=8), and implementing quiet hours (64%, n=7). Twenty-seven percent of hospitalist leaders (n=8/30; pediatric interviews=3/10; adult interviews=5/20) participated in interviews. Themes included: the importance of having a sleep-friendly culture, environmental changes, modified hospital practices, and external incentives to improve patient sleep. Conclusion Hospitalists recognize the importance of improving patient sleep, but few institutions have sleep-friendly practices in place. Most institutions have no sleep health equity practices in place in their hospital. Building sleep-friendly hospital cultures and establishing best practices should be a priority for clinicians. Support (If Any) The authors thank the Society of Hospital Medicine and the Pritzker School of Medicine for funding support.