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Simple Summary: The development of various molecular techniques has led to the introduction of a new classification for biliary tract cancer and a better understanding of the clinicopathological features of the disease. Furthermore, as new diagnostic modalities and research findings have been published, they enable accurate diagnoses, differentiations, and clinical assessments based on the characteristics of each subtype. This article reviews the current imaging and histologic diagnostic techniques along with future perspectives on molecular diagnosis, to approach precision medicine for biliary tract cancer. Biliary tract cancers (BTCs), including intrahepatic, perihilar, and distal cholangiocarcinomas, as well as gallbladder cancer, are a diverse group of cancers that exhibit unique molecular characteristics in each of their anatomic and pathological subtypes. The pathological classification of BTCs compromises distinct growth patterns, including mass forming, periductal infiltrating, and intraductal growing types, which can be identified through gross examination. The small-duct and large-duct types of intrahepatic cholangiocarcinoma have been recently introduced into the WHO classification. The presentation of typical clinical symptoms, as well as the extensive utilization of radiological, endoscopic, and molecular diagnostic methods, is thoroughly detailed in the description. To overcome the limitations of traditional tissue acquisition methods, new diagnostic modalities are being explored. The treatment landscape is also rapidly evolving owing to the emergence of distinct subgroups with unique molecular alterations and corresponding targeted therapies. Furthermore, we emphasize the crucial aspects of diagnosing BTC in practical clinical settings. [ABSTRACT FROM AUTHOR]

Heat waves are increasing in severity, duration, and frequency. The Multi-Scenario Extreme Weather Simulator (MEWS) models this using historical data, climate model outputs, and heat wave multipliers. In this study, MEWS is applied for planning of a community resilience hub in Hau'ula, Hawaii. The hub will have normal operations and resilience operations modes. Both these modes were modeled using EnergyPlus. The resilience operations mode includes cutting off air conditioning for many spaces to decrease power requirements during emergencies. Results were simulated for 300 future weather files generated by MEWS for 2020, 2040, 2060, and 2080. Shared socioeconomic pathways 2–4.5, 3–7.0 and 5–8.5 were used. The resilience operations mode results show two to six times increase of hours of exceedance beyond 32.2 °C from present conditions, depending on climate scenario and future year. The resulting decrease in thermal resilience enables an average decrease of energy use intensity of 26% with little sensitivity to climate change. The decreased thermal resilience predicted in the future is undesirable, but was not severe enough to require a more energy-intensive resilience mode. Instead, planning is needed to assure vulnerable individuals are given prioritized access to air-conditioned parts of the hub if worst-case heat waves occur. [ABSTRACT FROM AUTHOR]

Acute pancreatitis (AP) is a leading gastrointestinal disease that causes hospitalization. Initial management in the first 72 h after the diagnosis of AP is pivotal, which can influence the clinical outcomes of the disease. Initial management, including assessment of disease severity, fluid resuscitation, pain control, nutritional support, antibiotic use, and endoscopic retrograde cholangiopancreatography (ERCP) in gallstone pancreatitis, plays a fundamental role in AP treatment. Recent updates for fluid resuscitation, including treatment goals, the type, rate, volume, and duration, have triggered a paradigm shift from aggressive hydration with normal saline to goal-directed and non-aggressive hydration with lactated Ringer's solution. Evidence of the clinical benefit of early enteral feeding is becoming definitive. The routine use of prophylactic antibiotics is generally limited, and the procalcitonin-based algorithm of antibiotic use has recently been investigated to distinguish between inflammation and infection in patients with AP. Although urgent ERCP (within 24 h) should be performed for patients with gallstone pancreatitis and cholangitis, urgent ERCP is not indicated in patients without cholangitis. The management approach for patients with local complications of AP, particularly those with infected necrotizing pancreatitis, is discussed in detail, including indications, timing, anatomical considerations, and selection of intervention methods. Furthermore, convalescent treatment, including cholecystectomy in gallstone pancreatitis, lipid-lowering medications in hypertriglyceridemia-induced AP, and alcohol intervention in alcoholic pancreatitis, is also important for improving the prognosis and preventing recurrence in patients with AP. This review focuses on recent updates on the initial and convalescent management strategies for AP. [ABSTRACT FROM AUTHOR]

MT-102 is a new anti-inflammatory agent derived from Juglans mandshurica and Isatis indigotica. Its therapeutic potential is hindered by low aqueous solubility, impacting its in vivo efficacy. Therefore, this study aimed to develop a self-microemulsifying drug delivery system (SMEDDS) for MT-102 to enhance its oral efficacy in treating ulcerative colitis. Solubility assessment in different oils, surfactants, and cosurfactants led to a SMEDDS formulation of MT-102 using Capmul MCM, Tween 80, and propylene glycol. Based on a pseudoternary phase diagram, the optimal SMEDDS composition was selected, which consisted of 15% Capmul MCM, 42.5% Tween 80, and 42.5% propylene glycol. The resulting optimized SMEDDS (SMEDDS-F1) exhibited a narrow size distribution (177.5 ± 2.80 nm) and high indirubin content (275 ± 5.58 µg/g, a biomarker). Across an acidic to neutral pH range, SMEDDS-F1 showed rapid and extensive indirubin release, with dissolution rates approximately 15-fold higher than pure MT-102. Furthermore, oral administration of SMEDDS-F1 effectively mitigated inflammatory progression and symptoms in a mouse model of ulcerative colitis, whereas pure MT-102 was ineffective. SMEDDS-F1 minimized body weight loss (less than 5%) without any significant change in colon length and the morphology of colonic tissues, compared to those of the healthy control group. In addition, oral administration of SMEDDS-F1 significantly inhibited the secretion of pro-inflammatory cytokines such as IL-6 and TNF-α. In conclusion, the SMEDDS-F1 formulation employing Capmul MCM, Tween 80, and propylene glycol (15:42.5:42.5, w/w) enhances the solubility and therapeutic efficacy of MT-102. [ABSTRACT FROM AUTHOR]

Biosorptive treatment of industrial wastewater contaminated with heavy metals has been recognized as one of the most effective green tools, competing with traditional physical/chemical treatment processes. This study delves into the detailed investigation of the biosorbent prepared from fermentation biowaste, particularly focusing on the mechanism behind permanganate (Mn(VII)) removal. Various parameters including pH, biosorbent dosage, initial concentration, and temperature were examined. Among these factors, solution pH emerged as the most crucial in removing Mn(VII) using the biosorbent. The significant removal of Mn(VII) was attributed to both reduction and adsorption, as confirmed by X-ray photoelectron spectroscopy. Depending on the experimental conditions, the removal of Mn(VII) was influenced not only by simple adsorption but also by oxidation-reduction and precipitation processes. This study not only advances our understanding of biosorptive treatment but also highlights the promising potential of fermentation biowaste-based biosorbents for effective Mn(VII) removal. [ABSTRACT FROM AUTHOR]

We report on the fabrication and characterization of a Ga 2 O 3 -based UV-C photodetector using the aerosol deposition (AD) method. By optimizing the size and crystallinity of the Ga 2 O 3 powder, we were able to obtain a uniform thin film with high transmittance (70–80%) without the need for additional heat treatment or high vacuum environments. The resulting Ga 2 O 3 film exhibited a high and selective response to 254 nm wavelength light, even without any treatment, and remained stable when exposed to γ-radiation. The photodetector also performed well in extreme temperatures (−196 °C–150 °C), making it suitable for use in harsh environments, such as the space industry. Our findings demonstrate the potential of the AD method for the fabrication of high-quality Ga 2 O 3 thin films for photodetector applications. [ABSTRACT FROM AUTHOR]

Emerging contaminants are being detected at a high frequency, posing significant environmental and human health challenges. This study aimed to investigate the potential of using commercial granular activated carbon for adsorbing nine aqueous emerging contaminants (carbamazepine, phenacetin, pentoxifylline, norfloxacin, iprobenfos, isoprothiolane, metolachlor, tebuconazole, and hexaconazole). The adsorption study involved employing kinetic and isotherm models, using various concentrations of emerging contaminants and sorbents in a batch system. Additionally, the study explored the correlation between the characteristics of emerging contaminants and their adsorption values, which displayed a relatively linear relationship. While some previous papers have evaluated the performance of one or two substances, there is a lack of research on the adsorption mechanisms of all nine aqueous emerging contaminants. Therefore, the findings from this study on the adsorption potential of granular activated carbon can serve as a valuable foundation for further investigations into its effectiveness in adsorbing emerging contaminants. [ABSTRACT FROM AUTHOR]

Although detection of gram-negative bacteria (GNB) in body fluids is important for clinical purpose, traditional gram staining and other recently developed methods have inherent limitations in terms of accuracy, sensitivity, and convenience. To overcome the weakness, this study proposed a method detecting GNB based on specific binding of polymyxin B (PMB) to lipopolysaccharides (LPS) of GNB. Fluorescent microscopy demonstrated that surface immobilized PMB using a silane coupling agent was possible to detect fluorescent signal produced by a single Escherichia coli (a model GNB) cell. Furthermore, the signal was selective enough to differentiate between GNB and gram-positive bacteria. The proposed method could detect three cells per ml within one hour, indicating the method was very sensitive and the sensing was rapid. These results suggest that highly multifold PMB binding on each GNB cell occurred, as millions of LPS are present on cell wall of a GNB cell. Importantly, the principle used in this study was realized in a microfluidic chip for a sample containing E. coli cells suspended in porcine plasma, demonstrating its potential application to practical uses. In conclusion, the proposed method was accurate, sensitive, and convenient for detecting GNB, and could be applied clinically. [ABSTRACT FROM AUTHOR]

Mammalian DNA folds into 3D structures that facilitate and regulate genetic processes such as transcription, DNA repair, and epigenetics. Several insights derive from chromosome capture methods, such as Hi-C, which allow researchers to construct contact maps depicting 3D interactions among all DNA segment pairs. These maps show a complex cross-scale organization spanning megabase-pair compartments to short-ranged DNA loops. To better understand the organizing principles, several groups analyzed Hi-C data assuming a Russian-doll-like nested hierarchy where DNA regions of similar sizes merge into larger and larger structures. Apart from being a simple and appealing description, this model explains, e.g., the omnipresent chequerboard pattern seen in Hi-C maps, known as A/B compartments, and foreshadows the co-localization of some functionally similar DNA regions. However, while successful, this model is incompatible with the two competing mechanisms that seem to shape a significant part of the chromosomes' 3D organization: loop extrusion and phase separation. This paper aims to map out the chromosome's actual folding hierarchy from empirical data. To this end, we take advantage of Hi-C experiments and treat the measured DNA-DNA interactions as a weighted network. From such a network, we extract 3D communities using the generalized Louvain algorithm. This algorithm has a resolution parameter that allows us to scan seamlessly through the community size spectrum, from A/B compartments to topologically associated domains (TADs). By constructing a hierarchical tree connecting these communities, we find that chromosomes are more complex than a perfect hierarchy. Analyzing how communities nest relative to a simple folding model, we found that chromosomes exhibit a significant portion of nested and non-nested community pairs alongside considerable randomness. In addition, by examining nesting and chromatin types, we discovered that nested parts are often associated with active chromatin. These results highlight that cross-scale relationships will be essential components in models aiming to reach a deep understanding of the causal mechanisms of chromosome folding. Author summary: The 3D organization of mammalian DNA affects genetic processes, such as transcription, DNA repair, and epigenetics. To unravel the complexity of the 3D structure, researchers developed numerous experimental methods, the most advanced being Hi-C. This method enables scientists to create "contact maps" illustrating the 3D interactions among all pairs of DNA segments across the genome. These maps unveiled a multi-scale organization, ranging from megabase-pair compartments to short-range DNA loops. Common explanations for this organization rest on nested hierarchies, where DNA regions of similar sizes coalesce into larger structures. However, such a model is incompatible with competing molecular mechanisms, primarily loop extrusion and phase separation, that shape the chromosomes' 3D organization at different scales. Our study aims to map out the actual chromosome folding relationships using Hi-C data sets. Treating the data as a weighted network of DNA-DNA interactions, we identified 3D communities across different network scales using the Generalized Louvain method, a standard community detection algorithm. By building a tree linking these communities, we discovered that chromosome organization is more intricate than a perfect hierarchy suggests. Instead, we found that chromosomes exhibit a mix of nested and non-nested community pairs alongside considerable randomness. The nested parts often associate with active chromatin. These results highlight that cross-scale relationships are critical for understanding the causal mechanisms of chromosome folding. [ABSTRACT FROM AUTHOR]

A 57-year-old man presented with a pigmented papule, 0.4 cm in diameter, on the left lower eyelid. Skin biopsy revealed a basal cell carcinoma, which was excised through a wide excision followed by a full-thickness skin graft (FTSG). Two weeks after the surgery, an erythematous nodule developed in the lower margin of the graft recipient site. The nodule size increased rapidly over 2 weeks, becoming dome-shaped with a central hyperkeratotic plug. A diagnosis of keratoacanthoma (KA) was made, and surgical excision was performed. Histological findings revealed a large, well-differentiated squamous tumor with a central keratin-filled crater and buttress. The human papilloma virus (HPV) genotyping results were negative. Risk factors for KA include trauma, old age, exposure to ultraviolet (UV) radiation, immunosuppression, and HPV infection. KA has most often been reported to develop at the donor site. Although the pathogenesis of KA is unclear, trauma is believed to act as a second insult to a preceding oncogenic insult, such as exposure to UV radiation, resulting in a koebnerization. Herein, we report a case of solitary KA at a FTSG recipient site. This report presents information that may provide guidance during dermatologic surgeries. [ABSTRACT FROM AUTHOR]

Lumbar central spinal stenosis (LCSS) is a common disorder that causes disability and pain in the elderly. It causes pain in the radicular leg. Recently, transforaminal epidural steroid injection (TFESI) has been widely used to control radicular leg pain caused by LCSS. However, in cases of severe LCSS, drugs injected using TFESI cannot spread into the spinal canal and would have less therapeutic effects than in mild LCSS. To compensate for this limitation of TFESI, we injected steroids and botulinum toxin type A into the bilateral facet joints, evaluated their effects, and compared them with those of TFESI. One hundred patients with severe LCSS were included in the study and randomly allocated to either the facet injection (FI) or TFESI group. For 50 patients in the FI group, 30 mg (40 mg/mL) of triamcinolone with 50 IU of botulinum toxin type A mixed with a 1 mL solution of 100 mL of 50% dextrose water and 30 mL of 4% lidocaine were administered into the bilateral facet joints under fluoroscopy. For 50 patients in the TFESI group, 30 mg (40 mg/mL) of triamcinolone with 0.8 mL of 2% lidocaine and 2.5 mL of 50% dextrose water was injected bilaterally under fluoroscopy. Radicular leg pain (measured with a numeric rating scale) and pain-related disability (measured with the modified Oswestry Disability Index) due to severe LCSS were significantly reduced after facet joint injection. The therapeutic effects were greater after facet joint injection than after bilateral TFESI. The injection of a mixed solution of steroids and botulinum toxin type A into the bilateral facet joints would be a beneficial therapeutic option in patients with severe LCSS. [ABSTRACT FROM AUTHOR]

Asthma is one of the most common inflammatory diseases of the lung worldwide. There has been considerable progress in recent studies to treat and prevent allergic asthma, however, various side effects are still observed in clinical practice. Six-week-old male BALB/c mice were orally administered with either sword bean pod extracts (SBP; 100 or 300 mg/kg) or dexamethasone (DEX; 5 mg/kg) once daily over 3 weeks, followed by ovalbumin sensitization (OVA/Alum.; intraperitoneal administration, 50 μg/2 mg/per mouse). Scoring of lung inflammation was performed to observe pathological changes in response to SBP treatment compared to OVA/Alum.-induced lung injury. Additionally, inflammatory cytokines were quantified in serum, bronchoalveolar lavage fluid (BALF), and lung tissue using ELISA and Western blot analyses. SBP treatment significantly reduced the infiltration of inflammatory cells, and release of histamine, immunoglobulin E, and leukotriene in serum and BALF. Moreover, the therapeutic effect of SBP was also assessed to analyze the inflammatory changes in the lung tissues. SBP markedly suppressed the activation of the MAPK signaling pathway and the expression of key inflammatory proteins (e.g., TNF-α) and Th2 type cytokines (IL-5 and IL-13). SBP was effective in ameliorating the allergic inflammation against OVA/Alum.-induced asthma by suppressing pulmonary inflammation. [ABSTRACT FROM AUTHOR]

We employ tools and techniques from multivariable operator theory to obtain new proofs and extensions of well known inequalities regarding the norm and the numerical radius of elementary operators defined on the C ⁎ –algebra of all bounded operators on Hilbert space, or on the ⁎–ideal of Hilbert-Schmidt operators. In the process, we provide new insights on the study of Heinz-type inequalities related to the arithmetic-geometric mean inequality, and generalize results of several authors, including R. Bhatia, G. Corach, C. Davis, F. Kittaneh, and M.S. Moslehian. To estimate the norm, our approach exploits, in particular, the Spectral Mapping Theorem for the Taylor spectrum, and Ky Fan's Dominance Theorem. For the numerical radius, we use S. Hildebrandt's description of the numerical range of an operator in terms of the norm of its translates. [ABSTRACT FROM AUTHOR]

With the growing interest in 3D printing, many studies are being conducted to replace conventional manufacturing processes. In terms of mechanical applications, however, research on the tribological characteristics of 3D printing components has not been sufficiently conducted. This study investigated the influences of surface texturing and roughness on 3D printed specimens. Specimens with and without surface texture were printed using a 3D printer, and their frictional behavior was compared. The friction coefficient of the textured specimen was smaller than that of the untextured specimen. Contact analysis was conducted to evaluate the mechanism. The analysis suggested that the real contact area of the untextured specimen was similar to that of the textured specimen during the initial stage. However, the wear of asperities during the friction test increased the real contact area of the untextured specimen. Surface roughness was verified to influence the untextured specimen more significantly than the textured specimen in terms of tribological behavior. [ABSTRACT FROM AUTHOR]

Objectives: This research aims to apply an auditory display for tumor imaging using fluorescence data, discuss its feasibility for in vivo tumor evaluation, and check its potential for assisting enhanced cancer perception. Methods: Xenografted mice underwent fluorescence imaging after an injection of cy5.5-glucose. Spectral information from the raw data was parametrized to emphasize the near-infrared fluorescence information, and the resulting parameters were mapped to control a sound synthesis engine in order to provide the auditory display. Drag–click maneuvers using in-house data navigation software-generated sound from regions of interest (ROIs) in vivo. Results: Four different representations of the auditory display were acquired per ROI: (1) audio spectrum, (2) waveform, (3) numerical signal-to-noise ratio (SNR), and (4) sound itself. SNRs were compared for statistical analysis. Compared with the no-tumor area, the tumor area produced sounds with a heterogeneous spectrum and waveform, and featured a higher SNR as well (3.63 ± 8.41 vs. 0.42 ± 0.085, p < 0.05). Sound from the tumor was perceived by the naked ear as high-timbred and unpleasant. Conclusions: By accentuating the specific tumor spectrum, auditory display of fluorescence imaging data can generate sound which helps the listener to detect and discriminate small tumorous conditions in living animals. Despite some practical limitations, it can aid in the translation of fluorescent images by facilitating information transfer to the clinician in in vivo tumor imaging. [ABSTRACT FROM AUTHOR]

Aim: To provide in‐depth understanding of real‐world tumor necrosis factor inhibitor (TNFi) treatment patterns in patients with ankylosing spondylitis (AS) and treatment satisfaction, productivity loss, and associated factors. Methods: This was a multicenter observational hybrid retrospective chart review and cross‐sectional survey study. Disease activity and physical functioning were measured using the Bath AS Disease Activity Index and Bath AS Functional Index, respectively. Treatment satisfaction was determined with the Treatment Satisfaction Questionnaire for Medication (TSQM). Productivity loss was evaluated using the Korean version of the World Health Organization–Health and Work Performance Questionnaire. Results: A total of 497 patients were enrolled (mean age 40.3 years, 85.3% male, mean AS duration 10 years). The mean duration of TNFi treatment was 6.2 years. Among the four TNFi considered, adalimumab (39.6%) and etanercept (23.5%) were most commonly used at study enrollment. The TSQM convenience domain score was lower than scores in the effectiveness, adverse effects, and global satisfaction domains. Subcutaneous syringe‐type injection and intravenous injection were associated with lower patient convenience satisfaction than subcutaneous pen‐type injection. Increased costs of lost productivity time were associated with female sex, unemployed status, and higher disease activity. Conclusions: The most frequently prescribed TNFi was adalimumab, followed by etanercept. Etanercept was used for the longest duration. More convenient treatment options may enhance overall treatment satisfaction. Considerable loss in productivity due to AS was observed in this study. To reflect patients' perspectives, further attention should be paid to factors associated with treatment satisfaction and productivity loss when selecting treatment options. [ABSTRACT FROM AUTHOR]

Background: For patients with acute respiratory distress syndrome, a ventilator is essential to supply oxygen to tissues, but it may also cause lung damage. In this study, we investigated the role of NOX4 using NOX4 knockout (KO) mice and NOX4 inhibitors in a ventilator-induced lung injury (VILI) model.Methods: Wild-type (WT) male C57BL/6J mice and NOX4 knockout (KO) male mice were divided into five groups: (1) control group; (2) high tidal ventilation (HTV) group: WT mice + HTV ± DMSO; (3) NOX4 KO group; (4) NOX4 KO with HTV group; (5) NOX4 inhibitor group: WT mice + HTV + NOX4 inhibitor. In the VILI model, the supine position was maintained at 24 mL/kg volume, 0 cm H2O PEEP, 100/min respiratory rate, and 0.21 inspired oxygen fraction. In the NOX4 inhibitor group, 50 μL anti-GKT 137831 inhibitor was injected intraperitoneally, 2 h after ventilator use. After 5 h of HTV, mice in the ventilator group were euthanized, and their lung tissues were obtained for further analysis. In addition, the relationship between EphA2 (which is related to lung injury) and NOX4 was investigated using EphA2 KO mice, and NOX4 and EphA2 levels in the bronchoalveolar lavage fluid (BALF) of 38 patients with pneumonia were examined.Results: Cell counts from BALFs were significantly lower in the NOX4 KO with HTV group (p < 0.01) and EphA2 KO with HTV group (p < 0.001) compared to that in the HTV group. In the NOX4 inhibitor group, cell counts and protein concentrations from BALF were significantly lower than those in the HTV group (both, p < 0.001). In the NOX4 KO group and the NOX4 inhibitor group, EphA2 levels were significantly lower than those in the HTV group (p < 0.001). In patients with respiratory disease, NOX4 and EphA2 levels were significantly higher in patients with pneumonia and patients who received ventilator treatment in the intensive care unit.Conclusion: In the VILI model with high tidal volume, NOX4 KO, EphA2 KO or monoclonal antibodies attenuated the VILI. NOX4 and EphA2 levels were significantly higher in patients with pneumonia and especially in mechanical ventilated in the ICU. Inhibition of Nox4 is a potential therapeutic target for the prevention and reduction of VILI. [ABSTRACT FROM AUTHOR]

Although start-up is a critical procedure in biofilm-based processes, systematic research aimed at improving start-up efficiency in hydrogen-based membrane biofilm reactors (H 2 -MBfRs) is lacking. In this study, we investigated the effects of H 2 pressure on the stabilized denitrification performance of H 2 -MBfRs during start-up. Following inoculation with anoxic sludge, the biomass was acclimated to various H 2 pressures. The increase in denitrifying microbial activity under high H 2 pressures (i.e., H 2 flux) shortened the denitrification lag time and reduced NO 3 –N removal flux, indicating an improved acclimation efficiency. The acclimated biomass was attached to membranes under different H 2 pressures. High H 2 pressures impeded biomass attachment, possibly because of bubble-less evaporation. Reducing the H 2 pressure appeared to be necessary for improving the biomass attachment. However, this measure decreased previously acclimated denitrification activity. Therefore, the loss of both acclimation and biomass adhesion must be considered during the attachment phase. The highest removal flux (0.63 e- eq/m2-d) was obtained after just 3.5 d of acclimated biomass attachment (i.e., activated sludge floc) at 1.6 bar. During Phase 3, the initial performance was further improved to 0.89 e- eq/m2-d by gradually increasing the H 2 pressure. These results provide a start-up strategy for improving the initial performance of H 2 -MBfRs. [Display omitted] • The stabilization performance of H 2 -MBfRs was improved by adjusting the H 2 pressure. • High H 2 pressures can increase the acclimation efficiency of the inoculum. • Biomass can be hindered from membrane attachment by high H 2 pressures. • A gradual increase in H 2 pressure can further improve the initial performance. [ABSTRACT FROM AUTHOR]

BACKGOUND: Lateral epicondylitis (LE) is one of the most common musculoskeletal disorders that causes pain. OBJECTIVES: We evaluated the effect of the inclusion of a minimal dose of corticosteroid in a solution comprising autologous whole blood (AWB), 20% dextrose, and 2% lidocaine for treating LE. METHODS: In this randomized prospective trial LE patients were allocated to the CS + group (n = 70; solution comprising 1 mL AWB, 1 mL 20% dextrose, 0.4 mL 2% lidocaine, and 0.1 mL (0.4 mg) dexamethasone palmitate; injected into the common wrist extensor tendon) or the CS - group (n = 70; same solution as above but without dexamethasone palmitate). Five injections were administered at monthly intervals. At each visit, pain intensity was evaluated using the numeric rating scale (NRS), and grip strength was measured using a hand-grip dynamometer. RESULTS: In the CS + and CS - groups, 1 and 10 patients dropped out, respectively. In both groups, the NRS scores at each evaluation were significantly lower than the pretreatment scores. The NRS scores from pretreatment to the second and third visits were significantly lower in the CS + group than those in the CS - group. However, at the fourth and fifth visits, and 6 months after the last injection (the sixth visit), the degree of pain reduction between the groups was not significantly different. Grip strength increased significantly over time in both groups. At each evaluation, grip strength was significantly higher than that at the pretreatment stage. However, the degree of increase was not significantly different between groups. CONCLUSIONS: The inclusion of a minimal dose of corticosteroid in the AWB and 20% dextrose injection can reduce pain, especially during early treatment. [ABSTRACT FROM AUTHOR]

Many patients complain of chronic cervical radicular pain, and pulsed radiofrequency (PRF) is known to have a positive effect for alleviating neuropathic pain. In the present study, we used ultrasound (US) guidance and compared the effects of monopolar PRF with those of bipolar PRF in patients with chronic cervical radicular pain refractory to repeated transforaminal epidural steroid injections.Sixty-six patients with chronic cervical radicular pain were included in this study. Patients were randomly assigned to one of the two groups: monopolar or bipolar PRF group (n= 33 per group). Pain intensity was evaluated using a numeric rating scale (NRS) at pretreatment, and at 1 and 3 months after the treatment. Target stimulation site was the extraforaminal nerve root. Compared to the pretreatment NRS scores, patients in both groups showed a significant decrease in NRS scores at 1 and 3 months after the treatment. Reductions in the NRS scores over time were significantly larger in the bipolar PRF group. Three months after the treatment, 18 patients (54.5%) in the monopolar PRF group and 27 (81.8%) in the bipolar PRF group reported successful pain relief (pain relief of ⩾50%). US-guided PRF can be an effective interventional technique for the management of chronic refractory cervical radiculopathy. Moreover, bipolar PRF has better treatment outcome than monopolar PRF. [ABSTRACT FROM AUTHOR]

Chronic pancreatitis (CP) related main pancreatic duct (MPD) stricture has been a challenge for endoscopists. Fully covered self-expandable metal stents (FC-SEMS) has been tried in CP patients, but the efficacy and safety are still controversial. Thus, we aim to compare the long-term clinical efficacy of FC-SEMS vs. plastic stent placement in persistent MPD strictures secondary to CP. Between 2007 and 2018, 80 chronic pancreatitis patients (58 males, median age 49 years), who underwent endoscopic placement of FC-SEMS (n = 26) and plastic stent (n = 54) for persistent MPD strictures after at least 3 months of initial single plastic stenting, were retrospectively analyzed during a median follow-up duration of 33.7 months. As a result, MPD stricture resolution rate was statistically higher in FC-SEMS group (87.0% vs. 42.0%, p < 0.001). Although immediate complications occurred similarly (38.5% vs. 37.0%, p = 0.902), spontaneous migration (26.9%) and de novo strictures (23.1%) were pronounced delayed complications in FC-SEMS group. Pain relief during follow-up was significantly higher in FC-SEMS group (76.9% vs. 53.7%, p = 0.046). The total procedure cost was similar in both groups ($1,455.6 vs. $1,596.9, p = 0.486). In comparison with plastic stent, FC-SEMS placement for persistent MPD strictures had favorable long-term clinical efficacy, with its typical complications like spontaneous migration and de novo strictures. [ABSTRACT FROM AUTHOR]

Practical Application In this study, we optimized the composition of the browning inhibitor for apples and established a prediction model for the browning inhibitor concentration in mass‐processed fresh‐cut apples based on electrical conductivity measurements. The “Fuji” apples that were harvested in Chungju, Korea, were used for this study. Vitamin C mixture (VCM) and trehalose (Tre) were used as browning inhibitors at a 4% ratio. The browning reaction under Δ3 of BI (browning index) for 5 days was defined as the target shelf‐life of the apple flesh. The ΔBI of VCM and Tre was lower than that of VCM by 4%. It is revealed that the electrical conductivity of the browning inhibitor was highly correlated with its concentration and the number of soaked apples. Finally, the regression of the conductivity was fitted as Y = −0.0024 (number of soaked apples) + 0.5111 (R2 = 0.9931). In the validation test, the conductivity must be maintained at 0.4373 S/m or higher to maintain the target anti‐browning level of Δ3 or less, which corresponded to ∼80% of the initial qualitative level after manufacture. The conductivity measurement of the browning inhibitor is suitable for monitoring and predicting its concentration in the mass processing of fresh‐cut apple production due to the convenience of this method.The conductivity measurement of browning inhibitors can be applied not only to the mass processing of apple production but also to the anti‐browning treatment of other fruits and vegetables, due to the convenience of this method. From these research results, it is expected to derive a formula that can predict the concentration of browning inhibitors through simple experiments for other fruits or vegetables. [ABSTRACT FROM AUTHOR]

This article examines whether T.F. Torrance's theology can uphold the doctrine of divine simplicity, in a manner consistent with his accounts of the ascension of Jesus, God's eternity and divine im/passibility. This article indicates that Torrance's doctrine of simplicity does not fully accord with the traditional one that does not allow for any form of introduction of composites and any historical contingencies into the Being of God. On Torrance's account, God embraces created temporality and carnality into his eternal Being through Jesus Christ, but that does not undercut the significance of the divine indissoluble oneness by virtue of a christological and trinitarian notion of space. For Torrance, the one God embraces the creaturely others in his infinite, indivisible and comprehensive oneness. [ABSTRACT FROM AUTHOR]

In the western margin of the Ulleung Basin, a detailed analysis of cores with geophysical data from a fan-shaped body, just downslope of a submarine gully associated upslope with failure scars, reveals various modes of mass-transport processes. The arcuate failure scars occurs in water depths exceeding 600 m. The fan-shaped body, less than ca. 10 km long in radius, displays strong backscatter intensity in sonar images, and corresponds to the uppermost transparent mass in Chirp sub-bottom profiles. Sediment cores penetrating to the uppermost transparent mass consist mostly of various facies of mass-transport deposits (MTDs), causing the strong back-intensity in the sonar images. The interval of MTD facies comprises the upper and lower units without hemi-pelagic muds between them, implying that the fan-shaped body was probably deposited during a single event separated in at least two stages without a significant time break. The lower unit shows brittle to plastic deformation of soft muds (slides/slumps), whereas the upper units exhibits fully fragmented soft mud clasts (low viscous debris flows). Both the upper and lower units involve same original lithology (i.e., soft hemi-pelagic mud) prior to failures, suggesting that the lithology could not significantly affect depositional processes. The fully fragmented soft mud clasts of the upper unit are probably indicative of more shearing than the brittle to plastic deformation of soft muds in the lower unit. Considering the small dimension of the failure scars/gully and the same original lithology, the more shearing of the upper unit was most likely caused by longer transport distance than that of the lower unit. The rare turbidites with absence of channellevee systems in the fan-shaped body and the failure scars confined in the upper to middle slopes suggest that the submarine gully probably formed by slope failures, not by erosion of turbidity currents. [ABSTRACT FROM AUTHOR]

One of the most critical points in the study of LIB-related materials is the extremely high reactivity of Li. In addition to pure Li metal, many Li-containing materials employed in LIBs are highly reactive under ambient conditions. Therefore, they should be stored and treated in an inert environment, such as vacuum chambers and gloveboxes filled with inert gases. In particular, most pristine cathode materials contain Li and are more reactive in air than pristine anode materials are. For instance, various impurities, mostly Li 2 CO 3 , are grown on the surface of pristine NCA (LiNi x Co y Al z O 2 , x + y + z = 1) materials. The precise characterization of these ambient-induced surface impurities is critical for understanding the intrinsic properties of these cathode materials. In this study, we directly image and characterize ambient-induced surface impurities formed on the surface of high-Ni NCA (LiNi 0.8 Co 0.15 Al 0.05 O 2) materials using Kelvin probe force microscopy (KPFM) and scanning spreading resistance microscopy (SSRM). The ambient-induced surface impurities show clearly distinguishable work functions and resistance features compared with the pristine NCA surface. In particular, it is confirmed that the resistance of ambient-induced impurities is significantly higher than that of pristine NCA materials, which can deteriorate the performance of LIB cells. This study provides direction for the fabrication, storage, and processing of LIB cathode materials. • Ambient-induced surface impurities formed on the surface of NCA cathode materials were directly imaged and characterized. • KPFM and SSRM were used for measuring the work function and the resistance of ambient-induced impurities at the nanoscale. • The ambient-induced surface impurities have distinguishable work functions compared with the fresh NCA surface. • The resistance of ambient-induced impurities was significantly higher than that of the fresh NCA surface. [ABSTRACT FROM AUTHOR]

Background: There is a strong need for non-invasive and patient-friendly delivery systems of protein drugs for long-term therapy. However, oral delivery of protein drugs is a big challenge due to many barriers including instability in the gastrointestinal (GI) tract and low permeability. To overcome the absorption barriers in GI tract and improve the patient compliance, this study aimed to develop an M cell targeted-nanocomposite delivery system of protein drugs. Results: An aminoclay-protein core complex (AC-Ins) was prepared by using insulin as a model protein and then sequentially coated with Ulex europaeus agglutinin 1 (UEA-1) for M-cell targeting and the pH sensitive polymer, Eudragit® L100 (EUAC-Ins). All nanoparticles were obtained with a high entrapment efficiency (> 90%) and their structural characteristics were confirmed by Fourier transform-infrared spectroscopy, energy dispersive X-ray spectroscopy, and circular dichroism. Among the developed nanoparticles, EUAC-Ins effectively suppressed drug release at pH 1.2, while rapidly released drugs at pH 6.8 due to dissolution of the outer coating layer. The conformational stability of insulin entrapped in EUAC-Ins was well maintained in the presence of proteolytic enzymes. Compared to free insulin, EUAC-Ins increased the membrane transport of insulin by 4.4-fold in M cells. In parallel, oral administration of EUAC-Ins in mice enhanced insulin uptake by 4.1-fold in the intestinal Peyer's patches and 2.6-fold in intestinal epithelium tissues with normal villi, compared to free insulin. Orally administered EUAC-Ins decreased significantly the blood glucose level in diabetic mice, while the effect of oral insulin solution was negligible. Conclusion: An M cell targeted-ternary nanocomposite system obtained by dual coating of the aminoclay-protein core complex with UEA-1 and a pH dependent polymer is promising as an effective oral protein delivery carrier. [ABSTRACT FROM AUTHOR]

Given a pair T ≡ T 1 , T 2 of commuting subnormal Hilbert space operators, the Lifting Problem for Commuting Subnormals (LPCS) asks for necessary and sufficient conditions for the existence of a commuting pair N ≡ N 1 , N 2 of normal extensions of T 1 and T 2 ; in other words, T is a subnormal pair. The LPCS is a longstanding open problem in the operator theory. In this paper, we consider the LPCS of a class of powers of 2 -variable weighted shifts. Our main theorem states that if a "corner" of a 2-variable weighted shift T = W α , β ≔ T 1 , T 2 is subnormal, then T is subnormal if and only if a power T m , n ≔ T 1 m , T 2 n is subnormal for some m , n ≥ 1. As a corollary, we have that if T is a 2-variable weighted shift having a tensor core or a diagonal core, then T is subnormal if and only if a power of T is subnormal. [ABSTRACT FROM AUTHOR]

Background Botulinum toxin (BTX) is widely used for pain control in various musculoskeletal disorders. Objectives We evaluated the analgesic effect of botulinum toxin type A (BTX-A) in chronic lateral epicondylitis and compared the effect between 10 and 50 IU of BTX-A. Methods Sixty subjects with chronic lateral epicondylitis were included and underwent a BTX-A injection in the common extensor tendon. The subjects were randomly allocated into two groups: the small-dose group (SD group; 30 subjects, 10 IU) and large-dose group (LD group; 30 subjects, 50 IU). Treatment outcomes were evaluated by measuring the pain level using the numeric rating scale (NRS) and measuring grip strength before and one, two, three, four, five, and six months after treatment. Results Subjects in both groups showed a significant decrease in NRS scores at all evaluation time points after treatment. The reduction in NRS scores was significantly greater in the LD group at one, two, three, and four months after treatment. Six months after treatment, 19 subjects (63.3%) in the SD group and 21 (70%) in the LD group reported successful pain relief (pain relief ≥50%). The rate of successful pain relief was not significantly different between the two groups. Grip strength was more increased in the LD group at one, two, three, four, and six months after treatment. Conclusions BTX-A injection into the common extensor tendon can be a good treatment option for chronic lateral epicondylitis. The 50-IU BTX-A injection achieved a better outcome than the 10-IU injection. [ABSTRACT FROM AUTHOR]

Aim: Peripheral features contribute to disease burden in ankylosing spondylitis (AS). This study investigated the frequency of peripheral disease and effectiveness of adalimumab among Korean patients with AS. Methods: Peripheral disease was evaluated in consecutively enrolled patients with active AS (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] score ≥ 4). An adult subpopulation was subsequently enrolled in a prospective, observational study and received adalimumab 40 mg, every 2 weeks. During a 52‐week follow‐up, AS disease activity was assessed by BASDAI score, and effectiveness in peripheral disease assessed via changes in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES; 0‐13), swollen joint and tender joint counts (SJC, 0‐44; TJC, 0‐46), and dactylitic digits from baseline. Results: Of 1161 Korean patients with AS, 178 (15.3%) and 306 (26.4%) had enthesitis and peripheral arthritis, respectively; dactylitis was diagnosed in 28 patients (2.4%). Of 201 patients enrolled in the observational study, 46.3%, 33.3%, and 3.0% had enthesitis, peripheral arthritis, and dactylitis, respectively. Overall, 75.1% of patients achieved >50% improvement in BASDAI score by week 12. Mean MASES was significantly reduced from 2.67 at baseline to 0.85 and 0.34 at weeks 12 and 52, respectively (P <.0001). Similarly, SJC and TJC improved significantly from 2.58 and 3.49 at baseline to 0.80 and 1.68, respectively, by week 12 (P <.0001). Dactylitis was resolved in all affected patients by week 28. Conclusion: Of these Korean patients with AS, those who received adalimumab demonstrated higher prevalence for peripheral symptoms and, subsequently, adalimumab treatment improved peripheral features of their AS. [ABSTRACT FROM AUTHOR]

Detection rate of de novo EGFR T790 M mutation was increased up to 80% through recent ultrasensitive detection methods. Here, we investigated the clinical significance and its usefulness of detecting de novo EGFR T790 M using ultrasensitive droplet-digital polymerase chain reaction (ddPCR) method. In total, 102 cases diagnosed as lung adenocarcinoma with EGFR-tyrosine kinase inhibitor (TKI) sensitizing mutations (mEGFR) and had been treated with 1st ~ 2nd generation EGFR-TKI alone were enrolled for this study. De novo T790 M status was tested using the tissues at the initial diagnosis and positivity was defined as the ratio of T790 M/wild-type copies over 0.00294 by ddPCR. Seventy patients (68.6%) harbored the de novo T790 M. De novo T790 M was more frequently detected in cases with EGFR L858 R mutation than those with EGFR exon 19 deletion (E19d) mutations (P = 0.024). Forty-three patients underwent rebiopsy due to disease progression. The cases who experienced progression due to acquired T790 M were more likely to have E19d at initial diagnosis and the presence of de novo T790 M and the ratio of T790 M/wild-type copies did not relate to the emergence of acquired T790 M. On the other hand, the cases with a longer duration of disease-control by EGFR-TKI had higher change to get acquired T790 M mutation (P-value = 0.040). The presence of de novo T790 M has limitation in predicting disease progression by acquired T790 M, suggesting that identifying de novo T790 M through the ultrasensitive methods may not be necessary identifying patients who would be beneficial by 3rd-generation EGFR-TKI as the 1st line treatment. [ABSTRACT FROM AUTHOR]

Aim: Peripheral features contribute to disease burden in ankylosing spondylitis (AS). This study investigated the frequency of peripheral disease and effectiveness of adalimumab among Korean patients with AS. Methods: Peripheral disease was evaluated in consecutively enrolled patients with active AS (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] score ≥ 4). An adult subpopulation was subsequently enrolled in a prospective, observational study and received adalimumab 40 mg, every 2 weeks. During a 52‐week follow‐up, AS disease activity was assessed by BASDAI score, and effectiveness in peripheral disease assessed via changes in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES; 0‐13), swollen joint and tender joint counts (SJC, 0‐44; TJC, 0‐46), and dactylitic digits from baseline. Results: Of 1161 Korean patients with AS, 178 (15.3%) and 306 (26.4%) had enthesitis and peripheral arthritis, respectively; dactylitis was diagnosed in 28 patients (2.4%). Of 201 patients enrolled in the observational study, 46.3%, 33.3%, and 3.0% had enthesitis, peripheral arthritis, and dactylitis, respectively. Overall, 75.1% of patients achieved >50% improvement in BASDAI score by week 12. Mean MASES was significantly reduced from 2.67 at baseline to 0.85 and 0.34 at weeks 12 and 52, respectively (P < .0001). Similarly, SJC and TJC improved significantly from 2.58 and 3.49 at baseline to 0.80 and 1.68, respectively, by week 12 (P < .0001). Dactylitis was resolved in all affected patients by week 28. Conclusion: Of these Korean patients with AS, those who received adalimumab demonstrated higher prevalence for peripheral symptoms and, subsequently, adalimumab treatment improved peripheral features of their AS. [ABSTRACT FROM AUTHOR]

We demonstrate the differential detection of UV-A (ultra-violet 320–400 nm region) and UV-C (100–280 nm) using porous two-dimensional (2D) Nb2O5 and additional Ag nano-particle decoration. The 2D Nb2O5, which has band-absorption edge near the UV-A zone, was synthesized by thermodynamic conversion of 2D material NbSe2 (Nb2O5 has lower Gibbs formation energy than NbSe2). For the differential detection (to distinguish with UV-C absorption), we decorated the Ag nano-particles on the Nb2O5 surface. By coating Ag nano-particles, we can expect (i) a decrease in the area of light absorption by the Ag-coated area, and (ii) an increase of surface plasmon absorption by Ag nano-particles, especially the UV-A region, resulting in strong intensity ratio change UV-A/UV-C. [ABSTRACT FROM AUTHOR]

This study aimed to develop a ternary nanocomposite system of organoclay, glycol-chitosan, and Eudragit®S100 as an effective colon targeted drug delivery carrier to enhance the oral absorption of insulin. A nanocomplex of insulin and aminoclay was prepared via spontaneous co-assembly, which was then coated with glycol-chitosan and Eudragit S®100 (EGAC-Ins). The double coated nanocomplex, EGAC-Ins demonstrated a high entrapment efficiency of greater than 90% and a pH-dependent drug release. The conformational stability of insulin entrapped in EGAC-Ins was effectively maintained in the presence of proteolytic enzymes. When compared to a free insulin solution, EGAC-Ins enhanced drug permeability by approximately sevenfold in Caco-2 cells and enhanced colonic drug absorption in rats. Accordingly, oral EGAC-Ins significantly reduced blood glucose levels in diabetic rats while the hypoglycemic effect of an oral insulin solution was negligible. In conclusion, EGAC-Ins should be a promising colonic delivery system for improving the oral absorption of insulin. [ABSTRACT FROM AUTHOR]

Background: The rate of diagnosis of advanced lung adenocarcinoma must be improved. In this study, we compared the detection rates of EGFR-tyrosine kinase inhibitor-sensitizing mutations (mEGFRs) in bronchial washing fluid (BWF) and the plasma of patients with lung adenocarcinoma using the tissue genotype as the standard reference.Methods: Paired blood and BWF specimens were collected from 73 patients with lung cancer. The tumor EGFR mutation status was determined by genotyping of the plasma and BWF samples using droplet digital PCR (ddPCR).Results: The study cohort included 26, 10, 10, and 27 patients with stage I, II, III, and IV disease. Of the 73 cases, 35 had a wild-type EGFR, and 19 had the L858R substitution and exon 19 deletion mutations. The areas under the receiver operator characteristic curves for sensitivity vs. specificity of ddPCR were 0.895 [95% confidence interval (CI): 0.822-0.969] for BWF and 0.686 (95% CI: 0.592-0.780) for plasma (p < 0.001). The fractional abundance was higher in BWF of the mEGFR-positive cases than in the plasma (p = 0.004), facilitating easy threshold setting and discrimination between mEGFR-positive and negative cases. When genotyping results obtained using plasma and BWF were compared for early lung cancer (stages I-IIIA), the diagnostic yields were significantly higher for BWF ddPCR, and the same tendency was observed for the advanced stages, suggesting that the BWF data may reflect the genotype status in early-stage patients.Conclusions: The mEGFR genotyping results obtained using BWF showed a higher diagnostic efficacy than did those obtained using the plasma. Thus, BWF-based genotyping may be a useful substitute for that using plasma in lung cancer. [ABSTRACT FROM AUTHOR]

For Pannenberg, the eschatological future is considered as the locus where the ultimate causation lies. Such an idea shapes Pannenberg's doctrinal accounts of Christ and the Trinity in an idiosyncratic way. However, as this article will indicate, the idea is derived from the Plotinian myth that time can become a whole and so a vessel of divine infinity when it reaches the End. Dispensing with the faulty assumption but retaining the concept of the priority of the future, this article will argue that divine eternity as the totality can engage with history directly at any point of time, without a detour via the eschaton. [ABSTRACT FROM AUTHOR]

The anterior surgical approach to the cervical spine is known to be safe, and damage to the hypoglossal nerve and trigeminal pathway after the surgery is uncommon. However, once damage to those nerves occurs, the patient's quality of life can be severely impaired by discomfort and disability. We report the case of a 59-year-old male with concomitant and irreversible hypoglossal nerve and trigeminal system dysfunction after cervical spine surgery by the anterior approach confirmed by an electrodiagnostic study. He had undergone anterior cervical disc fusion through right-sided approach for a herniated intervertebral disc on the C3-4 level and direct cord compression. He had difficulty with tongue movement, dysarthria, and hypesthesia along the lower margin of the right mandible immediately after the surgery. An electrodiagnostic study revealed hypoglossal neuropathy and trigeminal somatosensory pathway dysfunction. Even though the patient received rehabilitation therapy for impaired tongue movement for more than 2 years, this function did not recover. It is important to be aware of the complexity of the anatomy of vulnerable structures, including hypoglossal nerves and the trigeminal nerve system at the cervical spine level, to prevent damage to important neural structures during surgical procedures. [ABSTRACT FROM AUTHOR]

Aim: This study examined the degree of gastrointestinal (GI) risk and patient‐reported outcomes including GI‐related symptoms, adherence to non‐steroidal anti‐inflammatory drugs (NSAIDs), disease activity and quality of life (QoL) in patients with ankylosing spondylitis (AS). Methods: Cross‐sectional, observational study conducted at six nationwide, university‐based hospitals of Korea. AS patients treated with NSAIDs for at least 2 weeks were included between March and September 2016. Demographic and clinical data were gathered through a medical chart review and patient survey. GI risk was estimated using Standardized Calculator of Risk for Events (SCORE). NSAIDs adherence was investigated with Morisky Medication Adherence Scale‐8 (MMAS‐8). Disease activity and QoL were examined with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and EuroQol‐3L (EQ‐5D, EQ‐visual analog scale [EQ‐VAS]), respectively. Path analysis was implemented to estimate pathways of GI risk, GI symptoms and NSAIDs adherence to QoL. Results: A total of 596 patients (age: 38.9 ± 12.6 years, male: 82.1%) participated in the study, of which 33.2% experienced GI symptoms during NSAID treatment, and 34.2% of them showed ongoing GI symptoms upon enrollment. According to SCORE, 37.1% of patients showed moderate to very high GI risk. No patient showed high adherence according to MMAS‐8, so 55.3% of patients with moderate adherence were considered adherent. BASDAI and QoL of the total patients were 3.5 ± 2.0, 0.6 ± 0.3 (EQ‐5D), and 67.4 ± 19.8 (EQ‐VAS), respectively. From path analyses, higher GI risk significantly lowered QoL. Conclusion: This study suggests timely therapeutic strategies should be implemented to manage GI risk during NSAID treatment in order to effectively manage AS. [ABSTRACT FROM AUTHOR]

Many studies have shown that Toll-like receptors (TLRs) and Nod-like receptors (NLRs) were expressed in B cells and their signaling affects B cell functions. Nonetheless, the roles played by these receptors in B cell antibody (Ab) production have not been completely elucidated. In the present study, we examined the effect of the Nod2 agonist muramyl dipeptide (MDP) in combination with the TLR4 agonist lipopolysaccharide (LPS), a well-known B cell mitogen, on B cell viability, proliferation, and activation, and Ab production by in vitro culture of purified mouse spleen resting B cells. MDP combined with LPS to reinforce B cell viability, proliferation, and activation. Moreover, MDP enhanced LPS-induced IgG2b production, germline γ2b transcript (GLTγ2b) expression, and surface IgG2b expression. In an experiment with Nod2- and TLR4-deficient mouse B cells, we observed that the combined effect of MDP and LPS is dependent on Nod2 and TLR4 receptors. Furthermore, the combined effect on B cell viability and IgG2b switching was not observed in Rip2-deficient mouse cells. Collectively, this study suggests that Nod2 signaling enhances TLR4-activated B cell proliferation, IgG2b switching, and IgG2b production. [ABSTRACT FROM AUTHOR]

This research aimed to develop a pH-responsive organic-inorganic hybrid nanocomposite as an effective oral delivery system for protein drugs. Three different nanocomposites were prepared by using bovine serum albumin (BSA) as a model protein. A nanocomplex of BSA with 3-aminopropyl functionalized magnesium phyllosilicate (AC-BSA) was obtained via the spontaneous co -assembly and then sequentially coated with glycol-chitosan (GAC-BSA) and the pH sensitive polymer, Eudragit®L100–55 (EGAC-BSA). These organic-inorganic hybrid nanocomposites exhibited high entrapment efficiency (86–99%) and their structural characteristics were confirmed by using energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and circular dichroism analysis, indicating that the secondary structure of BSA was well retained in the nanocomposites. At pH 1.2, AC-BSA achieved rapid drug release of about 80% within 2 h, while GAC-BSA and EGAC-BSA exhibited slow drug release of 30% and 15%, respectively, indicating that the surface-coated nanocomposites were more stable in the gastric condition. Furthermore, the conformational stability of BSA entrapped in EGAC-BSA was well retained in the presence of proteolytic enzymes, suggesting that EGAC-BSA should be effective in protecting the protein against gastrointestinal harsh environment. Compared to free BSA, all of tested nanocomposites demonstrated 2.1–3.8-fold higher cellular uptake in Caco-2 cells. Furthermore, energy-dependent endocytosis and paracellular pathway contributed to the cellular transport of nanoparticles. After oral administration in rats, EGAC-BSA significantly enhanced the intestinal permeation of BSA compared to free BSA. In conclusion, EGAC-BSA appears to be promising as an effective oral delivery system for proteins with enhanced intestinal absorption. Unlabelled Image • An organic-inorganic hybrid nanocomplex was developed for oral protein delivery. • Conformational stability of BSA was well retained in the nanocomplex (EGAC-BSA). • EGAC-BSA was stable in acidic conditions with minimal protein release. • The oral administration of EGAC-BSA significantly improved the intestinal permeation of BSA in rats. [ABSTRACT FROM AUTHOR]

We aimed to identify when magnetic resonance imaging (MRI) would be useful to diagnose patients with suspected axial spondyloarthropathy (AxSpA) without evidence of sacroiliitis on radiographs. We retrospectively reviewed electronic medical records of patients who underwent pelvis MRI after radiographs at the rheumatology clinic in a single tertiary center in Korea. Patients underwent imaging from January 2020 to July 2022. We collected data including complete blood count, erythrocyte sedimentation rate, C-reactive protein (CRP), human leukocyte antigen (HLA)-B27, history of acute anterior uveitis (AAU), peripheral arthritis, dactylitis, inflammatory bowel disease (IBD), enthesopathy, and psoriasis. A total of 105 patients who showed no evidence of sacroiliitis on radiographs were included. The median age of patients was 41.0 years, and 44.8% were male. Of them, 34 showed sacroiliitis on MRI (group 1), and 71 showed no evidence of sacroiliitis even on MRI (group 2). Known AxSpA-related clinical features including AAU, peripheral arthritis, dactylitis, IBD, enthesopathy, and psoriasis were not different between the two groups. HLA-B27 positivity (79.4% vs. 40.0%, p < 0.001), median white blood cell count (7700 vs. 6300, p = 0.007), mean platelet count (307.7 ± 69.7 vs. 265.3 ± 68.9 × 103/µL, p = 0.005), and median CRP level (0.38 vs. 0.10, p = 0.001) showed significant differences between the two groups. In a multivariate analysis, HLA-B27 positivity and platelet count were significantly associated with sacroiliitis on MRI. In our cohort, sacroiliitis was observed on MRI in one-third of patients without radiographic evidence. MRI could be recommended to evaluate sacroiliitis in patients with positive HLA-B27 and a high platelet count. [ABSTRACT FROM AUTHOR]

Purpose: An ideal, drug-induced sleep endoscopy (DISE) classification system should cover all the upper airways, be simple and practical, and quantify the severity of any obstruction. Excellent validity and reliability are essential. We explored the inter-rater reliability of Koo's DISE classification system in the hands of experienced and inexperienced otolaryngologists. Methods: We retrospectively analyzed video images of 100 patients who underwent DISE examination in our hospital between 2015 and 2018. Three experienced and three inexperienced otolaryngologists reviewed and scored all images. We calculated the inter-rater reliabilities of the two groups of otolaryngologists. Results: Independent of the extent of experience with DISE, detection of retropalatal obstructions (overall agreement: 0.87; kappa value: 0.60), and the degree of such obstructions (overall agreement: 0.67; kappa value: 0.52) were more consistent than were the detection of retrolingual obstructions (overall agreement: 0.61, kappa value: 0.37) and the degree of retrolingual obstructions (overall agreement: 0.20, kappa value: 0.35). Inexperienced observers were in good agreement for palatal obstructions and experienced observers were in good agreement for tongue-base obstructions. All of the otolaryngologists found it difficult to detect a lateral pharyngeal wall obstruction at the retrolingual level. Conclusion: Koo's DISE classification system focuses on surgical treatment, especially by otolaryngologists, and the degree of agreement between the experienced and inexperienced observers was relatively high. The participants' level of experience had a strong impact on scoring. The less-experienced otolaryngologists tended to overlook tongue-base obstructions, focusing instead on relatively simple retropalatal obstructions. In the future, development of a DISE classification system that can be accepted globally will be necessary. [ABSTRACT FROM AUTHOR]

In this paper, anchoring polymer layer (APL) solder anisotropic conductive films (ACFs) combined with an ultrasonic (US) bonding method are newly introduced. The effects of APL ACFs properties on conductive particle movement and interconnection stability for ultrafine-pitch chip-on-glass applications were reported earlier. It was found that the APL structure not only suppresses the conductive particles movement during the ACFs bonding process for ultrafine-pitch applications, but also prevents electrical short-circuit formation between neighboring bumps. However, to achieve a stable electrical interconnection, APL ACFs require additional process steps such as an oxygen plasma etch process to remove the APL polymer skins surrounding the conductive particles using a thermocompression bonding method. However, during the US bonding process, it was found that the polyacrylonitrile (PAN) polymer skin coated on conductive particles was successfully removed by vertical directional US vibration. Therefore, stable and metallurgical solder joint formation can be achieved without an additional oxygen plasma etching process. [ABSTRACT FROM AUTHOR]

Fine-pitch interconnection technology in electronic packaging has become very important because of electrical interconnection issues such as high contact resistance and open-/short-circuit failure. Nanofiber anisotropic conductive films (ACFs) and nanofiber sheet ACFs (NS ACFs) have been developed and reported by our research group to address the challenges for fine-pitch interconnection problems. However, they require complicated fabrication processes such as electrospinning, thermal compression, and plasma etching. In this paper, anchoring polymer layer (APL) ACFs and their fabrication process are introduced. The goal in employing the APL ACFs was to simplify the complex fabrication steps of nanofibers and NS ACFs by coating methods without compromising electrical performance. With the APL coating method, the electrospinning, thermal compression, and plasma etching steps can be reduced to a single process. Nonetheless, APL ACFs exhibit excellent electrical conduction at 20- $\mu \text{m}$ fine-pitch interconnections by successfully suppressing the movement of conductive particles in the ACF. The capture rate of the APL ACFs was 78%, which was comparable to the value 81% of NS ACFs. APL ACFs open the possibility of cost-effective production of ACFs interconnection materials for fine-pitch applications. Therefore, we use the word “anchoring” to suppress the movement of conductive particles during resin flow. In this paper, we discuss the fabrication process of APL structure and electrical properties of APL ACFs. [ABSTRACT FROM AUTHOR]

Abstract Navigation on graphs is the problem how an agent walking on the graph can get from a source to a target with limited information about the graph. The information and the way to exploit it can vary. In this paper, we study navigation on temporal networks—networks where we have explicit information about the time of the interaction, not only who interacts with whom. We contrast a type of greedy navigation – where agents follow paths that would have worked well in the past – with two strategies that do not exploit the additional information. We test these on empirical temporal network data sets. The greedy navigation finds the targets faster and more reliably than the reference strategies, meaning that there are correlations in the real temporal networks that can be exploited. We find that both topological and temporal structures affect the navigation. Highlights • Introducing the problem of navigation on temporal networks. • Exploring different ways to operationalize the incomplete information. • Proposing different navigation strategies that are only using ex ante information. • Found that both static and temporal network structure determine the navigability. • Shows that in real networks there are structures that could be exploited in navigation. [ABSTRACT FROM AUTHOR]

Comprehensive understanding of the effect of pig breed and sex on meat quality and post-mortem muscle conditions will be necessary to estimate meat quality post mortem. In this study, we applied multiple regression and principal component analysis (PCA) using conventional meat quality traits and muscle fibre characteristics on six pig breeds and different sexes. A total of 1374 pigs from six breeds [Berkshire, Duroc, Landrace, Meishan, Yorkshire, and LYD (Landrace × Yorkshire sows with Duroc as terminal sires) crossbreed] belonging to three sexes (male, castrated male and female) were used in this study. Most of the muscle fibre characteristics showed moderate to high significant correlations with conventional meat quality traits. In particularly, the cross-sectional area (CSAF) of muscle fibres was strongly correlated with muscle pH values, water-holding capacity values and lightness (0.10 < | r | <0.26 and P < 0.01). Multiple regression analysis by general linear model revealed that the effects of breed were significant on muscle pH24h, lightness, drip loss, and marbling score (P < 0.01), whereas sex had no significant effect on meat quality. In the muscle fibre characteristics, the effects of breed and sex were significant on composition of area and density of muscle fibres (P < 0.05). We observed that the Meishan breed was clearly inferior to other breeds, whereas the LYD or Berkshire breeds showed better meat quality and muscle fibre properties. Moreover, we observed clear separations between pig breeds based on the PCA, whereas the sexes in each breed presented a continuum cluster. In summary, we suggest that muscle pH24h, lightness, and drip loss are conventional meat quality traits that can be considered as quantitative factors important in estimating ultimate meat quality of pigs along with the CSAF of muscle fibres; we conclude that Meishan pigs have low meat quality, whereas Berkshire and LYD crossbred pigs have higher quality of pork. Comprehensive understanding of the effect of pig breed and sex on meat quality and post-mortem muscle conditions will be necessary to estimate post-mortem meat quality. Here, we applied multiple regression and principal component analysis on multiple breeds and sexes. We observed that muscle pH, lightness, and drip loss are useful for estimating ultimate pork quality. [ABSTRACT FROM AUTHOR]

Background: Pneumocystis jirovecii pneumonia (PCP) is often fatal in human immunodeficiency (HIV)-negative patients and typically presents with respiratory insufficiency. Predicting treatment failure is challenging. This study aimed to identify prognostic factors and examine PCP polymerase chain reaction (PCR)-negative conversion in non-HIV PCP patients with respiratory failure. Method: We retrospectively enrolled 81 non-HIV patients diagnosed with and treated for PCP with respiratory failure in the intensive care unit at a tertiary hospital over a 3-year period. PCP was diagnosed via nested PCR-mediated detection of Pneumocystis jirovecii in induced sputum samples, endotracheal aspirates, and bronchoalveolar lavage fluids. PCP PCR was performed weekly to check for negative conversion. Results: The overall survival rate was 35.8%. Seventy-four patients (91.3%) required mechanical ventilation, and 6 (7.4%) required high-flow nasal oxygen treatment. The PCP PCR-negative conversion rate was 70.5% (survivors, 97%; non-survivors, 63.5%); the median time to conversion was 10 (7.0–14.0) days. On univariate analysis, the APACHE II score (p < 0.001), renal failure requiring renal replacement therapy (p = 0.04), PCP PCR-negative conversion (p = 0.003), and the PaO2/FiO2 ratio (first 24 hours) (p < 0.001) significantly correlated with mortality. On multivariate analysis, PCP PCR-negative conversion (hazard ratio, 0.433; 95% confidence interval, 0.203–0.928; p = 0.031) and the PaO2/FiO2 ratio (first 24 hours) (hazard ratio, 0.988; 95% confidence interval, 0.983–0.993; p < 0.001) independently predicted prognosis. Conclusions: Determination of PCP PCR-negative conversion and PaO2/FiO2 ratios may help physicians predict treatment failure and mortality in non-HIV PCP patients with respiratory failure. [ABSTRACT FROM AUTHOR]

Electronic packaging technology has become very important in electronic devices, because electrical interconnection problems such as high contact resistance and short-circuit failure have become serious issues in ultrafine pitch interconnection. In this paper, a nylon anchoring polymer layer (APL) structure has been introduced into the anisotropic conductive films (ACFs) system. Then, the effects of nylon APL properties on conductive particle movement of ACFs and its interconnection stability for ultrafine pitch chip-on-glass (COG) applications were investigated. The APL structure can significantly suppress the particles’ movement for ultrafine pitch COG applications, and prevent the short-circuit problem between neighboring electrodes. After ACFs bonding process, the conductive particles capture rate of the conventional ACFs was 33%; however, that of the nylon APL ACFs showed 90%. In addition, the nylon APL ACFs showed excellent electrical interconnection properties such as stable contact resistances without any open or short-circuit failures. As a result, the nylon APL ACFs can be used as new interconnection materials for ultrafine pitch interconnection applications. [ABSTRACT FROM AUTHOR]

This study aimed to design the effective formulation of sorafenib (SF) to enhance the oral drug absorption. Three liposomal formulations of SF were prepared including uncoated liposome (SF-Lip), glycol chitosan-coated liposome (GC-SF-Lip), and Eudragit S100-glycol-chitosan coated liposome (SGC-SF-Lip). All formulations showed a narrow size distribution with a high encapsulation efficiency. Both GC-SF-Lip and SGC-SF-Lip exhibited good stability at acidic and neutral pHs without any significant drug leakage, while SF-Lip appeared to be unstable at pH 1.2. In the case of double coated SGC-SF-Lip, its size changed significantly at pH 7.4, due to the dissolution of Eudragit S100 coating layer into the surrounding medium. Compared to SF solution, all liposomal formulations demonstrated a higher cellular uptake in Caco-2 cells. In particular, SGC-SF-Lip displayed a lower cellular uptake than GC-SF-Lip at pH 6.5, but it achieved a similar cellular uptake to GC-SF-Lip at pH 7.4. Consistently, SGC-SF-Lip was less cytotoxic than GC-SF-Lip at pH 6.5, whereas it showed a comparable cytotoxicity to GC-SF-Lip at pH 7.4, implying the removal of the Eudragit S100 coating layer at pH 7.4. After an oral administration to rats, SGC-SF-Lip significantly improved the systemic exposure of SF, where its Cmax and AUC were approximately fourfold higher than the untreated drug. Collectively, SGC-SF-Lip appeared to be promising to enhance the oral absorption of SF. [ABSTRACT FROM AUTHOR]

The purposes of this study are to confirm the role of Fibroblast Growth Factor-2 (FGF-2) in bone regeneration by adding various concentrations of FGF-2 to the collagen membrane and applying it to the Biphasic Calcium Phosphate (BCP) bone graft site for guided bone regeneration, to explore the potential of collagen membrane as FGF-2 carrier, and to determine the optimum FGF concentration for enhancement of bone regeneration. Four bone defects of 8 mm in diameter were created in 18 New Zealand rabbit calvaria. After BCP bone graft, graft material was covered with collagen membranes adding various concentration of FGF-2. The concentration of FGF-2 was set at 1.0, 0.5, 0.1 mg/ml, and same amount of saline was used in the control group. To confirm the bone regeneration over time, six New Zealand rabbits were sacrificed each at 2, 4, and 12 weeks, and the amounts of new bone and residual bone graft material were analyzed by histologic and histomorphometric analysis. Qualitative analyses are also conducted through immunohistochemistry, Tetrate-resistant acid phosphatase (TRAP) stain and Russell-Movat pentachrome stain. As the healing period increased, the formation of new bone increased and the amount of residual graft material decreased in all experimental groups. Immunohistochemistry, TRAP staining and pentachrome staining further showed that the addition of FGF-2 promoted bone regeneration in all experimental groups. It was also confirmed that polymer collagen membrane can be used as a useful carrier of FGF-2 when enhanced early stage of new bone formation is required. [ABSTRACT FROM AUTHOR]