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Purpose: We aimed to develop and validate a new ultrasonography (US) index for the diagnosis of primary medial‐type knee osteoarthritis (OA). Methods: In total, 156 patients (203 limbs) underwent standing knee radiography and the US for suspected knee OA. Total osteophyte height (TOH) and distance between bones (DBB) aided diagnosis. Logistic regression identified optimal cutoff values. Thresholds from logistic regression informed recipient operating characteristic curve (ROC) analysis, balancing sensitivity and specificity. These thresholds were then applied in the differential thermal analysis (DTA) to construct a 2 × 2 table. Results: The TOH‐DBB index showed that a DBB of 5.6 mm or less was required to diagnose primary medial‐type knee arthropathy. The results in the 2 × 2 table were 41 true‐positive (TP), 10 false negative (FN), 22 true‐negative (TN), and 7 false positive (FP). A DBB of 5.6 mm or less and TOH of 4.7 mm or more were necessary to diagnose severe deformity. The results in the 2 × 2 table were 10 TP, 4 FN, 23 TN, and 4 FP. Conclusion: The TOH‐DBB index was confirmed to capture changes in primary medial‐type knee OA across various stages. [ABSTRACT FROM AUTHOR]

A study published in the journal Allergy investigated the potential immune-regulating genes that may alleviate Japanese cedar pollinosis (JCPsis) symptoms through the intake of Lactiplantibacillus plantarum YIT 0132 (LP0132), a type of lactic acid bacteria. The study found that the downregulation of IDO1 and upregulation of FOXP3 may be associated with the alleviation of JCPsis symptoms by LP0132 intake. However, the study did not compare results with individuals without JCPsis and did not clarify the gene expression profile in immune cells or local changes in mucosa. The study was funded by Yakult Honsha Co., Ltd. and the authors declare no conflicts of interest. [Extracted from the article]

Selenocysteine (Sec)‐derived cyclic selenenyl amides, formed by the intramolecular cyclization of Sec selenenic acids (Sec–SeOHs), have been postulated to function as protective forms in the bypass mechanism of glutathione peroxidase (GPx). However, their chemical properties have not been experimentally elucidated in proteins or small‐molecule systems. Recently, we reported the first nuclear magnetic resonance observation of Sec–SeOHs and their cyclization to the corresponding cyclic selenenyl amides by using selenopeptide model systems incorporated in a molecular cradle. Herein, we elucidate the structures and reactivities of Sec‐derived cyclic selenenyl amides. The crystal structures and reactions toward a cysteine thiol or a 1,3‐diketone‐type chemical probe indicated the highly electrophilic character of cyclic selenenyl amides. This suggests that they can serve not only as protective forms to suppress the inactivation of Sec–SeOHs in GPx but also as highly electrophilic intermediates in the reactions of selenoproteins. [ABSTRACT FROM AUTHOR]

Background: Redness of the facial skin is an important cosmetic concern. Although qualitative and quantitative modifications of sebum on the skin surface are major pathogenic factors of chronic inflammatory skin conditions, the relationship between skin redness, sebum, and mild inflammation on the cheeks of healthy subjects remains elusive. Aims: We aimed to explore the correlation between cheek redness and sebum and inflammatory cytokines in the stratum corneum (SC) of healthy subjects. We also examined the effects of representative sebum lipids on the gene expression of inflammatory cytokines in cultured keratinocytes. Patients/Methods: This study included 198 healthy participants. Skin sebum was analyzed using flow injection analysis, and skin redness was assessed using a spectrophotometer. Inflammatory cytokines in tape‐stripped SC were measured using enzyme‐linked immunosorbent assay. Results: Cheek redness parameters positively correlated with the amount of skin sebum and the proportion of monounsaturated free fatty acids (C16:1 and C18:1) in the sebum. They also positively correlated with the interleukin (IL)‐36γ/IL‐37 ratio in the SC. Among the representative sebum lipids examined, oleic acid (C18:1, cis‐9) dose‐ and time‐dependently regulated the mRNA expression of IL‐36γ and IL‐37 in cultured keratinocytes, and this effect was attenuated by the N‐methyl‐D‐aspartate (NMDA)‐type glutamate receptor antagonist, MK801. Conclusions: Skin surface sebum may be related to cheek redness in healthy subjects, and oleic acid‐induced IL‐36γ through NMDA‐type glutamate receptors may be a link between them. Our study provides a possible skincare strategy for mitigating unfavorable increase in skin redness by targeting the facial skin sebum, particularly oleic acid. [ABSTRACT FROM AUTHOR]

A remote electronic effect of chiral aminoindanol‐derived N‐heterocyclic carbene catalyst on an asymmetric benzoin reaction was investigated. The catalyst bearing remote electron‐withdrawing substituents increased enantioselectivity of the reaction at the cost of the reaction rate. DFT calculations rationalized the increased enantioselectivity. [ABSTRACT FROM AUTHOR]

Background: The molecular pathogenesis of atopic dermatitis (AD), presenting skin barrier dysfunction and abnormal inflammations around 1–2 months, is unreported. Objective: We aimed to examine the molecular pathogenesis of very early‐onset AD by skin surface lipid‐RNA (SSL‐RNA) using a non‐invasive technology in infants aged 1 and 2 months from a prospective cohort. Methods: We collected sebum by oil‐blotting film of infants aged 1 and 2 months and analysed RNAs in their sebum. We diagnosed AD according to the United Kingdom Working Party's criteria. Results: Infants with AD aged 1 month showed lower expression of genes related to various lipid metabolism and synthesis, antimicrobial peptides, tight junctions, desmosomes and keratinization. They also had higher expression of several genes involved in Th2‐, Th17‐ and Th22‐type immune responses and lower expression of negative regulators of inflammation. In addition, gene expressions related to innate immunity were higher in AD infants. Infants aged 1 month with neonatal acne and diagnosed with AD aged 2 months already had gene expression patterns similar to AD aged 1 month in terms of redox, lipid synthesis, metabolism and barrier‐related gene expression. Conclusion: We identified molecular changes in barrier function and inflammatory markers that characterize the pathophysiology of AD in infants aged 1 month. We also revealed that neonatal acne at 1 month could predict the subsequent development of AD by sebum transcriptome data. [ABSTRACT FROM AUTHOR]

Chronic thromboembolic pulmonary hypertension (CTEPH) is a group 4 pulmonary hypertension (PH) characterized by nonresolving thromboembolism in the central pulmonary artery and vascular occlusion in the proximal and distal pulmonary artery. Medical therapy is chosen for patients who are ineligible for pulmonary endarterectomy or balloon pulmonary angioplasty or who have symptomatic residual PH after surgery or intervention. Selexipag, an oral prostacyclin receptor agonist and potent vasodilator, was approved for CTEPH in Japan in 2021. To evaluate the pharmacological effect of selexipag on vascular occlusion in CTEPH, we examined how its active metabolite MRE-269 affects platelet-derived growth factor-stimulated pulmonary arterial smooth muscle cells (PASMCs) from CTEPH patients. MRE-269 showed a more potent antiproliferative effect on PASMCs from CTEPH patients than on those fromnormal subjects.DNAbinding protein inhibitor (ID) genes ID1 and ID3 were found by RNA sequencing and real-time quantitative polymerase chain reaction to be expressed at lower levels in PASMCs from CTEPH patients than in those from normal subjects and were upregulated by MRE-269 treatment. ID1 and ID3 upregulation by MRE-269 was blocked by co-incubation with a prostacyclin receptor antagonist, and ID1 knockdown by small interfering RNA transfection attenuated the antiproliferative effect of MRE-269. ID signaling may be involved in the antiproliferative effect of MRE-269 on PASMCs. This is the first study to demonstrate the pharmacological effects on PASMCs from CTEPH patients of a drug approved for the treatment of CTEPH. Both the vasodilatory and the antiproliferative effect of MRE-269 may contribute to the efficacy of selexipag in CTEPH. [ABSTRACT FROM AUTHOR]

Background and Aim: Direct‐acting antivirals (DAAs) have recently been developed to treat hepatitis C virus (HCV) infection. Additionally, interferon‐free DAA treatment has improved liver function and reduced the risk of hepatocellular carcinoma (HCC) following HCV eradication. Previous studies on HCV have focused mainly on the treatment rate and the risk of developing HCC, and less attention has been given to loss to follow‐up (LTFU) after DAA treatment. Therefore, the present study aimed to identify the definitive risk factors for LTFU after the start of DAA treatment. Methods: Between September 2017 and March 2022, 296 patients receiving glecaprevir and pibrentasvir for HCV infection were enrolled in this study. The incidence of LTFU following DAA treatment and the risk factors contributing to LTFU were identified using the patients' clinical characteristics. Results: In the present study, 75 patients (25.3%) interrupted their follow‐up visits. Multivariate logistic analysis revealed a history of injection drug use (hazard ratio [HR], 1.81; P = 0.017), treatment duration (8 weeks) (HR, 3.51; P = 0.0033), and age <70 years (HR, 1.9; P = 0.0422) as independent factors associated with LTFU after the start of DAA treatment. Conclusion: Young patients and those with injection drug use are likely to discontinue their follow‐up visits after the start of DAA treatment for HCV infection. Therefore, these patients require strict supervision. [ABSTRACT FROM AUTHOR]

During a single scan using computed tomography, an X‐ray tube orbits along a 360°‐circular path around the patient. A scan obtained using the half‐cylindrical type phantoms with a radiochromic film sandwiched in between reveals a pixel value map illustrating the two‐dimensional (2D) dose distribution. A three‐dimensional (3D) dose distribution can be obtained with a 360° rotation of the 2D dose map. This study evaluates the concept and methodology of creating a 3D dose map to develop a phantom with a radiochromic film for obtaining the 3D dose distribution. The coronal and axial plane dose distributions were also evaluated. A single scan computed tomography image obtained using a half‐cylindrical type of acrylic phantom with a sandwiched radiochromic film was studied. The diameters of the phantoms were 10 and 16 cm, and their lengths were 30 cm. A 2D image of the XR‐QA2 film was obtained using an image scanner and image processing software. A red channel image was used to obtain the 3D dose distribution using a computing platform. A pseudo color was applied to the red channel image from which cross‐sectional color images were obtained. Half of the cross‐sectional pixel data were rotated by 360° to generate the data for each axial plane. The image created was saved, and a 3D pixel value map was constructed. The dose measurement procedure for the 3D dose distribution was developed using half‐cylindrical acrylic phantoms with a radiochromic film. [ABSTRACT FROM AUTHOR]

To illuminate brittle and ductile fracturing of magma, we investigated bubble expansion and fracturing in two contrasting fluids: a Maxwell‐type viscoelastic fluid and a Bingham‐type yield‐strength fluid. Measurements of the complex shear modulus, G′ + iG″ (i is the imaginary unit), under small‐strain oscillation showed that both fluids are elastic (G′ > G″) with similar rigidity. Viscous behavior (G′ < G″) appeared at lower frequency in the Maxwell fluid but at larger strain in the Bingham fluid. When we injected air into the Maxwell fluid, bubbles expanded viscously at low flux, fractured in a brittle manner at high flux, and behaved transitionally at intermediate flux. In contrast, we observed no fracturing in the Bingham fluid. This demonstrates that the G′ > G″ condition is insufficient to infer that brittle fracturing can occur. Brittle fracturing of the Maxwell fluid occurred not at a critical strain rate but under decreasing strain rate and increasing stress. Plain Language Summary: The flow‐to‐fracture transition of magma is an essential process controlling eruption explosivity. This transition has been explained based on the linear Maxwell viscoelastic model: magma can flow slowly but breaks in a brittle manner under rapid deformation. The Bingham model represents another type of fluid‐solid transition: a material flows under a sufficiently large force but behaves elastically below this force. The present study investigates bubble growth and fracture by air injection in Maxwell‐type and Bingham‐type fluids, both having similar elasticity. We demonstrate that brittle fracture occurs in the Maxwell fluid at high air flux but never in the Bingham fluid. Detailed observations of the deformation until brittle fracture reveals a stress increase and strain rate decrease. The fracture onset is not determined by the critical strain rate, contrary to conventional brittle fragmentation criteria widely used in volcanology. These results will help improve brittle‐ductile transition models for complex fluids in volcanic eruptions. Key Points: Rapid air injection generated brittle fracture in a Maxwell fluid but not in a Bingham fluid, although they have similar elasticityThe observation of elasticity in small‐amplitude oscillation tests is not sufficient to infer that the fluid can fractureThe strain rate around a bubble decreased toward fracture, contrary to the conventional critical strain‐rate fracture criterion [ABSTRACT FROM AUTHOR]

A pharmacokinetics/pharmacodynamics (PK/PD) approach was used to determine the best empirical dosage regimen of cefazolin (CEZ) after intramuscular (IM) administration of CEZ in horses. Seven horses received a single IM or intravenous (IV) administration of CEZ of 5 mg/kg bodyweight (BW) according to a crossover design. CEZ plasma concentrations were measured using LC–MS/MS. The plasma concentrations in these seven horses and those of six other horses obtained in a previous study with an IV CEZ dose of 10 mg/kg were modelled simultaneously using NonLinear Mixed‐Effect modelling followed by Monte Carlo simulations to establish a rational dosage regimen. A 90% Probability of Target Attainment (PTA) for a PK/PD target of a free plasma concentration exceeding MIC90 (fT > MIC) for 40% of the dosing interval was set for selecting an effective dosing regimen. The typical half‐life of absorption and bioavailability after IM administration were 1.25 h and 96.8%, respectively. A CEZ dosage regimen of 5 mg/kg BW q12h IM administration achieved therapeutic concentrations to control both Streptococcus zooepidemicus and Staphylococcus aureus. For the same dose, the fT > MIC after IM administration was significantly longer than after IV administration, and the IM route should be favoured by clinicians for its efficiency and convenience. [ABSTRACT FROM AUTHOR]

The effect of N‐substituent of α‐hydroxyamides on the performance of chiral N‐heterocyclic carbene‐catalyzed kinetic resolution was examined. N‐tert‐Butyl‐α‐hydroxyamides provided the best performance and underwent enantioselective acylation with α‐bromo aldehyde by chiral N‐heterocyclic carbene/carboxylate anion co‐catalysis to realize kinetic resolution in high selectivity factor up to 128. [ABSTRACT FROM AUTHOR]

The shortwave direct radiative effect of dust, the difference between net shortwave radiative flux in a cloud free and cloud and aerosol free atmosphere, is typically estimated using forward calculations made with a radiative transfer model. However, estimates of the direct radiative effect made via this initial method can be highly uncertain due to difficultly in accurately describing the relevant optical and physical properties of dust used in these calculations. An alternative approach to estimate this effect is to determine the forcing efficiency, or the direct radiative effect normalized by aerosol optical depth. While this approach avoids the uncertainties associated with the initial method for calculating the direct effect, random errors and biases associated with this approach have not been thoroughly examined in literature. Here we explore biases in this observation‐based approach that are related to atmospheric water vapor. We use observations to show that over the Sahara Desert dust optical depth and column‐integrated atmospheric water vapor are positively correlated. We use three idealized radiative models of varying complexity to demonstrate that a positive correlation between dust and water vapor produces a positive bias in the dust forcing efficiency estimated via the observation‐based method. We describe a simple modification to the observation‐based method that correctly accounts for the correlation between dust and water vapor when estimating the forcing efficiency and use this method to estimate the instantaneous forcing efficiency of dust over the Sahara Desert using satellite data, obtaining −12.3 ± 6.68 to 20.9 ± 11.9 W m−2 per unit optical depth. Plain Language Summary: The presence of suspended dust in the Earth's atmosphere affects the planetary energy budget via the direct radiative effect, and researchers typically use radiative transfer models to quantify the magnitude of this effect. However calculations of the direct radiative effect made in this manner are highly uncertain due to a lack of precise knowledge of a number of relevant dust properties. An observation‐based approach that circumvents these challenges exists, yet uncertainties associated with this method have not been extensively investigated. Here we identify one physical mechanism that produces a bias when estimating the dust direct effect via the observational approach, which is the observed correlation between atmospheric water vapor and dust. We describe a simple solution to account for this effect in direct effect calculations and then use this corrected method along with data from satellites to estimate the dust direct effect over North Africa, finding a smaller value than what had been reported by earlier studies. Key Points: Biases in dust shortwave forcing efficiency estimated via observational methods arise due to solar aborption of water vaporAn observational method is described that accounts for potential biases in the dust shortwave forcing efficiencyWhen applied to data over North Africa we estimate the dust shortwave forcing efficiency to lie within in –12.3 to –20.9 W m−2 per unit optical depth [ABSTRACT FROM AUTHOR]

Summary: Background: For medication control in several jurisdictions, withdrawal time is the period of refrain from racing after drug administration. It is set by adding a safety period to an experimental detection time. However, there are no reports of statistical analyses of detection time for the determination of withdrawal time in flunixin meglumine‐treated horses. Objective: To analyse the population pharmacokinetics of flunixin in horses through the generation of a dataset for detection time statistical analysis and predictions via Monte Carlo simulation. Study design: Experimental study. Methods: Drug plasma and urine concentrations following single intravenous administration of flunixin 1.1 mg/kg bodyweight (BW) in 10 horses and multiple administration of q 24 hours for 5 days in 10 horses were measured using liquid chromatography with tandem mass spectrometry (LC‐MS/MS). Data were modelled using a nonlinear mixed effect model followed by Monte Carlo simulation. Irrelevant plasma concentration (IPC) and irrelevant urine concentration (IUC) were calculated using the Toutain approach. Detection times were obtained considering the time after the last administration for selected quantiles of 5000 hypothetical horses under the international screening limit (ISL) proposed by the International Federation of Horseracing Authorities (plasma: 1 ng/mL, urine; 100 ng/mL). Results: For a regimen of 1.1 mg/kg BW q 24 hours, the IPC and IUC values were 2.0 and 73.0 ng/mL respectively. Detection times in plasma above the ISL for 90% of simulated horses were estimated as 74 hours after a single 1.1 mg/kg dose administration, 149 and 199 hours after multiple doses over 5 days at either 24‐ or 12‐hour intervals respectively. Corresponding detection times in urine were 46, 68 and 104 hours respectively. Main limitation: Only female horses were investigated. Conclusions: Statistical detection times for different flunixin meglumine regimens indicated a delay of detection time in plasma after multiple administrations under ISL. [ABSTRACT FROM AUTHOR]

Background: Specimens for analysing the molecular pathology of skin disease are generally obtained through invasive methods, such as biopsy. However, less burdensome methods are desirable for paediatric patients. We recently established a method that comprehensively analyses RNA present in sebum (skin surface lipid–RNAs: SSL‐RNAs) using a next‐generation sequencer. Using this method, biological information can be obtained from the skin in a completely non‐invasive manner. Objectives: To verify the applicability of the SSL‐RNA method for analysis of paediatric skin and analyse the molecular pathology of mild‐to‐moderate atopic dermatitis (AD) in children. Methods: We collected sebum specimens from the whole faces of 23 healthy children and 16 children with mild‐to‐moderate AD (eczema area and severity index (EASI) score: 5.9 ± 2.6) ranging in age from 6 months to 5 years, using an oil‐blotting film. We then extracted SSL‐RNAs from the samples and performed an AmpliSeq transcriptomic analysis. Results: The expressions of genes related to keratinization (LCE, PSORS1C2, IVL and KRT17), triglyceride synthesis and storage (PLIN2, DGAT2 and CIDEA), wax synthesis (FAR2), ceramide synthesis (GBA2, SMPD3 and SPTLC3), antimicrobial peptides (DEFB1) and intercellular adhesion (CDSN), all of which are related to the skin barrier, are lower in children with AD than in healthy children. The children with AD also have higher expression of CCL17, a Th2‐cytokine and an increased Th2‐immune response as demonstrated by a gene set variation analysis. Moreover, KRT17 and CCL17 expression levels are significantly correlated with the EASI score. Conclusions: Molecular changes associated with abnormal immune responses and the epidermal barrier in children with mild‐to‐moderate AD can be determined using the SSL‐RNA method. This non‐invasive method could therefore be a useful means for understanding the molecular pathology of paediatric AD. [ABSTRACT FROM AUTHOR]

The risk of hepatocellular carcinoma (HCC) occurrence following hepatitis C virus (HCV) eradication has been previously reported, but the impact of HCV eradication on advanced HCC patient survival remains unclear. Therefore, the present study aimed to evaluate the effect of HCV eradication on the survival outcome of patients with advanced HCC treated with sorafenib. One hundred and three HCV‐related advanced HCC patients who were treated with sorafenib were enrolled in this study. Of these, 43 patients were administered antiviral therapy before sorafenib treatment (HCV eradication group), while 60 patients remained HCV‐infected (HCV non‐eradication group). We analysed the impact of HCV eradication on survival in advanced HCC treated with sorafenib. Median overall survival (OS) was significantly longer in the HCV eradication group than in the HCV non‐eradication group (24.0 months vs. 14.1 months; p = 0.001). Although there was no significant difference in the albumin‐bilirubin (ALBI) score at the start of treatment between the HCV eradication group and the non‐eradication group (p = 0.065), the ALBI score at 2 months after initiation of sorafenib treatment was significantly decreased in the HCV non‐eradication group (p < 0.001), but not in the HCV eradication group (p = 0.121). Multivariate logistic analysis revealed HCV eradication (hazard ratio [HR], 0.5; p = 0.006) and ALBI score at the start of treatment (HR, 2.47; p = 0.002) as factors that may contribute to OS. HCV eradication may serve an important role in the survival outcome of advanced HCC patients treated with sorafenib. [ABSTRACT FROM AUTHOR]

Background: Connexin is a basic molecule that forms gap junctions and undergoes localization changes to the cytoplasm in association with carcinogenesis. We aimed to investigate and clarify the significance of cytoplasmic Cx26 expression in gastric cancer. Methods: We included 87 patients with intestinal‐ and mix‐type gastric cancer and 111 patients with diffuse type gastric cancer who underwent surgery for gastric cancer between 1999 and 2006. Immunohistochemical staining for Cx26, β‐catenin, and Wnt3a was performed and analyses of the relationship to clinicopathological factors were conducted based on the Lauren classification. In an in vitro study, the gastric cancer cell lines MKN7, MKN74, and MKN45 were used to evaluate the proliferative capacity using the water‐soluble tetrazolium salt assay through forced expression of Cx26, and the relationship between Cx26 and β‐catenin was investigated using proximity ligation assay (PLA) and co‐immunoprecipitation. Additionally, functional analysis was performed by Cage analysis. Results: In this study, high cytoplasmic Cx26 expression was associated with favorable prognosis in intestinal‐ and mix‐type gastric cancer and could be an independent prognostic factor for overall survival. In terms of the mechanism, in in vitro experiments changes in Cx26 localization to the cytoplasm were shown to suppress the change of localization of β‐catenin to the nucleus by binding to it in the cytoplasm. Conclusions: Cytoplasmic Cx26 was found to be a prognostic factor in intestinal‐ and mix‐type gastric cancer. Regarding the mechanism, in vitro studies revealed that cytoplasmic Cx26 inhibits the translocation of β‐catenin to the nucleus. [ABSTRACT FROM AUTHOR]

Here we present observations of a dust storm that occurred on 22 February 2020 in the northwestern Sonoran Desert. In‐situ and remotely sensed measurements and output from numerical simulations suggest that evaporative cooling from cold frontal orographic precipitation spilling over an upwind mountain range generated a density current, with dust uplift occurring as the density current traveled over the emissive desert surface. Because the density current was laden with dust, time series of vertical profiles of aerosol backscatter and extinction from a ceilometer located 25 km downwind of the initial dust emission event show a well‐developed density current structure, including an overturning frontal head with a vertical extent of 1.2 km. Ceilometer measurements and soundings suggest a density current body depth of 400–500 m exhibiting a two‐layer structure that consisted of a positively sheared and dusty lower‐level, and a negatively sheared and pristine upper level. Kelvin‐Helmholtz instability at the top of the density current cold pool generated quasi‐regular oscillations in the height of the dust and pristine‐sky interfacial layer. Ridges and troughs in the height of this interfacial layer were coupled to maxima and minima in surface wind speed and near surface dust concentrations, respectively, with peak dust concentrations located directly under the interfacial layer ridges. These results corroborate several findings from model studies of dust emission and transport by density currents, and suggest that the internal circulation of a density current modifies the timing of dust emission and the patterns of dust concentration within the current body. Plain Language Summary: Here we discuss the case of a unique dust storm that occurred in the western end of the Sonoran Desert. Remote sensing and in‐situ measurements are used to demonstrate that the dust storm was generated by a density current. Lidar backscatter measurements during passage of this density current over a research site in the region are used to trace the path of dust laden air through the density current head and body, and reveal the internal circulation of this feature. These observational results corroborate findings from modeling studies of dust emission and transport by density currents, but also suggest a complex distribution of dust within the density current body. Key Points: Measurements of a dust storm in the western Sonoran Desert that was generated by a density current are presentedThe density current exhibits a 2‐layer internal circulation with a lower dusty layer and an upper pristine layerThese observations corroborate several findings from numerical simulations of dust emission and transport by density currents [ABSTRACT FROM AUTHOR]

Chiral C2‐symmetric 3,3′‐bisaminomethyl‐binaphthol (AMB) is an organocatalyst for the asymmetric epoxidation of trisubstituted acrylonitriles. Using cumene hydroperoxide (CHP) as an oxidant, 3,3′‐bis((R,R)‐2‐phenylethylaminomethyl)‐(R)‐binaphthol (AMB2) catalyzed epoxidation of trans‐2‐aroyl‐3‐arylacrylonitriles at −30 °C to give the chiral epoxides as a single diastereomer with enantioselective manner ranging from 15% ee to 97% ee. [ABSTRACT FROM AUTHOR]

Background & Aims: Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is a rare neuroendocrine neoplasm (NEN) comprising dual neuroendocrine and non-neuroendocrine components. Although the coexistence pattern of neuroendocrine and non-neuroendocrine components in definitive MiNEN is thought to overlap, there may be a coexistent pattern of both components, such as superficial carcinoma adjacent to NEN. The present study evaluated the histopathological findings of the coexistence pattern of superficial carcinomas adjacent to NENs in the esophagogastrointestinal tract. Methods: From 2000 to 2019, 35 serial NEN resections of the esophagus (n = 9), stomach (n = 3), and large intestine (n = 23), respectively, were performed at Gunma University Hospital. Borderline areas between NEN and resident superficial epithelium were observed in the 35 serial NEN cases as well as two additional cases from affiliated hospitals. Results: Among the 35 serial NEN samples, squamous cell carcinomatous/dysplastic components were identified 77.8% (7/9 cases) of esophageal NENs, and adenocarcinomatous areas were seen in 66.7% (2/3 cases) of gastric NENs and 26% (6/23 cases) of colorectal NENs. Thus, all superficial carcinomatous components adjacent to NENs were observed as squamous cell carcinoma/dysplasia in esophagus and adenocarcinoma in stomach and large intestine, which showed histological characteristics as the resident epithelial pattern in each organ. Conclusions: These findings suggested a potential "paratransformation" or "bystander effect" in resident epithelium by NENs. Thus, "bystander carcinogenesis" could be a pathogenic mechanism of resident epithelium transformation adjacent to NENs in the esophagogastrointestinal tract. [ABSTRACT FROM AUTHOR]

Direct‐acting antivirals (DAAs) have recently been developed to treat hepatitis C virus (HCV) infection, and interferon‐free DAA treatment has improved liver function of HCV patients. The risk of hepatocellular carcinoma (HCC) occurrence following HCV eradication has been previously reported, but HCC may have been missed following imaging diagnosis before DAA administration in previous studies. Therefore, the present study aimed to identify definite predictors of HCC occurrence ≥1 year after DAA treatment. Among 956 patients receiving DAAs for HCV infection, 567 patients who achieved sustained virologic response with no history of HCC treatment were enrolled in this study between September 2014 and July 2021. The incidence of HCC in HCV‐infected patients ≥1 year following DAA treatment, and the predictors contributing to HCC occurrence were identified using clinical characteristics and blood test results. In the present study, 25 patients developed HCC. The incidence of HCC was 1.4%, 3.2%, 4.9% and 6.8% at 2, 3, 4 and 5 years, respectively, from the end of treatment with DAAs. Multivariate logistic analysis revealed serum α‐fetoprotein level at end of treatment (EOT‐AFP) >3.8 ng/ml ≥1 year following treatment with DAAs (HR, 9.7; p <.0001) as an independent factor that may contribute to HCC occurrence following DAA treatment. In conclusion, serum EOT‐AFP level may serve an important role in determining the risk of HCC occurrence ≥1 year after DAA treatment. Regular examinations are required even if serum EOT‐AFP level is low at treatment completion. [ABSTRACT FROM AUTHOR]

Background: Infantile hemangioma (IH), formerly termed strawberry hemangioma, is a benign vascular tumor caused by capillary endothelial cell proliferation. The tumor regresses after 1 year of age, but sequelae occur in approximately half of the patients without systemic treatment. Propranolol (PPL) is currently the first-line therapeutic agent in Japan as well as in Western countries. It is not commonly known that PPL may induce severe hypoglycemia, in addition to cardiovascular and respiratory side effects. Methods: We retrospectively analyzed patients with severe PPL-induced hypoglycemia in the 3 years since the launch of Hemangiol®, a PPL preparation specific for IH, in Japan in 2016. Results: The incidence of severe hypoglycemia and of hypoglycemic convulsions following PPL treatment was estimated to be 0.54% and 0.35%, respectively. The incidence of hypoglycemic convulsions appeared to be higher in Japan than in Western countries. Severe hypoglycemia was common in infants aged >1 year, when PPL was used for ≥6 months. Severe hypoglycemia often develops from 05:00 a.m. to 09:00 a.m. and is frequently associated with prolonged periods of fasting, poor feeding, or poor physical conditions. Conclusion; To avoid the risk of hypoglycemia, the treatment should be initiated by 6 months of age during the proliferative phase at the latest, and should not be extended indiscriminately beyond 1 year of age. Guardians should be advised not to administer PPL on an empty stomach, in the presence of poor feeding, or who are in poor physical condition, not to prolong fasting after PPL administration, and to monitor the child's condition immediately after he or she wakes up. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is characterized by devastating and progressive lung parenchymal fibrosis, resulting in poor patient prognosis. An aberrant recapitulation of developmental lung gene expression, including genes for transforming growth factor (TGF)‐β and WNT, has been widely implicated in the pathogenic IPF wound healing process that results from repetitive alveolar epithelial injury. Extracellular vesicles (EVs) have been shown to carry bioactive molecules and to be involved in various physiological and pathological processes. Here, we demonstrate that, by attenuating WNT signalling, human bronchial epithelial cell‐derived EVs (HBEC EVs) inhibit TGF‐β mediated induction of both myofibroblast differentiation and lung epithelial cellular senescence. This effect of HBEC EVs is more pronounced than that observed with mesenchymal stem cell‐derived EVs. Mechanistically, the HBEC EV microRNA (miRNA) cargo is primarily responsible for attenuating both myofibroblast differentiation and cellular senescence. This attenuation occurs via inhibition of canonical and non‐canonical WNT signalling pathways. Among enriched miRNA species present in HBEC EVs, miR‐16, miR‐26a, miR‐26b, miR‐141, miR‐148a, and miR‐200a are mechanistically involved in reducing WNT5A and WNT10B expression in LFs, and in reducing WNT3A, WNT5A, and WNT10B expression in HBECs. Mouse models utilizing intratracheal administration of EVs demonstrate efficient attenuation of bleomycin‐induced lung fibrosis development accompanied by reduced expression of both β‐catenin and markers of cellular senescence. These findings indicate that EVs derived from normal resident lung HBECs may possess anti‐fibrotic properties. They further suggest that, via miRNA‐mediated inhibition of TGF‐β‐WNT crosstalk, HBEC EVs administration can be a promising anti‐fibrotic modality of treatment for IPF. [ABSTRACT FROM AUTHOR]

We herein report a case of allergic bronchopulmonary aspergillosis (ABPA) that occurred in a man treated with adalimumab for ankylosing spondylitis (AS). A 69‐year‐old man with a history of ankylosing spondylitis treated by adalimumab, an anti‐tumour necrosis factor‐α (TNF‐α) antibody, developed cough and wheezing. Chest computed tomography showed obstruction of dilated left upper lobe bronchus by high attenuation mucus as well as central bronchiectasis. Both Aspergillus‐specific immunoglobulin E (IgE) and Aspergillus precipitating antibody were positive and Aspergillus fumigatus was detected in a sputum culture. According to the new diagnostic criteria, the patient was diagnosed with ABPA. His condition rapidly improved after the withdrawal of adalimumab and initiation of prednisolone and itraconazole. Anti‐TNF‐α antibody might cause ABPA through both aggravation of the host's T‐helper 2 immunological response and anti‐fungal response. [ABSTRACT FROM AUTHOR]

The clinical manifestations of COVID‐19 vary broadly, ranging from asymptomatic infection to acute respiratory failure and death. But the predictive biomarkers for characterizing the variability are still lacking. Since emerging evidence indicates that extracellular vesicles (EVs) and extracellular RNAs (exRNAs) are functionally involved in a number of pathological processes, we hypothesize that these extracellular components may be key determinants and/or predictors of COVID‐19 severity. To test our hypothesis, we collected serum samples from 31 patients with mild COVID‐19 symptoms at the time of their admission for discovery cohort. After symptomatic treatment without corticosteroids, 9 of the 31 patients developed severe/critical COVID‐19 symptoms. We analyzed EV protein and exRNA profiles to look for correlations between these profiles and COVID‐19 severity. Strikingly, we identified three distinct groups of markers (antiviral response‐related EV proteins, coagulation‐related markers, and liver damage‐related exRNAs) with the potential to serve as early predictive biomarkers for COVID‐19 severity. As the best predictive marker, EV COPB2 protein, a subunit of the Golgi coatomer complex, exhibited significantly higher abundance in patients remained mild than developed severe/critical COVID‐19 and healthy controls in discovery cohort (AUC 1.00 (95% CI: 1.00‐1.00)). The validation set included 40 COVID‐19 patients and 39 healthy controls, and showed exactly the same trend between the three groups with excellent predictive value (AUC 0.85 (95% CI: 0.73‐0.97)). These findings highlight the potential of EV COPB2 expression for patient stratification and for making early clinical decisions about strategies for COVID‐19 therapy. [ABSTRACT FROM AUTHOR]

Interleukin (IL)‐17 plays critical roles in the pathogenesis of both psoriasis and interstitial pneumonia (IP). We hypothesized that anti‐IL‐17 biologics might suppress both clinically relevant and latent IP activity and decrease Krebs von den Lungen‐6 (KL‐6) level in psoriasis patients. We aimed to elucidate the effects of anti‐IL‐17 biologics on KL‐6 levels. We retrospectively analyzed the clinical data of psoriasis patients treated with anti‐IL‐17 biologics. KL‐6 levels were measured before treatment (baseline) and at 3 and 6 months after the initiation of the treatment, and ratios of KL‐6 levels at each time point to the baseline levels were calculated. Chest computed tomography (CT) was performed on patients with coexisting IP. The clinical characteristics and radiographic findings were evaluated. A total of 294 psoriasis patients were treated with anti‐IL‐17 biologics. Baseline KL‐6 levels were higher than 401 U/mL in 34 patients (high baseline KL‐6 group). While anti‐IL‐17 biologics did not affect KL‐6 levels and ratios of KL‐6 to the baseline levels at any time point in the overall study population, they decreased both KL‐6 levels and ratios at 6 months after the initiation of the treatment in the high baseline KL‐6 group. A total of 10 patients with coexisting IP showed decreasing ratios of KL‐6 to the baseline levels at 6 months without affecting coexisting IP in CT performed at 3–12 months. Anti‐IL‐17 biologics decreased KL‐6 levels in the high baseline KL‐6 group regardless of recognizable IP. A decrease in KL‐6 levels was not associated with a radiographic improvement of IP, which should be examined in large numbers with long‐term observations in future studies. [ABSTRACT FROM AUTHOR]

A stable, hypervalent cyclic dibenzoiodolium salt acted as a strong halogen bonding (XB)-donor catalyst for [4+2] cycloaddition of 2-alkenylindoles, and not as an oxidizing agent. The cross-[4+2] cycloaddition of 2-vinylindoles with 2-alkenylindoles was catalyzed smoothly by the hypervalent cyclic dibenzoiodolium triflate catalyst to give the tetrahydrocarbazoles in up to 99% yield with 17:1 diastereoselectivity. The hypervalent cyclic dibenzoiodolium salt was also applicable to the Povarov reaction of 2-vinylindole with N-p-methoxyphenyl (PMP) imine to give the indolyl-tetrahydroquinoline in 83% yield. [ABSTRACT FROM AUTHOR]

Nivolumab, a human monoclonal antibody against programmed death‐1, is approved for the treatment of non–small cell lung cancer (NSCLC). Although nivolumab is generally well tolerated, it can cause interstitial lung disease (ILD), a rare but potentially fatal immune‐related adverse event. Currently, there are limited data available on the treatment of nivolumab‐induced ILD and its outcome. This retrospective cohort study based on a post–marketing study described the treatment of nivolumab‐induced ILD and its outcome in NSCLC patients in Japan through the assessment of clinical and chest imaging findings by an expert central review committee. Treatment details for patients who experienced a relapse of ILD were also analyzed. Of the 238 patients identified as having nivolumab‐induced ILD, 37 patients died of ILD. Corticosteroids were used in 207 (87.0%) patients. Of those, 172 (83.1%) patients responded well and survived and 35 (16.9%) died (most died during corticosteroid treatment). A total of nine patients experienced a relapse; at the time of relapse, four patients were taking nivolumab. Of those who were receiving corticosteroids at the time of relapse, three of four patients were taking low doses or had nearly completed dose tapering. All patients (except one, whose treatment was unknown) received corticosteroids for the treatment of relapse, but one patient died. Patients with NSCLC who experience nivolumab‐induced ILD are treated effectively with corticosteroids, and providing extra care when ceasing or reducing the corticosteroid dose may prevent relapse of ILD. [ABSTRACT FROM AUTHOR]

Nivolumab can cause interstitial lung disease (ILD), which may be fatal; however, mortality risk factors have not been identified. This postmarketing study evaluated the poor prognostic factors of ILD in nivolumab‐treated patients with non–small cell lung cancer (NSCLC) in Japan. Clinical and chest imaging findings for each ILD case were assessed by an expert central review committee, and prognosis was evaluated by radiographic findings, including the presence/absence of peritumoral ground‐glass opacity (peritumoral‐GGO). Poor prognostic factors were identified by univariate and multivariate Cox regression analysis. Of the 238 patients with nivolumab‐induced ILD, 37 died. The main radiographic patterns of ILD were cryptogenic organizing pneumonia/chronic eosinophilic pneumonia–like (53.4%), faint infiltration pattern/acute hypersensitivity pneumonia–like (20.2%), diffuse alveolar damage (DAD)‐like (10.9%), and nonspecific interstitial pneumonia–like (6.3%). The main poor prognostic factors identified were DAD‐like pattern (highest hazard ratio: 10.72), ≤60 days from the start of nivolumab treatment to the onset of ILD, pleural effusion before treatment, lesion distribution contralateral or bilateral to the tumor, and abnormal change in C‐reactive protein (CRP) levels. Of the 37 deaths due to ILD, 17 had DAD‐like radiographic pattern, three had peritumoral‐GGO, and five had a change in radiographic pattern from non‐DAD at the onset to DAD‐like. Patients with NSCLC who develop ILD during nivolumab treatment should be managed carefully if they have poor prognostic factors such as DAD‐like radiographic pattern, onset of ILD ≤60 days from nivolumab initiation, pleural effusion before nivolumab treatment, lesion distribution contralateral or bilateral to the tumor, and abnormal changes in CRP levels. [ABSTRACT FROM AUTHOR]

Background: Patients with non‐small cell lung cancer (NSCLC) harboring activating EGFR mutations are sensitive to epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs) but inevitably develop resistance to the inhibitors mostly through acquisition of the secondary T790M mutation. Although third‐generation EGFR‐TKIs overcome this resistance by selectively inhibiting EGFR with EGFR‐TKI‐sensitizing and T790M mutations, acquired resistance to third‐generation EGFR‐TKIs invariably develops. Methods: Next‐generation sequencing (NGS) and fluorescence in situ hybridization (FISH) analysis were performed in an EGFR T790M‐mutated NSCLC patient who had progressed after a third‐generation EGFR‐TKI, TAS‐121. EGFR‐mutated cell lines were subjected to a cell proliferation assay and western blotting analysis with EGFR‐TKIs and a heat shock protein 90 (HSP90) inhibitor. Results: NGS and FISH analysis revealed EGFR amplification in the resistant cancer cells. While EGFR L858R/T90M‐mutated cell line was sensitive to osimertinib or TAS‐121 in vitro, EGFR‐overexpressing cell lines displayed resistance to these EGFR‐TKIs. Western blot analysis showed that EGFR phosphorylation and overexpression of EGFR in cell lines was not suppressed by third‐generation EGFR‐TKIs. In contrast, an HSP90 inhibitor reduced total and phosphorylated EGFR and inhibited the proliferation of resistant cell lines. Conclusions: EGFR amplification confers resistance to third‐generation EGFR‐TKIs which can be overcome by HSP90 inhibition. The results provide a preclinical rationale for the use of HSP90 inhibitors to overcome EGFR amplification‐mediated resistance. [ABSTRACT FROM AUTHOR]

The use of high-dose corticosteroids or immunosuppressants for these patients may help treat GVHD-like adverse events; however, these therapies predispose the patients to infections and other steroid-related adverse effects. 8 Yatsuzuka K, Tohyama M, Oda F, Hashimoto T, Sayama K. Case of thymoma-associated cutaneous graft-versus-host disease-like disease successfully improved by narrowband ultraviolet B phototherapy. Additionally, photochemotherapy restores Tregs, resolving the Th17/Treg imbalance.5 Thus, since the number of Tregs is reduced and not in their usual immunological state in patients with thymoma-associated GVHD-like disease, it is hypothesized that photochemotherapy may play a similar role in these patients as is observed in psoriasis. [Extracted from the article]

We have developed a piezoelectric acoustic sensor that responds to rodents' audible frequency range as a front‐end device for a small hearing prosthesis system appropriate for animal experiments. The proposed piezoelectric transducer uses a biomimetic hearing mechanism that mimics bandpass‐filtering functions realized biologically in the cochlear membranes and hair cells of rodents via a frequency‐selective piezoelectric cantilever beam array that will be used to stimulate auditory neurons in future applications to humans. First, to examine the frequency selectivity and response sensitivity, a piezoelectric acoustic transducer having a cantilever array structure with multiple beams were designed, and the mechanical resonance properties of the sensor‐device structure were analyzed using a numerical calculation method. Next, on the basis of the numerical results, we proposed a practical acoustic sensor design and sensor construction method using a multiple cantilever array structure and piezoelectric material. We built the sensor using standard microfabrication techniques and evaluated its piezoelectric properties in terms of sound sensitivity. Finally, we addressed future applications of an integrated system containing the proposed acoustic sensor, which could be combined with an electrical stimulation system and used as an auditory prosthesis system to compensate hearing losses in rodent models with hearing disorders and diseases. © 2020 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC. [ABSTRACT FROM AUTHOR]

Background: Dementia in people with intellectual disabilities (IDs) is difficult to detect because of preexisting cognitive deficits. An effective screening method is required. The Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID) was developed as an observer rating tool to screen dementia in people with ID. The aim of this study was to verify the screening accuracy of the DSQIID for Japanese people with ID. Methods: Four‐hundred ninety‐three subjects with ID participated in this study. Caregivers who had observed the participants for more than 2 years scored the Japanese version of the DSQIID (DSQIID‐J) of the participants. Three doctors examined participants directly and diagnosed dementia using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. To identify the key screening items that predict dementia, the specificities of a single and pairs of items with 100% sensitivity were evaluated relative to the dementia diagnosis. Results: Of 493 participants, 34 were people with Down syndrome (DS), and 459 were people without DS. Seventeen participants were diagnosed with dementia. The suitable cut‐off score of the DSQIID‐J was 10/11 (sensitivity 100% and specificity 96.8%) for screening dementia. The inter‐rater reliability, test–retest reliability and internal consistency of the DSQIID‐J were excellent. Regarding key items, there was no single item with 100% sensitivity, and the best two‐item combination was the pair of 'Cannot dress without help' and 'Walks slower' (sensitivity 100% and specificity 93.5%). Conclusions: We identified several important question items of the DSQIID‐J related to the diagnosis of dementia in people with ID. The DSQIID‐J is a useful screening tool for dementia in adults with ID. [ABSTRACT FROM AUTHOR]

Aim: Hikikomori, a form of pathological social withdrawal, has been suggested to have comorbidity with autism spectrum disorder (ASD). This study aimed to clarify how characteristics of hikikomori are associated with ASD, including undiagnosed autism spectrum conditions (ASC), in clinical settings. Methods: A total of 416 clinical patients were recruited through the Mood Disorder/Hikikomori Clinic at Kyushu University Hospital. A total of 103 hikikomori cases and 221 clinical controls without hikikomori conditions were extracted using a semi‐structured interview, and completed a series of self‐rated scales, including the Japanese version of the Autism‐Spectrum Quotient (AQ‐J). Results: Compared to non‐hikikomori controls, hikikomori cases were more likely to have higher autistic tendency based on the AQ‐J. The cases showed more severe subjective depressive symptoms based on the self‐rated Beck Depression Inventory II, whereas no significant difference was found on interview‐based severity evaluation using the Hamilton Depression Rating Scale. Comparison within hikikomori cases based on the AQ‐J cut‐off score revealed that hikikomori cases with high ASC were significantly more likely to have higher traits of modern‐type depression, smaller social networks, and less social support. Conclusion: The present data suggest that hikikomori sufferers are more likely to have autistic tendency, and that hikikomori sufferers with high ASC may have much more difficulty in social communication and social interaction. In addition, those with high ASC may also have lower self‐esteem and higher complaint tendencies as aspects of modern‐type depression traits, which may relate to the occurrence of hikikomori. Thus, evaluating autistic tendencies is important for appropriate interventions in hikikomori. Further investigations should be conducted to validate our pilot findings using structured diagnostic systems of ASD. [ABSTRACT FROM AUTHOR]

Chaperone‐mediated autophagy (CMA) is a lysosomal degradation pathway of selective soluble proteins. Lysosome‐associated membrane protein type 2a (LAMP2A) is the key receptor protein of CMA; downregulation of LAMP2A leads to CMA blockade. Although CMA activation has been involved in cancer growth, CMA status and functions in non–small cell lung cancer (NSCLC) by focusing on the roles in regulating chemosensitivity remain to be clarified. In this study, we found that LAMP2A expression is elevated in NSCLC cell lines and patient's tumors, conferring poor survival and platinum resistance in NSCLC patients. LAMP2A knockdown in NSCLC cells suppressed cell proliferation and colony formation and increased the sensitivity to chemotherapeutic drugs in vitro. Furthermore, we found that intrinsic apoptosis signaling is the mechanism of cell death involved with CMA blockade. Remarkably, LAMP2A knockdown repressed tumorigenicity and sensitized the tumors to cisplatin treatment in NSCLC‐bearing mice. Our discoveries suggest that LAMP2A is involved in the regulation of cancer malignant phenotypes and represents a promising new target against chemoresistant NSCLC. [ABSTRACT FROM AUTHOR]

Here we test the precursory enhancement in ionospheric total electron content (TEC) which has been reported by Heki (2011, https://doi.org/10.1029/2011GL047908) and numerous Global Navigation Satellite System (GNSS) TEC observational studies before the 2011 Mw9.0 Tohoku‐Oki and many great earthquakes. We verify the frequency of this TEC enhancement via analysis of a 2‐month vertical TEC (VTEC) time series that includes the Tohoku‐Oki earthquake using the procedure, based on Akaike's information criterion, and threshold of Heki and Enomoto (2015, https://doi.org/10.1002/2015JA021353). The averaged occurrence rate of the TEC enhancement is much larger than that reported by Heki and Enomoto (2015, https://doi.org/10.1002/2015JA021353) when all of the visible GPS satellites at a given station are taken into account. The frequency assessment by Heki and Enomoto (2015, https://doi.org/10.1002/2015JA021353) using only one satellite underestimates the frequency of the TEC enhancement. In fact, the TEC enhancement is sufficiently frequent to explain all the reported enhancements prior to the great earthquakes as a product of chance. We also analyze the spatial distribution of the preseismic TEC enhancement and coseismic TEC depletion for the Tohoku‐Oki earthquake with the data after reducing intertrace biases. We observe significant postseismic depletion that lasted at least 2 h after the earthquake and extended at least 500 km around the center of the large‐slip area. This means that evaluation of the enhancements using reference curves which was adopted by Heki (2011, https://doi.org/10.1029/2011GL047908) and even by the recent papers (e.g., He & Heki 2016, https://doi.org/10.1002/2016GL069863; 2017, https://doi.org/10.1002/2017JA024012; 2018, https://doi.org/10.1029/2017JA024871) is in danger of mistaking a large and long‐lasting postseismic TEC depletion for a preseismic enhancement. Key Points: Ionospheric TEC enhancement occurs so often without earthquakes, which can explain the "precursors" as just a product of chanceA large TEC depletion spreading 500 km in diameter and lasting at least 120 min after the Tohoku‐Oki earthquakeExcluding window is in danger of mistaking the postseismic depletion for a preseismic enhancement [ABSTRACT FROM AUTHOR]

The non‐bonding electron pair (n‐pair) of heteroatoms and π‐electrons are both efficient halogen bond (XB) acceptors. In solid and gas phase studies, n‐pairs generally prevail over π‐bonding orbitals as XB acceptors, whereas few studies have been conducted regarding the preference in solution phase. Herein, the Povarov reaction via the C−I⋅⋅⋅N XB interaction and [4+2] cycloaddition via the C−I⋅⋅⋅π XB interaction were evaluated, revealing that the n‐pair was more dominant in the XB catalysis system in solution. The XB donor‐catalyzed Povarov reaction gave diverse indolyl‐tetrahydroquinoline derivatives in good yields. Synthesis of indolyl‐quinolines was also developed. [ABSTRACT FROM AUTHOR]

A newly developed dinuclear bis(benzylimino)binaphthol (BIB)−Pd complex showed good catalytic activity for the Mannich reaction of aldimines and isatin‐derived ketimines with alkylmalononitriles to give the products in a highly enantioselective manner. [ABSTRACT FROM AUTHOR]

The relationship between the local immune status and cancer metabolism regarding 18F‐FDG and 18F‐FAMT uptake in esophageal squamous cell carcinoma (ESCC) remains unknown. The present study examined the correlations between tumor immune status, clinicopathological factors, and positron emission tomography (PET) tracer uptake in ESCC. Forty‐one ESCC patients who underwent 18F‐FDG PET and 18F‐FAMT PET before surgery were enrolled in the study. Immunohistochemistry was conducted for programmed death 1 (PD‐1), CD8, Ki‐67, CD34, GLUT1 (18F‐FDG transporter) and LAT1 (18F‐FAMT transporter). ESCC specimens with high tumoral PD‐L1 and high CD8‐positive lymphocytes were considered to have "hot tumor immune status." High PD‐L1 expression (53.7%) was significantly associated with tumor/lymphatic/venous invasion (P = 0.028, 0.032 and 0.018), stage (P = 0.041), CD8‐positive lymphocytes (P < 0.001), GLUT1 (P < 0.001), LAT1 expression (P = 0.006), Ki‐67 labelling index (P = 0.009) and CD34‐positive vessel counts (P < 0.001). SUVmax of 18F‐FDG was significantly higher in high PD‐L1 cases than in low PD‐L1 cases (P = 0.009). SUVmax of 18F‐FAMT was significantly higher in high PD‐L1 (P < 0.001), high CD8 (P = 0.012) and hot tumor groups (P = 0.028) than in other groups. High SUVmax of 18F‐FAMT (≥4.15) was identified as the only predictor of hot tumor immune status. High PET tracer uptake was significantly associated with cancer aggressiveness and hot tumor immune status in ESCC. PET imaging may be an effective tool to predict tumor immune status in ESCC with respect to immune checkpoint inhibitor sensitivity. [ABSTRACT FROM AUTHOR]

Chiral organic base catalyst with halogen bond donor functionality catalyzed asymmetric Mannich‐type reaction of malononitrile with α‐ketiminoesters to produce α,α‐disubstituted α‐amino acid derivatives in good yields with high enantioselectivities. The malononitrile‐derived amino acid was smoothly transformed to chiral aminomalonate without loss of ee. [ABSTRACT FROM AUTHOR]

Background: There are only a few studies of the prevalence of dementia in people with intellectual disability (ID) without Down syndrome (DS), and there is a large difference in the prevalences between reported studies. Moreover, the prevalence of mild cognitive impairment (MCI) in ID has not been reported. We aimed to evaluate the prevalence of dementia in adults of all ages and the prevalence of MCI in people with ID. Furthermore, we tried to clarify the differences depending on the various diagnostic criteria. Methods: The survey included 493 adults with ID at 28 facilities in Japan. The caregivers answered a questionnaire, and physicians directly examined the participants who were suspected of cognitive decline. Dementia and MCI were diagnosed according to ICD‐10, DC‐LD, and DSM‐5 criteria. Results: The prevalence of dementia was 0.8% for the 45 to 54 years old group, 3.5% for the 55 to 64 years old group, and 13.9% for the 65 to 74 years old group in people with ID without DS. The prevalence of MCI was 3.1% for patients 45 to 54, 3.5% for patients 55 to 64, and 2.8% for patients 65 to 74 with ID without DS. DSM‐5 was the most inclusive in diagnosing dementia and MCI in people with ID. Conclusions: People with ID without DS may develop dementia and MCI at an earlier age and higher rate than the general population. Among the diagnostic criteria, DSM‐5 was the most useful for diagnosing their cognitive impairment. [ABSTRACT FROM AUTHOR]

Mucin is a glycoprotein that is the primary component of the mucus overlaying the epithelial tissues. Because mucin functions as a first line of the innate immune system, Pseudomonas aeruginosa appears to require interaction with mucin to establish infection in the host. However, the interactions between P. aeruginosa and mucin have been poorly understood. In this study, using in vivo expression technology (IVET), we attempted to identify mucin‐inducible promoters that are likely to be involved in the establishment of P. aeruginosa infection. The IVET analysis revealed that the genes encoding glycosidases, sulfatases, and peptidases that are thought to be required for the utilization of mucin as a nutrient are present in 13 genes downstream of the identified promoters. Our results indicated that, among them, sdsA1 encoding a secreted sulfatase plays a central role in the degradation of mucin. It was then demonstrated that disruption of sdsA1 leads to a decreased release of sulfate from mucin and sulfated sugars. Furthermore, the sdsA1 mutant showed a reduction in the ability of mucin gel penetration and an attenuation of virulence in leukopenic mice compared with the wild‐type strain. Collectively, these results suggest that SdsA1 plays an important role as a virulence factor of P. aeruginosa. [ABSTRACT FROM AUTHOR]

This article, titled "Cover Feature: Highly Electrophilic Intermediates in the Bypass Mechanism of Glutathione Peroxidase: Synthesis, Reactivity, and Structures of Selenocysteine-Derived Cyclic Selenenyl Amides," explores the role of selenocysteine cyclic selenenyl amides in the catalytic cycle of the antioxidant enzyme glutathione peroxidase (GPx). The study reveals that these intermediates, previously overlooked, have dual functionality. They not only prevent the inactivation of GPx but also act as highly electrophilic intermediates in selenoprotein reactions. The researchers compare the roles of these intermediates to a chess king, dynamically adapting to their application. [Extracted from the article]

Chiral benzazaborole‐catalyzed regioselective sulfonylations of unprotected carbohydrate derivatives have been developed. This methodology enables direct regioselective functionalization of the secondary OH group in carbohydrate in the presence of the primary OH group. By using the chiral organoboron catalysis, kinetic resolution of the carbohydrate derivatives was also achieved. [ABSTRACT FROM AUTHOR]

Chemotherapy has been the treatment of choice for unresectable peritoneal dissemination; however, it is difficult to eradicate such tumors because of poor drug delivery. To solve this issue, we developed FF‐10832 as liposome‐encapsulated gemcitabine to maintain a high concentration of gemcitabine in peritoneal tumors from the circulation and ascites. A syngeneic mouse model of peritoneal dissemination using murine Colon26 cell line was selected to compare the drug efficacy and pharmacokinetics of FF‐10832 with those of gemcitabine. Despite the single intravenous administration, FF‐10832 treatment enabled long‐term survival of the lethal model mice as compared with those treated with gemcitabine. Pharmacokinetic analysis clarified that FF‐10832 could achieve a more effective gemcitabine delivery to peritoneal tumors owing to better stability in the circulation and ascites. The novel liposome‐encapsulated gemcitabine FF‐10832 may be a curative therapeutic tool for cancer patients with unresectable peritoneal dissemination via the effective delivery of gemcitabine to target tumors. [ABSTRACT FROM AUTHOR]

A neutral bis(imidazolidine)pyridine (PyBidine)‐CoCl2 complex showed catalytic activity for the Michael reaction of malonates with nitroalkenes. The results indicated that a weak amine base aided enolate formation from the neutral complex, in which the N−H proton of the imidazolidine ligand played a significant role. [ABSTRACT FROM AUTHOR]

Aim: Understanding premorbid personality is important, especially when considering treatment selection. Historically, the premorbid personality of patients with major depression in Japan was described as Shuchaku‐kishitsu [similar to Typus melancholicus], as proposed by Shimoda in the 1930s. Since around 2000, there have been increased reports in Japan of young adults with depression who have had premorbid personality differing from the traditional type. In 2005, Tarumi termed this novel condition 'dysthymic‐type depression,' and more recently the condition has been called Shin‐gata/Gendai‐gata Utsu‐byo [modern‐type depression (MTD)]. We recently developed a semi‐structured diagnostic interview to evaluate MTD. Development of a tool that enables understanding of premorbid personality in a short time, especially at the early stage of treatment, is desirable. The object of this study was to develop a self‐report scale to evaluate the traits of MTD, and to assess the scale's psychometric properties, diagnostic accuracy, and biological validity. Methods: A sample of 340 participants from clinical and community settings completed measures. Psychometric properties were assessed with factor analysis. Diagnostic accuracy of the MTD traits was compared against a semi‐structured interview. Results: The questionnaire contained 22 items across three subscales, thus we termed it the 22‐item Tarumi's Modern‐Type Depression Trait Scale: Avoidance of Social Roles, Complaint, and Low Self‐Esteem (TACS‐22). Internal consistency, test–retest reliability, and convergent validity were all satisfactory. Among patients with major depression, the area under the curve was 0.757 (sensitivity of 63.1% and specificity of 82.9%) and the score was positively correlated with plasma tryptophan. Conclusion: The TACS‐22 possessed adequate psychometric properties and diagnostic accuracy in an initial sample of Japanese adults. Additional research on its ability to support clinical assessment of MTD is warranted. [ABSTRACT FROM AUTHOR]