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Background: Detecting and analyzing Alzheimer's disease (AD) in its early stages is a crucial and significant challenge. Speech data from AD patients can aid in diagnosing AD since the speech features have common patterns independent of race and spoken language. However, previous models for diagnosing AD from speech data have often focused on the characteristics of a single language, with no guarantee of scalability to other languages. In this study, we used the same method to extract acoustic features from two language datasets to diagnose AD., Methods: Using the Korean and English speech datasets, we used ten models capable of real-time AD and healthy control classification, regardless of language type. Four machine learning models were based on hand-crafted features, while the remaining six deep learning models utilized non-explainable features., Results: The highest accuracy achieved by the machine learning models was 0.73 and 0.69 for the Korean and English speech datasets, respectively. The deep learning models' maximum achievable accuracy reached 0.75 and 0.78, with their minimum classification time of 0.01s and 0.02s. These findings reveal the models' robustness regardless of Korean and English and real-time diagnosis of AD through a 30-s voice sample., Conclusion: Non-explainable deep learning models that directly acquire voice representations surpassed machine learning models utilizing hand-crafted features in AD diagnosis. In addition, these AI models could confirm the possibility of extending to a language-agnostic AD diagnosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that may have influenced the work reported in this article., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Most coronavirus vaccines focus on the spike (S) antigen, but the frequent mutations in S raise concerns about the vaccine efficacy against new variants. Although additional antigens with conserved sequences are have been tested, the extent to which these vaccines can provide immunity against different coronavirus species remains unclear. In this study, we assessed the potential of nucleocapsid (N) as a coronavirus vaccine antigen. Immunization with MERS-CoV N induced robust immune responses, providing significant protection against MERS-CoV. Notably, MERS-CoV N elicited cross-reactive T cell responses to SARS-CoV-2 N and significantly reduced lung inflammation following a SARS-CoV-2 challenge in the transient hACE2 mouse model. However, in K18-hACE transgenic mice, the vaccine showed limited protection. Collectively, our findings suggest that coronavirus N can be an effective vaccine antigen against homologous viruses, but its efficacy may vary across different coronaviruses, highlighting the need for further research on pan-coronavirus vaccines using conserved antigens., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: This study investigated how high-definition transcranial direct current stimulation (HD-tDCS) over the primary motor cortex (M1) affects brain signal variability and functional connectivity in the trigeminal pain pathway, and their association with changes in migraine attacks., Methods: Twenty-five episodic migraine patients were randomized for ten daily sessions of active or sham M1 HD-tDCS. Resting-state blood-oxygenation-level-dependent (BOLD) signal variability and seed-based functional connectivity were assessed pre- and post-treatment. A mediation analysis was performed to test whether BOLD signal variability mediates the relationship between treatment group and moderate-to-severe headache days., Results: The active M1 HD-tDCS group showed reduced BOLD variability in the spinal trigeminal nucleus (SpV) and thalamus, but increased variability in the rostral anterior cingulate cortex (rACC) compared to the sham group. Connectivity decreased between medial pulvinar-temporal pole, medial dorsal-precuneus, and the ventral posterior medial nucleus-SpV, but increased between the rACC-amygdala, and the periaqueductal gray-parahippocampal gyrus. Changes in medial pulvinar variability mediated the reduction in moderate-to-severe headache days at one-month post-treatment., Conclusions: M1 HD-tDCS alters BOLD signal variability and connectivity in the trigeminal somatosensory and modulatory pain system, potentially alleviating migraine headache attacks., Significance: M1 HD-tDCS realigns brain signal variability and connectivity in migraineurs closer to healthy control levels., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: This study aimed to investigate the effect of human adipose tissue derived stromal vascular fraction (AD-SVF) and mesenchymal stem cells (AD-MSCs) on blood flow recovery and neovascularisation in a rat hindlimb ischaemia model., Methods: SVF was isolated using an automated centrifugal system, and AD-MSCs were obtained from adherent cultures of SVF cells. Rats were divided into four groups of six rats each: non-ischaemia (Group 1); saline treated ischaemia (Group 2); SVF treated ischaemia (Group 3); and AD-MSC treated ischaemia (Group 4). Unilateral hindlimb ischaemia was induced in Sprague-Dawley rats via femoral artery ligation. Saline, SVF, or AD-MSCs were injected intramuscularly into the adductor muscle intra-operatively. Cell viability was calculated as the percentage of live cells relative to total cell number. Blood flow improvement, muscle fibre injury, and angiogenic properties were validated using thermal imaging and histological assessment., Results: The viabilities of SVF and AD-MSCs were 83.3% and 96.7%, respectively. Group 1 exhibited no significant temperature difference between hindlimbs, indicating a lack of blood flow changes. The temperature gradient gradually decreased in SVF and AD-MSC treated rats compared with saline treated rats. In addition, only normal muscle fibres with peripherally located nuclei were observed in Group 1. Groups 3 and 4 exhibited significantly fewer centrally located nuclei, indicating less muscle damage compared with Group 2. Regarding angiogenic properties, CD31 staining of endothelial cells showed similar patterns among all groups, whereas expression of vascular endothelial growth factor, as a crucial angiogenesis factor, was enhanced in the SVF and AD-MSC treated groups., Conclusion: SVF and AD-MSCs improved blood flow and neovascularisation in a rat hindlimb ischaemia model, suggesting their potential ability to promote angiogenesis. Further extensive research is warranted to explore their potential applications in the treatment of severe lower extremity arterial disease., (Copyright © 2023. Published by Elsevier B.V.)

The northeastern East China Sea is a highly dynamic marine ecosystem influenced by seasonally varying water mass properties. However, despite being among the world's fastest-warming ocean, there has been limited investigation into the impacts of warming on protistan communities. We collected seawater from two stations (E42 and E46) with different natural protist communities and environmental attributes to investigate the acclimation of the two communities to artificially elevated temperatures (ambient T, +2, and +4 °C). Nutrient and Chl-a conditions reflected oceanographic differences, providing insights into protistan community dynamics. Notably, small-sized autotrophic protists prevailed in the phosphate-deficient E42 community, with mid-incubation heterotrophic conversions. Higher temperatures exacerbated the effects of the P deficiency on the E42 community. While the proportions of Bacillariophyta increased only in the nutrient-balanced E46 communities, those of mixotrophic dinoflagellates increased with elevated temperature, regardless of P deficiency, suggesting that mixotrophy likely aids adaptation in changing marine environments. In summary, the findings of this microcosm study illuminate the potential modulation of spring protistan communities in the northeastern East China Sea under anticipated future warming., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Influenza epidemics are a significant cause of mortality and morbidity in older adults; thus, vaccination is recommended. However, the coronavirus disease 2019 (COVID-19) pandemic could affect influenza vaccination., Methods: The influenza vaccination rate was estimated from the Korea Community Health Survey data from 2011 to 2021 using Joinpoint regression. We used multiple logistic regression analysis from each two flu seasons data before (2017-18 and 2018-19 seasons) and during (2019-20 and 2020-21 seasons) the COVID-19 pandemic to identify older adults who were not been vaccinated during the COVID-19 pandemic. Additionally, we stratified changes in influenza vaccination according to the flu season, demographic and socioeconomic characteristics, and health status., Results: The annual percentage change in influenza non-vaccination rate from 2010-11 to 2018-19 seasons and from 2019-20 to 2020-21 seasons was -8.31% (confidence interval (CI), -9.60 to -7.00) and 11.41% (CI, -3.22 to 28.25), respectively. Compared to before COVID-19, in the 2019-20 and 2020-21 seasons, the odds ratio (OR) of non-vaccination was 0.87 (CI, 0.83-0.91) and 1.18 (95% CI, 1.13-1.24), respectively. The decrease in influenza vaccination among older individuals with higher education (OR, 1.24; CI, 1.11-1.39) was greater than that among those with lower education (OR, 1.09; CI, 0.98-1.22). Older individuals with the lowest income level or poor self-rated health showed reduced influenza vaccination., Conclusions: We estimated the trends of influenza vaccination and identified subgroups with decreased vaccination rates during the COVID-19 pandemic among older adults in South Korea. Health policy decision-makers, practitioners, and researchers should consider the implications of COVID-19 on changes in influenza vaccination, particularly for older individuals at risk of influenza., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Motor imagery (MI)-based brain-computer interfaces are widely employed for improving the rehabilitation of paralyzed people and their quality of life. It has been well documented that brain activity patterns in the primary motor cortex and sensorimotor cortex during MI are similar to those of motor execution/imagery. However, individuals paralyzed owing to various neurological disorders have debilitated activation of the motor control region. Therefore, the differences in brain activation based on the paralysis location should be considered. We analyzed brain activation patterns using the electroencephalogram (EEG) acquired while performing MI on the right upper limb to investigate hemiplegia-related brain activation patterns. Participants with hemiplegia of the right upper limb (n=7) and left upper limb (n=4) performed the MI task within the right upper limb. EEG signals were acquired using 14 channels based on a 10-20 global system, and analyzed for event-related desynchronization (ERD) based on event-related spectral perturbation and functional connectivity, using the weighted phase-lag index of both hemispheres at the location of hemiplegia. Enhanced ERD was found in the ipsilateral region, compared to the contralateral region, after MI of the affected limb. The reduced difference in the centrality of the channels was observed in all subjects, likely reflecting an altered brain network from increased interhemispheric connections. Furthermore, the tendency of distinct network-based features depending on the MI task on the affected limb was diluted between the inter-hemispheres. Analysis of interaction between inter-region using functional connectivity could provide avenues for further investigation of BCI strategy through the brain state of individuals with hemiplegia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

A method for the reciprocal space treatment of high-resolution transmission electron microscopy (HR-TEM) and high-resolution scanning transmission electron microscopy (HR-STEM) images has been developed. Named "Absolute strain" (AbStrain), it allows for quantification and mapping of interplanar distances and angles, displacement fields and strain tensor components with reference to a user-defined Bravais lattice and with their corrections from the image distortions specific to HR-TEM and HR-STEM imaging. We provide the corresponding mathematical formalism. AbStrain goes beyond the restriction of the existing method known as geometric phase analysis by enabling direct analysis of the area of interest without the need for reference lattice fringes of a similar crystal structure on the same field of view. In addition, for the case of a crystal composed of two or more types of atoms, each with its own sub-structure constraint, we developed a method named "Relative displacement" for extracting sub-lattice fringes associated to one type of atom and measuring atomic columns displacements associated to each sub-structure with reference to a Bravais lattice or to another sub-structure. The successful application of AbStrain and Relative displacement to HR-STEM images of functional oxide ferroelectric heterostructures is demonstrated., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Competing Interests: Declaration of Competing Interest Daniel J. Kim is on the medical advisory board of Clarius Mobile Health. The remaining authors disclose no conflicts.

Objectives: Although primary motor cortex (M1) transcranial direct current stimulation (tDCS) has an analgesic effect in fibromyalgia (FM), its neural mechanism remains elusive. We investigated whether M1-tDCS modulates a regional temporal variability of blood-oxygenation-level-dependent (BOLD) signals, an indicator of the brain's flexibility and efficiency and if this change is associated with pain improvement., Materials and Methods: In a within-subjects cross-over design, 12 female FM patients underwent sham and active tDCS on five consecutive days, respectively. Each session was performed with an anode placed on the left M1 and a cathode on the contralateral supraorbital region. The subjects also participated in resting-state functional magnetic resonance imaging (fMRI) at baseline and after sham and active tDCS. We compared the BOLD signal variability (SD BOLD ), defined as the standard deviation of the BOLD time-series, between the tDCS conditions. Baseline SD BOLD was compared to 15 healthy female controls., Results: At baseline, FM patients showed reduced SD BOLD in the ventromedial prefrontal cortex (vmPFC), lateral PFC, and anterior insula and increased SD BOLD in the posterior insula compared to healthy controls. After active tDCS, compared to sham, we found an increased SD BOLD in the left rostral anterior cingulate cortex (rACC), lateral PFC, and thalamus. After sham tDCS, compared to baseline, we found a decreased SD BOLD in the dorsomedial PFC and posterior cingulate cortex/precuneus. Interestingly, after active tDCS compared to sham, pain reduction was correlated with an increased SD BOLD in the rACC/vmPFC but with a decreased SD BOLD in the posterior insula., Conclusion: Our findings suggest that M1-tDCS might revert temporal variability of fMRI signals in the rACC/vmPFC and posterior insula linked to FM pain. Changes in neural variability would be part of the mechanisms underlying repetitive M1-tDCS analgesia in FM., (Copyright © 2022. Published by Elsevier Inc.)

Aims: Nonalcoholic fatty liver disease (NAFLD) is becoming more common and severe. Individuals with NAFLD have an altered composition of gut- microbial metabolites. We used metabolomics profiling to identify microbial metabolites that could indicate gut-liver metabolic severity. Noninvasive biomarkers are required for NAFLD, especially for patients at high risk of disease progression., Main Methods: We compared the stool metabolomes, untargeted metabolomics, and clinical data of 80 patients. Patients with nonalcoholic fatty liver (NAFL: n = 16), nonalcoholic steatohepatitis (NASH: n = 26), and cirrhosis (n = 19) and healthy control individuals (HC: n = 19) were enrolled. The identified metabolites in NAFLD were evaluated by multivariate statistical analysis and metabolic pathotypic expression. Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography coupled to time-of-flight-mass spectrometry (LC-TOF-MS) were used to analyze metabolites., Key Findings: Untargeted metabolomics was used to identify and quantify 103 metabolites. Principal component analysis (PCA) was used to assess the metabolic discrimination of NAFL, NASH, and cirrhosis. Short-chain fatty acids (SCFA) levels were significantly lower in NAFLD patients, including those of acetate (p = 0.03), butyrate (p = 0.0008), and propionate. The stool cholic acid (p = 0.001) level was significantly increased in NAFLD patients. Palmitoylcarnitine and l-carnitine levels were significantly increased in NASH and cirrhosis patients. The phenotypic expression of these metabolites was linked to β-oxidation., Significance: We demonstrated a distinct metabolome profile in NAFLD patients with NAFL, NASH, and cirrhosis. We also discovered that the expression of certain metabolites and metabolic pathways was linked to NAFLD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

This study aimed to quantitatively analyze the degree and vector of commissure excursion following intraoral orthodromic temporalis transfer. Patients with unilateral facial paralysis who underwent intraoral temporalis transfer were included. Intra-oral coronoidectomy was followed by submucosa tunneling through two vertical intraoral incisions to fixate the temporalis tendon to the perioral location. Oral commissure excursion, upper lip and commissure height differences, and smile angle were measured. Postoperatively, the symmetry of commissure excursion improved in repose (affected side: 114.6 ± 7.0 mm, non-affected side: 115.2 ± 4.9 mm, p = 0.134), while asymmetry arose in smiling (affected side: 30.7 ± 3.4 mm, non-affected side: 34.5 ± 4.4 mm, p = 0.001). Furthermore, the postoperative smile angle demonstrated insufficient vertical movement on the affected side during smiling (affected side: 115.6 ± 5.8°, non-affected side: 118.4 ± 4.9°, p = 0.002) but no significant difference in repose (p = 0.134). Within the limitations of the study it seems that intraoral orthodromic temporalis transfer yields excellent resting symmetry, but smile asymmetry may occur owing to insufficient oral commissure excursion. Nevertheless, as a minimally invasive surgery, this technique can obviate visible scars and benefit patients wishing for the same and can have excellent resting symmetry., (Copyright © 2023 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Recanalization in cerebral venous thrombosis (CVT) can begin as early as 1 week after initiating therapeutic anticoagulation. The clinical significance of recanalization remains uncertain., Objectives: We aimed to investigate the association between recanalization and functional outcomes and explored predictors of recanalization., Methods: A systematic literature search was conducted (EMBASE, MEDLINE, Cochrane library) to identify: (1) patients with CVT aged ≥18 years treated with anticoagulation only; (2) case series, cohort, or randomized controlled trial studies; and (3) reported recanalization rates and functional outcomes using either a modified Rankin Scale (mRS) or sequelae of CVT at last follow-up. Meta-analysis was performed using pooled odds ratios (ORs) with exploration of sex and age effects using meta-regression., Results: Twenty-three studies were eligible with 1418 individual patients in total. Timing of reimaging and clinical reassessment was variable. Absence of recanalization was associated with increased odds of an unfavorable functional outcome (mRS 2-6 versus 0-1; OR, 3.66; 95% CI, 1.73-7.74; p  = 0.001), CVT recurrence (OR, 8.81; 95% CI, 1.63-47.7; p  = 0.01), and chronic headache (OR, 2.78; 95% CI, 1.16-6.70; p  = 0.02). On meta-regression, the relationship between recanalization and mRS differed by the proportion of female patients, where lower proportions of women were associated with higher likelihood of a worse outcome, but not by mean participant age. There was no incremental benefit of full compared with partial recanalization with respect to favorable mRS or recurrence, but odds of chronic headache were higher with partial versus full recanalization (OR, 3.80; 95% CI, 1.43-10.11; p  = 0.008). Epilepsy and visual sequelae were not associated with recanalization., Conclusions: Absence of recanalization was associated with worse functional outcomes, CVT recurrence, and headache, but outcomes were modified by sex. The degree of recanalization was significant in relation to headache outcomes, where partial compared with complete recanalization resulted in a greater likelihood of residual headache. Prospective studies with common timing of repeat clinical-neuroimaging assessments will help to better ascertain the relationship and directionality between the degree of recanalization and outcomes., (© 2023 The Author(s).)

Background: This study evaluated the effect of residual arch tears on late reinterventions and arch dilatation after hemiarch replacement for patients with acute DeBakey type I aortic dissection., Methods: Between January 1995 and October 2018, 160 consecutive patients who underwent hemiarch replacement for DeBakey type I dissection were retrospectively enrolled. They were divided into patients with (n = 73) and without (n = 87) residual arch tears. The arch tears group was subdivided into the proximal/middle arch (n = 26) and distal arch (n = 47) groups to evaluate arch growth rates according to the locations of residual arch tears. The endpoints were arch growth rate and late arch and composite events., Results: The arch diameter increased significantly over time in patients with residual arch tears (1.620 mm/y, P < .001). The increase occurred more rapidly when residual tears occurred at the distal arch than at the proximal/middle arch level (2.101 vs 1.001 mm/y). In the adjusted linear mixed model, residual arch tears or luminal communications at the distal arch level were significant factors associated with increases in the arch diameter over time. The 10-year freedom from late arch and composite event rate was significantly lower for patients with residual arch tears than for those without (82.4% vs 95.5%, P = .001; and 68.0% vs 89.3%, P = .002, respectively)., Conclusions: Residual arch tears are significant factors associated with late arch dilatation and reinterventions, especially for patients with distal arch tears. Extensive arch replacement during the initial surgery to avoid residual arch tears may improve long-term outcomes., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Novel clay (bentonite) supported Ag 0 nanoparticles (NPs) doped TiO 2 nanocomposite (Clay/TiO 2 /Ag 0 (NPs)) thin film was obtained by using template synthesis method. The nanocomposite material is decorated with cubical Ag 0 (NPs) and utilised successfully in the photocatalytic degradation of tetracycline (TC) and sulfamethazine (SMZ) from aqueous solutions utilizing visible light and UV-A radiations. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET), X-ray photoelectron spectroscopy (XPS) analyses were used to characterise the nanocomposite materials. Diffusion reflectance spectroscopy (DRS) was utilised to determine the bandgap energies of the materials and also to confirm that Ag 0 (NPs) was successfully doped with TiO 2 . The nanocomposite material showed highly efficient photocatalytic activity for the breaking down of TC/SMZ under visible light irradiation by the enhanced electron-hole separation and adsorption of antibiotics at the vicinity of the catalyst. The oxidative degradation of TC/SMZ were shown to be highly dependent on the pH, initial concentration of TC/SMZ, and various co-existing ions. Reusability test of Clay/Ag 0 (NPs)/TiO 2 nanocomposite revealed that the activity did not decline with repeated use. Treatment of TC and SMZ in real water system further enhanced the application potential of the novel catalysts for the treatment of full-scale wastewater polluted with these antibiotics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Alum sludge from water treatment was calcined and extracted to synthesize high quality boehmite and γ-alumina for phosphate removal. Synthesized boehmite and γ-alumina were able to remove phosphate quickly and effectively. Boehmite (hydrothermal treatment at 60 °C) showed maximum phosphate removal (adsorption) of 61 mg P/g followed by γ-alumina (50 mg P/g) and the boehmite hydrothermally treated at 120 °C (41 mg P/g). The degree of crystallinity gave more effect on phosphate adsorption of boehmite than that of γ-alumina. The lower the pH, the more phosphate adsorbed on the boehmite and γ-alumina (adsorb phosphate more than 4 times at pH 3 than at pH 11). Spectroscopic analysis (SEM-EDS and FTIR) indicates that phosphate are removed by ligand exchange, electrostatic attraction, and surface precipitation on the synthesized boehmite and γ-alumina., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Contamination of the aquatic environment with pharmaceutical compounds is a serious environmental concern. The present investigation aims to utilize the Ce 3+ /TiO 2 thin film catalyst to remove of potential antibiotics (amoxicillin and tetracycline) using the less harmful UV-A radiations. Reduced cerium ion-doped TiO 2 is obtained by a simple one-step facile template method using polyethylene glycol as the templating agent. The synthesized catalysts Ce 3+ @TiO 2 (non-template) and Ce 3+ @TiO 2 (T) (template) were characterized by spectroscopic methods. The XPS reaffirms the reduced Ce 3+ dispersed within the titania network, and the AFM showed the surface roughness of the thin films. Detailed physicochemical analyses were conducted to deduce the degradation mechanism, and repeated use of the thin film photocatalyst showed enhanced stability. Significant mineralization of the antibiotics indicates the potential applicability of the photocatalytic catalyst. Furthermore, the presence of Ce 3+ significantly restricted the recombination of electron/hole pairs in the photo-excited TiO 2 semiconductor and showed enhanced photocatalytic degradation of the antibiotics proceeded predominantly through the •OH., (Copyright © 2022 Elsevier Inc. All rights reserved.)

A frost filter (FRF) was developed as a humidity pretreatment device (HPD) to improve the measurement of ambient ozone (O 3 ). The FRF was produced in a tube, which was supercooled by a thermoelectric cooling device based on the Peltier effect. The relative humidity (RH) of the air samples varied from 30% to 80% at 25 °C, and the O 3 concentration was set as 100 ppbv. Besides O 3 , SO 2 at 150 ppbv was used for comparison. The density of the FRF was evaluated. Comparison studies on the humidity removal efficiencies and loss ratios of analytes among a FRF HPD, a short Nafion™ tube (NS), and a long Nafion™ tube (NL) HPDs were conducted. As results, the density of the FRF was dependent on the temperature at a fixed sampling flow rate. The outlet humidity of both the FRF and the NL HPDs were less than 8% RH at 25 °C. The mean concentrations of O 3 and SO 2 after the FRF HPD were similar to the initial concentrations at all humidity levels, whereas they were significantly different for both the NS and NL HPDs at higher humidity. This suggests that the FRF HPD is a reliable humidity pretreatment for O 3 measurements., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A new generation of booster biocides that include metal pyrithiones (PTs) such as copper pyrithione (CuPT) and zinc pyrithione (ZnPT) are being used as tributyltin alternatives. In the marine environment, ZnPT can easily transchelate Cu to form CuPT, and the environmental fate and persistence of these two metal pyrithiones are closely related. Although some data on the toxicity of biocides on marine fish are available, little is known about their toxicity and toxic pathway. We thus compared the toxic effects of CuPT and ZnPT on embryonic olive flounder (Paralichthys olivaceus) by investigating their adverse effects based on developmental morphogenesis and transcriptional variation. In our study, the toxic potency of CuPT was greater with respect to developmental malformation and mortality than ZnPT. Consistent with the developmental effects, the expression of genes related to tail fin malformation (including plod2, furin, and wnt3a) was higher in embryonic flounder exposed to CuPT than in those exposed to ZnPT. Genes related to muscle and nervous system development exhibited significant changes on differential gene expression profiles using RNA sequencing (cutoff value P < 0.05). Gene ontology analysis of embryos exposed to CuPT revealed affected cellular respiration and kidney development, whereas genes associated with cell development, nervous system development and heart development showed significant variation in embryonic flounder exposed to ZnPT. Overall, our study clarifies the common and unique developmental toxic effects of CuPT and ZnPT through transcriptomic analyses in embryonic flounder., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Influenza is an acute respiratory disease and a global health problem. Although influenza vaccines are commercially available, frequent antigenic changes in hemagglutinin might render them less effective or unavailable. We previously reported that modified outer membrane vesicle (fmOMV) provided immediate and robust protective immunity against various subtypes of influenza virus. However, the effect was transient because it was innate immunity-dependent. In this study, we investigated the effects of consecutive administration of fmOMV and influenza virus on the adaptive immune response and long-term protective immunity against influenza virus. When the mice were pretreated with fmOMV and subsequently infected with influenza virus, strong influenza-specific antibody and T cell responses were induced in both systemic and lung mucosal compartments without pathogenic symptoms. Upon the secondary viral challenge at week 4, the mice given fmOMV and influenza virus exhibited almost complete protection against homologous and heterologous viral challenge. More importantly, this strong protective immunity lasted up to 18 weeks after the first infection. These results show that pretreatment with fmOMV and subsequent infection with influenza virus efficiently induces broad and long-lasting protective immunity against various virus subtypes, suggesting a novel antiviral strategy against newly-emerging viral diseases without suitable vaccines or therapeutics., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2021 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Non-alcoholic fatty liver disease (NAFLD) includes a broad spectrum of liver diseases characterized by steatosis, inflammation, and fibrosis. This study aimed to investigate the potential of dipeptidyl peptidase-4 inhibitors and sodium-glucose cotransporter 2 inhibitors in alleviating the progression of NAFLD. The NAFLD model was generated by feeding male C57BL/6J mice a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) for 7 weeks. After 2 weeks of CDAHFD feeding, the NAFLD model mice were assigned to four groups, namely (ⅰ) VEHICLE, (ⅱ) gemigliptin (GEMI), (ⅲ) empagliflozin (EMPA), and (ⅳ) GEMI + EMPA. For the next 5 weeks, mice received the vehicle or the drug based upon the group to which they belonged. Thereafter, the triglyceride concentration, extent of fibrosis, and the expression of genes encoding inflammatory cytokines, chemokines, and antioxidant enzymes were analyzed in the livers of mice. The NAFLD activity score and hepatic fibrosis grade were assessed via hematoxylin and eosin and Sirius Red staining of the liver tissue samples. All mice belonging to the GEMI, EMPA, and GEMI + EMPA groups showed improvements in the accumulation of liver triglycerides and the expression of inflammatory cytokines and chemokines. Additionally, the oxidative stress was reduced due to inhibition of the c-Jun N-terminal kinase pathway and upregulation of the antioxidant enzymes. Furthermore, in these three groups, the galectin-3 and interleukin 33-induced activity of tumor necrosis factor-α was inhibited, thereby preventing the progression of liver fibrosis. These findings suggest that the GEMI, EMPA, and GEMI + EMPA treatments ameliorate hepatic steatosis, inflammation, oxidative stress, and fibrosis in CDAHFD-induced NAFLD mouse models., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Hae Jin Kim reports financial support was provided by National Research Foundation of Korea (NRF)., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Joint involvement is a common extraintestinal manifestation of Crohn's Disease (CD) that may require total knee arthroplasty (TKA). There is a paucity of evidence regarding the relationship between CD and postoperative outcomes after TKA surgery. This study seeks to evaluate the impact of CD on 90-day and ≥2-year follow-up postoperative outcomes of TKA patients., Methods: We retrospectively analyzed the Statewide Planning and Research Cooperative System database (2009-2013) and isolated ICD-9 codes for TKA patients (8154), while excluding those with any revision of knee replacements (0080-0084) and split into 2 groups with or without CD (5550-5559). Patient demographics and postoperative outcomes were compared. Logistic regression analyses with covariates (sex, race, Deyo score, age, and insurance) were utilized to evaluate the association of CD with 90-day and overall postoperative outcomes., Results: A total of 89,134 TKA patients were identified, 244 of whom had CD. Significant differences in age, race distribution, insurance, and Deyo score (all, p < 0.05) were found. Multivariable analysis demonstrated CD was an independent risk factor for 90-day and overall medical complications, surgical complications, and readmission. Univariate and multivariable analyses report CD had significant increased rates and was a predictor, respectively, of overall blood transfusions (OR 1.5 [95% CI 1.1-2.0] p < 0.01), acute renal failure (OR 1.7 [95% CI 1.1-2.6] p = 0.03), and pulmonary embolism (OR 2.5 [95% CI 1.3-4.6] p = 0.01)., Conclusion: Patients with CD undergoing TKA have increased risk both 90-day and overall surgical and medication complications, as well as readmissions compared to patients without CD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

Cerebellar-cortical resting-state functional connectivity (rsFC) has been reported to be altered in cannabis users. However, this association may be due to genetic and environmental confounding rather than a causal relationship between cannabis use and changes in rsFC. In this co-twin control study, linear mixed models were used to assess relationships between the number of lifetime cannabis uses (NLCU) and age of cannabis onset (ACO) with cerebellar-cortical rsFC. The rsFC with seven functional networks was evaluated in 147 monozygotic and 82 dizygotic twin pairs. Importantly, the use of genetically informed models in this twin sample facilitated examining whether shared genetic or environmental effects underlie crude associations between cannabis measures and connectivity. Individual-level phenotypic analyses (i.e., accounting for twin-pair non-independence) showed that individuals in the full sample with earlier ACO and higher NLCU had lower cerebellar rsFC within the VA, DA, and FP networks. Yet, there were no significant differences in cerebellar-cortical rsFC between monozygotic twins who were discordant for cannabis measures. These findings suggest shared genetic or environmental confounds contribute to associations between cannabis use and altered cerebellar-cortical rsFC, rather than unique causal impacts of cannabis use on cerebellar-cortical rsFC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

To better understand the outbreaks of paralytic shellfish poisoning and bloom dynamics caused by Alexandrium species in Jinhae-Masan Bay, Korea, the germination and distributions of ellipsoidal Alexandrium cysts were investigated, and paralytic shellfish toxins (PSTs) profiles and contents were determined using strains established from germling cells. The phylogeny and morphological observations revealed that the germinated vegetative cells from ellipsoidal cysts collected from the surface sediments in Jinhae-Masan Bay belong to Alexandrium catenella (Group I) and A. pacificum (Group IV) nested within A. tamarense species complex. Cyst germinations of A. catenella (Group I) were observed at only 10 °C, whereas cysts of A. pacificum (Group IV) could germinate at temperature ranges of 10 to 25 °C. Maximum germination success (85%) for isolated cysts occurred at 15 °C, and the germling cells were A. pacificum (Group IV). The results indicate that the variation in water temperature in Jinhae-Masan Bay can control the seasonal variations in germination of cysts of A. catenella (Group I) and A. pacificum (Group IV). The germination rates of ellipsoidal Alexandrium cysts were different among sampling sites in Jinhae-Masan Bay, probably because of differences in distribution and abundance of A. catenella (Group I) and A. pacificum (Group IV) in the sediments. The ellipsoidal Alexandrium cyst concentrations were much higher in February than in August, however the distributions were similar. Gonyautoxins 3 and 4 (GTX-3 and GTX-4) contributed a large proportion (>90%) of the toxins produced by strains A. catenella (Group I) and A. pacificum (Group IV) established from germling cells, and the total cellular contents were higher in A. catenella (Group I) than in A. pacificum (Group IV)., (Copyright © 2021. Published by Elsevier B.V.)

The first total syntheses of isocorniculatolide B, corniculatolide B, and corniculatolide C, consisting of isomeric corniculatolide skeletons, have been accomplished in a divergent manner. The key features of the synthesis involve the construction of diaryl ether linkages by nucleophilic aromatic substitution, installation of a C14-substituted alkyl side chain via a sequence of Baeyer-Villiger reaction and Claisen rearrangement, and efficient construction of corniculatolide and isocorniculatolide frameworks, including 17-membered (exterior) macrolactone skeletons from a versatile diaryl ether intermediate by Mitsunobu macrolactonization. Moreover, we prepared the structural congeners of isomeric corniculatolides via diverted total synthesis approach including desmethyl analogues and related dimeric macrolides. The anti-inflammatory activities of the synthesized natural products, analogues and synthetic intermediates were also investigated. In particular, corniculatolide B significantly inhibited the protein expression of COX-2 and the mRNA expressions of TNF-α, IL-1β and IL-6 by inhibiting of NF-κB signaling in intestinal epithelial cells induced by lipopolysaccharide treatment. It also significantly inhibited the promoter activity and the phosphorylation of subunits p50 and p65 of NF-κB to the same extent as Bay 11-7082, a potent IκB kinase inhibitor. These results suggest that corniculatolide B might have therapeutic potential in inflammatory bowel disease via NF-κB signaling pathway., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Alum sludge (AS) is an abundant and ubiquitous residue generated from drinking water treatment plants. AS was thermally treated to use as an adsorbent for phosphate removal from wastewater. Organic matter in the AS was a potential competitor and can deter phosphate adsorption. Pyrolysis and drying of AS were adopted to enhance phosphate removal by eliminating organic matter and enriching Al content. Adsorption kinetics showed that phosphate removal was highest with the AS pyrolyzed at 700 °C followed by 500 °C, air-dried and oven-dried (105 °C). Adsorption kinetic modelling showed that chemisorption is the operative mechanism of phosphate removal in all the AS. Adsorption isotherms also showed that the pyrolyzed AS and air-dried AS had similar adsorption capacity of 30.83-34.53 mg P/g AS. Al dissolution was less than 2 mg/g Al in all the AS samples. COD release was significant in the dried AS, up to 8.0 mg COD/g AS, whereas the pyrolyzed AS released less than 1 mg COD/g AS. FTIR and SEM-EDS analyses of the AS after phosphate adsorption showed the formation of aluminum-phosphate complex. Overall, the pyrolysis of AS at 700 °C was most effective in removing phosphate without leaving secondary pollution., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: On-line discussion boards (DBs) are used by patients and family members to pose questions and share experiences with a broader community. Systematic analysis of the text posted to DBs about congenital upper-extremity (UE) differences may allow physicians to identify and address patients' questions and concerns better., Methods: We used Google and Yahoo! Internet search engines to identify on-line DBs pertaining to congenital UE differences. Posts written between January 1, 2009 and January 1, 2019 were collected and analyzed. Each on-line post was coded by 2 researchers using 3 rounds of grounded theory: open coding, axial coding, and selective coding. This allowed comprehensive, central themes of the DBs to emerge., Results: We collected 521 posts and analyzed 420 posts from 152 threads. A total of 163 unique users contributed to posts. Parents of a child with a congenital UE difference accounted for the majority of users (65%), most of which were postnatal (91%). Of posts written by patients, 48% expressed negative emotions pertaining to their difference, whereas 17% conveyed a positive experience. Five selective codes were identified from posts written by non-administrators: (1) Connecting With Others, (2) Emotional Aspects, (3) Treatment, (4) Diagnosis, and (5) Function. Connecting With Others was the most frequently assigned selective code; users were looking to establish a connection in 73% of posts. Posts seeking information (n = 106) were more often technical in nature than were posts providing information (54% vs 44%). Posts providing information (n = 206) were more often emotional (18% vs 13%)., Conclusions: Individuals accessing on-line DBs are commonly searching for technical and emotional support from others. Through analysis and identification of the themes from these posts, we believe physicians should be proactive in addressing technical concerns through education and counseling, but should also validate emotional concerns and assist families and patients via support groups or connections to others., Clinical Relevance: Treating surgeons can improve their care of patients with congenital UE differences by better understanding the needs of patients and their families that may not be elucidated in a traditional patient encounter., (Copyright © 2021 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Introduction: Severe valgus-impacted femoral neck fractures are associated with femoral neck shortening (FNS). However, no study has focused on the effect of reduction for severe valgus impaction in terms of healing and restoration of the femoral neck length. This study aimed to compare FNS and treatment outcomes of in situ fixation and fixation after reduction for severe valgus-impacted femoral neck fractures in patients aged 65 years or younger., Methods: This retrospective study included 55 patients who underwent internal fixation with three parallel screws for femoral neck fractures with valgus impaction >15° (AO/OTA classification 31-B1.1) between January 2006 and December 2018. Twenty-eight and 27 patients underwent in situ fixation (in situ group) and fixation after reduction (reduction group), respectively. In the reduction group, reduction using lateral traction with a Schanz pin was performed before internal fixation. Complications such as fixation failure, non-union, and avascular necrosis (AVN), caput-collum-diaphysis (CCD) angle, posterior tilt angle, amount of FNS, and Harris Hip Score (HHS) were compared between the groups., Results: Bone union was achieved in all patients; AVN occurred in two patients in each group. No significant difference was seen in the preoperative characteristics between the groups. The CCD angle at 1 year postoperatively was significantly different between the groups, whereas the posterior tilt angle at 1 year postoperatively was not different. FNS at 1 year postoperatively was significantly lower in the reduction group than in the in situ group. FNS by >5 mm was significantly less frequent in the reduction group than in the in situ group (11% versus 75%). The mean HHS at 1 year and 2 years postoperatively was significantly higher in the reduction group than in the in situ group. FNS and HHS were negatively correlated; the mean HHS was significantly higher in patients with none/mild shortening (<5 mm) than in those with moderate/severe shortening (≥5 mm)., Conclusion: In patients aged 65 years or younger, internal fixation after reduction for severe valgus-impacted femoral neck fractures is safe and effective for achieving successful bone union and restoring the femoral neck length., Competing Interests: Declaration of Competing Interest Kyu-Hyun Yang designed the Limited Sliding Screw and received royalties from the TDM company. The remaining authors report no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: The treatment of radial longitudinal deficiency (RLD) is highly variable without clear guidelines in the literature. The current study investigated variability among hand surgeons in treatment approaches for RLD patients with anomalies of the thumb and forearm., Methods: An online survey was distributed to 105 self-identified North American pediatric hand surgeons and 23 international pediatric hand surgeons. The survey was developed after consideration of the controversies in RLD treatment. Variations in diagnostic approach, timing of treatment, surgical indications, and surgical techniques were presented in a 21-question survey., Results: Seventy-four (57.8%) surgeons completed the survey. For type 2 hypoplastic thumb reconstruction, 81% of surgeons prefer the flexor digitorum superficialis transfer with others using the abductor digiti minimi transfer. Ninety-four percent and 100% of surgeons favored pollicization for type 3B and type 4 hypoplastic thumb, respectively. When performing pollicization, 88% of surgeons strive for tip-to-tip pinch, with 50% preferring 100° rotation and 38% greater than 120°, compared with 12% who preferred tip-to-side pinch. Nearly half of surgeons stated they would not recommend pollicization for a patient with a stiff index finger who utilizes ulnar prehension. Ninety percent of surgeons preferred observation for a type 1 radius. Type 2 treatment preferences were highly variable, the most common response being radius lengthening. For type 3/4 radius deficiency, surgeons were divided between soft tissue release with bilobed flap and centralization (42% and 36%, respectively). If radial deviation could not be passively corrected, 63% preferred an external fixator for soft tissue distraction before centralizing. Ulnar prehension functional pattern changed treatment for 45% of surgeons in type 3/4 radius., Conclusions: This study provides information on areas of agreement and disagreement in the treatment of RLD. Specifically, there was consensus for treatment of types 3B and 4 thumbs and type 1 radius. Consensus was lacking for the amount of rotation in positioning of the pollicized digit, the role of pollicization with the stiff index finger, and also in the treatment of types 2, 3, or 4 radius., Clinical Relevance: This study provides a framework to establish treatment guidelines for thumb hypoplasia and RLD and has identified areas lacking consensus and that require additional study., (Copyright © 2021 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

The drawback of biochar as a soil ameliorant is its low-nutrient content while the bottleneck of struvite production is its high chemical cost. This drew the idea of using designed biochar for nutrient recovery from nutrient-rich wastewater as struvite. Mg-biochar was used for simultaneous P and N recovery from sewage sludge ash (SSA) and food wastewater (FW) by using ground coffee bean (GCB) and palm tree trunk (PTT) waste. PTT Mg-biochar could recover 92.2% of PO 4 3- -P and 54.8% of NH 4 + -N while GCB Mg-biochar could recover 79.5% of PO 4 3- -P and 38.6% of NH 4 + -N. Adsorption, precipitation and cation-exchange mechanisms are involved in the Mg-biochar for the simultaneous recovery of PO 4 3- -P and NH 4 + -N as struvite. Mg-biochars also showed higher struvite selectivity than the control samples. This method not only supports waste recycling and pollution mitigation but also highlights economical struvite production and the benefits of CO 2 sequestration., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background & Aims: Programmed cell death-1 (PD-1) inhibitor treatment can cause hyperprogressive disease (HPD), but the incidence, outcome, and predictive factors of HPD are unknown in patients with hepatocellular carcinoma (HCC). Herein, we assessed the existence and factors predictive of HPD in patients with advanced HCC treated with nivolumab., Methods: We enrolled 189 patients with advanced HCC treated with nivolumab. Occurrence of HPD was investigated using tumour growth dynamics based on tumour growth kinetics (TGK) and tumour growth rate (TGR) before and after treatment, or time to treatment failure. We additionally analysed patients treated with regorafenib (n = 95) or best supportive care (BSC)/placebo (n = 103) after progression on sorafenib to compare tumour growth dynamics., Results: Flare-up of tumour growth was observed in a fraction of patients upon PD-1 blockade, indicating the occurrence of HPD. Based on distinct patterns of disease progression exclusively observed in the nivolumab-treated cohort, but not in the regorafenib- or BSC/placebo-treated cohorts, 4-fold increases in TGK and TGR ratios as well as a 40% increase in TGR were the cut-off values used to define HPD; 12.7% of the patients (24/189) treated with nivolumab met all these criteria. Patients with HPD had worse progression-free survival (hazard ratio [HR] 2.194; 95% CI 1.214-3.964) and overall survival (HR 2.238; 95% CI 1.233-4.062) compared to patients with progressive disease without HPD. More than 90% of patients with HPD missed the opportunity for subsequent treatment because of rapid clinical deterioration. An elevated neutrophil-to-lymphocyte ratio (>4.125) was associated with HPD and an inferior survival rate., Conclusions: HPD occurs in a fraction of patients with HCC who receive PD-1 inhibitor treatment. Analyses of the baseline immune profile and on-treatment tumour growth dynamics could enable optimal patient selection and earlier identification of HPD., Lay Summary: Hyperprogressive disease is an unexpected response pattern observed in patients treated with an immune checkpoint inhibitor. This study revealed that hyperprogressive disease occurs in a fraction of patients with advanced hepatocellular carcinoma treated with an anti-PD-1 antibody, providing evidence to encourage careful monitoring of patients to prevent clinical deterioration induced by PD-1 blockade., Competing Interests: Conflicts of interest H.C.C. has a consulting or advisory role at Taiho, Celltrion, MSD, Lilly, Quintiles, BMS, Merck-Serono, Gloria, Beigene, Amgen, and Zymework, received research funding from Lilly, GSK, MSD, Merck-Serono, BMS/ONO, Taiho, Amgen, Beigene, and Incyte, and received honoria from Merck-Serono and Lilly. H.J.Chon has a consulting or advisory role at Roche, Bayer, Eisai, ONO, and MSD. H.J.Choi has a consulting or advisory role at Bayer, ONO, and MSD. H.Y.L. has a consulting or advisory role at Bayer, Eisai, BMS, Ipsen, MSD, Roche, and Merck-Serono, and received honoria from BMS. C.G.K., C.K., S.E.Y., K.H.K., S.J.C., B.K., H.R.K., S-H.P., E-C.S., Y-Y.K., and D.J.K. have nothing to disclose. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Bacterial infections can trigger the development of organ failure(s) and acute-on-chronic liver failure (ACLF). Geographic variations in bacteriology and clinical practice could lead to worldwide differences in ACLF epidemiology, phenotypes and associated outcomes. Herein, we aimed to evaluate regional differences in bacterial infection-related ACLF in patients with cirrhosis admitted to hospital., Methods: This post hoc analysis included 1,175 patients with decompensated cirrhosis (with bacterial infection on admission or nosocomial infection) from 6 geographic regions worldwide. Clinical, laboratory and microbiological data were collected from the diagnosis of infection. Patients were followed-up for organ failure(s) and ACLF development according to the EASL-CLIF criteria from enrolment to discharge/death., Results: A total of 333 patients (28%) had ACLF at diagnosis of infection, while 230 patients developed ACLF after diagnosis of infection, resulting in an overall rate of bacterial infection related-ACLF of 48%, with rates differing amongst different geographic regions (38% in Southern Europe vs. 75% in the Indian subcontinent). Bacterial infection related-ACLF more frequently developed in younger patients (55 ± 13 vs. 58 ± 14 years), males (73% vs. 62%), patients with alcohol-related cirrhosis (59% vs. 45%) and those with a higher baseline MELD score (25 ± 11 vs. 16 ± 5) (all p <0.001). Spontaneous bacterial peritonitis, pneumonia or infections caused by extensively drug resistant (XDR) bacteria were more frequently associated with ACLF development. More patients with ACLF had a positive quick sequential organ failure assessment score and septic shock, resulting in a lower infection resolution rate (all p <0.001)., Conclusions: Bacterial infections, especially with XDR organisms, are associated with the highest risk of ACLF development, accounting for almost half of cases globally. Geographic differences result in variable epidemiology and clinical outcomes., Lay Summary: Bacterial infections can trigger a sudden deterioration in an otherwise stable cirrhotic patient, a condition known as acute-on-chronic liver failure or ACLF. This study has found that the development of ACLF following bacterial infection occurs most commonly in the Indian subcontinent and less so in Southern Europe. The common infections that can trigger ACLF include infection of the abdominal fluid, known as spontaneous bacterial peritonitis, pneumonia and by bacteria that are resistant to multiple antibiotics. Patients who develop ACLF following a bacterial infection have high death rates and are frequently unable to clear the infection., Competing Interests: Conflict of interest Authors declare they have no conflict of interest regarding the content of this manuscript. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020. Published by Elsevier B.V.)

We aimed to identify brain structural changes in cortical and subcortical regions linked to recent suicidal behavior. We performed secondary analyses of structural MRI data of two independent studies, namely the Establishing Moderators/Biosignatures of Antidepressant Response - Clinical Care (EMBARC) study and a Little Rock study on acute suicidal behavior. Study 1 (EMBARC, N = 187), compared individuals with remote suicide attempts (Remote-SA), individuals with lifetime suicide ideation but no attempts (Lifetime-SI only), and depressed individuals without lifetime suicide ideation or attempts (non-suicidal depressed). Study 2 (Little Rock data, N = 34) included patients recently hospitalized for suicide ideation or attempt constituted by: patients who recently attempted suicide (Recent-SA), individuals with remote suicide attempts (Remote-SA), and Lifetime-SI only. Study 3 combined the EMBARC and Little Rock datasets including Recent-SA, Remote-SA, Lifetime-SI only and non-suicidal depressed individuals. In Study 1 and Study 2, no significant differences were observed between groups. In Study 3, significantly lower middle temporal gyrus thickness, insular surface area, and thalamic volume and higher volume in the nucleus accumbens were observed in Recent-SA. This pattern of structural abnormalities may underlie pain and emotion dysregulation, which have been linked to the transition from suicidal thoughts to action., (Copyright © 2020. Published by Elsevier B.V.)

Objectives: The purpose of the present study was to investigate which peri-transplant dental treatments were deemed necessary, and to determine retrospectively how often these treatments were actually performed, in patients who had received organ transplants., Materials and Methods: Medical records of the Department of Advanced General Dentistry at Yonsei University Dental Hospital were searched to identify liver or kidney transplant recipients who attended from 1st March 2014 to 31st December 2017. A total of 418 patients were identified, and their medical charts were reviewed. Sex, underlying systemic disease, oral hygiene status, dental treatment deemed necessary, dental treatment actually performed and durations of follow-up were tabulated., Results: More than half (53.8%) of the liver transplant recipients had poor oral hygiene, and poor oral hygiene was statistically significantly more prevalent in the liver transplant group than in the kidney transplant group (40.3%). In liver recipients in whom scaling was deemed to be required pre-transplant, the rate of it actually being performed pre-transplant was high (83.2%). By contrast, the rates of tooth extraction and prosthetic treatment actually being performed pre-transplant were low (12.8% and 0%, respectively). In kidney recipients, the rates of scaling, tooth extraction and prosthetic treatment actually performed pre-transplant, when deemed to be required, were 93.5%, 10.0% and 0.0%, respectively., Conclusions: We recommend that patients scheduled to receive an organ transplant be referred to a dental clinic as soon as possible beforehand, to remove any potential sources of oral infection. Educating physicians, as well as their patients, about the importance of early dental screening and pre-transplant dental treatment is essential., (© 2020 FDI World Dental Federation.)

By Asian digital economy , we refer to high-tech developments, business and social transformations, and information-driven changes in the region's growth. We discuss its background and foundations, significance in Asia and contribution to removal of historical barriers in traditional business. We assess how new value chains are transforming country-level involvement in worldwide manufacturing and note "smiling curve theory" predictions about the global value chain in Asia for high-tech firms and their economies. The takeaway is that the digital economy in Asian nations involves revamping business processes through technology innovation, government policies for growth, and digital entrepreneurship. We analyze the "digital economy and society index", and attributes of nations, societies and economies, as a basis for framing our ideas. We consider research directions prompted by data analytics and AI, the platform economy, digital trade, fintech innovation, and societal and economic sustainability. We further highlight new issues in light of the COVID-19 pandemic., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that could inappropriately influence (bias) their work or state., (© 2020 Elsevier B.V. All rights reserved.)

There is accruing evidence of cerebellar abnormalities in individuals with schizophrenia as measured by performance on a variety of tasks believed to be dependent on cerebellar integrity, including delay eyeblink conditioning. There is also evidence of cerebellar dysfunction on a neural level in schizophrenia from both task-based and resting state neuroimaging studies, however few studies have examined cerebellar neural function while the cerebellum is directly recruited in individuals with schizophrenia. In the current pilot study, we examined neural activity during an explicitly cerebellar task in individuals with schizophrenia or schizoaffective disorder and non-psychiatric controls. Participants underwent delay eyeblink conditioning during fMRI. Results indicated eyeblink conditioning impairment in patients as evidenced by a group by time interaction for conditioned responses. A significant cluster of cerebellar activation was present in controls but not patients during the first half of conditioning; there were no significant differences in activation between groups. An ROI analysis focused on the cerebellum in patients revealed two significant clusters that were inversely associated with negative symptom severity. These results are broadly consistent with the theory of cognitive dysmetria, wherein cerebellar abnormalities are theorized to contribute to motor as well as cognitive and affective disturbances in schizophrenia., Competing Interests: Declarations of Competing Interests None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Patients who undergo endovascular aneurysm repair (EVAR) often require reintervention after the index repair. The long-term rate of reintervention and how this has changed with newer device technology are poorly understood. Therefore, we performed a systematic review and meta-analysis of the available literature to determine long-term freedom from reintervention after EVAR and the change in reintervention rates over time., Methods: We performed a systematic review of MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included randomized controlled trials and observational studies that documented the rate of reintervention after EVAR. We performed a meta-analysis of Kaplan-Meier freedom from reintervention at each year after EVAR. We used linear regression to evaluate change in reintervention rate over time with newer device technology., Results: We included a total of 30 studies (randomized trials, n = 3; observational studies, n = 27) comprising 32,126 patients in this review and meta-analysis. Studies ranged in the implantation date of the EVAR device from 1996 to 2014. The probability of freedom from reintervention was 81% (95% confidence interval [CI], 77%-85%) at 5 years, 70% (95% CI, 65%-76%) at 10 years, and 64% (95% CI, 46%-79%) at 14 years. Linear regression demonstrated an improvement in freedom from reintervention when results were stratified by the year of device implantation. At 1 year, estimated freedom from reintervention improved from 90% in 1998 to 94% in 2008 (n = 26 studies; R 2  = 0.11; P = .10). At three years, estimated freedom from reintervention improved from 77% in 1998 to 90% in 2008 (n = 26 studies; R 2  = 0.27; P = .006). At 5 years, estimated freedom from reintervention improved from 68% in 1998 to 81% in 2008 (n = 22 studies; R 2  =0.12; P = .12). At 7 years, estimated freedom from reintervention improved from 51% in 1998 to 86% in 2011 (n = 22 studies; R 2  = 0.40; P = .015)., Conclusions: EVAR patients remain at risk for reintervention indefinitely, and therefore lifelong surveillance is imperative. Encouragingly, reintervention rates have improved over time, with newer devices exhibiting lower rates. Reintervention rate remains an important metric for new devices and registries., (Published by Elsevier Inc.)

Background & Aims: Patients undergoing veno-arterial extracorporeal membrane oxygenation (VA-ECMO) are likely to be develop malnutrition because of catabolism and protein consumption. Administration of appropriate nutrition to these patients is difficult because of hemodynamic instability and multiorgan failure. The aim of this study was to evaluate the relationship between nutritional supply and clinical outcomes in patients undergoing VA-ECMO., Methods: Patients who received VA-ECMO in a single tertiary teaching hospital between 2013 and 2018 were reviewed retrospectively. Linear regression and Cox regression were performed to assess the relationship between the following factors and clinical outcomes: sex, age, BMI, modified nutrition risk in the critically ill (mNUTRIC) score, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation (APACHE II) score, ENCOURAGE score, daily average achievement of an energy target (%), and average protein intake during the first week and second week., Results: Forty-one patients were included. Patients on VA-ECMO received lower amounts of energy and protein in the first week than in the second week (33.9 vs 77.7% target/day, 0.24 vs. 0.74 g/kg/day) and achieved 70% of their energy requirement at a median of 8 days after the initiation of VA-ECMO. Multiple Cox regression analysis revealed an association among energy received daily during the second week of VA-ECMO, mNUTRIC score, and 90-day mortality (hazard ratio, 0.82, 95% confidence interval [0.69-0.97], P = 0.018 vs. hazard ratio, 1.51, 95% confidence interval [1.06-2.15], P = 0.022)., Conclusion: In VA-ECMO patients, when the daily average energy intake increased by 10% of the target over 8-14 days, the 90-day mortality decreased by 18%., Competing Interests: Conflicts of Interest All authors declare that there are no conflicts of interest., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Recent research revealed that doxorubicin (DOX) decreased expression of programmed death-ligand 1 (PD-L1) in cancer cells. However, the detailed mechanisms underlying this effect are not well established. Here, we demonstrate that doxorubicin down-regulates PD-L1 expression through induction of AU-rich element (ARE) binding protein tristetraprolin (TTP) in cancer cells. PD-L1 mRNA contain three AREs within its 3'UTR. Doxorubicin induced expression of TTP, increased TTP binding to the 3rd ARE of the PD-L1 3'UTR, and increased decay of PD-L1 mRNA. Inhibition of TTP abrogates the inhibitory effect of doxorubicin on PD-L1 expression. Our data suggest that TTP plays a key role in doxorubicin-mediated down-regulation of PD-L1 by enhancing degradation of PD-L1 mRNA in cancer cells., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Long-term outcomes of mitral valve replacement (MVR) recipients with pulmonary hypertension (PH) remain unclear. We determined the effect of concomitant PH on the clinical outcomes and late-onset progression of tricuspid regurgitation (TR) after MVR for rheumatic mitral stenosis., Methods: We retrospectively reviewed 394 patients who underwent MVR between January 2000 and December 2013. PH was defined as systolic pulmonary arterial pressure (sPAP) >50 mm Hg. Changes in echocardiographic parameters (preoperative to postoperative), TR progression (grade ≥ II), and long-term survival were evaluated according to the presence of PH at MVR (non-PH, n = 322; PH, n = 72)., Results: The 10-year overall survival rate was significantly lower in the PH group (79.7% vs 90.7%, P = .04), whereas the rate of freedom from TR progression was similar between groups (76.9% vs 80.5%, P = .373). High preoperative sPAP and right ventricular systolic pressure (RVSP) did not affect TR progression. However, substantial postoperative reductions in sPAP and RVSP protected against TR progression (hazard ratio [95% confidence interval], 0.966 [0.942-0.991], P = .008, and 0.973 [0.960-0.986], P < .001, respectively). The 10-year rate of freedom from TR progression was significantly higher in patients with substantial sPAP and RVSP reductions (sPAP, 84.2% vs 70.6%, P = .003; RVSP, 84.9% vs 71.0%, P < .001)., Conclusions: Although concomitant PH at MVR is associated with poor long-term survival, adequate sPAP and RVSP reduction can prevent TR progression even in patients with severe PH preoperatively. Therefore, we suggest careful monitoring of PAP and RVSP after MVR and should make an effort to reduce postoperative PAP., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases 3 (PFKFB3) catalyzes the first committed rate-limiting step of glycolysis and is upregulated in cancer cells. The mechanism of PFKFB3 expression upregulation in cancer cells has not been fully elucidated. The PFKFB3 3'-UTR is reported to contain AU-rich elements (AREs) that are important for regulating PFKFB3 mRNA stability. However, the mechanisms by which PFKFB3 mRNA stability is determined by its 3'-UTR are not well known. We demonstrated that tristetraprolin (TTP), an ARE-binding protein, has a critical function regulating PFKFB3 mRNA stability. Our results showed that PFKFB3 mRNA contains three AREs in the 3'-UTR. TTP bound to the 3rd ARE and enhanced the decay of PFKFB3 mRNA. Overexpression of TTP decreased PFKFB3 expression and ATP levels but increased GSH level in cancer cells. Overexpression of PFKFB3 cDNA without the 3'-UTR rescued ATP level and GSH level in TTP-overexpressing cells. Our results suggested that TTP post-transcriptionally downregulated PFKFB3 expression and that overexpression of TTP may contribute to suppression of glycolysis and energy production of cancer cells in part by downregulating PFKFB3 expression., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Osteoarthritis (OA) is the most common form of arthritis, is the leading cause of impaired mobility in the elderly, and accounts for more than a third of chronic moderate to severe pain. As a degenerative joint disorder, OA affects the whole joint and results in synovial hyperplasia, degradation of articular cartilage, subchondral sclerosis, osteophyte formation, and chronic pain. Currently, there is no effective drug to decelerate OA progression and molecular targets for drug development have been insufficiently investigated. Anti-OA drug development can benefit from more and precise knowledge of molecular targets for drug development. Runt-related transcription factor 2 (Runx2) is a key transcription factor controlling osteoblast and chondrocyte differentiation and is among the most promising potential therapeutic targets. Notably, Runx2 expression is upregulated in several murine OA models, suggesting a role in disease pathogenesis. In this review article, we summarized recent findings on Runx2 related to OA development and evaluated its potential as a therapeutic target., The Translational Potential of This Article: A better understanding of the role of Runx2 in osteoarthritis pathogenesis will contribute to the development of novel intervention of osteoarthritis disease., (© 2019 The Authors.)