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Background: The incidence of hepatitis A virus (HAV) infection is on the rise, with a minority of patients at risk for poor outcomes. This study investigates the prognostic impacts of race and gender on hospital outcomes among admitted HAV-infected patients., Methods: Using the National Inpatient Sample from 2012 to 2017, patients admitted with HAV were selected and stratified by gender (male and female) and race (White, Black, Hispanic, Asian-Pacific Islander, Other). Propensity score-matching and statistical analysis were implemented with comparison to the controls ("Female" and "White"). Primary endpoints included mortality, length of stay (LOS), and hospitalization costs, while secondary endpoints consisted of hepatic-related medical complications such as ascites, hepatic encephalopathy, varices, and acute liver failure., Results: Females with compensated cirrhosis had increased odds of mortality (aOR 2.59, 95% CI: 1.14-5.91, P  = 0.02). Otherwise, no other differences in mortality were detected between genders and races. Females had a shorter hospital LOS (aOR 0.97, 95% CI: 0.96-0.98, P  < 0.001), lower adjusted cost ($12,241 vs. $13,510, aOR 0.92, 95% CI: 0.92-0.92, P  < 0.001), lower odds of esophageal varices (aOR 0.74, 95% CI: 0.57-0.97, P  = 0.03) and hepatic encephalopathy (aOR 0.67, 95% CI: 0.53-0.84, P  < 0.001) compared to males. Black patients exhibited higher LOS (aOR 1.06, 95% CI: 1.04-1.08, P  < 0.001) and adjusted costs ($13,392 vs $12,592, aOR 1.02, 95% CI: 1.02-1.03, P  < 0.001). Hispanic patients exhibited higher rates of esophageal varices (aOR 2.19, 95% CI: 1.28-3.76, P  = 0.005) and adjusted costs ($14,202 vs. $12,381, aOR 1.07, 95% CI: 1.07-1.07, P  < 0.001), and Asian patients experienced higher adjusted costs ($18,426 vs. $13,137, aOR 1.10, 95% CI: 1.10-1.10, P  < 0.001) compared to White patients., Conclusion: Various nuanced impacts of gender and race on hospitalization outcomes in HAV infection were observed, with only one subgroup analysis demonstrating a higher rate of mortality. Further research is warranted to better understand these findings and their implications., (© 2024 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Introduction: We assessed the accuracy and fit of 3-dimensional (3D)-printed indirect bonding (IDB) trays fabricated using various photopolymer resin materials., Methods: A maxillary plaster model and 60 plaster replicas were created. IDB trays with arbitrary bracket configurations were 3D-printed using 3 hard resins (Amber [AB], TC85DAC [TC], Orthoflex [OF]) and 3 soft resins (IBT [IT], IDB2 [ID], and MED625FLX [MD]). A reference plaster model with a computer-aided design-designed IDB tray attached with nonfunctional, arbitrary bracket configurations on the buccal surface serving as reference points for measurement was superimposed on scanned plaster replicas holding 3D-printed trays to assess transfer accuracy and clinically acceptable error. Printing accuracy was assessed by comparing computer-aided design trays to printed trays, and tray fit was measured by the gap volume between the tray and plaster replica using a Fit-Checker (GC Corp, Tokyo, Japan)., Results: Six tray groups showed significant linear transfer errors, particularly in the vertical direction (0.15 mm [95% confidence interval {CI}, 0.10-1.15]; P = 0.004). The OF group exhibited the largest vertical error (0.27 mm [95% CI, 0.19-0.35]), whereas the ID group had the smallest (0.10 mm [95% CI, 0.06-0.14]). Angular errors did not exhibit significant differences across the groups. Linear precision error was the highest in OF, followed by ID, TC, and MD, then AB and IT (P <0.001). Of all tray groups, 90.1% and 68.8% met the clinically acceptable linear (<0.25 mm) and angular errors (1°)., Conclusions: Linear errors, particularly vertical errors, are more material-dependent than angular errors. Gap volume alone was not a reliable predictor of IDB tray accuracy. Therefore, material-specific designs are needed to control the optimal fit and facilitate precise bracket placement., (Copyright © 2024. Published by Elsevier Inc.)

Evaluating and predicting the natural attenuation capacity (AC) of a vadose zone is essential for determining groundwater vulnerability to contamination from upper sources. However, it remains unclear how the physicochemical properties of vadose zone soils affect AC owing to their complexity and spatial heterogeneity. In this study, we developed a regression model for estimating the AC of a vadose zone against diesel using datasets from different soils with a wide range of physicochemical properties. Among the 17 properties, six (i.e., organic matter (OM), total phosphorous (TP), coefficient of uniformity, particle size (D 30 ), van Genuchten's n, saturation degree (SD)) were selected as primary regressors. The results indicate that biogeochemical factors, including OM and TP, have decisive effects on the AC. Finally, the regression model was expanded to a GIS-based spatial model and applied to Namyangju, Korea using the index-overlay method. The produced AC map showed a nonmonotonic decrease along the depth, and the areas closer to the water bodies generally represented low AC values, most likely due to the lower OM, TP, and higher SD. This study provides an empirical basis for future research initiatives for spatial and temporal AC dynamics, which complements conventional intrinsic groundwater vulnerability models such as DRASTIC., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

A naturally occurring stilbene, resveratrol, shows promising effects in the treatment of malignant pleural mesothelioma (MPM) both as a single agent and in combination with chemotherapeutic drugs. To discover new anticancer agents targeting MPM, stilbene-targeted isolation was performed on the roots of Polygonum multiflorum Thunb., an herbal medicine rich in stilbene compounds. In this study, seven stilbene glycosides (1-7) were isolated, along with four non-stilbenes (8-11), of which compounds 4 and 9-11 have not previously been isolated from this species. Stiquinoside A (1) is a previously undescribed stilbene glycoside, and its structure was elucidated as (E)-2,3,5,4'-tetrahydroxystilbene 2-O-β-d-quinovopyranoside based on 1D and 2D-NMR, HR-ESI-MS, and acid hydrolysis experiments. Compounds 1, 4, 6, and 8 significantly inhibit the growth of MPM cancer cells H2452. These results demonstrate the potential utility of stilbenes in new strategies for the treatment of MPM., 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. Published by Elsevier B.V.)

Objectives: To create bacteria-resistant dental CAD-CAM blocks with a biofilm-resistant effect by incorporating Nano-crystalline ceramic and polymer (NCP) with 2-methacryloyloxyethyl phosphorylcholine (MPC) and sulfobetaine methacrylate (SBMA) and at an equimolar ratio, referred to as MS., Methods: Experimental groups comprised NCP blocks containing zwitterions at 0.15wt% (MS015) and 0.45wt% (MS045). NCP blocks without MS served as control (CTRL). Flexural strength, surface hardness, water sorption and solubility, photometric properties, and cytotoxicity were assessed for all samples. Additionally, the resistance to single and multi-species bacterial adhesion was investigated., Results: MS045 showed significant reduction in flexural strength (P < 0.01) compared to both CTRL and MS015. Both MS015 and MS045 showed significantly increased water sorption and significant reduction in water solubility compared to CTRL. Light transmission remained consistent across all MS content levels, but the irradiance value decreased by 12 % in the MS045 group compared to the MS015 group. Notably, compared to the CTRL group, the MS015 group exhibited enhanced resistance to adhesion by Porphyromonas gingivalis and a multi-species salivary biofilm, with biofilm thickness and biomass reduced by 45 % and 56 %, respectively., Conclusions: NCP containing 0.15 % MS can effectively reduce adhesion of multiple species of bacteria while maintaining physical and mechanical properties., Clinical Significance: NCP integrating zwitterions is clinically advantageous in resisting bacterial adhesion at internal and external margins of milled indirect restoration., 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: Magnetic stimulation, represented by transcranial magnetic stimulation (TMS), is used to treat neurological diseases. Various strategies have been explored to improve the spatial resolution of magnetic stimulation. While reducing the coil size is the most impactful approach for increasing the spatial resolution, it decreases the stimulation intensity and increases heat generation., Objective: We aim to demonstrate the feasibility of magnetic stimulation using an epidurally implanted millimeter-sized coil and that it does not damage the cortical tissue via heating even when a repetitive stimulation protocol is used., Methods: A coil with dimensions of 3.5 × 3.5 × 2.6 mm 3 was epidurally implanted on the left motor cortex of rat, corresponding to the right hindlimb. Before and after epidural magnetic stimulation using a quadripulse stimulation (QPS) protocol, changes in the amplitude of motor evoked potentials (MEPs) elicited by a TMS coil were compared., Results: The experimental group showed an average increase of 88 % in MEP amplitude in the right hindlimb after QPS, whereas the MEP amplitude in the left hindlimb increased by 18 % on average. The control group showed no significant change in MEP amplitude after QPS in either hindlimb. The temperature changes at the coil surface remained <2 °C during repetitive stimulation, meeting the thermal safety limit for implantable medical devices., Conclusion: These results demonstrate the feasibility of epidural magnetic stimulation using an implantable coil to induce neuromodulation effects. This novel method is expected to be a promising alternative for focal magnetic stimulation with an improved spatial resolution and lowered stimulus current than previous magnetic stimulation methods., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Because ischemic stroke is heterogeneous, the associations between low-density lipoprotein (LDL)-cholesterol levels and early vascular outcomes might be different according to the stroke subtype in acute ischemic stroke patients., Methods: This study was an analysis of a prospective, multicenter, stroke registry. Acute ischemic stroke patients previously not treated with statins were included. Admission LDL-cholesterol levels were divided into 7 groups at 20 mg/dl intervals for comparison. The primary early vascular outcome was a composite of stroke, myocardial infarction (MI) and all-cause mortality within 3 months., Results: A total of 38,531 patients (age, 68.5 ± 12.8 yrs; male, 59.6%) were analyzed for this study. The 3-month cumulative incidences of the composite of stroke, MI, and all-cause mortality significantly differed among the LDL-cholesterol level groups, with the highest event rate (11.11%) in the lowest LDL-cholesterol group (<70 mg/dl). After adjustment, the U-shaped associations of LDL-cholesterol levels with primary outcome and all-cause mortality were observed. For the stroke subtypes, there were substantial interactions between the LDL-cholesterol groups and stroke subtype and all-cause mortality (P interaction =0.07). Different patterns, with higher risks of all-cause mortality in the lower LDL-cholesterol in the large artery atherosclerosis subtype (adjusted hazard ratio [aHR] 1.29, 95% confidence interval [CI] 0.98-1.69), but in the higher LDL-cholesterol in the cardioembolism subtype (aHR 1.71 95% CI [1.28-2.29]), were observed among stroke subtypes., Conclusion: We found that there were differential associations of admission LDL-cholesterol levels with all-cause mortality within 3 months among stroke subtypes. These results suggest that admission LDL-cholesterol and early vascular outcomes had complex relationships in patients with ischemic stroke according to the stroke subtypes., (Copyright © 2023. Published by Elsevier Inc.)

Early detection of melanoma is critical to good patient outcomes, but we still know little about the mechanisms of early melanoma development. Normal epidermis has many of the sequence variants and genetic architecture disruptions found in both benign nevi, melanomas, and other skin cancers, yet continues to behave more or less normally. One hypothesis is that many melanocytes in this context are "tumor competent" but are regulated by the microenvironment provided by the surrounding keratinocytes to inhibit progress to nevi or melanoma. There is evidence of accumulating disorder in several measures of the genomic and epigenomic landscape from normal skin through nevi to melanoma that may be key to promoting nevogenesis and melanomagenesis., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Autoimmune hepatitis (AIH) is a prominent cause of chronic liver disease in the United States. This study aims to characterize the incidence, mortality, and cost implications of this condition using a national database., Method: The 2016-2019 National Inpatient Sample was used to select patients with AIH. After adjusting for inflation, weighted charge data were used to calculate the admission costs using charge-to-cost ratios. Demographic, socioeconomic status, and comorbidity values were used to build strata to characterize admission incidence, mortality data and aggregate and per-capita cost values. Furthermore, additional sensitivity analysis was performed using a stratified set of patients with AIH as one of the top 10 diagnosis (AIH-specific subsample). Multinomial regression curves were graphed and assessed to derive goodness-of-fit for each trend. R 2 and P -values were calculated., Results: From 2016 to 2019, the total admissions related to AIH were approximately 20,984, 21,905, 22,055, and 22,680 cases, respectively (R 2 : 0.93, P -value: 0.03). AIH-related hospitalization aggregate costs came to $338.18, $369.17, $355.98, and $387.25 million dollars (R 2 : 0.75, P -value: 0.17). Significant admission growth was seen in the Southern region (R 2 : 0.91, P -value: 0.05). Most notably, increasing trends in total admissions were found across older age, those of White and Hispanic descent, and those with comorbidities. On the other hand, the AIH-specific subsample illustrated decreasing trends in admissions across demographics (i.e., age, gender, and race) and comorbidities; however, those with hepatic complications saw a rise in the admission trends (cirrhosis - R 2 : 0.98, P -value: 0.009; multiple liver complications - R 2 : 0.95, P -value: 0.03)., Conclusion: Among AIH-specific admissions, there was a decreasing trend overall; however, there was an exceptional increase in the admissions among those with hepatic complications., (© 2023 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Adhesive remnants post-orthodontic treatment might have deleterious effects on oral health, including enamel demineralization, plaque accumulation, and elevated risk of caries development. The aim of this study was to identify and characterize adhesive residues in an ex vivo environment rich in salivary microbiota using quantitative light-induced fluorescence (QLF) technology., Methods: Disc-shaped adhesive samples with thickness ranging from 800 to 100 µm were prepared using GC Ortho, GOTO, T Orthobond, and Transbond XT and subsequently evaluated utilizing a QLF system. Bovine teeth containing GC Ortho and GOTO adhesives and isolated human premolar teeth bonded with brackets were subjected to a 10-day incubation in an artificial saliva environment. Daily imaging was conducted using QLF during incubation. Data with ΔR > 30% and simple hygiene score (SHS) were obtained with a software for further analysis., Results: Fluorescence intensity exhibited significant differences among the four orthodontic adhesives (p < 0.05). Results of incubation in artificial saliva revealed that red fluorescence surrounding the adhesive on the tooth surface was distinctly observable from day five onwards, with ΔR > 30% and SHS levels higher than those of the control group without adhesive (p < 0.05). Observation of fluorescence images of isolated human premolar teeth with bonded brackets indicated that red fluorescence was primarily present around the brackets., Conclusions: Application of QLF is efficacious in identifying and demarcating adhesive residues within an environment rich in salivary microbiota., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: The objective of this study was to evaluate and compare the 3-dimensional (3D) aging changes of the lips among adult skeletal Class I, II, and III malocclusion., Methods: Female adult orthodontic patients aged 20-50 years with pretreatment cone-beam computed tomography scans were retrospectively classified according to age (20s [20-29 years], 30s [30-39 years], and 40s [40-49 years]) and then subclassified by malocclusion into skeletal Class I, II, and III relationship (9 groups; n = 30 per group). Positional differences in midsagittal and parasagittal soft-tissue landmarks and 3D morphologic aging changes of the lips were evaluated using cone-beam computed tomography scans., Results: Labiale superius and cheilion for patients in their 40s indicated a significant downward and backward position compared with those in their 20s, regardless of skeletal classifications (P <0.05). Accordingly, the upper lip height decreased, and the mouth width increased significantly (P <0.05). For Class III malocclusion, the upper lip vermilion angle was greater for patients in their 40s than those in their 20s (P <0.05), whereas the lower lip vermilion angle was only lower for patients with Class II malocclusion (P <0.05)., Conclusions: Middle-aged adult females (40-49 years) had a lower upper lip height and greater mouth width than those in their 20s, regardless of skeletal malocclusion. However, prominent morphologic aging changes of the lips were noted on the upper lip for skeletal Class III malocclusion and the lower lip for skeletal Class II malocclusion, implying that the underlying skeletal features (or malocclusion) may influence 3D aging changes of the lips., (Copyright © 2023 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed at demonstrating the remineralization effect of the enamel around the brackets to aid reduction in white spot lesions (WSLs) with use of zinc-doped phosphate-based glass (Zn-PBG) containing orthodontic adhesives., Methods: Zn-PBG powder was synthesized, and particle morphology, size, and density were evaluated. Orthodontic adhesives with increasing loading percentage of Zn-PBG powder were prepared: ZnPG3 (3 wt.%), ZnPG6 (6 wt.%), and ZnPG9 (9 wt.%). Brackets were bonded on the etched enamel surface and stored in distilled water (DW) for 1 h. Following, Shear bond strength (SBS) along with adhesive remnant index were analyzed. The release of calcium (Ca), phosphorus (P), and zinc (Zn) from adhesive specimens in DW was evaluated after 7, 15 and 30 days of immersion. The remineralization effect was confirmed by microhardness and surface morphology analysis with scanning electron microscopy., Results: The SBS value was observed between 20 and 22 MPa on enamel surface. The concentration of Ca, P and Zn released in DW increased with loading percentage of Zn-PBG. The microhardness increased in the experimental groups after immersion in artificial saliva for 7 days. Apatite-like crystal formation was observed after 30 days in the ZnPG 9 group., Conclusions: The orthodontic adhesive containing Zn-PBG with an optimal SBS performance has an enamel remineralization effect, and therefore can aid in prevention of WSLs., Clinical Significance: The orthodontic adhesive containing Zn-PBG is clinically advantageous as it can promote remineralization and resist the formation of WSLs that may occur during orthodontic therapy., 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 Ltd. All rights reserved.)

Background & Aims: In this study, we evaluate the effects of donor gender on post-liver transplant (LT) prognosis. We specifically consider patients with primary biliary cholangitis (PBC)., Methods: The 2005 to 2019 UNOS transplant registry was used to select patients with PBC. The study cohort was stratified by donor gender. All-cause mortality and graft failure hazards were compared using iterative Cox regression analysis. Subanalyses were performed to evaluate gender mismatch on post-LT prognosis., Results: There were 1885 patients with PBC. Of these cases, 965 entries had male donors and 920 had female donors. Median follow-up was 4.82 (25-75% IQR 1.83-8.93) years. Having a male donor was associated with higher all-cause mortality (aHR 1.28 95%CI 1.03-1.58) and graft failure (aHR 1.70 95%CI 1.02-2.82). Corresponding incidence rates were also relatively increased. In the sub-analysis of female recipients (n = 1581), those with gender-mismatch (male donors, n = 769) were associated with higher all-cause mortality (aHR 1.41 95%CI 1.11-1.78) but not graft failure. In the male recipient subanalysis (n = 304), no associations were found between gender-mismatch (female donors, n = 108) and all-cause mortality or graft failure., Conclusion: This study shows that recipients who have male donors experienced higher rates of all-cause mortality following LT. This finding was consistent in the female recipient-male donor mismatch cohort., Competing Interests: Declaration of Competing Interest The authors of this manuscript certify they share no affiliation or involvement with any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. None declared., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Lipid paradox of low LDL-C may cause physicians to be reluctant to use statins in acute ischemic stroke (AIS) patients with low LDL-C levels at admission., Objective: This study investigated the association between LDL-C levels and early vascular outcomes and assessed the potential interaction effect between LDL-C and statin pretreatment on early outcomes., Patients and Methods: This was a study of a prospective, multicenter, registry of AIS patients with admission LDL-C. The subjects were divided into 3 groups according to LDL-C levels: low LDL-C (≤100 mg/dL); intermediate LDL-C (>100, <130 mg/dL); and high LDL-C (≥130 mg/dL). The primary early vascular outcome was a composite of stroke (ischemic or hemorrhagic), myocardial infarction and all-cause mortality within 3 months. The associations of LDL-C levels as a continuous variable and the risks of primary outcome using Cox proportional hazards models with restricted cubic splines were explored., Results: A total of 32,505 patients (age, 69 ± 12; male, 58.6%) were analyzed. The 3 groups showed significant differences in the 3-month primary outcome, with highest events in the low LDL-C group; after adjustment, no significant associations with the 3-month primary outcome remained. U-shaped nonlinear relationships of LDL-C levels with the 3-month primary outcome were observed (P non-linearity <0.001), with substantial relationships in the no pretreatment subgroup., Conclusions: The relationships between admission LDL-C levels and early outcomes are complex but appear to be paradoxical in patients with low LDL-C and no statin pretreatment. The results suggest that statin pretreatment might offset the paradoxical response of low LDL-C on early vascular outcomes. Further study would be warranted., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

Background: Sutures exist in the craniofacial area, and the pattern of maturation and synostosis of facial sutures is largely unknown., Methods: For a comprehensive understanding of the three-dimensional circummaxillary suture micromorphology, human midpalatal suture (MPS) and pterygomaxillary articular complex from eight subjects' (five males, three females, 72-88 years old) autopsies were longitudinally scanned with microcomputed tomography. Additional histology was performed for hematoxylin and eosin staining. Sutural micromorphology was assessed by interdigitation index (II), obliteration index (OI) and obliteration number. Intergroup comparisons were performed with Kruskal-Wallis and Mann-Whitney U with Bonferroni correction (α = 0.005). Correlation with anteroposterior and craniocaudal gradients was assessed with Spearman's correlation test (α = 0.05)., Results: Maxillary region of MPS presented a higher II 1.50 (0.61) and obliteration number per slice 8 (9) (P < 0.005). OI was increased in palatomaxillary 35% (47%) followed by pterygopalatine suture 25% (49%) (P < 0.005). The II and OI of the MPS exhibited only a weak anteroposterior gradient, with relatively low correlations. Obliteration areas were found sporadically along the entire MPS., Conclusions: Based on these findings, it is conceivable that the success of nonsurgical maxillary expansion largely depends on individual variations in sutural morphology and maturation rather than appliance design., (Copyright © 2023 World Federation of Orthodontists. Published by Elsevier Inc. All rights reserved.)

DNA adducts and strand breaks are induced by various exogenous and endogenous agents. Accumulation of DNA damage is implicated in many disease processes, including cancer, aging, and neurodegeneration. The continuous acquisition of DNA damage from exogenous and endogenous stressors coupled with defects in DNA repair pathways contribute to the accumulation of DNA damage within the genome and genomic instability. While mutational burden offers some insight into the level of DNA damage a cell may have experienced and subsequently repaired, it does not quantify DNA adducts and strand breaks. Mutational burden also infers the identity of the DNA damage. With advances in DNA adduct detection and quantification methods, there is an opportunity to identify DNA adducts driving mutagenesis and correlate with a known exposome. However, most DNA adduct detection methods require isolation or separation of the DNA and its adducts from the context of the nuclei. Mass spectrometry, comet assays, and other techniques precisely quantify lesion types but lose the nuclear context and even tissue context of the DNA damage. The growth in spatial analysis technologies offers a novel opportunity to leverage DNA damage detection with nuclear and tissue context. However, we lack a wealth of techniques capable of detecting DNA damage in situ. Here, we review the limited existing in situ DNA damage detection methods and examine their potential to offer spatial analysis of DNA adducts in tumors or other tissues. We also offer a perspective on the need for spatial analysis of DNA damage in situ and highlight Repair Assisted Damage Detection (RADD) as an in situ DNA adduct technique with the potential to integrate with spatial analysis and the challenges to be addressed., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The desorption of cesium (Cs) from contaminated clay minerals remains challenging because of the restricted efficiency of the removal process. Therefore, in the present study, a bead-type adsorbent was added during the conventional acid washing process to improve the removal of Cs + from a clay mineral. As the Cs + adsorbent, polyacrylonitrile-based nickel potassium hexacyanoferrate (NiFC-PAN) was used to selectively adsorb Cs + in a strongly acidic solution containing competing ions. To prevent erosion of the adsorbent under harsh environmental conditions and to facilitate the separation of clay particles, PAN was deliberately constructed as large beads. The synthesized adsorbent (NiFC/PAN in a 2:1 ratio) showed high selectivity for Cs + , with a maximum capacity for Cs + adsorption of 162.78 mg/g in 0.5 M HNO 3 solution. Because the NiFC-PAN demonstrated greater Cs + selectivity than the clay mineral (hydrobiotite, HBT), the addition of NiFC-PAN during the acid washing significantly increased Cs + desorption (73.3%) by inhibiting the re-adsorption of Cs + on the HBT. The radioactivity of 137 Cs-HBT was substantially decreased from 209 to 27 Bq/g by the acid treatment in the presence of NiFC-PAN, corresponding to a desorption efficiency of 87.1%. Therefore, these results suggest that the proposed technique is a potentially useful and effective method for decontamination of radioactive clay., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Background & Aims: We investigate the effects of advancing donor age on the prognostic outcomes of patients with NASH who undergo liver transplant (LT), with a specialized attention toward infectious outcomes post-LT., Methods: The UNOS-STAR registry was used to select 2005 to 2019 LT recipients with NASH, who were stratified by donor age into the following categories: recipients with younger donors (less than 50 years of age-reference), quinquagenarian donors, sexagenarian donors, septuagenarian donors, and octogenarian donors. Cox regression analyses were conducted for all-cause mortality, graft failure, infectious causes of death., Results: From a total of 8888 recipients, the quinquagenarian, septuagenarian, and octogenarian donor cohorts showed greater risk of all-cause mortality (quinquagenarian: aHR 1.16 95%CI 1.03-1.30; septuagenarian: aHR 1.20 95%CI 1.00-1.44; octogenarian: aHR 2.01 95%CI 1.40-2.88). With advancing donor age, there was an increased risk of death from sepsis (quinquagenarian: aHR 1.71 95% CI 1.24-2.36; sexagenarian: aHR 1.73 95% CI 1.21-2.48; septuagenarian: aHR 1.76 95% CI 1.07-2.90; octogenarian: aHR 3.58 95% CI 1.42-9.06) and infectious causes (quinquagenarian: aHR 1.46 95% CI 1.12-1.90; sexagenarian: aHR 1.58 95% CI 1.18-2.11; septuagenarian: aHR 1.73 95% CI 1.15-2.61; octogenarian: aHR 3.70 95% CI 1.78-7.69)., Conclusion: NASH patients who receive grafts from elderly donors exhibit higher risk of post-LT mortality, especially due to infection., Competing Interests: Conflict of Interest The authors of this manuscript certify they share no affiliation or involvement with any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. None declared., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Poly (methyl methacrylate) (PMMA) is a commonly used material for the fabrication of biomedical appliances. Although PMMA has several advantages, it is susceptible to microbial insults with practical use. Therefore, different bioactive nanomaterials, such as nanoceria (CeN), have been proposed to enhance the properties of PMMA. In this study, we investigated the effect of the incorporation of CeN into PMMA with and without the use of mesoporous silica nanoparticle (SBA-15) carriers. The unmodified PMMA specimens (control, CTRL) were compared to groups containing SBA-15, CeN, and the synthesized SBA-15 impregnated with CeN (SBA-15@CeN) at different loading percentages. The mechanical and physical properties of the different SBA-15@CeN groups and their effects on cell viability were investigated, and the optimal CeN concentration was identified accordingly. Our results revealed that flexural strength was significantly (P < 0.01) reduced in the SBA-15@CeN 3× group (containing 3-fold the CeN wt. %). Although the surface microhardness increased with the increase in the wt. % of SBA-15@CeN, cell viability was significantly reduced (P < 0.001). The SBA-15@CeN 1× group had the optimal concentration and displayed significant resistance to single-and multispecies microbial colonization. Finally, the enzymatic activity of CeN was significantly high in the SBA-15@CeN 1× group. The proinflammatory markers (IL-6, IL-1β, TNF-α, CD80, and CD86) showed a significant (P < 0.001) multifold reduction in lipopolysaccharide-induced RAW cells treated with a 5-day eluate of the SBA-15@CeN 1× group. These results indicate that the addition of SBA-15@CeN at 1.5 wt % improves the biological response of PMMA without compromising its mechanical properties., 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 Ltd. All rights reserved.)

We evaluated the neuroprotective effect of L-theanine in Parkinson's disease and the underlying mechanism focusing on WNT/β-catenin signaling mediated by the MAPK pathway. We treated MPTP-induced SH-SY5Y cells with various concentrations of L-theanine (50, 100, 200, and 500 μg/mL), and we also treated Parkinson's model mice with L-theanine. L-theanine treatment effectively reduced the immunohistochemical hallmarks of Parkinson's disease, particularly Lewy bodies and α-synuclein, and increased the number of tyrosine hydroxylase-positive cells. L-theanine also improved the motor dysfunction in MPTP-induced Parkinson's disease model mice as measured by the rotarod test. The levels of several pro-inflammatory mediators that are overexpressed in Parkinson's disease, namely TNF-α, IL-6, COX-2, and MAC-1, were reduced following L-theanine treatment, and the levels of the pro-apoptotic proteins Bcl-2, caspase-3, p53, and PARP-1 were significantly reduced. L-theanine regulated the oxidative stress-related factors SOD-1, GST, and NOX-4 by targeting several proteins related to WNT/β-catenin signaling, i.e., β-catenin, WNT-3a, WNT-5a, TCF1/TCF7, and LEF1, via the MAPK pathway (p-JNK, p-ERK, and p-p38). Our results indicate that L-theanine is neuroprotective and has anti-inflammatory effects that could be beneficial for treating Parkinson's disease., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

Purpose: (1) To analyze three-dimensional (3D) morphologic features of atypical femur fracture at actual size without projection error; and (2) to provide clinical implications of cephalomedullary nail (CMN) fixation by separating the medullary canal and the cortex., Materials and Methods: Fifty-nine atypical femurs (opposite non-fractured femurs) were reconstructed as 3D models with medullary canal by importing CT data into Mimics® software. A reference line was drawn from the tip of the greater trochanter to the center of the intercondylar notch and used for classifying bowing grade according to the centerline of medulla. Proximal and distal straight lines (length of 60 mm, diameter of 1 mm) were placed in the centerline of medulla. Acute angles between the two straight lines were measured as lateral and anterior bowing. The acute angle by straight line and reference line was measured as proximal and distal bowing in both AP and lateral view. The diameter of curve (DOC) of medulla along the posterior border was measured., Results: The anterior bowing of all femur on lateral view was an average of 13.82° (range, 6.2°-31.1°, SD 3.91), and the values of proximal and distal anterior bowing were an average of 7.82° (range, 2.7°-14.3°, SD 2.23) and 6.0° (range, 2.2°-16.8°, SD 2.31), respectively. The lateral bowing of all femur on AP view was an average of 5.49° (range, 0.1°-17.3°, SD 4.48), and the values of proximal and distal anterior bowing were an average of 3.64° (range, 0.1°-11.3°, SD 2.70) and 2.48° (range, 0-7.4°, SD 1.98), respectively. The medullary canal was changed to be straightened and more bowed anteriorly. Concerning the lateral bowing grade of entire diaphysis, it was grade -I for 15 femurs, grade 0 for 21 femurs, grade I for nine femurs, grade II for five femurs, and grade III for nine femurs. Regarding anterior bowing grade, it was grade II for 14 femurs and grade III for 45 femurs. The average diameter of medullary canal was 1276.3 ± 232.25 mm., Conclusion: Asian atypical femur had three morphologic features: (1) straightened medullary canal, (2) positive values of lateral bowing, and (3) significantly increased ante-curvature of medullary canal. Considering that conventional CMN had about 4° of mediolateral angle, the disparity between implant and medullary canal might be clear. Thus, new nail design for Asian atypical femur that could increase the radius of curve (ROC) but decrease the mediolateral angle needs to be introduced., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2022. Published by Elsevier Ltd.)

Purpose: The hand has unique skin characteristics. Intrinsic flap donors are limited due to functional specificity and compactly connected structures. The hypothenar area is a reliable option for the reconstruction of finger defects. We performed anatomic studies elucidating the blood supply of this area and hypothesized that the fourth common palmar digital artery perforator free flap can be used to reconstruct soft tissue defects in fingers with minimal donor site morbidity., Methods: From November 2017 to February 2020, 30 procedures of fourth common digital artery perforator free flaps were performed to cover digital skin defects. A retrospective chart review was performed, and the cases were analyzed., Results: The mean patient age was 42.4 years (range, 1-75 years; median age, 40 years). Defects were located at the fingertip (n = 12), the dorsum (n = 3), the palmar (n = 9) aspect of the finger, and both the dorsal and palmar aspects of the finger (n = 6). Indications included emergent coverage (n = 13), coverage after necrosis (n = 11), oncological resection (n = 1), and contracture release (n = 5). The defect size ranged from 1.5 × 0.8 cm (1.2 cm 2 ) to 6 × 2.5 cm (15 cm 2 ). The perforator was located approximately 1 cm proximal to the distal palmar crease as it arose from the fourth common digital artery at a right angle. It continued to the ulnar border of the hand through the superficial fascia of the hypothenar muscles before running in a proximoulnar direction toward the dorsum of the hand. The diameter of the perforator was between 0.5 and 0.7 mm. All flaps survived. One case required a split-thickness skin graft for donor site closure, and all others could be closed primarily., Conclusions: The fourth common digital artery perforator is a versatile flap and can be used for both palmar and dorsal defects, including for the fingertip. The location of the perforator used differs from previous descriptions but is routinely and reliably located., Type of Study/level of Evidence: Therapeutic IV., (Copyright © 2022 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Background: Endoscopic biliary drainage is the treatment of choice for patients with malignant distal common bile duct obstruction. Self-expandable metal stents have clinical advantages including an increased duration of patency that may be prolonged by acetylsalicylic acid (ASA) use. The aim of this study was to investigate whether ASA had a positive effect on the patency of self-expandable metal stents compared with placebo., Methods: This prospective, multicenter, double-blinded, and randomized placebo-controlled trial was conducted from October 2017 to May 2020 in Korea. Patients who underwent palliative endoscopic biliary drainage with self-expandable metal stents for malignant distal bile duct obstruction were enrolled, and allocated to ASA treatment or placebo. The study outcomes were the rate of stent dysfunction at 6 months, duration of stent patency, risk factors for stent dysfunction, and any adverse events., Results: Interim analysis included 24 and 28 patients in the ASA and placebo groups, respectively. There was no significant difference between the ASA and placebo groups in stent dysfunction (25.0% vs. 20.7%, P = 0.761) or the duration of stent patency (150.97 ± 10.55 vs. 158.07 ± 8.70 days, P = 0.497). Six patients experienced suspected ASA-related adverse events, and there was one lethal case., Conclusions: ASA did not prolong stent patency. This study was terminated early because of the possibility of serious adverse events related to ASA treatment of these patients receiving palliative care., (Copyright © 2021 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Bicyclization has proven to be an effective strategy for significantly restricting conformational flexibility in peptides and peptidomimetics such as peptoids. Such constrained bicyclic peptoids would have far higher conformational rigidity than monocyclic and linear ones, allowing them to have enhanced binding affinity and selectivity for their biological targets. Herein, we show that bicyclic peptoids have superior cellular uptake efficiency than their linear counterparts regardless of their side chains and ring sizes. As a representative example, an 8-mer bicyclic peptoid achieves a CP 50 value of 1.2 μM, which is > 5-times superior to the corresponding linear peptoid. Additionally, we also demonstrate that bicyclic peptide-peptoid hybrids are much more cell-permeable than native peptides. Due to their favorable properties including improved cellular uptake, resistance to proteolytic degradation, relatively large sizes, and enormous structural diversity, constrained bicyclic peptoids and peptide-peptoid hybrids will play an important role as potential drug leads, especially in targeting intracellular protein-protein interactions, which are traditionally considered undruggable., (Copyright © 2022. Published by Elsevier Inc.)

Cerebral palsy (CP) is a nonprogressive neurological disorder and the most common physical disability of childhood. There is no cure for CP, but stem cells have the potential to improve brain injury and hence function. This phase 1 clinical trial investigated the safety of the intravenous infusion of full-matched sibling cord blood cells for children with CP aged 1 to 16 years. Preliminary efficacy outcomes were also investigated. Twelve participants received 12/12 HLA-matched sibling cord blood cell infusions. One treatable serious adverse reaction to cryoprotectant was observed, and no adverse reactions occurred beyond 24 h after infusion. Gross motor function measure (GMFM-66) scores did not improve compared with baseline beyond what could be expected from developmental levels, and participants had varied changes in the Quality of Upper Extremity Skills Test (QUEST) and Vineland Adaptive Behavior Scales (VABS-II) scores. In conclusion, matched sibling cord blood cell infusion for children with CP is relatively safe when conducted in an appropriate facility. Australian and New Zealand Clinical Trials Registry (ACTRN12616000403437) and Clinicaltrials.gov (NCT03087110)., Competing Interests: Declaration of Competing Interest Cell Care Australia is a private cord blood bank with a representative on the Trial Steering Committee. There is, therefore, a potential conflict of interest which has been declared to HREC and Steering Committee and is well recognized. No one affiliated with Cell Care Australia was involved in data analysis or interpretation., (Copyright © 2022 International Society for Cell & Gene Therapy. All rights reserved.)

Introduction: In this study, we aimed to evaluate and compare the bracket positioning accuracy of the indirect bonding (IDB) transfer tray fabricated in-clinic using the tray printing (TP) and marker-model printing methods (MP)., Methods: The TP group was further divided into 2 groups (single-tray printing [STP] and multiple-tray printing [MTP]) depending on the presence of a tray split created using the 3-dimensional (3D) software. Five duplicated plaster models were used for each of the 3 experimental groups, and a total of 180 artificial teeth, except the second molar, were evaluated in the experiment. The dental model was scanned using a model scanner (E3; 3Shape Dental Systems, Copenhagen, Denmark). Virtual brackets were placed on facial axis points, and the IDB trays were designed and fabricated using a 3D printer (VIDA; EnvisionTEC, Mich). The accuracy of bracket positioning was evaluated by comparing the planned bracket positions and the actual bracket positions using 3D analysis on inspection software. The main effects and first-order interaction effects were analyzed together by analysis for the analysis of variance., Results: The mean distance and height errors were significantly lower in the STP group than those in the MP and MTP groups (P <0.05). The mean distance error was 0.06 mm in the STP group and 0.09 mm in the MP and MTP groups. The mean height error was 0.10 mm in the STP group and 0.15 mm and 0.18 mm in MP and MTP groups, respectively. However, no significant differences were observed in the angular errors among the 3 groups., Conclusions: The in-office-fabricated IDB system with computer-aided design and 3D printer is clinically applicable after considering the linear and angular errors. We recommend IDB trays fabricated using the STP method owing to the lower frequency of bracket positioning errors and ease of fabrication., (Copyright © 2022. Published by Elsevier Inc.)

Questions have arisen around new metrics for organ procurement organizations (OPO) due to the perception that low-performing OPOs may be limited by local centers' acceptance of marginal organs. We reviewed 2013-2019 Organ Procurement and Transplantation Network (OTPN) and National Centers for Health Statistics (NCHS) data to explore the relationship between objectively measured OPO performance and utilization of deceased donor kidneys. We found that although donor recovery declined with rising age and kidney donor profile index (KDPI), OPO performance differences were evident within each age/KDPI group. By contrast, the number of discards per donor did not vary with OPO performance. Centers in donor service areas (DSAs) with lower-performing OPOs had higher local utilization and greater import of high-KDPI kidneys than did those with higher-performing OPOs. Lower rates of donor availability relative to waitlist additions may contribute to observed center acceptance behavior. Differences in center-level performance were highly visible in Scientific Registry of Transplant Recipients (SRTR) organ acceptance metrics, while SRTR OPO metrics did not detect large or persistent variation in procurement performance. Cumulatively, our findings suggest that objective measures of procurement performance can inform discussions of organ utilization, allowing for alignment of metrics in all elements of the procurement-transplantation system., (© 2022 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: IQSEC3, a gephyrin-binding GABAergic (gamma-aminobutyric acidergic) synapse-specific guanine nucleotide exchange factor, was recently reported to regulate activity-dependent GABAergic synapse maturation, but the underlying signaling mechanisms remain incompletely understood., Methods: We generated mice with conditional knockout (cKO) of Iqsec3 to examine whether altered synaptic inhibition influences hippocampus-dependent fear memory formation. In addition, electrophysiological recordings, immunohistochemistry, and behavioral assays were used to address our question., Results: We found that Iqsec3-cKO induces a specific reduction in GABAergic synapse density, GABAergic synaptic transmission, and maintenance of long-term potentiation in the hippocampal CA1 region. In addition, Iqsec3-cKO mice exhibited impaired fear memory formation. Strikingly, Iqsec3-cKO caused abnormally enhanced activation of ribosomal P70-S6K1-mediated signaling in the hippocampus but not in the cortex. Furthermore, inhibiting upregulated S6K1 signaling by expressing dominant-negative S6K1 in the hippocampal CA1 of Iqsec3-cKO mice completely rescued impaired fear learning and inhibitory synapse density but not deficits in long-term potentiation maintenance. Finally, upregulated S6K1 signaling was rescued by IQSEC3 wild-type, but not by an ARF-GEF (adenosine diphosphate ribosylation factor-guanine nucleotide exchange factor) inactive IQSEC3 mutant., Conclusions: Our results suggest that IQSEC3-mediated balanced synaptic inhibition in hippocampal CA1 is critical for the proper formation of hippocampus-dependent fear memory., (Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Context: Missing data are common in hospice/palliative care randomized trials due to high drop-out because of the demographic of interest. It can introduce bias in the estimate of the treatment effect and its precision., Objectives: The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) released updated guidance on statistical principles for clinical trials introducing the estimand framework to align trial objectives, trial conduct, statistical analysis and interpretation of results. Our objective is to present how the estimand framework can be used to guide the handling of missing data in palliative care trials., Methods: We outline the estimand framework by highlighting the five elements of an estimand: treatment, population, variable, summary measure and intercurrent event handling. We list common intercurrent events in palliative care trials and present the five strategies for handling intercurrent events outlined in the ICH guidance., Results: We describe common intercurrent events in palliative care trials and discuss and justify what analytic strategies could be followed with each. We provide an example using a palliative care trial comparing two opioids for pain relieve in participants with cancer pain., Conclusion: When planning a palliative care trial, the estimand should be explicitly stated, including how intercurrent events will be handled in the analysis. This should be informed by the scientific objectives of the trial. The estimand guides the handling of missing data during the conduct and analysis of the trial. Defining an estimand is not a statistical activity, but a multi-disciplinary process involving all stakeholders., (Copyright © 2021 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Organoid cryopreservation method is one of key step in the organoid culture. We aimed to establish a simple and efficient cryopreservation method for mouse small intestinal organoids (MIOs) and colon organoids (MCOs) using various concentrations of cryoprotectant. Based on the theoretical simulation, we optimized the dimethyl sulfoxide (DMSO) concentration by pretreating the organoids with 5, 7.5, and 10% DMSO for 30 min at 4 °C to allow penetration into the organoids and evaluated their viability, proliferation, and function after cryopreservation. Gene expression in the MIOs and staining of lineage markers were examined real-time PCR. The organoids in the DMSO-treated groups as well as the control, expressed ChrgA, Ecad, Muc2, Lyz, villin, and Lgr5, and there are no significant. A forskolin-induced swelling assay for MIOs was performed to confirm normal cystic fibrosis transmembrane conductance regulator (CFTR) activity. Similar forskolin-induced swelling was observed in the DMSO-treated groups and the control. In addition, MCOs were transplanted into mouse colon for confirmation of regeneration therapy efficacy. Thawing organoids were cultured for two and four sequential passages after cryopreservation with 5% DMSO to confirm any changes in the gene expression of lineage markers after subculture. We developed a simple and efficient organoid freezing method using 5% DMSO with low potential toxicity and validated our findings with theoretical simulation., 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 Inc.)

To meet new Centers for Medicare and Medicaid Services (CMS) metrics, organ procurement organizations (OPOs) will benefit from understanding performance across decedent and hospital types. We sought to determine the utility of existing data-reporting structures for this purpose by reviewing Scientific Registry of Transplant Recipient (SRTR) OPO-Specific Reports (OSRs) from 2013 to 2019. OSRs contain both the Standardized donation rate ratio (SDRR) metric and OPO-reported numbers of "eligible deaths" and donors by hospital. Donor hospitals were characterized using information from Homeland Infrastructure Foundation-Level Data, Dartmouth Atlas Hospital Service Area data, and the US Census Bureau. Hospital data reported by OPOs showed 51% higher eligible death donors and 140% higher noneligible death donors per 100 inpatient beds in CMS ranked top versus bottom-quartile OPOs. Top-quartile OPOs by the CMS metric recovered 78% more donors than those in the bottom quartile, but were indistinguishable by SDRR rankings. These differences persisted across hospital sizes, trauma case mix, and area demographics. OPOs with divergent performance were indistinguishable over time by SDRR, but showed changes to hospital-level recovery patterns in SRTR data. Contemporaneous recognition of underperformance across hospitals may provide important and actionable data for regulators and OPOs for focused quality improvement projects., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

We investigated the immunomodulatory and anti-inflammatory efficacy of hederagenin coating on maghemite (γ-Fe 2 O 3 ) nanoparticles (HM) in atopic dermatitis (AD), as well as the physical and optical properties of maghemite nanoparticles (MP) using SEM, XRD spectroscopy, UV-vis spectra, Raman spectra, and FTIR spectroscopy. Dose-dependent treatment with HM (10, 50, 100, 200 μg/mL) inhibited the expression of Interleukin-2 (IL-2) and Tumor necrosis factor- α (TNF-α) in inflammatory induced HaCaT and Jurkat cells with inflammation caused by TNF/IFN-γ and PMA/A23187. AD model was induced by performing topical application of 2,4-dinitrochlorobenzene (DNCB) and dermatophagoides farinae extract (DFE) for a 31-day period on 8-week-old BALB/c mice. The HM treatments efficiently diminished the AD-like cutaneous lesion induced by DNCB-DFE sensitization in mice. Compared to the AD-only groups, HM treatment considerably attenuated mast cell infiltration and lowered epidermal, and dermal thickness of mice ears skin. In addition, HM treatment prominently alleviated the enlarged size and weight of lymph nodes. Furthermore, HM treatment resulted in a notable reduction in the mRNA expression of Th1 cytokines (TNF-α and IFN-γ), Th2 cytokines (IL-4 and IL-6), Th17 (IL-17), and TSLP. Our data showed that HM provides better AD attenuation compared to MP. Additionally, HM had synergistic effect and act as anti-inflammatory and immunomodulatory agent. Thus, HM shows great potential in AD medication and as a substitution of non-steroid-based medication., (Copyright © 2021. Published by Elsevier B.V.)

Background: Post-stroke cognitive impairment (PSCI) is a common consequence of stroke. Accurate prediction of PSCI risk is challenging. The recently developed network impact score, which integrates information on infarct location and size with brain network topology, may improve PSCI risk prediction., Aims: To determine if the network impact score is an independent predictor of PSCI, and of cognitive recovery or decline., Methods: We pooled data from patients with acute ischemic stroke from 12 cohorts through the Meta VCI Map consortium. PSCI was defined as impairment in ≥ 1 cognitive domain on neuropsychological examination, or abnormal Montreal Cognitive Assessment. Cognitive recovery was defined as conversion from PSCI < 3 months post-stroke to no PSCI at follow-up, and cognitive decline as conversion from no PSCI to PSCI. The network impact score was related to serial measures of PSCI using Generalized Estimating Equations (GEE) models, and to PSCI stratified according to post-stroke interval (<3, 3-12, 12-24, >24 months) and cognitive recovery or decline using logistic regression. Models were adjusted for age, sex, education, prior stroke, infarct volume, and study site., Results: We included 2341 patients with 4657 cognitive assessments. PSCI was present in 398/844 patients (47%) <3 months, 709/1640 (43%) at 3-12 months, 243/853 (28%) at 12-24 months, and 208/522 (40%) >24 months. Cognitive recovery occurred in 64/181 (35%) patients and cognitive decline in 26/287 (9%). The network impact score predicted PSCI in the univariable (OR 1.50, 95%CI 1.34-1.68) and multivariable (OR 1.27, 95%CI 1.10-1.46) GEE model, with similar ORs in the logistic regression models for specified post-stroke intervals. The network impact score was not associated with cognitive recovery or decline., Conclusions: The network impact score is an independent predictor of PSCI. As such, the network impact score may contribute to a more precise and individualized cognitive prognostication in patients with ischemic stroke. Future studies should address if multimodal prediction models, combining the network impact score with demographics, clinical characteristics and other advanced brain imaging biomarkers, will provide accurate individualized prediction of PSCI. A tool for calculating the network impact score is freely available at https://metavcimap.org/features/software-tools/lsm-viewer/., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

This study aimed to utilize cationic protein extracted from the Moringa oleifera seed in the fabrication of cationic starch crosslinked with magnetic nanoparticles (MagCS). Important synthesis parameters include starch to cationic protein volume ratio, magnetic nanoparticles mass fraction, reaction and crosslinking time, reaction and crosslinking temperature and crosslinker concentration. At optimum synthesis conditions, MagCS yield a 38.55% amide content, 2.46 degree of substitution, 1.1 mmol/g charge density and 78.6% crosslinking, which are much higher compared to other starch derivatives. A series of characterization analyses such as Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, elemental analysis and vibrating sample magnetometer concluded that MagCS was embedded with amide group, has high crystallinity structure, is thermally stable and shows a promising magnetic characteristic. Based on the synthesis parameters and characterization studies, the synthesis mechanism of MagCS was also postulated. The flocculation performance of MagCS was successfully assessed for the treatment of palm oil mill effluent. At optimum dosage, initial pH and settling time of 1.0 g/L, 9.0 and 15 min, the MagCS flocculant was able to remove 90.48, 83.95 and 58.19% of turbidity, color and chemical oxygen demand, respectively. This study provides an alternative eco-friendly materials in the wastewater treatment application., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Recent changes to organ procurement organization (OPO) performance metrics have highlighted the need to identify opportunities to increase organ donation in the United States. Using data from the Organ Procurement and Transplantation Network (OPTN), Scientific Registry of Transplant Recipients (SRTR), and Veteran Health Administration Informatics and Computing Infrastructure Clinical Data Warehouse (VINCI CDW), we sought to describe historical donation performance at Veteran Administration Medical Centers (VAMCs). We found that over the period 2010-2019, there were only 33 donors recovered from the 115 VAMCs with donor potential nationwide. VA donors had similar age-matched organ transplant yields to non-VA donors. Review of VAMC records showed a total of 8474 decedents with causes of death compatible with donation, of whom 5281 had no infectious or neoplastic comorbidities preclusive to donation. Relative to a single state comparison of adult non-VA inpatient deaths, VAMC deaths were 20 times less likely to be characterized as an eligible death by SRTR. The rate of conversion of inpatient donation-consistent deaths without preclusive comorbidities to actual donors at VAMCs was 5.9% that of adult inpatients at non-VA hospitals. Overall, these findings suggest significant opportunities for growth in donation at VAMCs., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

The keratinocytes in UV-irradiated skin produce and secrete α-melanocyte-stimulating hormone. α-Melanocyte-stimulating hormone upregulates the expression of MITF in melanocytes through the cAMP‒protein kinase A‒CREB signaling pathway. Thereafter, MITF induces the expression of melanogenic genes, including the tyrosinase gene TYR and TYRP-1 and TYRP-2 genes, which leads to the synthesis and accumulation of melanin. In this study, we examined whether MITF basic region-derived tripeptides can bind to the DNA-binding domain of MITF and inhibit MITF-induced melanogenesis through the inhibition of MITF‒DNA binding. MITF-KGR, a representative MITF-derived tripeptide, suppressed the transcriptional activity of MITF by disrupting its binding to the promoter region of the target genes, which resulted in the inhibition of skin epidermis thickness and melanin synthesis in vivo and in vitro. Our results indicate that MITF-KGR exerts an inhibitory effect on melanogenesis by targeting MITF., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Prenatal particulate matter <2.5 μm (PM 2.5 ) is associated with adverse birth growth. However, the longitudinal growth impacts have been little studied, and no mechanistic relationships have been described. We investigated the association between prenatal PM 2.5 exposure and growth trajectories, and the possible role of epigenetics. We enrolled 1313 neonates with PM 2.5 data measured by ordinary kriging from the COhort for Childhood Origin of Asthma and allergic diseases, followed up at 1, 3, and 5 years to evaluate growth. Differential DNA methylation and pyrosequencing of cord blood leukocytes was evaluated according to the prenatal PM 2.5 levels and birth weight (BW). PM 2.5 exposure during the second trimester (T2) caused the lowest BW in both sexes, further adjusted for indoor PM 2.5 levels [female, aOR 1.39 (95% CI 1.05-1.83); male, aOR 1.36 (95% CI 1.04-1.79)]. Bayesian distributed lag models with indoor PM 2.5 adjustments revealed a sensitive window for BW effects at 10-26 weeks gestation, but only in females. Latent class mixture models indicated that a persistently low weight-for-height percentile trajectory was more prevalent in the highest PM 2.5 exposure quartile at T2 in females, compared to a persistently high trajectory (36.5% vs. 20.3%, P = 0.022). Also, in the females only, the high PM 2.5 and low BW neonates showed significantly greater ARRDC3 methylation changes. ARRDC3 methylation was also higher only in females with low weight at 5 years of age. Higher fetal PM 2.5 exposure during T2 may cause a decreased growth trajectory, especially in females, mediated by ARRDC3 hyper-methylation-associated energy metabolism., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The application of 3D imaging is at its cusp in craniofacial diagnosis and treatment planning. However, most applications are limited to simple subjective superimposition-based analysis. As the diagnostic accuracy dictates the precision in operability, we propose a novel method that enables objective clinical decision making for patients with mandibular asymmetry. We analyzed cone-beam computed tomography (CBCT) scans of 34 patients who underwent surgical correction for mandibular asymmetry using a high-throughput computing algorithm. Radiomic segmentation of quantitative features of surface and volume followed by exploration resulted in identification of a computed modified absolute mandibular midsagittal plane (cmAMP). Tomographic similarity scan (ToSS) curves were generated via bilateral equidistant scanning in an antero-posterior direction with cmAMP as the reference. ToSS comprised of a comprehensive similarity index (SI) score curve and a segment-wise volume curve. The SI score was computed using the Sørensen-Dice similarity coefficient ranging from 0 to 1. The volumetric analysis was represented as the non-overlapping volume (NOV) and overlapping volume (OV) for each segment, with two segmentation lines, at the mental foramen anteriorly and the intraoral vertical ramus osteotomy region posteriorly. Statistical analysis showed strong negative correlation between the NOV and SI scores for the anterior, middle, and total mandible (P < 0.001). Additionally, a significant correlation was observed between the change in the SI scores for anterior (P = 0.044) and middle segments (P < 0.001) to the total mandible when comparing the data before and after the surgery. This work demonstrated the potential of incorporating ToSS curves in surgical simulation software to improve precision in the clinical decision-making process., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background & Aims: The benefits of farnesoid X receptor (FXR) agonists in patients with non-alcoholic steatohepatitis (NASH) have been validated, although improvements in efficacy and/or tolerability remain elusive. Herein, we aimed to assess the performance of a structurally optimized FXR agonist in patients with NASH., Methods: In this 12-week, randomized, placebo-controlled study, we evaluated MET409 - a non-bile acid agonist with a unique chemical scaffold - in patients with NASH. Patients were randomized to receive either 80 mg (n = 20) or 50 mg (n = 19) of MET409, or placebo (n = 19)., Results: At Week 12, MET409 lowered liver fat content (LFC), with mean relative reductions of 55% (80 mg) and 38% (50 mg) vs. 6% in placebo (p <0.001). MET409 achieved ≥30% relative LFC reduction in 93% (80 mg) and 75% (50 mg) of patients vs. 11% in placebo (p <0.001) and normalized LFC (≤5%) in 29% (80 mg) and 31% (50 mg) of patients vs. 0% in placebo (p <0.05). An increase in alanine aminotransferase (ALT) was observed with MET409, confounding Week 12 changes from baseline (-25% for 80 mg, 28% for 50 mg). Nonetheless, MET409 achieved ≥30% relative ALT reduction in 50% (80 mg) and 31% (50 mg) of patients vs. 17% in placebo. MET409 was associated with on-target high-density lipoprotein cholesterol decreases (mean changes of -23.4% for 80 mg and -20.3% for 50 mg vs. 2.6% in placebo) and low-density lipoprotein cholesterol (LDL-C) increases (mean changes of 23.7% for 80 mg and 6.8% for 50 mg vs. -1.5% in placebo). Pruritus (mild-moderate) occurred in 16% (50 mg) and 40% (80 mg) of MET409-treated patients., Conclusion: MET409 lowered LFC over 12 weeks in patients with NASH and delivered a differentiated pruritus and LDL-C profile at 50 mg, providing the first clinical evidence that the risk-benefit profile of FXR agonists can be enhanced through structural optimization., Lay Summary: Activation of the farnesoid X receptor (FXR) is a clinically validated approach for treating non-alcoholic steatohepatitis (NASH), although side effects such as itching or increases in low-density lipoprotein cholesterol are frequently dose-limiting. MET409, an FXR agonist with a unique chemical structure, led to significant liver fat reduction and delivered a favorable side effect profile after 12 weeks of treatment in patients with NASH. These results provide the first clinical evidence that the risk-benefit profile of FXR agonists can be enhanced., Competing Interests: Conflict of interest SAH and EJL are advisors of Metacrine, Inc. MRB serves as Principal Investigator on grants provided to his institution by Metacrine, Inc. K-JL, JS-L, JL, BW, NDS and HCC are employees of Metacrine, Inc. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Missing data are ubiquitous in medical research. Although there is increasing guidance on how to handle missing data, practice is changing slowly and misapprehensions abound, particularly in observational research. Importantly, the lack of transparency around methodological decisions is threatening the validity and reproducibility of modern research. We present a practical framework for handling and reporting the analysis of incomplete data in observational studies, which we illustrate using a case study from the Avon Longitudinal Study of Parents and Children. The framework consists of three steps: 1) Develop an analysis plan specifying the analysis model and how missing data are going to be addressed. An important consideration is whether a complete records' analysis is likely to be valid, whether multiple imputation or an alternative approach is likely to offer benefits and whether a sensitivity analysis regarding the missingness mechanism is required; 2) Examine the data, checking the methods outlined in the analysis plan are appropriate, and conduct the preplanned analysis; and 3) Report the results, including a description of the missing data, details on how the missing data were addressed, and the results from all analyses, interpreted in light of the missing data and the clinical relevance. This framework seeks to support researchers in thinking systematically about missing data and transparently reporting the potential effect on the study results, therefore increasing the confidence in and reproducibility of research findings., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Many studies on the relation between maternal health and infant health, including the effect of structured antenatal education, have been published and expanded over the years., Aim: Investigate the impact of various antenatal education programmes on pregnancy outcomes to aid the development of future guidelines related to maternal and foetal health., Methods: Bibliographic databases (Cochrane, PubMed, EMBASE, CINAHL, Korean Studies Information Service System) were searched up to November 2018, following the PICO criteria: population (pregnant women), intervention (antenatal education), comparison (not specified), and outcome (maternal and foetal outcome including physical or mental health components)., Findings: We included 23 eligible studies consisting of 14 controlled trials and 9 observational studies. The maternal physical outcomes depending on participation in antenatal education were not significantly different; however, the caesarean birth rate was lower in the antenatal education group (relative risk, RR, 0.90; 95% confidence interval, CI, 0.82-0.99), as was the use of epidural anaesthesia (RR, 0.84; 95% CI, 0.74-0.96). The maternal mental health outcomes of stress and self-efficacy significantly improved in the antenatal education group, although there was no difference in anxiety and depression. The foetal outcomes of birth weight or gestational age at birth were also not different between the groups., Conclusion: Antenatal education can reduce maternal stress, improve self-efficacy, lower the caesarean birth rate, and decrease the use of epidural anaesthesia; however, there is limited evidence of its effects on maternal or foetal physical outcomes. Therefore, antenatal education should be standardised to elucidate its actual mental and physical health effects., (Copyright © 2020 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: Declaration-of Competing Interest The authors declare that they have no competing interests.

Ulaanbaatar City, Mongolia is rapidly becoming urbanized and attracts great attention because of environmental issues. This study was performed to assess the status of groundwater quality in Ulaanbaatar at an early but growing stage of urbanization, focusing on nitrate contamination in relation to land use. Along with high total dissolved solids and NO 3 - concentrations, significant contamination of groundwater is indicated by positive loadings of NO 3 - , Cl - and δ 15 N-NO 3 - along the first principal component of the principal component analysis (PCA). Based on the concentrations and δ 15 N values of nitrate, groundwater is classified into two groups: Group I (baseline quality) and II (contaminated). Nitrate in Group II water in urbanized (esp. peri-urban) areas is higher in concentration (> 10 mg/l NO 3 - ) and N-isotopic values (> 10‰ δ 15 N-NO 3 - ), while pristine hydrochemistry is observed restrictedly in grassland and forest areas. Other ions (e.g., Cl - and SO 4 2- ) are also higher in Group II water. The δ 15 N-NO 3 - values in Group II water in combination with the spatial distribution on the land use map indicate that nitrate originates from untreated sewage effluents including pit-latrine leakage in peri-urban areas, while nitrate in Group I water originates from soil organic matter. The relationship between nitrate concentrations and δ 2 H (and δ 18 O) values of water suggests that nitrate enrichment is also influenced by evaporation during groundwater recharge. With the help of PCA for compositional data, we suggest a hydrochemical index for groundwater contamination assessment; i.e., the Groundwater Quality Index (GQI) that consists of three variables (concentrations of dissolved silica, nitrate and chloride) and can be used to delineate zones vulnerable to nitrate contamination as a crucial step for the efficient monitoring and management of groundwater quality. The study results suggest an urgent need for the management of unsealed pit latrines that are common in peri-urban areas with high population density., 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 © 2020 Elsevier B.V. All rights reserved.)

Enzyme immobilization provides substantial advantages in terms of improving the efficiency of enzymatic process as well as enhancing the reusability of enzymes. Phasins (PhaPs) are naturally occurring polyhydroxyalkanoate (PHA)-binding proteins, and thus can potentially be used as a fusion partner for oriented immobilization of enzymes onto PHA supports. However, presently available granular PHA supports have low surface-area-to-volume ratio and limited configurational flexibility of enzymatic reactions. In this study, we explored the use of electrospun polyhydroxybutyrate (PHB) nanofibers as an alternative support for high density immobilization of a PhaP-fused lipase. As envisioned, the electrospun PHB nanofibers could anchor 120-fold more enzyme than PHB granules of the same weight. Furthermore, the enzymes immobilized onto the PHB nanofibers exhibited markedly higher stability and activity compared to when immobilized on conventional immobilization supports. Our approach combines the advantageous features of nanofibrous material and specificity of biomolecular interaction for the efficient use of enzymes, which can be widely adopted in the development of various enzymatic processes., (Copyright © 2021 Elsevier Inc. All rights reserved.)