Search

Nickel ditelluride (NiTe2), a recently discovered Type-II Dirac semimetal with topological Dirac fermions near the Fermi energy, is expected to exhibit strong thickness-mediated electronic tunability and intrinsic two-gap superconductivity in the single-layer limit. Realizing such intriguing phenomena requires the fabrication of ultrathin NiTe2 films and an understanding of the underlying physics that is still under debate. By conducting experimental band mappings of ultrathin films prepared with molecular beam epitaxy, we reveal spectroscopic evidence for the dimensionality crossover of single-crystalline ultrathin NiTe2 films as a function of film thickness. As the film thickness increases from one to five layers, the gap in the conical topological surface states closes. Comparisons of experimental to first-principles results also highlight difficulties in fabricating atomically smooth single-layer NiTe2 films. Our results not only provide further impetus for studying emergent phenomena in NiTe2 but also underscore the limitations of fabricating NiTe2 films for device applications.

Layered quasi-two-dimensional transition-metal dichalcogenides (TMDCs), which can be readily made in ultrathin films, offer excellent opportunities for studying how dimensionality affects electronic structure and physical properties. Among all TMDCs, NbSe2 is of special interest; bulk NbSe2 hosts a charge-density-wave phase at low temperatures and has the highest known superconducting transition temperature, and these properties can be substantially modified in the ultrathin film limit. Motivated by these effects, we report herein a study of few-layer NbSe2 films, with a well-defined single-domain orientation, epitaxially grown on GaAs. Angle-resolved photoemission spectroscopy was used to determine the electronic band structure and the Fermi surface as a function of layer thickness; first-principles band-structure calculations were performed for comparison. The results show interesting changes as the film thickness increases from a monolayer (ML) to several layers. The most notable changes occur between a ML and a bilayer, where the inversion symmetry in bulk NbSe2 is preserved in the bilayer but not in the ML. The results illustrate some basic dimensional effects and provide a basis for further exploring and understanding the properties of NbSe2.

© 2018 American Physical Society. Stanene (single-layer gray tin), with an electronic structure akin to that of graphene but exhibiting a much larger spin-orbit gap, offers a promising platform for room-temperature electronics based on the quantum spin Hall (QSH) effect. This material has received much theoretical attention, but a suitable substrate for stanene growth that results in an overall gapped electronic structure has been elusive; a sizable gap is necessary for room-temperature applications. Here, we report a study of stanene, epitaxially grown on the (111)B-face of indium antimonide (InSb). Angle-resolved photoemission spectroscopy measurements reveal a gap of 0.44 eV, in agreement with our first-principles calculations. The results indicate that stanene on InSb(111) is a strong contender for electronic QSH applications.

In this paper, we present a three-dimensional one-step photoemission model that can be used to calculate the quantum efficiency and momentum distributions of electrons photoemitted from ordered single-crystal surfaces close to the photoemission threshold. Using Ag(111) as an example, we show that the model can not only calculate the quantum efficiency from the surface state accurately without using any ad hoc parameters, but also provides a theoretical quantitative explanation of the vectorial photoelectric effect. This model in conjunction with other band structure and wave function calculation techniques can be effectively used to screen single-crystal photoemitters for use as electron sources for particle accelerator and ultrafast electron diffraction applications.

Spin-helical Dirac Fermions at a doped topological insulator's boundaries can support Majorana quasiparticles when coupled with s -wave superconductors, but in n -doped systems, the requisite induced Cooper pairing in topological states is often buried at heterointerfaces or complicated by degenerate coupling with bulk conduction carriers. Rarely probed are p -doped topological structures with nondegenerate Dirac and bulk valence bands at the Fermi level, which may foster long-range superconductivity without sacrificing Majorana physics. Using ultrahigh-resolution photoemission, we report proximity pairing with a large decay length in p -doped topological Sb 2 Te 3 on superconducting Nb. Despite no momentum-space degeneracy, the topological and bulk states of Sb 2 Te 3 /Nb exhibit the same isotropic superconducting gaps at low temperatures. Our results unify principles for realizing accessible pairing in Dirac Fermions relevant to topological superconductivity.

Cervical synovial cyst (CSC) is a rare condition that often leads patients to seek medical attention due to cervical stenosis symptoms. There's ongoing debate about the best management strategy. To address this, a review of literature from the past 20 years (2003-2023) was conducted using keywords like "cervical synovial cyst," "cervical ganglion cyst," and "cervical juxtafacet cyst." Data on patient demographics, imaging characteristics, treatment methods, and clinical outcomes were collected. A total of 79 patients were diagnosed with CSCs, averaging 62.3 years old, with a slight male predominance (45 males, 34 females). Most cysts were located at the C1-2 and C7-T1 joints, with myelopathy being the most common symptom. Subaxial CSCs had a higher incidence of radiculopathy compared to axial CSCs. Most cases were treated surgically, with decompression performed with or without fusion. Patients generally reported symptom improvement regardless of the surgical method. Overall, surgical intervention effectively improved neurological symptoms associated with CSCs., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The prevalence of obesity in the United States has continued to increase over the past several decades. Understanding how diet-induced obesity modulates mucosal immunity is of clinical relevance. We previously showed that consumption of a high fat, high sugar "Western" diet (WD) reduces the density and function of small intestinal Paneth cells, a small intestinal epithelial cell type with innate immune function. We hypothesized that obesity could also result in repressed gut adaptive immunity. Using small intestinal intraepithelial lymphocytes (IEL) as a readout, we found that in non-inflammatory bowel disease (IBD) subjects, high body mass index correlated with reduced IEL density. We recapitulated this in wild type (WT) mice fed with WD. A 4-week WD consumption was able to reduce IEL but not splenic, blood, or bone marrow lymphocytes, and the effect was reversible after another 2 weeks of standard diet (SD) washout. Importantly, WD-associated IEL reduction was not dependent on the presence of gut microbiota, as WD-fed germ-free mice also showed IEL reduction. We further found that WD-mediated Farnesoid X Receptor (FXR) activation in the gut triggered IEL reduction, and this was partially mediated by intestinal phagocytes. Activated FXR signaling stimulated phagocytes to secrete type I IFN, and inhibition of either FXR or type I IFN signaling within the phagocytes prevented WD-mediated IEL loss. Therefore, WD consumption represses both innate and adaptive immunity in the gut. These findings have significant clinical implications in the understanding of how diet modulates mucosal immunity., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: T. Stappenbeck advises Janssen, Boehringer Ingelheim, Kallyope, Takada, and Roche. T.C. Liu has research contracts with Denali Therapeutics and Interline Therapeutics. All other authors declare no relevant competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Anterior cranial fossa (ACF) dural arteriovenous fistulas (DAVFs) are notoriously malignant vascular abnormalities, and their drainage into the cortical vein poses a high risk of intracranial hemorrhage (ICH). Stereotactic radiosurgery (SRS) is increasingly seen as an alternative to microsurgery or embolization for the treatment of DAVFs; however, researchers have yet to report on its applicability to ACF DAVFs. This paper summarizes the authors' experience in the use of SRS for ACF DAVFs. The authors' objective was to gain a preliminary overview of SRS outcomes in the treatment of ACF DAVFs., Methods: This retrospective study examined all patients who underwent SRS for ACF DAVFs at a single academic medical center between November 2000 and November 2023. Demographic data, DAVF characteristics, and clinical outcomes were obtained from medical records., Results: A total of 12 patients diagnosed with ACF DAVFs were treated using SRS. One patient was lost to follow-up. The mean age was 54.8 years and men comprised 82% of the cohort. The most common presenting symptoms included headache (n = 5), ocular symptoms (n = 3), seizure (n = 2), anosmia (n = 1), and tinnitus (n = 1). Two patients were asymptomatic. Four patients (36%) initially presented with ICH. Nine patients exhibited DAVF Cognard type IV, and 2 patients exhibited Cognard type III. DAVF obliteration in 7 of the 11 patients (64%) was confirmed by brain MR angiography (n = 4) or digital subtraction angiography (n = 3). No post-SRS episodes of ICH were reported. Most of the patients (10 of 11) reported improvements in clinical symptoms., Conclusions: SRS appears to be a viable alternative treatment for ACF DAVFs, particularly for patients who are not suitable candidates for surgery or those with an unfavorable angioarchitecture.

Reflectin is an intrinsically disordered protein known for its ability to modulate the biophotonic camouflage of cephalopods based on its assembly-induced osmotic properties. Its reversible self-assembly into discrete, size-controlled clusters and condensed droplets are known to depend sensitively on the net protein charge, making reflectin stimuli-responsive to pH, phosphorylation, and electric fields. Despite considerable efforts to characterize this behavior, the detailed physical mechanisms of reflectin's assembly are not yet fully understood. Here, we pursue a coarse-grained molecular understanding of reflectin assembly using a combination of experiments and simulations. We hypothesize that reflectin assembly and phase behavior can be explained from a remarkably simple colloidal model whereby individual protein monomers effectively interact via a short-range attractive and long-range repulsive (SA-LR) pair potential. We parameterize a coarse-grained SA-LR interaction potential for reflectin A1 from small-angle x-ray scattering measurements, and then extend it to a range of pH values using Gouy-Chapman theory to model monomer-monomer electrostatic interactions. The pH-dependent SA-LR interaction is then used in molecular dynamics simulations of reflectin assembly, which successfully capture a number of qualitative features of reflectin, including pH-dependent formation of discrete-sized nanoclusters and liquid-liquid phase separation at high pH, resulting in a putative phase diagram for reflectin. Importantly, we find that at low pH size-controlled reflectin clusters are equilibrium assemblies, which dynamically exchange protein monomers to maintain an equilibrium size distribution. These findings provide a mechanistic understanding of the equilibrium assembly of reflectin, and suggest that colloidal-scale models capture key driving forces and interactions to explain thermodynamic aspects of native reflectin behavior. Furthermore, the success of SA-LR interactions presented in this study demonstrates the potential of a colloidal interpretation of interactions and phenomena in a range of intrinsically disordered proteins., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Environmental enteric dysfunction (EED) is an asymptomatic intestinal disorder associated with growth impairment, delayed neurocognitive development, and impaired oral vaccine responses., Objectives: We set out to develop and validate a histopathologic scoring system on duodenal biopsies from a cohort study of children with growth failure in Bangladesh, Pakistan, and Zambia ("EED") with reference to biopsies from United States children with no clinically reported histologic pathology (referred to hereafter as "normal") or celiac disease., Methods: Five gastrointestinal pathologists evaluated 745 hematoxylin and eosin slide images from 291 children with EED (mean age: 1.6 y) and 66 United States children (mean age: 6.8 y). Histomorphologic features (i.e., villus/crypt architecture, goblet cells, epithelial and lamina propria acute/chronic inflammation, Brunner's glands, Paneth cells, epithelial detachment, enterocyte injury, and foveolar metaplasia) were used to score each histopathologic slide. Generalized estimating equations were used to determine differences between EED, normal, and celiac disease, and receiver operating characteristic curves were used to assess predictive value., Results: Biopsies from the duodenal bulb showed higher intramucosal Brunner's gland scores and lower intraepithelial lymphocyte scores than from the second or third parts of the duodenum (D2/3), so only D2/3 were included in the final analysis. Although 7 parameters differed significantly between EED and normal biopsies in regression models, only 5 (blunted villus architecture, increased intraepithelial lymphocytosis, goblet cell depletion, Paneth cell depletion, and reduced intramucosal Brunner's glands) were required to create a total score percentage (TSP-5) that correctly identified EED against normal biopsies (AUC: 0.992; 95% CI: 0.983, 0.998). Geographic comparisons showed more severe goblet cell depletion in Bangladesh and more marked intraepithelial lymphocytosis in Pakistan., Conclusions: This scoring system involving 5 histologic parameters demonstrates very high discrimination between EED and normal biopsies, indicating that this scoring system can be applied with confidence to studies of intestinal biopsies in EED., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Coupling Weyl quasiparticles and charge density waves (CDWs) can lead to fascinating band renormalization and many-body effects beyond band folding and Peierls gaps. For the quasi-one-dimensional chiral compound (TaSe 4 ) 2 I with an incommensurate CDW transition at T C = 263 K, photoemission mappings thus far are intriguing due to suppressed emission near the Fermi level. Models for this unconventional behavior include axion insulator phases, correlation pseudogaps, polaron subbands, bipolaron bound states, etc. Our photoemission measurements show sharp quasiparticle bands crossing the Fermi level at T > T C , but for T < T C , these bands retain their dispersions with no Peierls or axion gaps at the Weyl points. Instead, occupied band edges recede from the Fermi level, opening a spectral gap. Our results confirm localization of quasiparticles (holes created by photoemission) is the key physics, which suppresses spectral weights over an energy window governed by incommensurate modulation and inherent phase defects of CDW.

A two-dimensional (2D) Weyl semimetal, akin to a spinful variant of graphene, represents a topological matter characterized by Weyl fermion-like quasiparticles in low dimensions. The spinful linear band structure in two dimensions gives rise to distinctive topological properties, accompanied by the emergence of Fermi string edge states. We report the experimental realization of a 2D Weyl semimetal, bismuthene monolayer grown on SnS(Se) substrates. Using spin and angle-resolved photoemission and scanning tunneling spectroscopies, we directly observe spin-polarized Weyl cones, Weyl nodes, and Fermi strings, providing consistent evidence of their inherent topological characteristics. Our work opens the door for the experimental study of Weyl fermions in low-dimensional materials., (© 2024. The Author(s).)

Background & Aims: Biomarkers that integrate genetic and environmental factors and predict outcome in complex immune diseases such as inflammatory bowel disease (IBD; including Crohn's disease [CD] and ulcerative colitis [UC]) are needed. We showed that morphologic patterns of ileal Paneth cells (Paneth cell phenotype [PCP]; a surrogate for PC function) is one such cellular biomarker for CD. Given the shared features between CD and UC, we hypothesized that PCP is also associated with molecular/genetic features and outcome in UC. Because PC density is highest in the ileum, we further hypothesized that PCP predicts outcome in UC subjects who underwent total colectomy and ileal pouch-anal anastomosis (IPAA)., Methods: Uninflamed ileal resection margins from UC subjects with colectomy and IPAA were used for PCP and transcriptomic analyses. PCP was defined using defensin 5 immunofluorescence. Genotyping was performed using Immunochip. UC transcriptomic and genotype associations of PCP were incorporated with data from CD subjects to identify common IBD-related pathways and genes that regulate PCP., Results: The prevalence of abnormal ileal PCP was 27%, comparable to that seen in CD. Combined analysis of UC and CD subjects showed that abnormal PCP was associated with transcriptomic pathways of secretory granule maturation and polymorphisms in innate immunity genes. Abnormal ileal PCP at the time of colectomy was also associated with pouch complications including de novo CD in the pouch and time to first episode of pouchitis., Conclusions: Ileal PCP is biologically and clinically relevant in UC and can be used as a biomarker in IBD., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background/purpose: Taiwan's dentistry entered into a new era of modernization and flourished during the Japanese colonial period. However, we know very little about the composition of dentists at that time. This study attempted to analyze the ethnicity, gender, and geographical distribution of dentists in Taiwan in 1939 (Showa 14)., Materials and Methods: The methods of documentary analysis and secondary data analysis were adopted to find the composition of dentists during the late Japanese colonial period through a name list of contract dentists for the Postal Savings Insurance published in August 1939 (Showa 14) by the Taiwan Government Transportation Department Information Bureau., Results: The total number of contract dentists was 368, accounting for 86.79% of the 424 practicing dentists in Taiwan in 1939 (Showa 14). Of the 368 contract dentists (328 males and 40 females), 225 (61.14%) were Taiwanese and 143 (38.86%) were Japanese. Among the 8 prefectures in Taiwan, Tainan Prefecture had the largest number of dentists (97), followed by Taipei (84) and Taichung (78) prefectures. The number of contract dentists per 100,000 people was 6.24, equivalent to 16,021 people served by each contract dentist in 1939 (Showa 14). The chi-square test for the trend analysis of gender distribution indicated a significantly higher proportion of male than female contract dentists in either Taiwanese or Japanese ethnic group., Conclusion: In the late Japanese colonial period, the number of Taiwanese dentists exceeded that of Japanese dentists. Furthermore, there were more male than female dentists in either the Taiwanese or the Japanese population., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2024 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Many crucial components inside electronic devices are made from non-renewable, non-biodegradable, and potentially toxic materials, leading to environmental damage. Finding alternative green dielectric materials is mandatory to align with global sustainable goals. Carboxymethyl cellulose (CMC) is a bio-polymer derived from cellulose and has outstanding properties. Herein, citric acid, dextrin, and CMC based hydrogels are prepared, which are biocompatible and biodegradable and exhibit rubber-like mechanical properties, with Young modulus values of 0.89 MPa. Hence, thin film CMC-based hydrogel is explored as a suitable green high-k dielectric candidate for operation at low voltages, demonstrating a high dielectric constant of up to 78. These fabricated transistors reveal stable high capacitance (2090 nF cm -2 ) for ≈±3 V operation. Using a polyelectrolyte-type approach and poly-(2-vinyl anthracene) (PVAn) surface modification, this study demonstrates a thin dielectric layer (d ≈30 nm) with a small voltage threshold (V th ≈-0.8 V), moderate transconductance (g m ≈65 nS), and high ON-OFF ratio (≈10 5 ). Furthermore, the dielectric layer exhibits stable performance under bias stress of ± 3.5 V and 100 cycles of switching tests. The modified CMC-based hydrogel demonstrates desirable performance as a green dielectric for low-voltage operation, further highlighting its biocompatibility., (© 2024 Wiley‐VCH GmbH.)

Crohn disease (CD) burden has increased with globalization/urbanization, and the rapid rise is attributed to environmental changes rather than genetic drift. The Study Of Urban and Rural CD Evolution (SOURCE, n = 380) has considered diet-omics domains simultaneously to detect complex interactions and identify potential beneficial and pathogenic factors linked with rural-urban transition and CD. We characterize exposures, diet, ileal transcriptomics, metabolomics, and microbiome in newly diagnosed CD patients and controls in rural and urban China and Israel. We show that time spent by rural residents in urban environments is linked with changes in gut microbial composition and metabolomics, which mirror those seen in CD. Ileal transcriptomics highlights personal metabolic and immune gene expression modules, that are directly linked to potential protective dietary exposures (coffee, manganese, vitamin D), fecal metabolites, and the microbiome. Bacteria-associated metabolites are primarily linked with host immune modules, whereas diet-linked metabolites are associated with host epithelial metabolic functions., (© 2024. The Author(s).)

Introduction: Circulating tissue transglutaminase immunoglobulin A concentration is a sensitive and specific indicator of celiac disease, but discrepancies between serologic and histologic findings occur. We hypothesized that fecal markers of inflammation and protein loss would be greater in patients with untreated celiac disease than in healthy controls. Our study aims to evaluate multiple fecal and plasma markers in celiac disease and correlate these findings with serologic and histologic findings as noninvasive means of evaluating disease activity., Methods: Participants with positive celiac serologies and controls with negative celiac serologies were prospectively enrolled before upper endoscopy. Blood, stool, and duodenal biopsies were collected. Concentrations of fecal lipocalin-2, calprotectin, and alpha-1-antitrypsin and plasma lipocalin-2 were determined. Biopsies underwent modified Marsh scoring. Significance was tested between cases and controls, modified Marsh score and tissue transglutaminase immunoglobulin A concentration., Results: Lipocalin-2 was significantly elevated in the stool ( P = 0.006) but not the plasma of participants with positive celiac serologies. There was no significant difference in fecal calprotectin or alpha-1 antitrypsin between participants with positive celiac serologies and controls. Fecal alpha-1 antitrypsin >100 mg/dL was specific, but not sensitive for biopsy-proven celiac disease., Discussion: Lipocalin-2 is elevated in the stool but not the plasma of patients with celiac disease suggesting a role of local inflammatory response. Calprotectin was not a useful marker in the diagnosis of celiac disease. While random fecal alpha-1 antitrypsin was not significantly elevated in cases compared with controls, an elevation of greater than 100 mg/dL was 90% specific for biopsy-proven celiac disease., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Composite topological heterostructures, wherein topologically protected states are electronically tuned due to their proximity to other matter, are key avenues for exploring emergent physical phenomena. Particularly, pairing a topological material with a superconductor such as Pb is a promising means for generating a topological superconducting phase with exotic Majorana quasiparticles, but oft-neglected is the emergence of bulklike spin-polarized states that are quite relevant to applications. Using high-resolution photoemission spectroscopy and first-principles calculations, we report the emergence of bulk-like spin-polarized topological quantum well states with long coherence lengths in Pb films grown on the topological semimetal Sb. The results establish Pb/Sb heterostructures as topological superconductor candidates and advance the current understanding of topological coupling effects required for realizing emergent physics and for designing advanced spintronic device architectures.

Background/purpose: Taiwan's eight dental schools are all located in the western region. This study attempted to analyze the relationship between the geographical distribution of dentists in Taiwan and their graduation school background and to develop several statistical indicators to analyze the geographical distribution of dentists., Materials and Methods: The method of the secondary data analysis was adopted to collect the open information related to the number of the practicing dentists based on their graduation schools and practice locations by cities and counties in Taiwan in January 2023. The data were used to develop several statistical indicators to analyze the geographical distribution of dentists., Results: There were 16,533 practicing dentists in Taiwan in January 2023. Of the 16,533 dentists, 15,687 (94.88 %) graduated from domestic dental schools and 846 (5.12 %) graduated from foreign dental schools. For the school location, the coefficient of variation, Gini coefficient, population proportion index, and population density index were the largest (168.57 %, 0.47, 10.76 %, and 3927.01 people/square kilometer) in the dentists graduating from the northern dental schools. In overall, the dentists were concentrated in municipalities, cities, and the northern region of Taiwan, especially those graduating from the northern dental schools., Conclusion: In Taiwan, the geographical distribution of dentists is highly related to their graduation school background. Promoting a balanced distribution of dental enrollment quotas and dental student sources from different geographical locations and inducing the movement of dentists to the dentist-shortage areas may be the more feasible ways to solve the uneven geographical distribution of dentists in Taiwan., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2024 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Competing Interests: A conflict of interest occurs when an individual's objectivity is potentially compromised by a desire for financial gain, prominence, professional advancement or a successful outcome. JDS Editors strive to ensure that what is published in the Journal is as balanced, objective and evidence-based as possible. Since it can be difficult to distinguish between an actual conflict of interest and a perceived conflict of interest, the Journal requires authors to disclose all and any potential conflicts of interest.

Background: Pancreatic neuroendocrine tumors (PNETs) with low microvessel density and fibrosis often exhibit clinical aggressiveness. Given the contribution of cancer-associated fibroblasts (CAFs) to the hypovascular fibrotic stroma in pancreatic ductal adenocarcinoma, investigating whether CAFs play a similar role in PNETs becomes imperative. In this study, we investigated the involvement of CAFs in PNETs and their effects on clinical outcomes., Methods: We examined 79 clinical PNET specimens to evaluate the number and spatial distribution of α-smooth muscle actin (SMA)-positive cells, which are indicative of CAFs. Then, the findings were correlated with clinical outcomes. In vitro and in vivo experiments were conducted to assess the effects of CAFs (isolated from clinical specimens) on PNET metastasis and growth. Additionally, the role of the stromal-cell-derived factor 1 (SDF1)-AGR2 axis in mediating communication between CAFs and PNET cells was investigated., Results: αSMA-positive and platelet-derived growth factor-α-positive CAFs were detected in the hypovascular stroma of PNET specimens. A higher abundance of α-SMA-positive CAFs within the PNET stroma was significantly associated with a higher level of clinical aggressiveness. Notably, conditioned medium from PNET cells induced an inflammatory phenotype in isolated CAFs. These CAFs promoted PNET growth and metastasis. Mechanistically, PNET cells secreted interleukin-1, which induced the secretion of SDF1 from CAFs. This cascade subsequently elevated AGR2 expression in PNETs, thereby promoting tumor growth and metastasis. The downregulation of AGR2 in PNET cells effectively suppressed the CAF-mediated promotion of PNET growth and metastasis., Conclusion: CAFs drive the growth and metastasis of aggressive PNETs. The CXCR4-SDF1 axis may be a target for antistromal therapy in the treatment of PNET. This study clarifies mechanisms underlying PNET aggressiveness and may guide future therapeutic interventions targeting the tumor microenvironment., (© 2024. The Author(s).)

Surface electroactive sites for tungstate zirconia (WZ) were created by utilizing tungstate-immobilized UiO-66 as precursors via a double-solvent impregnation method under a mild calcination temperature. The WZ-22-650 catalyst, containing a moderate W content (22%), demonstrated a high density of surface electroactive sites. Proper heat treatment facilitated the binding of oligomeric tungsten clusters to stabilized tetragonal ZrO 2 , resulting in improved catalytic performance toward the VO 2+ /VO 2 + redox couples compared to other tested samples. The substantial surface area, mesoporous structure, and establishment of new W-O-Zr bonds affirm the firm anchoring of WO x to ZrO 2 . This robust attachment enhances surface electroactive sites, elevating the electrochemical performance of vanadium redox flow batteries (VRFBs). Charge-discharge tests further demonstrate that the superior voltage efficiency (VE) and energy efficiency (EE) for VRFBs using the WZ-22-650 catalyst are 87.76 and 83.94% at 80 mA cm -2 , which are 13.42% VE and 10.88% EE better than heat-treated graphite felt, respectively. Even at a higher current density of 160 mA cm -2 , VRFBs utilizing the WZ-22-650 catalyst maintained considerable efficiency, recording VE and EE values of 76.76 and 74.86%, respectively. This facile synthesis method resulted in WZ catalysts displaying superior catalytic activity and excellent cyclability, offering a promising avenue for the development of metal-oxide-based catalysts.

Background: Artificial intelligence (AI) has become a promising tool in medicine. ChatGPT, a large language model AI Chatbot, shows promise in supporting clinical practice. We assess the potential of ChatGPT as a clinical reasoning tool for mechanical thrombectomy in patients with stroke., Methods: An internal validation of the abilities of ChatGPT was first performed using artificially created patient scenarios before assessment of real patient scenarios from the medical center's stroke database. All patients with large vessel occlusions who underwent mechanical thrombectomy at Tulane Medical Center between January 1, 2022 and December 31, 2022 were included in the study. The performance of ChatGPT in evaluating which patients should undergo mechanical thrombectomy was compared with the decisions made by board-certified stroke neurologists and neurointerventionalists. The interpretation skills, clinical reasoning, and accuracy of ChatGPT were analyzed., Results: 102 patients with large vessel occlusions underwent mechanical thrombectomy. ChatGPT agreed with the physician's decision whether or not to pursue thrombectomy in 54.3% of the cases. ChatGPT had mistakes in 8.8% of the cases, consisting of mathematics, logic, and misinterpretation errors. In the internal validation phase, ChatGPT was able to provide nuanced clinical reasoning and was able to perform multi-step thinking, although with an increased rate of making mistakes., Conclusion: ChatGPT shows promise in clinical reasoning, including the ability to factor a patient's underlying comorbidities when considering mechanical thrombectomy. However, ChatGPT is prone to errors as well and should not be relied on as a sole decision-making tool in its present form, but it has potential to assist clinicians with more efficient work flow., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Environmental enteric dysfunction (EED) is a diffuse small bowel disorder associated with poor growth, inadequate responses to oral vaccines, and nutrient malabsorption in millions of children worldwide. We identify loss of the small intestinal Paneth and goblet cells that are critical for innate immunity, reduced villous height, increased bile acids, and dysregulated nicotinamide adenine dinucleotide (NAD + ) synthesis signaling as potential mechanisms underlying EED and which also correlated with diminished length-for-age z score. Isocaloric low-protein diet (LPD) consumption in mice recapitulated EED histopathology and transcriptomic changes in a microbiota-independent manner, as well as increases in serum and fecal bile acids. Children with refractory EED harbor single-nucleotide polymorphisms in key enzymes involved in NAD + synthesis. In mice, deletion of Nampt , the gene encoding the rate-limiting enzyme in the NAD + salvage pathway, from intestinal epithelium also reduced Paneth cell function, a deficiency that was further aggravated by LPD. Separate supplementation with NAD + precursors or bile acid sequestrant partially restored LPD-associated Paneth cell defects and, when combined, fully restored all histopathology defects in LPD-fed mice. Therapeutic regimens that increase protein and NAD + contents while reducing excessive bile acids may benefit children with refractory EED.

Angiopoietin-like protein 3 (ANGPTL3) plays an important role in lipid and lipoprotein trafficking and metabolism and is positively correlated with cardiovascular disease. Our objective was to evaluate the association between serum ANGPTL3 levels and endothelial function in patients on maintenance hemodialysis (MHD). We enrolled 116 patients on MHD and obtained their blood test results from their medical records. Using a noninvasive digital thermal monitor, we determined the vascular reactivity index (VRI) as a measure of endothelial function. Serum ANGPTL3 concentration was measured by a commercial-enzyme-linked immunosorbent assay. Vascular reactivity was classified as poor in 17 (14.7%) patients, intermediate (1.0 ≤ VRI < 2.0) in 50 (43.1%) patients, and high (VRI ≥ 2.0) in 49 (42.2%) patients. Serum levels of ANGPTL3 ( p < 0.001) and alkaline phosphatase (ALP, p = 0.025) increased significantly as the VRI decreased. The log-transformed serum ALP (log-ALP, r = -0.187, p = 0.045) and log-ANGPTL3 ( r = -0.319, p < 0.001) showed a negative correlation with the VRI on univariate linear regression analysis. A significant negative correlation was found between log-ANGPTL3 and VRI ( p < 0.001) on multivariate stepwise linear regression analysis. The findings of our investigation showed that, in patients with MHD, the ANGPTL3 concentration had a negative correlation with the VRI.

Heme-oxidized IRP2 ubiquitin ligase-1 (HOIL1)-deficient patients experience chronic intestinal inflammation and diarrhea as well as increased susceptibility to bacterial infections. HOIL1 is a component of the linear ubiquitin chain assembly complex that regulates immune signaling pathways, including NF-κB-activating pathways. We have shown previously that HOIL1 is essential for survival following Citrobacter rodentium gastrointestinal infection of mice, but the mechanism of protection by HOIL1 was not examined. C. rodentium is an important murine model for human attaching and effacing pathogens, enteropathogenic and enterohemorrhagic Escherichia coli that cause diarrhea and foodborne illnesses and lead to severe disease in children and immunocompromised individuals. In this study, we found that C. rodentium infection resulted in severe colitis and dissemination of C. rodentium to systemic organs in HOIL1-deficient mice. HOIL1 was important in the innate immune response to limit early replication and dissemination of C. rodentium. Using bone marrow chimeras and cell type-specific knockout mice, we found that HOIL1 functioned in radiation-resistant cells and partly in radiation-sensitive cells and in myeloid cells to limit disease, but it was dispensable in intestinal epithelial cells. HOIL1 deficiency significantly impaired the expansion of group 3 innate lymphoid cells and their production of IL-22 during C. rodentium infection. Understanding the role HOIL1 plays in type 3 inflammation and in limiting the pathogenesis of attaching and effacing lesion-forming bacteria will provide further insight into the innate immune response to gastrointestinal pathogens and inflammatory disorders., (Copyright © 2023 by The American Association of Immunologists, Inc.)

Paneth cells (PCs), a specialized secretory cell type in the small intestine, are increasingly recognized as having an essential role in host responses to microbiome and environmental stresses. Whether and how commensal and pathogenic microbes modify PC composition to modulate inflammation remain unclear. Using newly developed PC-reporter mice under conventional and gnotobiotic conditions, we determined PC transcriptomic heterogeneity in response to commensal and invasive microbes at single cell level. Infection expands the pool of CD74 + PCs, whose number correlates with auto or allogeneic inflammatory disease progressions in mice. Similar correlation was found in human inflammatory disease tissues. Infection-stimulated cytokines increase production of reactive oxygen species (ROS) and expression of a PC-specific mucosal pentraxin (Mptx2) in activated PCs. A PC-specific ablation of MyD88 reduced CD74 + PC population, thus ameliorating pathogen-induced systemic disease. A similar phenotype was also observed in mice lacking Mptx2. Thus, infection stimulates expansion of a PC subset that influences disease progression., (© 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)

Background: ChatGPT is a large language model artificial intelligence chatbot that has been applied to different aspects of the medical field. Our study aims to assess the quality of chatGPT to evaluate patients based on their exams for different scores including Glasgow Coma Scale (GCS), intracranial hemorrhage score (ICH), and Hunt & Hess (H&H) classification., Methods: We created batches of patient test cases with detailed neurological exams, totaling 20 cases and created variants of increasing complex phrasing of the test cases. Using ChatGPT, we assessed repeatability and quantified the errors, including the average error rate (AER) and magnitude of errors (AME). We repeated this process for the H&H and the ICH score using base cases. Specific prompts were created for each calculator., Results: The GCS calculator on 10 base test cases had an AER/AME of 10%/0.150. The accuracy of ChatGPT decreased with increasing complexity; for example, in a variation where crucial information was missing, the AER was 45% for 20 cases. For H&H, AER/AME was 13%/0.13 and for ICH, AER/AME was 27.5%/0.325. Using a simple prompt resulted in a significantly higher error rate of 70%., Conclusions: ChatGPT demonstrates ability in this proof-of-concept experiment in evaluating neuroexams using established assessment scales including GCS, ICH, and H&H. However, it has limitations in accuracy and may "hallucinate" with complex or vague descriptions. Nonetheless, ChatGPT, has promising potential in medicine., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Stunting is known to be heavily influenced by environmental factors, so the genetic contribution has received little attention. Here we report an exploration of genetic influences in stunted Zambian children with environmental enteropathy., Method: Children with stunting (LAZ < -2) were enrolled and given nutritional therapy. Those that were non-responsive to therapy were designated as cases, and children with good growth (LAZ > -1) from the same community as controls. Blood and stool samples were taken to measure biomarkers of intestinal inflammation, epithelial damage, and microbial translocation. Single nucleotide polymorphism array genotyping was carried out on saliva samples using the H3Africa consortium array., Results: Genome wide associations were analysed in 117 cases and 41 controls. While no significant associations with stunting were observed at P<5x10-8, likely due to the small sample size, interesting associations were observed at lower thresholds. SNPs associated with stunting were in genomic regions known to modulate neuronal differentiation and fatty acid biosynthesis. SNPs associated with increased microbial translocation were associated with non-integrin membrane ECM interactions, tight junctions, hemostasis, and G-alpha signalling events. SNPs associated with increased inflammation were associated with, ECM interactions, purine metabolism, axon guidance, and cell motility. SNPs negatively associated with inflammation overlapped genes involved in semaphoring interactions. We explored the existing coeliac disease risk HLA genotypes and found present: DQ2.5 (7.5%), DQ8 (3.5%) and DQ2.2 (3.8%); however, no children were positive for coeliac antibodies. We detected HLA-DRB:1301 and HLA-C:1802 with high odds ratios and P<0.05 in stunted children compared to controls., Conclusion: Genetic variations associated with stunting and the enteropathy underlying it, include variants associated with multiple pathways relating to gene expression, glycosylation, nerve signalling, and sensing of the nutritional and microbiological milieu., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mweetwa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Dietary fiber improves metabolic health, but host-encoded mechanisms for digesting fibrous polysaccharides are unclear. In this work, we describe a mammalian adaptation to dietary chitin that is coordinated by gastric innate immune activation and acidic mammalian chitinase (AMCase). Chitin consumption causes gastric distension and cytokine production by stomach tuft cells and group 2 innate lymphoid cells (ILC2s) in mice, which drives the expansion of AMCase-expressing zymogenic chief cells that facilitate chitin digestion. Although chitin influences gut microbial composition, ILC2-mediated tissue adaptation and gastrointestinal responses are preserved in germ-free mice. In the absence of AMCase, sustained chitin intake leads to heightened basal type 2 immunity, reduced adiposity, and resistance to obesity. These data define an endogenous metabolic circuit that enables nutrient extraction from an insoluble dietary constituent by enhancing digestive function.

The characteristic excitation of a metal is its plasmon, which is a quantized collective oscillation of its electron density. In 1956, David Pines predicted that a distinct type of plasmon, dubbed a 'demon', could exist in three-dimensional (3D) metals containing more than one species of charge carrier 1 . Consisting of out-of-phase movement of electrons in different bands, demons are acoustic, electrically neutral and do not couple to light, so have never been detected in an equilibrium, 3D metal. Nevertheless, demons are believed to be critical for diverse phenomena including phase transitions in mixed-valence semimetals 2 , optical properties of metal nanoparticles 3 , soundarons in Weyl semimetals 4 and high-temperature superconductivity in, for example, metal hydrides 3,5-7 . Here, we present evidence for a demon in Sr 2 RuO 4 from momentum-resolved electron energy-loss spectroscopy. Formed of electrons in the β and γ bands, the demon is gapless with critical momentum q c  = 0.08 reciprocal lattice units and room-temperature velocity v = (1.065 ± 0.12) × 10 5 m s -1 that undergoes a 31% renormalization upon cooling to 30 K because of coupling to the particle-hole continuum. The momentum dependence of the intensity of the demon confirms its neutral character. Our study confirms a 67-year old prediction and indicates that demons may be a pervasive feature of multiband metals., (© 2023. The Author(s).)

Brown rice has been advocated for as a healthier alternative to white rice. However, the concentration of arsenic and other pesticide contaminants is greater in brown rice than in white. The potential health risks and benefits of consuming more brown rice than white rice remain unclear; thus, mainstream nutritional messaging should not advocate for brown rice over white rice. This mini-review aims to summarize the most salient concepts related to dietary arsenic exposure with emphasis on more recent findings and provide consumers with evidence of both risks and benefits of consuming more brown rice than white rice. Despite risk-benefit assessments being a challenging new frontier in nutrition, researchers should pursue an assessment to validate findings and solidify evidence. In the interim, consumers should be cognizant that the dose of arsenic exposure determines its toxicity, and brown rice contains a greater concentration of arsenic than white rice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Su, Chiang and O’Connor.)

Curcumin (Cur) is a beneficial phytochemical with numerous health advantages. However, its limited solubility in oil and poor stability hinder its potential for biomedical applications. In this study, we employed a mixture of food-grade Tween 60, a polymeric surfactant, and Span 60 to adjust the hydrophilic lipophilic balance number (HLB t ) and prepared nanoemulsions (NEs) of coconut oil (Cc oil) as carriers for Cur. The effects of HLB t values, surfactant-to-oil ratio, and oil ratio on the physicochemical characteristics of the food-grade oil-NEs were investigated using dynamic light scattering, transmission electron microscopy, differential scanning calorimetry, fluorescence polarization spectroscopy, and viscometry. Increasing the addition ratio of Tween 60 in the NEs, thereby increasing the HLB t , resulted in a reduction in NE size and an improvement in their storage stability. The temperature and size of the phase transition region of the NEs decreased with increasing HLB t . NEs with higher HLB t exhibited a disordering effect on the intra-NE molecular packing of Cc oil. NEs with high HLB t displayed low viscosity and demonstrated nearly Newtonian fluid behavior, while those with lower HLB t exhibited pseudoplastic fluid behavior. Cur was effectively encapsulated into the Cc oil-NEs, with higher encapsulation efficiency observed in NEs with higher HLB t values. Furthermore, the Cur remaining activity was significantly enhanced through encapsulation within stable NEs. The biocompatibility of the Cc oil-NEs was also demonstrated in vitro. In summary, this study highlights the preparation of stable NEs of Cc oil by adjusting the HLB t using Tween 60, facilitating effective encapsulation of Cur. These findings provide valuable insights for the development of Cur carriers with improved solubility, stability, and bioavailability., Competing Interests: The authors declare that they have no conflict of interest.

Non-alcoholic fatty liver disease is associated with ageing, and impaired mitochondrial homeostasis is the main cause for hepatic ageing. Caloric restriction (CR) is a promising therapeutic approach for fatty liver. The purpose of the present study was to investigate the possibility of early-onset CR in decelerating the progression of ageing-related steatohepatitis. The putative mechanism associated with mitochondria was further determined. C57BL/6 male mice at 8 weeks of age were randomly assigned to one of three treatments: Young-AL (AL, ad libitum), Aged-AL, or Aged-CR (60% intake of AL). Mice were sacrificed when they were 7 months old (Young) or 20 months old (Aged). Aged-AL mice displayed the greatest body weight, liver weight, and liver relative weight among treatments. Steatosis, lipid peroxidation, inflammation, and fibrosis coexisted in the aged liver. Mega mitochondria with short, randomly organized crista were noticed in the aged liver. The CR ameliorated these unfavourable outcomes. The level of hepatic ATP decreased with ageing, but this was reversed by CR. Ageing caused a decrease in mitochondrial-related protein expressions of respiratory chain complexes (NDUFB8 and SDHB) and fission (DRP1), but an increase in proteins related to mitochondrial biogenesis (TFAM), and fusion (MFN2). CR reversed the expression of these proteins in the aged liver. Both Aged-CR and Young-AL revealed a comparable pattern of protein expression. To summarize, this study demonstrated the potential of early-onset CR in preventing ageing-associated steatohepatitis, and maintaining mitochondrial functions may contribute to CR's protection during hepatic ageing., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

RNA-binding protein 47 (RBM47) is required for embryonic endoderm development, but a role in adult intestine is unknown. We studied intestine-specific Rbm47-knockout mice (Rbm47-IKO) following intestinal injury and made crosses into ApcMin/+ mice to examine alterations in intestinal proliferation, response to injury, and tumorigenesis. We also interrogated human colorectal polyps and colon carcinoma tissue. Rbm47-IKO mice exhibited increased proliferation and abnormal villus morphology and cellularity, with corresponding changes in Rbm47-IKO organoids. Rbm47-IKO mice adapted to radiation injury and were protected against chemical-induced colitis, with Rbm47-IKO intestine showing upregulation of antioxidant and Wnt signaling pathways as well as stem cell and developmental genes. Furthermore, Rbm47-IKO mice were protected against colitis-associated cancer. By contrast, aged Rbm47-IKO mice developed spontaneous polyposis, and Rbm47-IKO ApcMin/+ mice manifested an increased intestinal polyp burden. RBM47 mRNA was decreased in human colorectal cancer versus paired normal tissue, along with alternative splicing of tight junction protein 1 mRNA. Public databases revealed stage-specific reduction in RBM47 expression in colorectal cancer associated independently with decreased overall survival. These findings implicate RBM47 as a cell-intrinsic modifier of intestinal growth, inflammatory, and tumorigenic pathways.

The need for a lightweight and reliable segmentation algorithm is critical in various biomedical image-prediction applications. However, the limited quantity of data presents a significant challenge for image segmentation. Additionally, low image quality negatively impacts the efficiency of segmentation, and previous deep learning models for image segmentation require large parameters with hundreds of millions of computations, resulting in high costs and processing times. In this study, we introduce a new lightweight segmentation model, the mobile anti-aliasing attention u-net model (MAAU), which features both encoder and decoder paths. The encoder incorporates an anti-aliasing layer and convolutional blocks to reduce the spatial resolution of input images while avoiding shift equivariance. The decoder uses an attention block and decoder module to capture prominent features in each channel. To address data-related problems, we implemented data augmentation methods such as flip, rotation, shear, translate, and color distortions, which enhanced segmentation efficiency in the international Skin Image Collaboration (ISIC) 2018 and PH2 datasets. Our experimental results demonstrated that our approach had fewer parameters, only 4.2 million, while it outperformed various state-of-the-art segmentation methods.

An electrocardiogram (ECG) is a basic and quick test for evaluating cardiac disorders and is crucial for remote patient monitoring equipment. An accurate ECG signal classification is critical for real-time measurement, analysis, archiving, and transmission of clinical data. Numerous studies have focused on accurate heartbeat classification, and deep neural networks have been suggested for better accuracy and simplicity. We investigated a new model for ECG heartbeat classification and found that it surpasses state-of-the-art models, achieving remarkable accuracy scores of 98.5% on the Physionet MIT-BIH dataset and 98.28% on the PTB database. Furthermore, our model achieves an impressive F1-score of approximately 86.71%, outperforming other models, such as MINA, CRNN, and EXpertRF on the PhysioNet Challenge 2017 dataset.

In this work, the authors demonstrate a novel vertically-stacked thin film transistor (TFT) architecture for heterogeneously complementary inverter applications, composed of p-channel polycrystalline silicon (poly-Si) and n-channel amorphous indium tungsten oxide (a-IWO), with a low footprint than planar structure. The a-IWO TFT with channel thickness of approximately 3-4 atomic layers exhibits high mobility of 24 cm 2 V -1 s -1 , near ideally subthreshold swing of 63 mV dec -1 , low leakage current below 10 -13 A, high on/off current ratio of larger than 10 9 , extremely small hysteresis of 0 mV, low contact resistance of 0.44 kΩ-µm, and high stability after encapsulating a passivation layer. The electrical characteristics of n-channel a-IWO TFT are well-matched with p-channel poly-Si TFT for superior complementary metal-oxide-semiconductor technology applications. The inverter can exhibit a high voltage gain of 152 V V -1 at low supply voltage of 1.5 V. The noise margin can be up to 80% of supply voltage and perform the symmetrical window. The pico-watt static power consumption inverter is achieved by the wide energy bandgap of a-IWO channel and atomically-thin channel. The vertically-stacked complementary field-effect transistors (CFET) with high energy-efficiency can increase the circuit density in a chip to conform the development of next-generation semiconductor technology., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Electrons and holes can spontaneously form excitons and condense in a semimetal or semiconductor, as predicted decades ago. This type of Bose condensation can happen at much higher temperatures in comparison with dilute atomic gases. Two-dimensional (2D) materials with reduced Coulomb screening around the Fermi level are promising for realizing such a system. Here we report a change in the band structure accompanied by a phase transition at about 180 K in single-layer ZrTe 2 based on angle-resolved photoemission spectroscopy (ARPES) measurements. Below the transition temperature, gap opening and development of an ultra-flat band top around the zone center are observed. This gap and the phase transition are rapidly suppressed with extra carrier densities introduced by adding more layers or dopants on the surface. The results suggest the formation of an excitonic insulating ground state in single-layer ZrTe 2 , and the findings are rationalized by first-principles calculations and a self-consistent mean-field theory. Our study provides evidence for exciton condensation in a 2D semimetal and demonstrates strong dimensionality effects on the formation of intrinsic bound electron-hole pairs in solids., (© 2023. The Author(s).)

Glide-mirror symmetry in nonsymmorphic crystals can foster the emergence of novel hourglass nodal loop states. Here, we present spectroscopic signatures from angle-resolved photoemission of a predicted topological hourglass semimetal phase in Nb 3 SiTe 6 . Linear band crossings are observed at the zone boundary of Nb 3 SiTe 6 , which could be the origin of the nontrivial Berry phase and are consistent with a predicted glide quantum spin Hall effect; such linear band crossings connect to form a nodal loop. Furthermore, the saddle-like Fermi surface of Nb 3 SiTe 6 observed in our results helps unveil linear band crossings that could be missed. In situ alkali-metal doping of Nb 3 SiTe 6 also facilitated the observation of other band crossings and parabolic bands at the zone center correlated with accidental nodal loop states. Overall, our results complete the system's band structure, help explain prior Hall measurements, and suggest the existence of a nodal loop at the zone center of Nb 3 SiTe 6 .

Objective: To evaluate treatment satisfaction, level of anxiety, confidence about traveling with midazolam nasal spray (MDZ-NS), and health-related quality of life in patients with seizure clusters and their caregivers after repeated, intermittent use of MDZ-NS in the outpatient setting., Methods: We analyzed the psychosocial outcome data from a phase 3, open-label extension trial (ARTEMIS-2; P261-402; NCT01529034) in patients 12 years of age and older with seizure clusters on a stable regimen of antiseizure medications. Caregivers administered MDZ-NS 5 mg when patients experienced a seizure cluster. A second dose could be given if seizures did not terminate within 10 min or recurred from 10 min to 6 h. Treatment Satisfaction Questionnaire for Medication (TSQM), the Intranasal Therapy Impact Questionnaire (ITIQ), and the Short Form-12 Health Survey version 2 (SF-12v2) were self-administered by patients and/or caregivers at prespecified visits., Results: Of the one hundred and seventy-five patients enrolled in ARTEMIS-2, 161 (92.0%) received ≥ 1 dose of MDZ-NS and had a post-treatment seizure-related assessment and were included in the Efficacy Evaluable Set in this analysis, with a total of 1,998 treated seizure clusters over a median duration of 16.8 months. All TSQM scales showed improvement from the baseline of the double-blind ARTEMIS-1 trial (NCT01390220) to the last visit in ARTEMIS-2, indicating greater satisfaction with MDZ-NS across all domains, with a mean change from baseline of 8.8, 6.1, 4.3, and 6.2 for effectiveness (n = 135), side effects (n = 139), convenience (n = 139), and global satisfaction (n = 138), respectively. Change from baseline in TSQM scores generally increased with repeated MDZ-NS use. In both patients and caregivers, anxiety generally lessened with repeated MDZ-NS use, with a mean improvement in ITIQ scores in patients' anxiety since receiving MDZ-NS from 2.5 (n = 138) to 3.5 (n = 145) from visit 1 to the last visit (and from 2.6 [n = 156] to 3.6 [n = 160] for caregivers), respectively. From visit 1 (screening and enrollment in ARTEMIS-2) to visit 10 (after 16 seizure cluster episodes treated with MDZ-NS), the proportions of patients and caregivers who answered "strongly agree" or "agree" for confidence about traveling with an intranasal spray remained ≥ 79% and generally increased over repeated MDZ-NS use. Small positive mean changes in SF-12v2 scores from baseline to the last visit were observed in both patients and caregivers, respectively, for the domains of physical functioning (0.9, 1.1), role-physical (2.4, 0.3), bodily pain (1.7, 0.3), general health (0.6, 1.2), and role-emotional (2.1, 0.3), and in the physical health component (1.6, 1.0)., Conclusion: Patients and caregivers perceived MDZ-NS favorably, with improvement from baseline on perceived effectiveness, side effects, convenience, and global satisfaction in the TSQM. This is supported by progressively lower anxiety and higher confidence levels about traveling with MDZ-NS over repeated intermittent use in the ITIQ. The positive mean changes observed in SF-12v2 scores from baseline to the last visit were small in magnitude. Limitations of this exploratory analysis include the open-label trial design and that these questionnaires have not been directly validated in epilepsy to identify clinically important changes; however, this does not mean these findings are not clinically meaningful. Overall, MDZ-NS is a socially acceptable drug device for outpatient treatment of seizure clusters that has the potential to improve quality of life and overall independence., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tze-Chiang Meng was an employee of Proximagen LLC at the time this trial was conducted and is currently an Independent Consultant to Proximagen LLC and Managing Director of T. Meng Consulting, LLC. Jerzy P. Szaflarski has been on scientific advisory boards of GW Pharmaceuticals, SK Life Science, and UCB Pharma; has received research support from the Charles Shor Foundation for Epilepsy Research, Eisai, GW Pharmaceuticals, LivaNova, NeuroPace Inc, Serina Therapeutics, and UCB Pharma; and serves as a scientific advisor to iFovea and AdCel Biopharma. Linda Chen was an employee of UCB Pharma at the time this trial was conducted and is currently an independent researcher. Marcus Brunnert is a salaried employee of UCB Pharma. Rita Campos is a salaried employee of UCB Pharma and receives stock options from her employment. Peter Van Ess was an employee of Proximagen LLC at the time this trial was conducted and is currently Vice President of Early Development, DepYmed, Inc. William E. Pullman was an employee of Proximagen LLC at the time this trial was conducted and is currently an Independent Consultant and President of Pullman Drug Development Consultants, LLC. Toufic Fakhoury has served as a consultant or speaker for or has received research support from Aquestive, Eisai, SK Life Science, Sunovion, and UCB Pharma. Part of this work was presented as a poster at the 74th Annual Meeting of the American Epilepsy Society (virtual meeting); on December 5, 2020., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Various stem cell markers (eg, epithelial cell adhesion molecule [EpCAM], cytokeratin 19 [K19]) have been reported as predictors of poor prognosis in hepatocellular carcinoma (HCC). However, the data remain limited, particularly in Western populations, and are often contradictory. In this study, the prognostic value of positive SOX9 immunohistochemistry was compared with that of more established markers EpCAM and K19 in a large cohort (n=216) of North American patients. The independent HCC cohort in The Cancer Gene Atlas (n=360) was utilized to validate our findings. Finally, molecular signatures associated with SOX9 -high HCC were determined. We found that the expression of SOX9, but not EpCAM or K19, was associated with worse overall survival and disease-free survival (DFS) and was an independent prognostic factor for DFS in our North American cohort, in which hepatitis C infection was the most common underlying etiology. High SOX9 mRNA level, but not increased expression of EpCAM mRNA or K19 mRNA, was also associated with worse DFS and was an independent prognostic factor for DFS in The Cancer Gene Atlas cohort. This group had underlying causes, including an increased incidence of hepatitis B, significantly different from our initial cohort. High SOX9 mRNA level is associated with molecular pathways important in HCC pathogenesis. Increased SOX9 expression is clinically and biologically relevant for HCC arising in patients with a variety of underlying etiologies. Immunohistochemistry for SOX9 is a reliable proxy for increased SOX9 mRNA and can be used to predict prognosis in HCC cases., Competing Interests: Conflicts of Interest and Source of Funding: Supported in part by Digestive Disease Research Core Center at Washington University by grant P30DK052574 from the NIH. T.-C.L. was funded by NIH grants R01 DK125296 and R01 DK124274. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Metaverse, which is anticipated to be the future of the internet, is a 3D virtual world in which users interact via highly customizable computer avatars. It is considerably promising for several industries, including gaming, education, and business. However, it still has drawbacks, particularly in the privacy and identity threads. When a person joins the metaverse via a virtual reality (VR) human-robot equipment, their avatar, digital assets, and private information may be compromised by cybercriminals. This paper introduces a specific Finger Vein Recognition approach for the virtual reality (VR) human-robot equipment of the metaverse of the Metaverse to prevent others from misappropriating it. Finger vein is a is a biometric feature hidden beneath our skin. It is considerably more secure in person verification than other hand-based biometric characteristics such as finger print and palm print since it is difficult to imitate. Most conventional finger vein recognition systems that use hand-crafted features are ineffective, especially for images with low quality, low contrast, scale variation, translation, and rotation. Deep learning methods have been demonstrated to be more successful than traditional methods in computer vision. This paper develops a finger vein recognition system based on a convolution neural network and anti-aliasing technique. We employ/ utilize a contrast image enhancement algorithm in the preprocessing step to improve performance of the system. The proposed approach is evaluated on three publicly available finger vein datasets. Experimental results show that our proposed method outperforms the current state-of-the-art methods, improvement of 97.66% accuracy on FVUSM dataset, 99.94% accuracy on SDUMLA dataset, and 88.19% accuracy on THUFV2 dataset., Competing Interests: Conflict of interestThe authors declare no conflicts of interest regarding the publication of this paper., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022.)