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Small-for-size syndrome (SFSS) may occur when graft volume is less than 45% of the standard liver volume, and it manifests as retarded growth and failure of the grafts and more mortality. However, its pathogenesis is poorly understood, and few effective interventions have been attempted.The present study aimed to delineate the critical role of oxidant stress in SFSS and protective effects of a superoxide dismutase mimetic, Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP), on graft function, growth, and survival in the recipient rats.Small size graft liver transplantation (SSGLT) was performed to determine the survival, graft injury, and growth. MnTBAP was administered in SSGLT recipients (SSGLT+MnTBAP).Serum alanine aminotransferase levels were sustained higher in SSGLT recipients, which were correlated with an increased apoptotic cell count and hepatocellular necrosis in liver sections. Malondialdehyde content, gene expression of tumor necrosis factor α and interleukin 1β, and DNA binding activity of nuclear factor-κB in the grafts were increased significantly in SSGLT recipients compared with sham-operated controls. Both phosphorylated p38 mitogen-activated protein kinase and nuclear c-Jun were increased in SSGLT. All these changes were strikingly reversed by the administration of MnTBAP, with an increase in serum superoxide dismutase activity. Moreover, in situ bromodeoxyuridine incorporation demonstrated that graft regeneration was much more profound in the SSGLT+MnTBAP group than in the SSGLT group. Finally, the survival of recipients with MnTBAP treatments was significantly improved.Enhanced oxidant stress with activation of the p38/c-Jun/nuclear factor-κB signaling pathway contributes to SFSS-associated graft failure, retarded graft growth, and poor survival. MnTBAP effectively reversed the pathologic changes in SFSS-associated graft failure.

This paper describes a new and facile method, ‘solvent capillary contact printing(SCCP)’, that fabricates micro-patterned hydrophilic/hydrophobic surface causedby the selective manipulation of nanometre-scale block copolymer micelles. Themethod is based on using capillary injection and evaporation of a solvent, which ispreferential to a core block of micelles, through poly(dimethylsiloxane) (PDMS)microchannels placed on a pre-formed block copolymer micelle monolayer. Weproduced well-defined surface micropatterns where a nanostructure consistingof core-opened micelles gave rise to hydrophilic surface property in the regionsin contact with solvent while one consisting of hemispherical micelles remainedhydrophobic in the regions contacted by the PDMS mould. Our method allows repetitivemicropatterning; a surface micropattern previously formed is simply erased byexposure of preferential solvent vapour due to reversible structure modificationof micelles. Furthermore, SCCP with various metal salts, precursors of metalnanoparticles, enables us to fabricate micropatterned arrays of well-separated metalnanoparticles which can be used as a catalyst for synthesizing nanowires. Themicropatterned arrays of GaN nanowires are demonstrated, fabricated by SCCP. [ABSTRACT FROM AUTHOR]

Backgrounds: This study aimed to examine the individual and combined effects of serum BDNF (sBDNF) levels and alcohol consumption status, assessed shortly after a physical injury, on the development of post-traumatic stress disorder (PTSD) over two years., Methods: Participants were consecutively recruited from a trauma center and followed prospectively for two years. At baseline, sBDNF levels and alcohol consumption history were assessed. A range of socio-demographic and clinical covariates were also collected. PTSD diagnosis during follow-up (3, 6, 12, and 24 months post-injury) was established using the Clinician-Administered PTSD Scale for DSM-5. Binary and multinomial logistic regression analyses were employed to investigate the relationships between sBDNF levels, alcohol consumption status, and PTSD onset., Results: Out of 923 participants analyzed, 112 (12.1%) developed PTSD at some point during the study, with prevalence rates of 8.8% at 3 months, 7.6% at 6 months, 4.8% at 12 months, and 3.7% at 24 months. The study found no individual associations between sBDNF levels or alcohol consumption status and PTSD development. However, lower sBDNF levels significantly predicted PTSD in individuals who consumed alcohol, a relationship not observed in non-drinkers, with significant interaction terms. This pattern was consistent at later follow-up points from 12 to 24 months, but not at earlier assessments at 3 and 6 months., Limitations: The study's reliance on participants from a single trauma center with moderate to severe injuries may limit the generalizability of the findings., Conclusions: A significant interaction between sBDNF levels and alcohol consumption in relation to PTSD development was observed, particularly in the long term. These findings highlight the necessity of considering both sBDNF levels and alcohol consumption in strategies aimed at preventing PTSD among individuals with physical injuries, underscoring the need for tailored approaches based on these factors., Competing Interests: Declaration of competing interest No potential conflict of interest relevant to this article was reported., (Copyright © 2024. Published by Elsevier Inc.)

Galectins exhibit a variety of biological functions through interactions with their ligands, including galactose and its derivatives. Tandem-repeat galectins, such as Galectin-8, can act as pattern recognition receptors to aggregate and neutralize bacterial pathogens. In this study, Galectin-8 was identified in Trachinotus ovatus (golden pompano). Galectin-8 consists of two carbohydrate recognition domains (CRDs) connected by a linker region. Furthermore, molecular docking analysis suggests that the C-terminal CRD can bind galactose, mannose, and N-acetylglucosamine at similar binding sites. ToGal-8 expression levels were highest in the brain and blood of healthy T. ovatus. However, following infection with Streptococcus agalactiae, expression levels in the spleen and head kidney surged at 48 h, while liver expression significantly decreased by 96 h. Cytoplasmic Galectin-8 expression was upregulated after stimulation by peptidoglycan compared with lipopolysaccharide. Recombinant ToGal-8 (rToGal-8) was produced using a prokaryotic expression system. This protein could agglutinate red blood cells from rabbits, carp, and T. ovatus independently of Ca 2+ . Moreover, it was also effective in aggregating and eliminating several bacterial strains, such as Staphylococcus aureus, Bacillus subtilis, Vibrio vulnificus, S. agalactiae, Pseudomonas aeruginosa, and Aeromonas hydrophila. Therefore, this study provides an in-depth analysis of the function of T. ovatus Galectin-8 for the first time, offering guidance for the healthy aquaculture of T. ovatus., Competing Interests: Declarations. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: In emergency general surgery (EGS), rapid judgement and prompt emergency surgery play a significant role in determining the patient's prognosis. This study aimed to evaluate whether implementing the acute care surgery (ACS) system in Korea has improved the clinical outcomes of patients., Methods: This retrospective cohort study was conducted at three tertiary hospitals in Korea. The study included patients aged 18-99 years who required EGS due to acute abdomen or abdominal trauma. A window period of 4 months was set after the implementation of the ACS system, and the clinical outcomes before and after the implementation were compared., Results: A total of 2146 patients were enrolled in the study, with 1008 in the pre-ACS group and 1138 in the post-ACS group. After propensity score matching, 901 patients were selected in the pre-ACS group and 906 patients were selected in the post-ACS group. The time from emergency room admission to operating room transfer was reduced in the post-ACS group, with a mean of 452.2 ± 347.0 min compared to 522.1 ± 416.5 min in the pre ACS group (P = 0.001). Moreover, the complication rates were reduced in the post-ACS group (38.3% vs. 31.3%, P = 0.006)., Conclusions: The implementation of the ACS system can lead to faster surgical decision-making and the prompt execution of emergency surgery for patients, thereby reducing postoperative complications., (© 2024 The Author(s). ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Extracellular vesicles (EVs) possess the characteristics of their parent cells, based on which various studies have actively investigated treatments for diseases using mesenchymal stem cell-derived EVs due to their regenerative activity. Furthermore, in recent years, there have been significant efforts to engineer EVs to improve their native activities and integrate additional functions. Although both endogenous and exogenous methods are used for engineering EVs, endogenous methods may pose the problem of administering substances to cells undergoing metabolic changes, which can cause potential side effects. In addition, exogenous methods may have the limitation of losing beneficial factors inside EVs due to membrane disruption during engineering processes. Surface modification of EVs may also impair efficiency due to the presence of proteins on the EV surface. Therefore, in this study, a stable and efficient engineering method was achieved through the ethanol-mediated hybridization of EVs and functionalized lipid nanoparticles (LNPs) with a fusogenic lipid component. During hybridization, the internal bioactive factors and targeting moiety were maintained to possess the characteristics of both LNPs and EVs. The Ab-Hybrid, which was successfully synthesized through hybridization with nicotinamide-encapsulated and Col2A1 antibody-modified liposome and Transforming growth factor-β1 (TGF-β1) - overexpressed EVs, was administered to osteoarthritis (OA)-induced rats undergoing the destabilization of the medial meniscus surgery. Ultimately, the Ab-Hybrid demonstrated excellent chondroprotective and anti-inflammatory effects with targeting and long-lasting properties in OA lesions. We anticipate that this approach for manufacturing hybrid particles will serve as a valuable EV engineering method and a versatile platform technology applicable to various diseases.

Acute myocardial infarction (AMI) is one of the most common causes of sudden death in cardiovascular disease, and myoglobin (Myo) is the first protein to be released in the blood after the attack, which is an important biomarker for clinical detection of AMI. The "Golden Rescue Time" for acute myocardial infarction is to intervene within the first 30 min after the attack; therefore, a rapid and accurate Myo detection method is needed urgently. In this study, we designed a combined enzyme-linked immunosorbent assay (ELISA) technique with surface-enhanced Raman scattering (SERS) immunoassay (ELI-SERS), which integrates the small sample volume, ease of operation, and excellent linearity of ELISA while utilizing the SERS technique and selecting the molecule with the Raman signal (IR-808), which is in resonance with the excitation wavelength, for further signal enhancement. The sensitivity of the system was further improved by optimizing the key factors in the assay such as incubation time, particle concentration, and temperature. Compared with the sandwich-structured magnetic bead method, no collection and concentration steps are required, simplifying the operation and ultimately realizing a sensitivity of a 5.3 pg/mL antigen detectable in 6 min. In actual serum samples, we achieve 100% accuracy and sensitivity by adding blockers to exclude the effect of heterophilic antibodies in serum and to reduce false positives in blank samples. We also validated the hepatitis B surface antigen test, demonstrating the universality of our system. Overall, this study designed an ultrasensitive and convenient SERS sensor for the detection of Myo, which extends the practical application of SERS and also contributes methods for the detection of other biomarkers.

Recently, cytosine base editors (CBEs) have emerged as a promising therapeutic tool for specific editing of single nucleotide variants and disrupting specific genes associated with disease. Despite this promise, the currently available CBEs have the significant liabilities of off-target and bystander editing activities, partly due to the mechanism by which they are delivered, causing limitations in their potential applications. In this study, we engineered optimized, soluble and stable Cas-embedded CBEs (CE_CBEs) that integrate several recent advances, which were efficiently formulated for direct delivery into cells as ribonucleoprotein (RNP) complexes. Our resulting CE_CBE RNP complexes efficiently target cytosines in TC dinucleotides with minimal off-target or bystander mutations. Delivery of additional uracil glycosylase inhibitor protein in trans further increased C-to-T editing efficiency and target purity in a dose-dependent manner, minimizing indel formation. A single electroporation was sufficient to effectively edit the therapeutically relevant locus BCL11A for sickle cell disease in hematopoietic stem and progenitor cells in a dose-dependent manner without cellular toxicity. Significantly, these CE_CBE RNPs permitted highly efficient editing and engraftment of transplanted cells in mice. Thus, our designed CBE proteins provide promising reagents for RNP-based editing at disease-related sites., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Chemical interface damping (CID) in gold nanorods (AuNRs) significantly influences their optical properties due to the direct transfer of hot electrons from the AuNRs to adsorbed molecules. Despite ongoing research on CID, reversible tuning of CID at the single particle level remains a challenging task. In this study, we investigated the adsorption and removal of thiol-functionalized aromatic molecules, specifically thiophenol (TP) and benzene-1,2-dithiol (BDT), using sodium borohydride (NaBH 4 ) solution as a reagent, with confirmation through surface-enhanced Raman scattering (SERS) measurements. We further examined the effect of NaBH 4 solution pH, immersion time in solution, and the number of thiol groups in the adsorbate (TP and BDT) on removal efficiency from the AuNR surfaces. Additionally, we extended this approach to directly control CID in single AuNRs via the adsorption and desorption of TP and BDT molecules under dark-field microscopy and spectroscopy. Therefore, this study provides insights into the removal of aromatic thiol molecules using NaBH 4 , as well as the direct control of CID in individual AuNRs.

The importance of hardware security increases significantly to protect the vast amounts of private data stored on edge devices. Physical unclonable functions (PUFs) are gaining prominence as hardware security primitives due to their ability to generate true random digital keys by exploiting the inherent randomness of the physical devices. Traditional approaches, however, require significant data movement between memory units and PUF generation circuits to perform encryption, presenting considerable energy efficiency and security challenges. This study introduces an innovative approach where PUF key generation and encryption are accomplished in the same vertically integrated resistive random access memory (V-RRAM), alleviating the data movement issue. The proposed V-RRAM encryption machine offers concealable PUFs, high area efficiency, and multi-thread data handling using parallel XOR logic operations. The encryption machine is compared with other machines, demonstrating the highest spatiotemporal cost-effectiveness.

Early mycosis fungoides (MF) and inflammatory dermatoses including psoriasis and chronic spongiotic dermatitis are often difficult to differentiate. We explored diagnostic markers differentiating MF from psoriasis and chronic spongiotic dermatitis via spatially resolved single-cell transcriptome analysis. Single-cell transcriptomics of intraepidermal T cells of MF patches, psoriasis and chronic spongiotic dermatitis were analyzed using CosMx TM spatial molecular imager utilizing surface markers, including CD3 and CD4. An immunohistochemical study with potential markers was performed to verify clinical utility. Compared to psoriasis and chronic spongiotic dermatitis, 41 upregulated differentially expressed genes (DEGs) in MF were associated with T-cell receptor (TCR) signaling pathway and apoptosis regulation. Protein-protein interaction network analysis of these DEGs revealed a main cluster associated with TCR signaling. Pathway enrichment analysis showed that apoptosis, Th17 cell differentiation, and TCR signaling pathways were enriched in MF. GNLY and FYB1, DEGs with the highest fold change values, were selected as potential diagnostic biomarkers for MF. For immunohistochemistry, biopsy specimens from 150 patients diagnosed with patch MF with CD4 + immunophenotype (n = 56), psoriasis (n = 48), and chronic eczema (n = 46) were included. The sensitivity and specificity of GNLY for distinguishing MF and psoriasis/chronic spongiotic dermatitis were 67.9% and 93.6%, respectively. For FYB1, those values were 73.2% and 69.2%, respectively. The AUC values of GNLY and FYB1 were 0.86 and 0.79, respectively. In conclusion, GNLY and FYB1 can be promising diagnostic biomarkers for differentiating early-stage MF from psoriasis and chronic spongiotic dermatitis., (Copyright © 2024. Published by Elsevier Inc.)

New lipodepsipeptides, octaminomycins C and D ( 1 and 2 ), were discovered in an engineered Streptomyces sp. strain overexpressing the LysR transcriptional regulator family. The structures of 1 and 2 were elucidated by comprehensive analysis of their UV, HRMS, and NMR data. The absolute configurations were determined using spectroscopic analysis, the advanced Marfey's method, and genomic analysis. Genomic analysis enabled the identification of the nonribosomal peptide synthetase (NRPS) biosynthetic pathway of the octaminomycins.

Bullous pemphigoid (BP) is the most prevalent autoimmune blistering disorder, triggered by autoantibodies targeting hemidesmosome components. It is associated with substantial morbidity and increased mortality. No studies comprehensively evaluate all comorbidities before and after diagnosing patients with BP. We aimed to investigate all BP-associated comorbid diseases and their patterns of associations. This nationwide population-based study included 5066 patients with BP and 10 132 controls between 2011 and 2021. We performed an automated mass screening of 546 diagnostic codes to identify BP-associated comorbidities 5 years before and after BP diagnosis, and analyzed associations patterns of comorbidities. Patients with BP had increased odds of having pressure ulcers, intracerebral hemorrhage, scabies, neuropsychiatric disorders, psoriasis, drug eruption, and acute renal failure before BP diagnosis. After BP diagnosis, they had increased odds pneumonia, sepsis, chronic renal disease, and cardiac arrest. Strong interrelationships were observed between five neuropsychiatric conditions before BP diagnosis and a strong bidirectional association between Alzheimer's dementia and pneumonia after BP diagnosis. This large case-control study of patients with BP thoroughly identified all relevant comorbidities before and after BP diagnosis, highlighting their clinical significance as predisposing and prognostic factors in patients with BP., (© 2024 Japanese Dermatological Association.)

Plumerianoids A-D (1-4) with a new intact spirocyclic iridoid alkaloid skeleton, along with a new degraded alkaloid 8- epi -plumerianine (5), and a known one (6), were isolated and characterized from Plumeria rubra . The structure of 6 was revised as (8 R ,13 S )-plumerianine. These alkaloids consist of three epimeric pairs (1/2, 3/4, and 5/6), exhibiting virtually identical NMR spectra within each pair. Furthermore, the electronic circular dichroism (ECD) curves of each epimeric pair are roughly mirror-like, reminiscent of enantiomers. This study calls for attention on the structural elucidation of special compound classes when the associated chiral centers are far away from the chromophores and/or at the terminal of the molecules. In addition, compound 3 exhibited moderate antiplasmodial activity.

The recent SARS-CoV-2 pandemic underscores the need for rapid and accurate prediction of clinical thrombotic events. Here, we developed nanoengineered multichannel immunosensors for rapid detection of circulating biomarkers associated with thrombosis, including C-reactive protein (CRP), calprotectin, soluble platelet selectin (sP-selectin), and D-dimer. We fabricated the immunosensors using fiber laser engraving of carbon nanotubes and CO 2 laser cutting of microfluidic channels, along with the electrochemical deposition of gold nanoparticles to conjugate with biomarker-specific aptamers and antibody. Using unsupervised clustering based on four biomarker concentrations, we predicted thrombotic events in 49 of 53 patients. The four-biomarker combination yielded an area under the receiver operating characteristic curve (AUC) of 0.95, demonstrating high sensitivity and specificity for acute thrombosis prediction compared to the AUC values for individual biomarkers: CRP (0.773), calprotectin (0.711), sP-selectin (0.683), and D-dimer (0.739). Thus, a nanoengineered multichannel platform with unsupervised clustering provides accurate and efficient methods for predicting thrombosis, guiding personalized medicine.

Endothelin (ET)-1 contributes to melanoma progression via cell proliferation, invasion, and migration. We previously reported that annexin A2 (AnxA2) binds to ET receptors. In this study, we aimed to further investigate role of AnxA2 in melanoma cell proliferation after ET-1 stimulation. AnxA2 knockdown inhibited ET-1-stimulated cell proliferation and AKT activation in SK-MEL28 melanoma cells. ET-1 stimulation phosphorylated serine on AnxA2, and AnxA2 Ser25 phosphorylation-deficient mutant (AnxA2 S25A) cells showed lower ET-1-stimulated cell proliferation and AKT activation than the rescue AnxA2 knockdown (AnxA2 res) and AnxA2 Ser11 phosphorylation-deficient mutant (AnxA2 S11A) cells. Although AnxA2 S25A was localized to the plasma membrane, it exhibited lower colocalization with ET receptors than AnxA2 res and AnxA2 S11A on the plasma membrane. These results suggest that phosphorylation of AnxA2 Ser25 affects the colocalization of AnxA2 and ETRs and plays an important role in cell proliferation and AKT activation in ET-1 stimulated melanoma cells., 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 Inc. All rights reserved.)

To determine the efficacy and adverse consequences between KangDuo and Da Vincii surgical robotic systems in facilitating radical prostatectomy. All the papers, that were included in the current analysis, were identified with PubMed, Embase, and the Cochrane Library through October 1, 2024. To make the comparison easier, only the English-language articles have been used for the analysis and only those focusing on comparing the use of the KangDuo and da Vinci robotic systems in radical prostatectomy were used. There are several avenues of bias when considering articles to include, when selecting the articles for this study to adopt the RCTs and cohort studies and excluding the others, the bias selection targeted was minimal. For the systematic review, 1 cohort study was found as well as 2 RCTs were found that involved 150 adult patients assigned to undergo urological surgery. Of those, 76 patients operated by the Kang Duo robotic system, and the remaining 74 patients operated by the Da Vinci system. In conclusion from this study, it was noted that though there was an increase in the operative time used in the KangDuo system, the estimated blood loss, number of days needed to stay in hospital, and the incidences of postoperative complications were comparable to the other system. Compared to the da Vinci robotic system, the KangDuo robotic system, while associated with longer operative times for radical prostatectomy, showed no significant difference in perioperative or short-term outcomes. In addition, the KangDuo system is more cost-effective and easier to implement in developing countries or other regions. However, further high-quality studies are needed to confirm these findings., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

The photocatalytic conversion of biomass-based platform molecules, such as 5-hydroxymethylfurfural (HMF), holds significant importance for the utilization of biomass resources. This study focuses on the unique ability of atomically bridged indium (In) atoms that encourages inactive SnS2 surface and steer the selective HMF oxidation process under solar light. Experimental results suggest that In confined SnS2 structure provides not only favorable sites and electronic structures for the synergistic activation of HMF/O2 but also benefit in charge carrier dynamics, thus influencing the overall activity and selectivity of the SnS2 catalyst. In addition, in-situ spectroscopy and density functional theory (DFT) analysis uncovered the multifunctional role of In sites in promoting the key steps of the catalytic process, from ROS generation to regulated adsorption/activation of *HMF which serves as the rate limiting step of the overall HMF oxidation process. Consequently, the optimized In-SnS2-0.75 photocatalyst demonstrated excellent photo oxidation performance, reaching a high HMF conversion efficiency, yield, and selectivity of 91.2, 73 and 80% respectively, in just two hours of the reaction. This study highlights the strategic approach of rationally designed catalytic systems in order to tune the ROS and the product distribution of the HMF oxidation process., (© 2024 Wiley‐VCH GmbH.)

Nanowire (NW) field-effect transistors (FETs) have great potential in next-generation integrated circuits. InAs NWs are suitable for N-type transistors because of their excellent electrical properties. However, unlike the Si/SiO 2 system, the loose and defective native oxide of InAs is unable to passivate the channel surface and serve as an efficient isolation layer (IL) in the gate stack. Here, we, for the first time, demonstrate that using a stable dielectric Y 2 O 3 to replace the native oxide IL can effectively passivate the NW surface, isolate the channel surface from high-k HfO 2 , and improve the electrical properties of InAs NW FETs significantly. First, top-gate devices with Y 2 O 3 IL outperform the devices with native oxide or chemically generated oxide of InAs as the IL, exhibiting a small subthreshold swing (SS) of 77 mV/dec, a large on-off ratio, a high field-effect mobility (μ FE ) of 1845 cm 2 /V·s, and an extremely low interface trap density ( D it ) of 9.1 × 10 11 eV -1 cm -2 . Double-gate FETs with Y 2 O 3 IL also show excellent gate control (drain-induced barrier lowering (DIBL) down to 35 mV/V) and a high μ FE of 2711 cm 2 /V·s (the highest in the multigate structure). In addition, InAs NW FETs with Y 2 O 3 IL show greater stability after long-term air exposure than those with native oxide IL, demonstrating retained on-off ratio, DIBL, transconductance, and even smaller SS (from 89 to 77 mV/dec). Finally, the results of low-temperature measurement suggest that Y 2 O 3 IL can effectively improve interface qualities. Our results indicate that Y 2 O 3 /HfO 2 InAs NW FETs have great potential in digital units of integrated circuits for future nodes. Our strategy for improving the interface between InAs NW and the dielectric layer is also valuable for other III-V NW devices.

Background & Aims: Sleep disorders (SDs) are common in chronic liver diseases (CLDs). Some SDs arise from impaired internal clock and are hence circadian rhythm SDs (CRSDs). Bile acids (BAs), whose levels are increased in many CLDs, reciprocally interact with circadian rhythm. This study explores the mechanisms underlying CRSDs in CLDs and novel therapies., Methods: We monitored the sleep of CLD patients using actigraphic watch and established male mouse cholemia models by feeding with BA or bile duct ligation. Sleep-wake cycle and circadian rhythm were analyzed by electroencephalogram-electromyography and locomotor wheel-running experiments., Results: CLD patients showed CRSD-like phenotypes including increased night activity and early awakening, which were strongly correlated with increased BA levels, i.e. cholemia. CRSDs including shortened circadian period were recapitulated in two cholemic mouse models. Mechanistically, elevated BAs in the suprachiasmatic nucleus (SCN) activated BA receptor Tgr5 (Takeda G protein-coupled receptor 5), which in turn increased the level and phosphorylation of Period2 (Per2), a master rhythm regulator, through Erk (extracellular signal-regulated kinase) and casein kinase 1ε (CK1ε). Per2 phosphorylation inhibited its nuclear import, which would release its transcriptional inhibition and expedite the circadian cycle. Cholemia also blunted the light entrainment response and light-induced phase change of SCN mediated by the neurons expressing gastrin releasing peptide through Tgr5-Per2 axis. BA sequestrant or CK1 inhibitor reversed the CRSDs in cholemic mice by restoring Per2 distribution., Conclusions: Cholemia is a major risk factor for CRSDs in CLDs and hence promising target in future clinical study., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Rice cultivated in seemingly arsenic (As) uncontaminated soils may accumulate As levels exceeding food safety standards, a phenomenon often overlooked by current soil quality standards. This study investigated the effectiveness of iron (Fe)-inspired barriers in limiting As dissolution and translocation in uncontaminated paddy fields, addressing the need for safe rice production under global warming and extreme weather pressures. We hypothesized that Fe-based materials could inspire Fe barriers in the soil-rice system. Our experiments demonstrated that application of 0.25 % (w/w) FeSO 4 and 1 % (w/w) ferrihydrite reduced inorganic As in brown rice grains by 29.8 % and 37.1 %, respectively, under the conventional water management practice, which included both flooded and intermittent drainage periods. Path analysis revealed a negative correlation between increased soil amorphous Fe oxide content and bioavailable As. Mössbauer spectroscopy confirmed microcrystalline Fe oxide enrichment in soil clay-sized fractions due to FeSO 4 application, activating the soil matrix Fe barrier. Ferrihydrite reduced As translocation through adsorption and lattice sequestration. Iron plaques on rice roots were also inspired as a second Fe barrier: FeSO 4 application increased total Fe content on iron plaques by 35.1 % and As proportion in high-crystallinity Fe oxide fraction by 11 %, thus limiting As uptake by white root. However, combining FeSO 4 with organic fertilizer application resulted in excess As release from the soil matrix, and dissolved organic carbon encroached on the adsorption sites of the Fe barrier, nullifying the barriers' effectiveness. Our results demonstrate the potential of Fe-inspired barriers in the soil-rice system as an effective solution to As anomalies in rice from uncontaminated areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Current guidelines recommend the perioperative continuation of aspirin in patients with coronary drug-eluting stents (DES) undergoing noncardiac surgery. However, supporting evidence is limited., Objectives: This study aimed to compare continuing aspirin monotherapy vs temporarily holding all antiplatelet therapy before noncardiac surgery in patients with previous DES implantation., Methods: We randomly assigned patients who had received a DES >1 year previously and were undergoing elective noncardiac surgery either to continue aspirin or to discontinue all antiplatelet agents 5 days before noncardiac surgery. Antiplatelet therapy was recommended to be resumed no later than 48 hours after surgery, unless contraindicated. The primary outcome was a composite of death from any cause, myocardial infarction, stent thrombosis, or stroke between 5 days before and 30 days after noncardiac surgery., Results: A total of 1,010 patients underwent randomization. Among 926 patients in the modified intention-to-treat population (462 patients in aspirin monotherapy group and 464 patients in the no-antiplatelet therapy group), the primary composite outcome occurred in 3 patients (0.6%) in the aspirin monotherapy group and 4 patients (0.9%) in the no antiplatelet group (difference, -0.2 percentage points; 95% CI: -1.3 to 0.9; P > 0.99). There was no stent thrombosis in either group. The incidence of major bleeding did not differ significantly between groups (6.5% vs 5.2%; P = 0.39), whereas minor bleeding was significantly more frequent in the aspirin group (14.9% vs 10.1%; P = 0.027)., Conclusions: Among patients undergoing low-to-intermediate risk noncardiac surgery >1 year after stent implantation primarily with a DES, in the setting of lower-than-expected event rates, we failed to identify a significant difference between perioperative aspirin monotherapy and no antiplatelet therapy with respect to ischemic outcomes or major bleeding. (Perioperative Antiplatelet Therapy in Patients With Drug-eluting Stent Undergoing Noncardiac Surgery [ASSURE-DES]; NCT02797548)., Competing Interests: Funding Support and Author Disclosures This research was supported by the CardioVascular Research Foundation (Seoul, Korea) (grant number: AMCCV2016-10), a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (grant number: HC19C0022), and Medtronic. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study explored capabilities of completely autotrophic nitrogen removal over nitrite (CANON) process under co-regulation of hydroxylamine (NH 2 OH) and hydrazine (N 2 H 4 ). Results indicated that granular (R 1 ) and flocculated (R 2 ) sludge CANON systems were started-up respectively on day 14 and day 17 by co-introduction of 0.50 + 1.00 mg/L and 1.00 + 5.00 mg/L NH 2 OH and N 2 H 4 , with ammonia removal efficiency (ARE) of 53.75 % ± 8.30 % and 54.17 % ± 7.40 %, respectively. Furthermore, the relative abundance of Nitrosomonas, Nitrospira, Candidatus_Nitrotoga and Nitrobacter reduced after NH 2 OH and N 2 H 4 was supplied into R 1 and R 2 for 30 days, thereby inhibiting ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB) activity. Nevertheless, the relative abundance of Candidatus_Kuenenia and Candidatus_Jettenia recovered once NH 2 OH and N 2 H 4 were absent, produced reversible inhibitory on anaerobic ammonia-oxidation bacteria (AnAOB) activity. Results will demystify the nitrogen elimination performance and mechanism of the CANON process from a novel viewpoint., 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.)

In this study, we aimed to explore the relationships between knowledge of emergence delirium (ED) and nursing stress, practice, confidence, and performance levels, as well as to identify factors influencing the performance of recovery room nurses. We conducted a cross-sectional study with 135 recovery room nurses at a general hospital in South Korea. The nurses completed a questionnaire from April 12 to April 25, 2023. Data were analyzed using multiple linear regression to examine factors associated with nursing performance in relation to ED. Nursing performance showed a significant negative correlation with nursing stress levels and a moderate positive correlation with nursing practice and confidence levels. Furthermore, ED education, nursing practice, and nursing confidence are factors influencing nursing performance. To enhance the performance of recovery room nurses in caring for patients with ED, we recommend developing a tailored educational program that focuses on increasing both the confidence levels and practical skills of nurses, thereby meeting the specific needs of the patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ban 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.)

Autotrophic denitrification in sulfur packed-bed reactors (S 0 PBR) has been widely employed for treating municipal secondary effluent. However, the fixed volume of packed sulfur in S 0 PBR restricts the ability to adjust denitrification efficiency in response to fluctuating influent nitrate levels, leading to either effluent standard exceedances or unnecessary sulfur consumption. Here, we proposed a novel method for directionally regulating nitrate removal efficiency (NRE) in S 0 PBR by adjusting the bed-immersion-ratio (BIR). The results demonstrated that the NRE could be effectively controlled through adjustments of BIR, with the maximum NRE achieved when BIR was increased to 1.00. Notably, a non-zero minimum NRE was observed when BIR decreased to 0.00. This could be associated with actual hydraulic retention time (aHRT), with a strong correlation observed between aHRT and BIR. Based on these findings, a kinetic model was developed that integrated both exposure and immersion parts, expressed as R j =(C in-0 1/2 -C e 1/2 )Q2.54AH t -0.65. This model proved effective for describing the nitrate reduction kinetics in the S 0 PBR under BIR variation. The effluent concentration achieved a more stable designed nitrate level under BIR variation guided by our developed model, compared to the effluent nitrate concentration under full immersion. Besides, sulfur consumption could be reduced by 7.8 % to 31.6 % under BIR variation due to the reduced nitrate removal. Overall, this study proposed a novel approach for achieving stable nitrate effluent guided by our developed model under fluctuating influent nitrate loadings, which was both efficient and economical., 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.)

Adventitious root (AR) culture of Atractylodes chinensis is an efficient platform for sustainable production of its sesquiterpenoid compounds (atractylon and β-eudesmol). However, their limited accumulation levels need an effective elicitation approach, and the present study solved this problem using methyl jasmonate (MeJA) as an elicitor. The effects of its treatment concentration and duration on metabolite production were investigated. The ARs treated with 100 µM MeJA for 7 d increased atractylon and β-eudesmol by 3.64- and 1.90-fold, respectively, compared with the control. We further performed transcriptome analysis to explore the transcriptional regulation mechanism of the MeJA elicitation. A total of 124,464 unigenes were identified in A. chinensis ARs, of which 3,568 genes were upregulated and 3,864 genes were downregulated with the MeJA treatment. The MeJA treatment activated the endogenous jasmonic acid biosynthesis and signaling pathways and sesquiterpenoid biosynthesis. In addition, MeJA treatment more significantly activated genes of the methylerythritol phosphate pathway than of the mevalonate pathway. In addition, 14 genes encoding terpene synthase were identified to be significantly upregulated. A total of 2,700 transcription factors (TFs) were identified in A. chinensis ARs, of which Tify, MYB and MADS were significantly enriched under the MeJA treatment. We predicted a new antagonistic interaction between MYC2 and CPP TFs, which was significantly regulated by the MeJA treatment. The results of real-time quantitative PCR and enzyme activity assays proved the reliability of the transcriptome data. This study will help improve the in vitro production system of A. chinensis sesquiterpenoids and understand the transcriptional regulation mechanism of MeJA elicitation., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. 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.)

During the celebration of the 50th anniversary of the founding of the Korean Cancer Association, articles published in Cancer Research and Treatment from 2004 to 2023 were assessed based on the subject and design of each study. Based on this analysis, trends in domestic cancer research were inferred and directions were suggested for the future development of Cancer Research and Treatment.

To investigate the safety, efficacy and risk factors for complications of stenting with optional coiling versus coiling alone for acutely ruptured cerebral aneurysms (ARCAs) using different antiplatelet schemes, 2021 patients were prospectively enrolled into the stenting group (n = 967) and the coiling group (n = 1054). Four different antiplatelet regimens were used. The clinical and treatment data were analyzed and compared. In the stenting group, the common antiplatelet regimen was applied in 259 patients (26.8%), loading regimen in 210 (21.7%), intravenous tirofiban regimen in 240 (24.8%), and premedication free regimen in 258 (26.7%). The aneurysm occlusion degrees in the coiling vs. stenting group were not significantly (P > 0.05) different after treatment. Complications occurred in 168 (15.94%) and 171 (17.68%) patients in the coiling and the stenting group, respectively. Fifteen (1.55%) patients experienced stent-related ischemic complications. The only significant (P < 0.05) independent protective factor for complete occlusion was stent-assisted coiling in the stenting group but aneurysm daughter sac in the coiling group. Significant (P < 0.05) independent risk factors for poor mRS (3-6) were posterior circulation aneurysms and neurological bleeding complications in the stenting group and neurological complications in the coiling group. In the stenting group, the only independent risk factor was parent artery stenosis for neurological complications, Raymond grade III for neurological ischemic complications, and the ice cream technique for total complications in the stenting group. In conclusion, different antiplatelet schemes can be safely and efficiently used for intracranial stenting with optional coiling as compared with coiling alone for ARCAs., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Nano- and microplastics (NMPs), ubiquitous in the environment, pose significant health risks. We report for the first time a comprehensive study using in-vitro, in-vivo, and ex-vivo models to investigate the penetration and inflammatory effects of fragmented polystyrene (fPS) on human skin, including the analysis of both penetration depth and fPS amounts that penetrate the skin. Human keratinocyte (HaCaT) and human dermal fibroblast (HDF) cells exposed to fPS exhibited notable internalization and cytotoxicity. In a 3D human skin model, fPS particles penetrated the dermal layer within one hour, with an average maximum penetration of 4.7 μg for particles smaller than 2 µm. Similarly, mouse dorsal skin and human abdominal skin models confirmed fPS penetration. RNA sequencing revealed substantial upregulation of inflammatory genes, including IL-1α, IL-1β, IL-18, IL-6, IL-8, ICAM-1, FOS, and JUN, following fPS exposure. These findings were validated at both the mRNA and protein levels, indicating a robust inflammatory response. Notably, the inflammatory response in both the 3D human skin and mouse models increased in a dose-dependent manner, underscoring the toxicological impact of fPS on skin health. This study provides crucial insights into the mechanisms through which NMPs affect human health and underscores the need for further research to develop effective mitigation strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The aim of this study was to assess the learning curve of robotic-assisted sacrocolpopexy by applying CUSUM analysis based on operation time, complication rate and conversion rate to open laparotomy., Methods: A retrospective study was conducted with 50 consecutive robotic-assisted sacrocolpopexy surgeries performed from June 2018 and June 2023 by a single experienced gynecologist. Baseline patient demographics, intraoperative parameters and postoperative outcomes were collected. Cumulative sum (CUSUM) of robotic-assisted sacrocolpopexy operation time was analyzed to determine breakpoints between learning phases using piecewise linear regression. This allowed the detection of subtle shifts in surgical parameters and ultimately surgeon proficiency and competency. Continuous variables, such as age, length of hospitalization and op time, were reported as mean (standard deviation). One-way analysis of variance was employed to compare continuous variables. Categorical variables were expressed as percentages and analyzed using the chi-square test., Results: The regression identified breakpoints at case 8.47 (95% CI 8.0, 9.0) and case 34.41 (95% CI 32.7, 36.1), with an R 2 value of 0.87, which agrees with that of the second-order polynomial equation. The breakpoints were rounded to the next whole number at case 9 and 35. The Learning, Proficiency, and Competency phases consisted of 9, 26, and 15 cases, respectively in this consecutive series. This suggests that the surgeon achieved proficiency after the first 9 cases and competency after 35 cases. There were no intraoperative nor short-term post-operative complications during the span of this study. Furthermore, there were no conversions to open laparotomy. CUSUM analysis based on complication and conversion rate, therefore, was not available., Conclusion: According to CUSUM analysis, surgical proficiency of robotic-assisted sacrocolpopexy was attained after the first 9 cases, and stabilization of operation time was achieved after 35 cases. This statistical tool has proven to be useful in objectively assessing learning curves for new surgical techniques, and the transition from laparoscopic sacrocolpopexy to robotic-assisted sacrocolpopexy seems achievable. This, however, may vary with each surgeon's manual dexterity and experience level. Further investigation with several surgeons and institutions is needed to define a more accurate and generalized learning curve of robotic-assisted sacrocolpopexy., Competing Interests: Declarations. Ethics approval and consent to participate: The Institutional Review Board of the Kyung Hee University Hospital at Gangdong approved our retrospective study and issued a waiver of informed consent (KHNMC 2024-01-025). Consent for publication: All the authors have approved the manuscript and agree with submission. The manuscript does not contain any individual person’s data in any form. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The coronavirus disease 2019 (COVID-19) pandemic has globally impacted healthcare systems, delaying cancer screening, diagnosis, and treatment. South Korea experienced a 3-month lockdown during the peak of the pandemic, leading to postponements in breast cancer diagnosis and treatment. Although the pandemic's severity has decreased, addressing the treatment gap remains a concern., Methods: This retrospective cohort study included patients diagnosed with breast cancer at five academic hospitals in South Korea during the pre-COVID (May-July 2019) and COVID (May-July 2020) periods. The primary endpoint was recurrence-free survival (RFS), and secondary endpoints included overall survival (OS), stage distribution, and age subgroup analyses., Results: Among 716 patients (374 pre-COVID, 342 COVID), the 3-year RFS was significantly lower in the COVID group (88.3 vs. 89.7%, p = 0.030), while the 3-year OS was similar between groups (96.2 vs. 95.5%, p = 0.439). Age subgroup analysis revealed a significant RFS difference in patients under 65 years of age (p = 0.005) but not in those aged 65 years and older (p = 0.682). Stage distribution did not differ significantly between groups (p = 0.531)., Conclusions: The COVID-19 pandemic adversely affected 3-year RFS, especially among younger patients, despite no significant increase in advanced-stage distribution. Timely cancer screening remains crucial for young patients with fewer infectious disease complications., Competing Interests: Disclosure: Jae Pak Yi, Chang Ik Yoon, Su Hyun Lim, Hoon Choi, Se Jeong Oh, Hyobin Kim, Dae Sun Park, Jong Min Baek, Yong-seok Kim, Ye Won Jeon, Jiyoung Rhu, and Young-Joon Kang have no conflicts of interest to declare that may be relevant to the contents of this study., (© 2024. Society of Surgical Oncology.)

Background: The positive relationship between triiodothyronine (T3) and steatotic liver disease (SLD) demonstrated only in crosssectional study. We aimed to evaluated whether total T3 (TT3) is associated with the development/resolution of SLD in longitudinal design., Methods: This retrospective, longitudinal, population-based cohort study included 1,665 South Korean euthyroid adults with ≥4 thyroid function test. We explored the impact of mean TT3 during follow-up on development/resolution of either SLD (diagnosed by ultrasound) or modified metabolic dysfunction-associated steatotic liver disease (MASLD) using Cox proportional hazards regression models., Results: During about median 5 years follow-up, 807/1,216 (66.3%) participants among participants without SLD at baseline developed SLD, and 253/318 (79.5%) participants among participants with SLD at baseline SLD resolved fatty liver. Mean TT3 rather than thyroid stimulating hormone or mean free thyroxine was significantly related with development (adjusted hazard ratio [HR], 1.01; 95% confidence interval [CI], 1.00 to 1.02; P=0.002) and resolution (adjusted HR, 0.97; 95% CI, 0.96 to 0.99; P=0.005) of SLD. Compared with low mean TT3 group, high mean TT3 group was positively associated with development of SLD (adjusted HR,1.20; 95% CI, 1.05 to 1.38; P=0.008) and inversely associated with resolution of SLD (adjusted HR, 0.66; 95% CI, 0.51 to 0.85; P=0.001). The statistical significance remained for development (adjusted HR, 1.29; 95% CI, 1.10 to 1.51; P=0.001) and resolution (adjusted HR, 0.71; 95% CI, 0.54 to 0.94; P=0.018) of modified MASLD., Conclusion: In Korean euthyroid adults, TT3 level was associated with development and resolution of either SLD or modified MASLD.

Despite widespread interest in nanoscale pillar structures for various optical devices, including solar cells, photonic crystal lasers, and sensors, the critical challenges for mass production are the high equipment costs and limited scalability of traditional manufacturing methods. To overcome these hurdles, this study develops a simple and highly scalable etch-mask superposition technique based on thermally assisted nanotransfer printing (T-nTP) of Cr line patterns. The orthogonal superposition of linear Cr mask patterns creates double-height cross-point arrays that effectively and selectively protect the underlying SiO 2 during subsequent reactive ion etching. This process generates highly uniform nanoscale pillar arrays with an extremely high density of 0.1 tera-pillars per square inch, eliminating the need for high-cost patterning platforms. As an exemplary application, we demonstrate the use of these perfectly ordered nanopillar arrays as high-performance surface-enhanced Raman scattering (SERS) sensors through the deposition of noble metal films on the nanopillar surface. These nanopillars enable exceptionally uniform SERS intensity with spot variations of less than 7% in methylene blue (MB) measurements. Additionally, they exhibit sensitive detections and accurate quantification for thiabendazole (TBZ) at concentrations as low as 10 -8 M, along with multicycle reusability without noticeable degradation, owing to the outstanding robustness of the SiO 2 nanopillars.

Breast ultrasound is used in a wide variety of clinical scenarios, including both diagnostic and screening applications. Limitations of ultrasound, however, include its low specificity and, for automated breast ultrasound screening, the time necessary to review whole-breast ultrasound images. As of this writing, four AI tools that are approved or cleared by the FDA address these limitations. Current tools, which are intended to provide decision support for lesion classification and/or detection, have been shown to increase specificity among nonspecialists and to decrease interpretation times. Potential future applications include triage of patients with palpable masses in low-resource settings, preoperative prediction of axillary lymph node metastasis, and preoperative prediction of neoadjuvant chemotherapy response. Challenges in the development and clinical deployment of AI for ultrasound include the limited availability of curated training datasets compared with mammography, the high variability in ultrasound image acquisition due to equipment- and operator-related factors (which may limit algorithm generalizability), and the lack of postimplementation evaluation studies. Furthermore, current AI tools for lesion classification were developed based on 2D data, but diagnostic accuracy could potentially be improved if multimodal ultrasound data were used, such as color Doppler, elastography, cine clips, and 3D imaging.

It is important to establish the relationship between appropriate nutritional intake and improvements in activities of daily living (ADLs) in elderly hospitalized patients. This prospective observational study aimed to investigate diet order compliance (DOC) during 8 weeks of hospitalization and calculate the odds of improved functional independence measure (FIM) scores for high- and low-DOC groups using covariate-adjusted models in geriatric convalescent hospitals. The study subjects were elderly inpatients (>65 years old) with degenerative disease who consumed prescribed oral meals (Functional Oral Intake Scale (FOIS) = 6/7) and who did not receive physical/occupational therapy. The personalized diet order was prescript, and the DOC was calculated using dietitian-monitored daily intake data. The 73 patients were divided into a low-DOC group (< 84.0%, n = 35) and a high-DOC group (≥ 84.0%, n = 38) on the basis of the median DOC (84.0%, average for 8 weeks). Twenty (52.6%) high-DOC patients and nine (25.7%) low-DOC patients experienced motor-FIM improvements (P = 0.017). After 8 weeks, the change in motor-FIM in the high-DOC group (1.6±0.3) was greater than that in the low-DOC group (0.3±0.1; P = 0.001). According to the baseline and nutrition-intake-adjusted model of multiple logistic regression analysis, in the high-DOC group, the motor-FIM improvement OR was 5.102 (95% CI: 1.100-16.233, P = 0.036), and the total-FIM improvement OR was 5.273 (95% CI: 1.102-25.238, P = 0.037). High compliance with individualized nutritional prescriptions can increase FIM scores in clinical settings. Thus, comprehensive approaches to increase dietary compliance are needed for elderly long-term care patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cho 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.)

This study explores the potential of seven ferrocenyl (Fc) compounds with cross-linking groups as alternative redox labels to methylene blue (MB) for electrochemical aptamer-based (E-AB) sensors. The cross-linking efficiency, formal potential ( E 0 '), and electrochemical durability of these compounds were evaluated. Compound Fc1a-X exhibited superior performance, characterized by efficient cross-linking, a moderate and pH-insensitive E 0 ', and enhanced durability during repeated potential scans. The attachment of Fc1a-X , which includes a 3-carbon chain spacer and an N -hydroxysuccinimide-ester cross-linking group, to an amine-terminated monolayer on a Au electrode demonstrated high cross-linking efficiency, which is critical for achieving high sensitivity. The E 0 ' of Fc1a-X attached to the aptamer monolayer was 0.14 V, which is within the optimal range of -0.2 to 0.2 V vs Ag/AgCl. Square wave voltammetry showed that the peak potential and current of Fc1a-X are pH-insensitive, which is critical for versatile use. In serum, Fc1a-X maintained stable peak current levels without a gradual decrease after an initial rapid decrease during the first 2 h with considerably less reduction over 12 h compared to MB. Using Fc1a-X as the redox label, an E-AB sensor effectively detected doxorubicin in serum, covering the clinical range. These findings suggest Fc1a-X as a promising candidate for developing robust, versatile, and sensitive E-AB sensors.

Purpose: To assess the efficacy of contrast vector imaging (CVI) in detecting tumoral vascular structures and flow characteristics of focal liver lesions (FLLs) for differential diagnosis., Materials and Methods: In this prospective study, 65 participants with FLLs underwent CEUS using SonoVue with high-frame-rate imaging technique between July 2019 and October 2020. CVI was obtained by post-processing arterial cine imaging of CEUS. Tumoral vascular structures, velocity histogram, and mean velocities were compared among hepatocellular carcinoma (HCC), non-HCC malignancies, and benign tumors using the Chi-square and Kruskal-Wallis tests, respectively. The areas under the receiver operating characteristic curve (AUC) of CEUS in determining HCC probability was compared to that of CEUS with CVI using a z-test., Results: CVI was technically successful in 52 of 65 (80%) participants (19 HCCs, 13 non-HCC malignancies, and 20 benign tumors). The detectability of tumoral vascular structures was significantly higher in CEUS with CVI, compared to CEUS alone (46.2% [24/52] vs. 100.0% [52/52], p<0.001). On CEUS with CVI, complex intratumoral and peripheral vessels were frequent in HCCs (100% of HCCs, 46.2% of non-HCC malignancies, and 70.0% of benign tumors), while detour vessels were frequent in non-HCC malignancies (none of HCCs, 53.8% of non-HCC malignancies, and 10.0% of benign tumors) (p<0.001). The mean velocity of HCC (26.3 mm/s) was the highest, while that of non-HCC malignancy (20.6 mm/s) was the lowest (p<0.001). CEUS with CVI showed higher AUC, compared to CEUS in both reviewers (0.851 vs. 0.963, p = 0.005 for reviewer 1; 0.853 vs. 0.982, p = 0.023 for reviewer 2)., Conclusion: CEUS with CVI better visualized vascular structures and flow characteristics of FLLs, and showed better diagnostic performance in determining HCC probability than CEUS., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yoo 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.)

Japanese encephalitis (JE) is a widespread flavivirus that induces brain inflammation and affects the central nervous system (CNS). Deferoxamine, an iron chelator, has shown promising results in stabilizing HIF-1α, a protein that improves hypoxic conditions, offers protective effects against neurological, and neurodegenerative diseases. This study aimed to assess the impact of HIF-1α stabilization during JEV infection using SH-SY5Y neuroblastoma cell lines as a model. Our findings demonstrated that deferoxamine treatment increased HIF-1α protein levels, leading to a reduction in JEV propagation. Moreover, RT-PCR analysis revealed that deferoxamine ameliorated JEV-induced neuroinflammation and neurotoxicity. We proved that inducing HIF-1α is essential for having an impact of deferoxamine against JEV-mediated neurotoxicity. Thus, our findings offer a potential therapeutic approach to mitigate the detrimental effects of JEV infection on neuronal cells. Further investigations also demonstrated that deferoxamine could reverse JEV-induced autophagy inhibition by stabilizing HIF-1α, which plays a crucial role in mitigating neuronal cell damage and neuroinflammation. Based on our data, HIF-1α stabilization emerges as a vital factor against JEV infection in the neurons, highlighting deferoxamine as a promising and innovative target for developing anti-JEV agents., 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.)

Objectives: This study aimed to develop machine learning (ML) prediction models for identifying bloodstream infection (BSI) and septic shock (SS) in pediatric patients with cancer who presenting febrile neutropenia (FN) at emergency department (ED) visit., Materials and Methods: A retrospective study was conducted on patients, aged younger than 18 years, who visited a tertiary university-affiliated hospital ED due to FN between January 2004 and August 2022. ML models, based on XGBoost, were developed for BSI and SS prediction., Results: After applying the exclusion criteria, we identified 4423 FN events during the study period. We identified 195 (4.4%) BSI and 107 (2.4%) SS events. The BSI and SS models demonstrated promising performance, with area under the receiver operating characteristic curve values of 0.87 and 0.88, respectively, which were superior to those of the logistic regression models. Clinical features, including body temperature, some laboratory results, vital signs, and diagnosis of acute myeloblastic leukemia were identified as significant predictors., Conclusions: The ML-based prediction models, which use data obtainable at ED visits may be valuable tools for ED physicians to predict BSI or SS., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: The purpose of this study was to assess the effects of tourniquet use on operative time, muscular injury, and postoperative pain in anterior cruciate ligament (ACL) reconstruction., Methods: This study was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search was performed in EMBASE, PubMed, Web of Science, and the Cochrane Library for relevant randomized controlled trials (RCTs) (level of evidence: 1), from inception to February 6, 2024. Data extraction included details such as first author, country, publication year, sample size, age, sex, tourniquet parameters (including inflation time and pressure), anesthesia, arthroscopic visualization , operative time, postoperative visual analog score(VAS), postoperative blood loss, postoperative morphine consumption within 24 h, postoperative serum creatine phosphokinase(CPK) levels, side-to-side thigh circumference difference after 3 weeks of surgery, and knee functional scores at the 6 month follow-up. Studies that met the inclusion criteria were assessed for risk of bias using the Cochrane Collaboration's tool., Results: Seven RCTs involving 471 participants were included in this study. Compared the non-tourniquet group, the tourniquet group had a significantly decreased operative time (MD -10.11, 95%CI -15.74 to -4.49, p=0.0004, I 2 =49%). In addition, the tourniquet group significantly increased the CPK levels compared to non-tourniquet group (MD 12.70, 95%CI 2.47 to 22.92, p=0.01, I 2 =0%). Moreover, the tourniquet group had significantly higher VAS scores 1 day post-operatively (MD 0.31, 95% CI 0.10 to 0.53, p=0.005, I 2 =21%), and significantly higher postoperative blood loss (MD 156.33, 95%CI 134.05 to 178.60, p<0.00001, I 2 = 63%)., Conclusions: This meta-analysis found that the use of tourniquet in ACL reconstruction may decrease operative time, but is associated with thigh muscle injury and increased postoperative pain., Level of Evidence: Level I, meta-analysis of level I studies., (Copyright © 2024. Published by Elsevier Inc.)

Background: The literature provides limited evidence regarding postoperative outcomes and complications following simultaneous bilateral medial opening-wedge high tibial osteotomy (MOWHTO). This study aimed to investigate the clinical outcomes and complications associated with simultaneous bilateral MOWHTO., Methods: We retrospectively evaluated 72 knees from 36 patients (mean age, 58.6 ± 8.2 years) who underwent simultaneous bilateral MOWHTOs between December 2011 and January 2021. Locking compression plates were used for simultaneous bilateral MOWHTOs. The Oxford Knee Score (OKS) was used to assess clinical outcomes at the last follow up. Complications (lateral hinge fracture (LHF), nonunion, and loss of correction) were evaluated using postoperative serial plain radiography and computed tomography (CT)., Results: At the last follow up (range, 2.0-11.1 years), the mean OKS for the 72 knees was 36.8 ± 10.4. According to the OKS, 42 knees (58.3%) scored 'excellent', 16 (22.2%) scored 'good', eight (11.1%) scored 'moderate', and six (8.3%) scored 'poor'. LHFs occurred in 11 of the 72 knees (15.3%). Among these, five LHFs were identified on postoperative plain radiographs and CT scans (acute LHFs), whereas six fractures were identified only on follow up plain radiographs (delayed LHFs). Loss of correction occurred in one patient with delayed LHFs. The patient required an additional surgical treatment to achieve bone healing at the osteotomy site., Conclusion: Simultaneous bilateral MOWHTO is a viable treatment option for patients with bilateral medial osteoarthritis of the knee joint. Serial plain radiographs at short-term intervals are recommended to detect delayed LHFs and prevent complications such as fixation failure and loss of correction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Intestinal stem cells (ISCs) are highly vulnerable to damage, being in a constant state of proliferation. Reserve stem cells repair the intestinal epithelium following damage-induced ablation of ISCs. Here, we report that the epigenetic regulator plant homology domain (PHD) finger protein 16 (PHF16) restores homeostasis of the intestinal epithelium after initial damage-induced repair. In Phf16 -/Y mice, revival stem cells (revSCs) showed defects in exiting the regenerative state, and intestinal crypt regeneration failed even though revSCs were still induced in response to tissue damage, as observed by single-cell RNA sequencing (scRNA-seq). Analysis of Phf16 -/Y intestinal organoids by RNA sequencing (RNA-seq) and ATAC sequencing identified that PHF16 restores homeostasis of the intestinal epithelium by inducing retinoic acid receptor (RAR)/retinoic X receptor (RXR) target genes through HBO1-mediated histone H3K14 acetylation, while at the same time counteracting YAP/TAZ activity by ubiquitination of CDC73. Together, our findings demonstrate the importance of timely suppression of regenerative activity by PHF16 for the restoration of gut homeostasis after acute tissue injury., Competing Interests: Declaration of interests The authors declare that no potential conflicts of interest exist., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Bardet-Biedl syndrome (BBS) is a rare syndromic ciliopathy characterized with retinal degeneration and a broad range of systemic features. Twenty-six BBS-associated genes have been identified to date and clinical genetic testing resolves around 80% of the cases. Two BBS cases unsolved by clinical genetic testing were recruited to identify causative variants using next-generation sequencing., Methods: Genomic DNA of the probands from both families was extracted from peripheral blood. Whole genome or exome sequencing results were analyzed with comprehensive variant filtering on structural variants, single nucleotide variants (SNVs), insertions/deletions (indels)., Results: Family 1: A novel rare deletion NM&#95;024649.5( BBS1 ): c.830 + 554&#95;1110 + 1052del; p.(Asp278Metfs*3) was identified in the female proband in trans with a known pathogenic missense variant p.(Met390Arg). This 3k base pair (bp) deletion was predicted to cause a loss in exons 10-11, resulting in a premature stop codon. Family 2: Variant filtering in the male proband identified two rare (gnomAD AF < 0.01%) nonsense SNVs in trans in BBS9 , NM&#95;198428.3: c.724 G>T; p.(Gly242*) and c.966 G>A; p.(Trp322*), one of them being a novel pathogenic variant., Conclusion: All the novel variants identified fell into the pathogenic variant classification following ACMG/AMP criteria. This report highlights the role of whole exome and genome sequencing in unsolved cases.

Background: Alopecia areata (AA) is characterized by an autoimmune inflammatory response to hair follicles. Several studies have suggested that infection and vaccination can trigger an autoimmune process around hair follicles. Moreover, reports of AA and various other autoimmune diseases have increased since the coronavirus disease 2019 (COVID-19) pandemic became established., Objective: We assessed the clinical characteristics and treatment response in patients who developed AA following COVID-19 infection or vaccination., Methods: This retrospective study involved patients who had developed COVID-19 or received a COVID-19 vaccination within 3 months before the onset or aggravation of AA from January 2020 to December 2022., Results: Fifty patients met the inclusion criteria. Eighteen patients had a history of COVID-19 infection, and 32 had a history of COVID-19 vaccination. The mean onset of AA after COVID-19 infection and vaccination was 5.22±3.35 and 4.13±2.73 weeks, respectively. The most common COVID-19-associated symptoms before AA were fever (88.9%) in the infection group and myalgia (50.0%) in the vaccination group. In the vaccination group, AA most commonly occurred after receiving the Pfizer-BioNTech vaccine (BNT162b2, 46.9%) or Moderna vaccine (mRNA-1273, 34.4%). The vaccination group showed more rapid improvement than the infection group; however, both showed significant improvement after 6 months of treatment of AA., Conclusion: We examined the clinical characteristics and treatment responses of patients who developed AA after COVID-19 infection or vaccination. Further research is needed to evaluate the detailed pathogenesis and association between COVID-19 and AA., Competing Interests: The authors have nothing to disclose., (© 2024 The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)

The implementation of deep neural networks has spurred the creation of deep learning reconstruction (DLR) CT algorithms. DLR CT techniques encompass a spectrum of deep learning-based methodologies that operate during the different steps of the image creation, prior to or after the traditional image formation process (eg, filtered backprojection [FBP] or iterative reconstruction [IR]), or alternatively by fully replacing FBP or IR techniques. DLR algorithms effectively facilitate the reduction of image noise associated with low photon counts from reduced radiation dose protocols. DLR methods have emerged as an effective solution to ameliorate limitations observed with prior CT image reconstruction algorithms, including FBP and IR algorithms, which are not able to preserve image texture and diagnostic performance at low radiation dose levels. An additional advantage of DLR algorithms is their high reconstruction speed, hence targeting the ideal triad of features for a CT image reconstruction (ie, the ability to consistently provide diagnostic-quality images and achieve radiation dose imaging levels as low as reasonably possible, with high reconstruction speed). An accumulated body of evidence supports the clinical use of DLR algorithms in abdominal imaging across multiple CT imaging tasks. The authors explore the technical aspects of DLR CT algorithms and examine various approaches to image synthesis in DLR creation. The clinical applications of DLR algorithms are highlighted across various abdominal CT imaging domains, with emphasis on the supporting evidence for diverse clinical tasks. An overview of the current limitations of and outlook for DLR algorithms for CT is provided. © RSNA, 2024.

In Asia-Pacific region, hepatocellular carcinoma is a serious health threat attributing to over 600,000 deaths each year and account for over 70% of global cases. Clinically, the major unmet needs are recurrence after curative-intent surgery, liver transplantation or local ablation and disease progression in those with hepatocellular carcinoma not eligible for resection or failed locoregional therapy. In the recent few years, new targeted therapy and immune-checkpoint inhibitors have been registered as systemic therapy to address these issues. Notably, new forms of systemic therapy, either as first-line or second-line therapy for unresectable hepatocellular or those not eligible for locoregional therapy, are now available. New data is also emerging with the use of systemic therapy to prevent hepatocellular carcinoma recurrence after curative-intent resection or local ablation therapy and to retard disease progression after locoregional therapy. In the future, further implementation of immune-checkpoint inhibitors and other forms of immunotherapy are expected to bring a new paradigm to the management of hepatocellular carcinoma. New insight related to immune-related adverse events with the use of immunotherapy has allso enabled optimization of the therapeutic approach to patients with hepatocellular carcinoma. The purpose of this clinical practice guideline is to provide an up-to-date recommendation based on clinical evidence and experience from expert Asia-Pacific key opinion leaders in the field of hepatocellular carcinoma. Three key questions will be addressed, namely: (1) Which patients with hepatocellular carcinoma should be considered for systemic therapy? (2) Which systemic therapy should be used? (3) How should a patient planned for immune checkpoint-based systemic therapy be managed and monitored?, Competing Interests: Declarations. Conflict of interest: George LAU reported lecture fees from AstraZeneca. Shuntaro OBI reported research grants from Eisai, Otsuka pharmaceutical, and Mochida pharmaceutical. Ryosuke TATEISHI reported lecture fees from Abbvie, AstraZeneca, Chugai, Eisai, Gilead Sciences, MSD and Takeda. Sadahisa OGASAWARA reported honoraria from Bayer, Eisai, Eli Lilly, consulting or advisory fees from Bayer, Eisai, Merck & Co. Inc., Chugai Pharma, Eli Lilly, and research grants from Bayer and Eisai. Naoya KATO reported honoraria payment from Bayer and Chugai; research funding from Bayer, Chugai, and Roche. Stephen L CHAN reported consulting or advisory board fees from AstraZeneca, Eisai, and MSD; reports being an invited speaker for AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, IPSEN, MSD, and Roche; and research funding from Bayer, Eisai, IPSEN, MSD, and Sirtex Medical. Yoshiyuki UENO reported honoraria payment from Chugai and Eisai. Ann-Lii CHENG reported consulting or advisory board fees from AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, Eisai, Genentech/Roche, Ipsen, IQVIA, MSD, Ono Pharmaceutical, and Roche; and honoraria from AstraZeneca, Bayer, Eisai, and Genentech/Roche. Yock Young DAN reported consulting or advisory board fees from Boehringer Ingelheim, MSD, Norvo Nordisk, Roche, and research grants from MSD, Norvo Nordisk, Perspectum, Siemens. Jeong Min LEE reported lecture fees from Samsung Medison, GE Healthcare, Philips Healthcare, Starmed, and research grants from Samsung Medison, Siemens Healthineers, Philips Healthcare, GE Healthcare, Bayer, Guerbet, CMS, Canon Healthcare, Dongkuk Pharma. Diana A. Payawal reported lecture, consulting or advisory board fees from Gilead Sciences, Mylan Pharmaceuticals, Echosense, Getz and Abbott. Ekaphop SIRACHAINAN reported honoraria payment from MSD, Sanofi/Aventis, Merck, Amgen, Roche, Mundipharma, AstraZeneca, LF Asia, Diethelm Keller Group, Bristol Myers Squibb, Boehringer Ingelheim, Taiho Pharmaceutical, Dr Reddy's Laboratories, Zuellig Pharma, Meda Pharmaceuticals, Pfizer, Novo Nordisk, Novartis. Tawesak Tanwandee reported research grants from Bristol Myers Squibb and Merck. Masao Omata reported lecture, consulting or advisory board fees from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Otsuka, Astellas, Gilead Sciences, Chugai, Mitsubishi Tanabe, Kyorin, Merck Sharp and Dohme, Dainippon Sumitomo, Vertex Pharmaceuticals, Takeda, Merck Serono, and Zeria. Jian ZHOU, Shukui QIN, Haitao ZHAO, Motoyuki OTSUKA, Jacob GEORGE, Pierce KH CHOW, Jianqiang CAI, Shuichiro SHIINA, Osamu YOKOSUKA, Kyoko OURA, Thomas YAU, Ming KUANG, Minshan CHEN, Gregory CHENG, Wan-Long CHUANG, Oidov BAATARKHUU, Feng BI, Rino A GANI, Atsushi TANAKA, Wasim JAFRI, Ji-Dong JIA, Jia-Horng KAO, Kiyoshi HASEGAWA, Patrick LAU, Jun LIANG, Zhenwen LIU, Yinying LU, Hongming PAN, Salimur RAHMAN, Jinsil SEONG, Feng SHEN, Gamal SHIHA, Tianqiang SONG, Hui-Chuan SUN, Tsutomu MASAKI, Lai WEI, Jin Mo YANG, Jose D SALLANO, Yanqiao ZHANG,, A Kadir DOKMECI, Shu-sen ZHENG, Jia FAN, Sheung-Tat FAN and Shiv Kumar Sarin reported that they have no conflict of interest. Ethical approval: Not applicable. Informed consent: Not applicable., (© 2024. Asian Pacific Association for the Study of the Liver.)

This longitudinal study explored the intricate relationships between serum Brain-Derived Neurotrophic Factor (sBDNF) levels, exposure to childhood adversities, and the subsequent development of Post-Traumatic Stress Disorder (PTSD), distinguishing between earlier- and delayed-onset forms over a two-year follow-up period in individuals sustaining physical injuries. We recruited patients presenting with moderate to severe physical injuries at a trauma center, conducting baseline assessments of sBDNF levels and childhood adversities through the Adverse Childhood Experiences (ACE) questionnaire. Additionally, detailed socio-demographic and clinical data were compiled. The Clinician-Administered PTSD Scale for DSM-5 was employed to diagnose PTSD at 3, 6, 12, and 24 months post-injury. Binary and multinomial logistic regression analyses were applied to elucidate the interactions between sBDNF levels, childhood adversities, and PTSD onset patterns. Among 895 participants, PTSD was diagnosed in 107 individuals (11.9 %), with 76 (8.4 %) exhibiting symptoms indicative of earlier-onset PTSD and 31 (3.5 %) demonstrating delayed-onset PTSD. Significantly, lower sBDNF levels were associated with a higher risk of earlier-onset PTSD specifically in the context of childhood adversities. This association was not observed in individuals without childhood adversities or in those with delayed-onset PTSD. The findings suggest a complex and critical interplay between neurobiological factors, specifically sBDNF levels, and early life adversities in influencing the timing of PTSD onset, potentially deepening the understanding of PTSD etiology., Competing Interests: Declaration of Competing Interest No potential conflict of interest relevant to this article was reported., (Copyright © 2024 Elsevier Ltd. All rights reserved.)