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Tian-Ming Gao,1,&ast; Sheng-Jie Jin,1,&ast; Fang Fang,2,&ast; Jian-Jun Qian,1 Chi Zhang,1 Bao-Huan Zhou,1 Dou-Sheng Bai,1 Guo-Qing Jiang1 1Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, 225001, People’s Republic of China; 2Department of Gastrointestinal Surgery, Clinical Medical College, Yangzhou University, Yangzhou, 225001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guo-Qing Jiang; Dou-Sheng Bai, Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, 98 West Nantong Road, Yangzhou, 225000, People’s Republic of China, Email jgqing2003@hotmail.com; bdsno1@hotmail.comPurpose: Although laparoscopic splenectomy and azygoportal disconnection (LSD) can significantly decrease portal vein pressure and even the incidence of hepatocellular carcinoma (HCC) in patients with cirrhotic portal hypertension (CPH), postoperative HCC inevitably occurs in certain patients. The purpose of this study was to seek a novel preoperative non-invasive predictive indicator to predict the occurrence of postoperative HCC.Patients and Methods: From April 2012 to April 2022, we collected clinical data of 178 hepatitis B virus (HBV)-related CPH patients. Based on inverse treatment probability weighting, candidate variables for predicting postoperative HCC were determined by means analysis. Then, a novel preoperative non-invasive prediction indicator (ie, type IV collagen-alpha fetoprotein-fibrosis-4 score [IVAF-FIB-4]) was established based on candidate variables, and its predictive ability was explored.Results: Postoperative HCC occurred in 9 (5.1%) patients. Correlation analyses showed that the IVAF-FIB-4 had a significant positive correlation with HCC (r = 0.835, P < 0.001). IVAF-FIB-4 showed a high accuracy (the area under the receiver operating characteristic curve: 0.939, 95% confidence interval [CI]: 0.818– 1.000; sensitivity: 88.9%; specificity: 93.5%). At the end of follow-up, the incidence density of HCC in patients with IVAF-FIB-4 (1) was significant higher than that in patients with IVAF-FIB-4 (0) (138.1/1000 vs 1.1/1000 person-years; rate ratio: 130.475, 95% CI: 16.318– 1043.227). In logistic regression, IVAF-FIB-4 was an independent risk factor for HCC (odds ratio: 668.000, 95% CI: 53.895– 8279.541; P < 0.001).Conclusion: IVAF-FIB-4 is a novel preoperative noninvasive predictive indicator for predicting postoperative HCC in HBV-related CPH patients after LSD, with satisfactory predictive ability.Keywords: liver fibrotic markers, splenectomy, azygoportal disconnection, hepatocellular carcinoma, risk

Inelastic neutron scattering measurements have been performed to investigate the spin waves of the quasi-one-dimensional antiferromagnetic ladder compound BaFe2S3, where a superconducting transition was observed under pressure [H. Takahashi, Nat. Mater. 14, 1008 (2015)1476-112210.1038/nmat4351; T. Yamauchi, Phys. Rev. Lett. 115, 246402 (2015)PRLTAO0031-900710.1103/PhysRevLett.115.246402]. By fitting the spherically averaged experimental data collected on a powder sample to a Heisenberg Hamiltonian, we find that the one-dimensional antiferromagnetic ladder exhibits a strong nearest-neighbor ferromagnetic exchange interaction (SJR=-71±4 meV) along the rung direction, an antiferromagnetic SJL=49±3 meV along the leg direction, and a ferromagnetic SJ2=-15±2 meV along the diagonal direction. Our data demonstrate that the antiferromagnetic spin excitations are a common characteristic for the iron-based superconductors, while specific relative values for the exchange interactions do not appear to be unique for the parent states of the superconducting materials.

Jin-Yong Lin,1,2,* Dou-Sheng Bai,1,* Bao-Huan Zhou,1,2,* Ping Chen,1 Jian-Jun Qian,1 Sheng-Jie Jin,1 Guo-Qing Jiang1 1Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, China; 2Department of Hepatobiliary Surgery, The Second Clinical College, Dalian Medical University, Dalian, China *These authors contributed equally to this work Background: Although the prognostic implications of negative lymph nodes (NLNs) has been reported for a variety of tumors, little information has been published about the NLNs in gallbladder cancer (GBC).Patients and methods: In this study, clinicopathological characteristics and survival times of patients who had undergone surgery for GBC were collected from the Surveillance, Epidemiology, and End Results Program-registered TNM stage database and analyzed. Univariate and multivariate Cox proportional hazards models were used to identify the predictors of survival.Results: It was found that a cutoff of one to two NLNs is optimal when assessing the association with survival, survival rates being consistently better with two or more NLNs than with fewer than two. This optimal cutoff value of 2 was identified as an independent prognostic factor by univariate and multivariate analyses (all P

This study investigated the effects of various binary sweetener mixtures on sweetness enhancement and their interactions with sweet or bitter taste receptors, focusing on sensory perception and receptor activity. Acesulfame K or saccharin was mixed with allulose, aspartame, erythritol, fructose, glucose, or sucrose to match a target sucrose sweetness. The effects of the mixtures on sweet and bitter taste receptors (in the human embryonic kidney -293 cells) and sensory taste intensities were evaluated. Sweetness enhancement at the sweet taste receptor level was observed in some cases, with several monosaccharides reducing the acesulfame K- or saccharin-induced bitter taste receptor activity. Combining acesulfame K or saccharin with any of the six sweeteners perceptually enhanced sweetness (60% ∼ 100% in 50:50 ratio), correlating with a reduction in inherent bitterness (-35% ∼ -63% in 50:50 ratio). This finding suggests that sweetness perception likely increased because the monosaccharides mitigate the activation of bitter receptors caused by high-potency sweeteners., 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 Ltd.. All rights reserved.)

Importance: In patients with atherosclerotic cardiovascular disease (ASCVD), intensive lowering of low-density lipoprotein (LDL) cholesterol levels with high-intensity statins is generally recommended. However, alternative approaches considering statin-related adverse effects and intolerance are needed., Objective: To compare the long-term efficacy and safety of an alternative LDL cholesterol-lowering strategy vs high-intensity statin strategy in patients with ASCVD in randomized clinical trials., Data Sources: PubMed, Embase, and other websites (ClinicalTrials.gov, European Society of Cardiology, tctMD) were systematically searched from inception to April 19, 2024., Study Selection: Randomized clinical trials comparing an alternative LDL cholesterol-lowering strategy vs a high-intensity statin strategy in patients with ASCVD, with presence of cardiovascular events as end points., Data Extraction and Synthesis: Individual patient data were obtained from randomized clinical trials that met the prespecified eligibility criteria: RACING (Randomized Comparison of Efficacy and Safety of Lipid-Lowering With Statin Monotherapy vs Statin/Ezetimibe Combination for High-Risk Cardiovascular Disease) and LODESTAR (Low-Density Lipoprotein Cholesterol-Targeting Statin Therapy vs Intensity-Based Statin Therapy in Patients With Coronary Artery Disease). The moderate-intensity statin with ezetimibe combination therapy in the RACING trial and the treat-to-target strategy in the LODESTAR trial were classified as alternative LDL cholesterol-lowering strategies. The primary analysis was based on a 1-stage approach., Main Outcomes and Measures: The primary end point was a 3-year composite of all-cause death, myocardial infarction, stroke, or coronary revascularization. The secondary end points comprised clinical efficacy and safety end points., Results: Individual patient data from 2 trials including 8180 patients with ASCVD (mean [SD] age, 64.5 [9.8] years; 2182 [26.7%] female; 5998 male [73.3%]) were analyzed. The rate of the primary end point did not differ between the alternative strategy and high-intensity statin strategy groups (7.5% [304 of 4094] vs 7.7% [310 of 4086]; hazard ratio, 0.98; 95% CI, 0.84-1.15; P = .82). The mean (SD) LDL cholesterol level during treatment was 64.8 (19.0) mg/dL in the alternative strategy group and 68.5 (20.7) mg/dL in the high-intensity statin strategy group (P < .001). The alternative strategy group had a lower rate of new-onset diabetes (10.2% [271 of 2658] vs 11.9% [316 of 2656]; P = .047), initiation of antidiabetic medication for new-onset diabetes (6.5% [173 of 2658] vs 8.2% [217 of 2656]; P = .02), and intolerance-related discontinuation or dose reduction of assigned therapy (4.0% [163 of 4094] vs 6.7% [273 of 4086]; P < .001)., Conclusions and Relevance: Results of this systematic review and individual patient data meta-analysis suggest that compared with a high-intensity statin strategy, the alternative LDL cholesterol-lowering strategy demonstrated comparable efficacy regarding 3-year death or cardiovascular events in patients with ASCVD, with an associated reduction in LDL cholesterol levels and risk for new-onset diabetes and intolerance., Study Registration: PROSPERO CRD42024532550.

Ingestible devices (ID) provide a safe and noninvasive method for monitoring, diagnosing, and delivering drugs to specific sites in the human body, particularly within the gastrointestinal (GI) tract. However, the GI environment is highly acidic and humid, which can cause IDs to fail, and their corrosion in the acidic environment can cause leaching of toxic metal ions, thereby substantially limiting their long-term use. Thus, an efficient method is required to protect IDs, especially in the chemically and mechanically harsh GI environment. However, an anticorrosive polymer coating that can safeguard IDs in the GI environment without delamination or performance degradation has not been developed to date. The protective layer must satisfy several critical requirements, e.g., high biocompatibility, mechanical durability, and superior anticorrosion performance. This paper reports a highly cross-linked but submicron-thick siloxane-based anticorrosive polymer thin film that can be deposited directly onto IDs without damaging them. The 500 nm-thick cross-linked polymer coating demonstrates exceptional corrosion resistance and chemical and mechanical stability in the GI environment without cytotoxicity. A printed circuit board (PCB) coated with the developed ultrathin protective film sustained performance after exposure to a pH 1.00 phosphate buffered saline solution at 37 °C for 72 h without leaching of metal ions. The ID continued to operate effectively under such challenging conditions; thus, the developed film is suitable for applications that require prolonged functionality, e.g., diagnostics, drug delivery, and continuous health monitoring in the GI tract.

Background: It remains unclear if there is an endometrial thickness (ET) threshold below which malignancy can be excluded. Guidance on whether endometrial biopsy is needed based on ET varies among regions in New Zealand and there is a desire to standardise guidance nationwide. This study evaluates the potential impact of limiting endometrial biopsy in pre-menopausal persons with abnormal uterine bleeding (AUB) to those with an ET of less than 12 mm., Aims: To determine the number of pre-menopausal patients with AUB with an ET of less than 12 mm undergoing endometrial sampling annually and assess the prevalence of pathology among these patients., Materials and Methods: Endometrial samples from patients aged 18-50 years processed at a tertiary hospital between 15/06/2022 and 13/06/2023 were identified via a pathology lab search. Clinical, radiologic, and pathological data were obtained by case note review for those with AUB whose ET was less than 12 mm., Results: Of 1271 endometrial samples, 355 patients met the eligibility criteria, and 2.2% of these were cancerous (three cases) or pre-malignant (five cases)., Conclusions: If sampling thresholds would change to not perform biopsies in those with an ET of less than 12 mm, eight cases of treatable disease would be missed in pre-menopausal people. This represents 13.6% of all endometrial cancers diagnosed in pre-menopausal people in the same time period. There is no ET cut-off to reliably exclude high-risk pathology and endometrial sampling should be performed in all cases of AUB with risk factors., (© 2024 Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: Tourette syndrome (TS) is recognized as a neurodevelopmental disorder profoundly influenced by familial factors, particularly family functioning. However, the relationship among family functioning, tic severity, and quality of life in individuals with TS during childhood and adolescence remains unclear. We hypothesized that family functioning plays a role in the association between the severity of TS and quality of life in children., Aim: To determine the role of family functioning in the relationship between TS severity and quality of life., Methods: This study enrolled 139 children (male/female = 113/26) with TS. We assessed tic severity using the Yale Global Tic Severity Scale, quality of life via the Tourette Syndrome Quality of Life Scale, and family functioning through the Family Assessment Device. Our analysis focused on correlating these measures and exploring the mediating role of family functioning in the relationship between tic severity and quality of life. Additionally, we examined if this mediating effect varied by gender or the presence of comorbidity., Results: We found that family communication dysfunction had a significant mediating effect between tic severity and both psychological symptoms (indirect effect: Β = 0.0038, 95% confidence interval: 0.0006-0.0082) as well as physical and activities of daily living impairment (indirect effect: Β = 0.0029, 95% confidence interval: 0.0004-0.0065). For vocal tic severity, this mediation was found to be even more pronounced. Additionally, in male participants and those without attention deficit hyperactivity disorder, the mediating effect of family communication dysfunction was still evident., Conclusion: Our study highlights the impact of family functioning on the tic severity and the quality of life in children. This relationship is influenced by gender and comorbid conditions like attention deficit hyperactivity disorder., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Extracellular vesicles (EVs) are promising therapeutic biomaterials capable of transferring their cargo molecules and external drugs to other cells in vivo and contain various biomarkers that can be used in liquid biopsies. The clinical application of EVs requires an efficient EV enrichment system for the large-scale production or high-throughput isolation of EVs from liquid samples, such as culture media, plant juices, and body fluids. However, current EV enrichment methods, such as ultrafiltration and ultracentrifugation, have limited applicability owing to their associated costs, inefficiency, scalability, and centrifugation time. Herein, we describe the development of a nanosieve based on a superabsorbent polymer for selective EV enrichment. The nanosieve absorbs small molecules while expelling large molecules, such as EVs, through the nanosized channels. We successfully concentrated EVs from clinical samples, such as serum and plasma, with superior cost and time efficiencies. The nanosieves did not interact with the EVs during enrichment, allowing the retention of their therapeutic functions. In addition, the nanosieve surface was specifically engineered to provide multifunctionality to effectively promote EV capture from bulk solutions. Overall, our nanosieve-based EV enrichment method is effective, time- and cost-saving, versatile, scalable, and modulable, and is an excellent option for EV production.

Purpose: Autologous arteriovenous fistulas (AVFs) are considered the gold standard for hemodialysis access, with outcomes largely dependent on the surgeon's experience. Nevertheless, few studies have been conducted on the learning curve of junior vascular surgeons in AVF creation. This study aims to address this by examining the development of surgical skills among junior vascular surgeons., Materials and Methods: A retrospective analysis was conducted on 100 patients who underwent autologous AVF procedures performed by five junior surgeons between January 2018 and December 2023. To establish the cutoff number of cases for the learning curve, we examined the cubic spline curve using the hazard ratio for primary failure., Results: The cutoff number for operation cases was 15.33, and we divided the analysis into a pre-learning curve period (≤15 cases of AVF) and a post-learning curve period (>15 cases of AVF). The 1-year primary patency rate for AVF during the post-learning curve period was 84.0%, which was higher than the 65.5% rate observed during the pre-learning curve period. In a subgroup analysis based on AVF type, the radiocephalic fistula patient group demonstrated a significant increase in 1-year primary patency in the post-learning curve period compared to that in the pre-learning curve period (80.0% vs. 43.0%, log-rank P=0.033). In contrast, there was no significant difference in the primary patency rates between the post- and pre-learning curve periods in the brachiocephalic fistula patient group (90.0% vs. 89.2%, log-rank P=0.930)., Conclusion: Junior vascular surgeons demonstrated improved primary AVF patency beyond the learning curve benchmark in 15 patients, with particularly notable enhancements in radiocephalic fistulas.

The cosmetics industry is increasingly focusing on developing sustainable and environmentally friendly products while maintaining high performance. In color cosmetics, achieving long-lasting durability of water-soluble dyes remains a challenge. This study presents a sustainable approach to enhance the durability of water-soluble dyes in cosmetics using biopolymer-based films. The casein films were fabricated through riboflavin phosphate (RFP)-mediated photo-crosslinking, with tannic acid (TA) incorporated to improve mechanical properties. The fabrication process, characterization, and performance evaluation of the biopolymer-based films were investigated. Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) analyses confirmed the successful crosslinking and formation of a porous network structure. Rheological measurements revealed that the incorporation of TA significantly enhanced the mechanical strength of the films. Cytocompatibility assessment using NIH/3T3 fibroblasts demonstrated the films' excellent biocompatibility. The durability and color retention of a water-soluble red dye in the biopolymer-based films were evaluated on human skin. The films formed under blue light irradiation exhibited superior dye retention compared to non-irradiated films, with TA addition providing a minor improvement in durability. This study bridges the gap between cosmetic science and biomaterials research, providing a foundation for future investigations into bio-interactive materials for dermal applications. These findings highlight the potential of RFP-mediated photo-crosslinked casein films as a sustainable and effective solution for enhancing the durability of water-soluble dyes in color cosmetics.

Objective: Medication-related osteonecrosis of the jaw (MRONJ) is a rare but debilitating disease characterized by a progressive necrosis of jaw bones in patients who have received anti-resorptive or anti-angiogenic therapies. Unfortunately, we still have no validated preventive or pharmaceutical interventions to help these patients, primarily due to our limited understanding of MRONJ pathogenesis. Here, we offer an extensive review of recent studies relevant to MRONJ pathogenesis. We present a hypothesis regarding the coupling of bone resorption and angiogenesis that relies on osteoblast-derived, matrix-bound vascular endothelial growth factors to explain why ONJ is associated with both anti-resorptive and anti-angiogenic agents., Methods: A narrative review was conducted by searching databases, including PubMed, Scopus, Google Scholar, and Web of Science, to retrieve relevant reports., Results: Reduced bone resorption leads to reduced angiogenesis, and vice versa, creating a vicious cycle that ultimately results in ischemic necrosis of the jaw. Additionally, we suggest that reduced angiogenesis, induced by anti-resorptive or anti-angiogenic agents, aggravates bacterial infection-induced bone necrosis, explaining why the jaw bone is particularly susceptible to necrosis., Conclusion: Our novel hypothesis will facilitate the advancement of future research and the development of more targeted approaches to managing MRONJ., (© 2024 The Author(s). Oral Diseases published by John Wiley & Sons Ltd.)

Background: Predose trough concentrations (C trough ) of intravenous infliximab (IV-IFX) during maintenance therapy are associated with therapeutic outcomes in patients with Crohn's disease (CD). A subcutaneous formulation of infliximab (SC-IFX) has shown high C trough values due to its favourable pharmacokinetics., Aims: To evaluate the association of C trough of SC-IFX with therapeutic outcomes and the threshold of SC-IFX C trough for achieving mucosal healing (MH) and transmural healing (TH) in patients with CD., Methods: We performed this cross-sectional study in patients with CD who had received SC-IFX maintenance therapy for ≥ 6 months. We measured SC-IFX C trough immediately before SC-IFX injection. We performed ileocolonoscopy/single-balloon enteroscopy and/or magnetic resonance enterography within 3 months of SC-IFX C trough measurement. MH was defined as SES-CD-ulcerated surface subscore of 0. TH was defined as simplified MaRIA score of 0., Results: We enrolled 124 patients with MH in 77.9% (74/95) and TH in 36.3% (37/102). SC-IFX C trough was significantly higher in patients with MH (24.1 vs.16.9 μg/mL; p = 0.001) and TH (26.0 vs. 20.5 μg/mL; p = 0.007) than in those without. ROC analysis identified that the threshold of SC-IFX C trough for MH and TH were 17.5 and 30.3 μg/mL, respectively. Multivariate logistic regression showed that SC-IFX C trough was significantly associated with MH (OR 1.16; 95% CI 1.05-1.27; p = 0.002) and TH (OR 1.08; 95% CI 1.02-1.14; p = 0.005)., Conclusions: SC-IFX C trough was positively associated with MH (≥ 18 μg/mL) and TH (≥ 30 μg/mL) in patients with CD, which may guide treatment decisions to optimise therapeutic response in the era of treat-to-target., (© 2024 John Wiley & Sons Ltd.)

Background: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors in multiple endocrine organs, caused by variants in the MEN1 gene. This study analyzed the clinical and genetic features of MEN1 in a Korean cohort, identifying prevalent manifestations and genetic variants, including novel variants., Methods: This multicenter retrospective study reviewed the medical records of 117 MEN1 patients treated at three tertiary centers in Korea between January 2012 and September 2022. Patient demographics, tumor manifestations, outcomes, and MEN1 genetic testing results were collected. Variants were classified using American College of Medical Genetics and Genomics (ACMG) and French Oncogenetics Network of Neuroendocrine Tumors propositions (TENGEN) guidelines., Results: A total of 117 patients were enrolled, including 55 familial cases, with a mean age at diagnosis of 37.4±15.3 years. Primary hyperparathyroidism was identified as the most common presentation (84.6%). The prevalence of gastroenteropancreatic neuroendocrine tumor and pituitary neuroendocrine tumor (PitNET) was 77.8% (n=91) and 56.4% (n=66), respectively. Genetic testing revealed 61 distinct MEN1 variants in 101 patients, with 18 being novel. Four variants were reclassified according to the TENGEN guidelines. Patients with truncating variants (n=72) exhibited a higher prevalence of PitNETs compared to those with non-truncating variants (n=25) (59.7% vs. 36.0%, P=0.040)., Conclusion: The association between truncating variants and an increased prevalence of PitNETs in MEN1 underscores the importance of genetic characterization in guiding the clinical management of this disease. Our study sheds light on the clinical and genetic characteristics of MEN1 among the Korean population.

Competing Interests: Conflicts of interest S.J.J. reported receiving grants and/or personal fees for lectures or consultation outside of this study from AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion Healthcare, Daewoong, Eli Lilly and Company, Green Cross Laboratories, Janssen Pharmaceuticals, Kolon Pharma, LEO Pharma, Novartis, Pfizer, Sanofi, UCB and Yuhan. The other authors declare no conflicts of interest.

Contraction of heart muscle requires activation of both the actin and myosin filaments. The mechanism of myosin filament activation is unknown, but the leading candidate hypothesis is direct mechano-sensing by the filaments. Here, we tested this hypothesis by activating intact trabeculae from rat heart by electrical stimulation under different loads and measuring myosin filament activation by X-ray diffraction. Unexpectedly, we found that the distinct structural changes in the myosin filament associated with activation had different dependences on the load. In early activation, all the structural changes indicated faster activation at higher load, as expected from the mechano-sensing hypothesis, but, at later times, the helical order of the myosin motors characteristic of the inactivated state was lost even at very low load. We conclude that mechano-sensing does operate in heart muscle, but it is supplemented by a previously undescribed mechanism that links myosin filament activation to actin filament activation. KEY POINTS: Myosin filament activation controls the strength and speed of contraction in heart muscle. Early activation of the myosin filament is determined by the filament load. At later times, myosin filament activation is controlled by a load independent pathway. This load independent pathway provides new targets and assays for drug development., (© 2024 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Saccharomyces cerevisiae accumulates glycogen, a hyperbranched glucose polymer with multiple bio-functionalities. In this study, mutants of S. cerevisiae that accumulate excessive amounts of glycogen were developed through UV mutagenesis. From over 30,000 mutants, the mutant strain CEY1, which exhibited the highest glycogen production, was selected using iodine vapor screening. The glycogen structures of wild type (WT) and CEY1 were analyzed and found to be relatively similar in molecular weight, hydrodynamic diameter, and side-chain distribution. The glycogen from CEY1 contained long branches (DP >12) 23.6 % greater than those in Escherichia coli TBP38. In addition, WT and CEY1 glycogen showed 32 %-34 % digestibility, which is significantly lower than E. coli glycogen. The glycogen content in dried CEY1 cells was increased to 21.7 % during laboratory-scale fed-batch fermentation. Glycogen with a homogeneous structure was accumulated to 17.5 % (w/w dried cell), and the total glucan content was increased by 33.2 % during large-scale fed-batch fermentation. In a mouse model, a diet containing 30 % CEY1 increased the production of butyrate and populations of beneficial bacteria, including Bacteroides and Parabacteroides. Therefore, glycogen from CEY1 exhibits a distinct structure from other polysaccharides, with notably slow and low digestibility, thereby indicating its potential application as a dietary supplement., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Sphingosine-1-phosphate (S1P) is a multifunctional sphingolipid that has been implicated in regulating cellular activities in mammalian cells. Due to its therapeutic potential, there is a growing interest in developing efficient methods for S1P production. To date, the production of S1P has been achieved through chemical synthesis or blood extraction, but these processes have limitations such as complexity and cost. In this study, we generated an S1P-producing Saccharomyces cerevisiae strain by using metabolic engineering and introducing a heterologous sphingolipid biosynthetic pathway to demonstrate the possibility of microbial S1P production., Results: To construct the sphingosine-producing S. cerevisiae strain, both the sphingolipid delta 4 desaturase gene (DES1) and the alkaline ceramidase gene (ACER1) derived from Homo sapiens were introduced into the genome of S. cerevisiae by deleting the dihydrosphingosine phosphate lyase gene (DPL1) and the sphingoid long-chain base kinase gene (LCB5) to prevent S1P degradation and byproduct formation, respectively. The sphingosine-producing strain, DDLA, produced sphingolipids containing sphingosine. In flask fed-batch fermentation, the DDLA strain showed a higher production level of sphingosine under aerobic conditions with high initial cell density. The S1P-producing strain was generated by expressing the human sphingosine kinase gene (SPHK1) under the control of the inducible promoter, while deleting the ORM1 gene involved in the regulation of sphingolipid biosynthesis. The S1P-producing strain, DDLAOgS, exhibited the highest sphingosine production level under fed-batch fermentation in a bioreactor, achieving a 2.6-fold increase compared to flask fermentation. S1P biosynthesis in the DDLAOgS strain was verified by qualitative analysis using electrospray ionization mass spectrometry (ESI-MS)., Conclusions: We successfully developed a metabolically engineered S. cerevisiae as a platform strain for microbial production of S1P by introducing an exogenous pathway of sphingolipids metabolism. The engineered yeast strains showed significant capabilities for sphingolipid production, including S1P. To our knowledge, this is the first report demonstrating that engineered S. cerevisiae can be a major platform strain for producing microbial S1P., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Aimed to report the prevalence and predisposing factors affecting subscapularis muscle atrophy and fatty infiltration (MAFI) in patients without a subscapularis tear, and to analyze the effect of this condition on surgical outcomes., Methods: Between 2020 and 2022, 153 patients (mean age 58.1 ± 10.2 years; 84 men and 69 women) who underwent repair of posterosuperior cuff tears, with no subscapularis tears identified during arthroscopy were retrospectively analyzed. Baseline characteristics, preoperative and follow-up (6 months) magnetic resonance imaging findings, arthroscopic findings, and clinical outcomes (>1 year) were recorded., Results: The prevalence of subscapularis MAFI (Goutallier grade 1 or 2) was 73.9% (113/153), of which the prevalence of Goutallier grade 2 was 23.5% (36/153). From multivariable logistic regression analysis, female sex (odds ratio [OR], 5.6; 95% CI, 1.7-18.6; P=0.005), older age (OR, 1.1; 95% CI, 1.0-1.1; P=0.052), advanced supraspinatus MAFI by Goutallier grade (OR, 3.2; 95% CI, 1.5-6.9; P=0.004), and synovitis (OR, 2.8; 95% CI, 1.1-7.9; P=0.030) were identified as independent predisposing factors for subscapularis MAFI. However, patients with preoperative subscapularis MAFI exhibited similar final range of motion, pain and function, and belly press strength compared to those without preoperative subscapularis MAFI., Conclusions: Subscapularis MAFI is frequently observed conditions even in the absence of subscapularis tears, and this condition could be affected by supraspinatus MAFI, female sex, older age, and synovitis. However, because subscapularis MAFI does not affect the surgical outcome, surgeons need not be concerned about this condition when repairing posterosuperior rotator cuff tear. Level of evidence: IV.

Background: Despite available treatment approaches, including surgical resection along with chemotherapy and radiotherapy, glioblastoma (GBM), the most prevalent primary brain tumor, remains associated with a grim prognosis. Although radiotherapy is central to GBM treatment, its combination with bioenergetics regulators has not been validated in clinical practice. Here, we hypothesized that bioenergetics regulators can enhance the radio-sensitivity of GBM tumorspheres (TSs)., Methods: Gene expression profiles of GBM patient-derived TSs were obtained through microarray and RNA-seq. In vitro treatment efficacy was assessed using clonogenic assay, 3D invasion assay, neurosphere formation assay, and flow cytometry. Protein expression was measured via western blot, and γH2AX foci were detected via immunofluorescence. In vivo efficacy was confirmed in an orthotopic xenograft model., Results: Based on radiation response-associated gene expression, GBM TSs were classified into high- or low-radioresistant groups. Among the five bioenergetics regulators, the pentose phosphate pathway inhibitor DHEA and the glycolysis inhibitor 2-DG notably enhanced the efficacy of ionizing radiation (IR) efficacy in vitro, reducing the survival fraction, stemness, and invasiveness in high- and low-radioresistant TSs. Combination with 2-DG further stimulated IR-induced DNA damage response and apoptosis in low-radioresistant GBM TSs. RNA-seq analysis revealed a downregulation of bioenergetics- and cell cycle-associated genes, whereas extracellular matrix- and cell adhesion-associated genes were enhanced by combined IR and 2-DG treatment. This therapeutic regimen extended survival and diminished tumor size in mouse xenograft models., Conclusions: Our data suggest that combination with bioenergetics regulator 2-DG enhances the radio-sensitivity of GBM TSs, highlighting the clinical potential of this combined regimen., 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. The author is an Editorial Board Member/Editor-in-Chief/Associate Editor/Guest Editor for [Journal name] and was not involved in the editorial review or the decision to publish this article., (Copyright © 2024. Published by Elsevier Inc.)

The early microbiota of neonates is crucial for developing the postnatal immune system and establishing normal physiological, metabolic, and neurological functions. This study aimed to investigate the factors influencing the diversity of the neonatal oral microbiome, including mother-to-newborn microbial transmission. The study includes a prospective cohort comprising 73 mothers and 87 neonates and a retrospective cohort comprising 991 mothers and 1,121 neonates. Samples from the maternal cervix and neonatal gastric, bronchial, and oral cavities were analyzed using culture-based methods. Neonatal oral swab samples were also analyzed using 16S rRNA gene sequencing to characterize microbial diversity and composition. Similar genera were detected in the neonatal gastric, bronchial, and oral samples, and the neonatal gastric culture was the most similar to the maternal cervical culture. In addition to mother-to-newborn microbial transmission, various natal factors including birth type, birth weight, delivery mode, maternal chorioamnionitis, maternal diabetes and the presence of microbes in other sites influenced neonatal oral microbiome diversity. Among these factors, the birth type was the most significant, and preterm neonates exhibited decreased oral microbiome diversity, with fewer beneficial bacteria and more pathogens. These findings could serve as a baseline for research on the establishment of the oral microbiota in preterm neonates and its health implications., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: Polymeric and metallic stents are commonly used to manage patients with chronic malignant ureteric obstruction (CMUO). This paper compares the outcomes of ureteral stenting via the Resonance ® metallic stent against its polymeric counterpart in published literature, as well as between antegrade and retrograde approaches., Methods: A retrospective case series was conducted whereby patients who had undergone Resonance ® stent insertions via an antegrade route from June 2022 to May 2023 were reviewed through our electronic medical record system. Descriptive statistics were used to summarise patient demographics and clinical outcomes., Results: 11 patients who presented with CMUO underwent 12 separate procedures of either unilateral or bilateral ureteral stenting. Total number of stents inserted was 16. Median age of patients was 65 (Range = 32) and 72.73% were males. 66.67% of the procedures yielded an improvement in the estimated glomerular filtration rate (eGFR) in patients as compared to before stenting. Stent failure, defined by stent removal before recommended removal date, occurred in 4 out of 16 (25%) stents. The median duration of Resonance ® stent in situ at the time of data collection (4th December 2023) was 245 days., Conclusion: We conclude that the Resonance ® stent is more effective at providing long term urinary drainage for CMUO, compared to its polymeric counterpart. However, antegrade insertion of the Resonance ® stent does not significantly decrease indwelling stent duration compared to retrograde insertion., Competing Interests: Declarations Conflict of interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Twelve neomanoalide derivatives (1-12) and two halisulfate derivatives (13 and 14), nine of which are unprecedented (4-9, 11, 12, and 14; coscilides A-H and halisulfate 11, respectively), were isolated from the sponge Coscinoderma bakusi. The previously unreported neomanoalide derivatives show distinct features in their 6,7-double bond geometry (4 and 9) or terpenoid moieties (5-8, 11, and 12) compared to the reported ones, as elucidated using NMR spectroscopy and HRMS analysis. Among these derivatives, compounds 11 and 12 contain terpenoid moieties that are rarely found in marine natural products. The isolated compounds showed low activity against hTRPA1, six pathogenic bacterial strains, 10 cancer cell lines, except in the case of 7, which exhibited activity against hTRPA1 (IC 50 , 34.5 μM) and Staphylococcus aureus (MIC, 32.0 μg/mL). The halisulfate derivative 14 inhibited NO production in LPS-activated RAW 246.7 macrophage by 45% at a concentration of 10.0 μM. Although no significant activity was observed for the compounds in this study, the compounds reported herein would contribute to the chemical diversity of marine sesterterpenoids., 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.)

Inhalation toxicity assessment is a crucial tool for the identification and classification of hazardous materials like volatile organic carbons, aerosols, and particulate matter. Unlike traditional acute inhalation toxicity studies that use mortality as an endpoint, the Fixed Concentration Procedure (FCP) emphasizes "evident toxicity" by monitoring behavior, weight, and food intake. This reduces reliance on mortality but doesn't directly address respiratory system impact. The present study introduced a respirometer-based inhalation toxicity and respiratory status assessment method. The toxicity evaluation system integrated a respirometric system with an animal exposure chamber, enabling real-time monitoring of oxygen consumption. The ICR mice were exposed to various concentrations of benzene (10, 20, 40, and 80 mg/L of air), toluene (7.5, 15, 30, and 60 mg/L of air), and xylene (7.5, 15, 30, and 60 mg/L of air). The respiration rate decreased by 70 % and 69 % for benzene (80 mg/L of air) and toluene (60 mg/L of air), respectively, with EC 50 values of 32.5 mg/l and 21.2 mg/L based on oxygen consumption. Xylene did not exhibit EC 50 values at the tested concentrations. However, the oxygen consumption rate significantly decreased (46 %) at high concentrations (60 mg/L of air), indicating sub-lethal toxicological effects. Furthermore, the present study was also validated in the bleomycin-induced idiopathic pulmonary fibrosis (IPF) model, demonstrating its reliability as a respiratory impairment marker. The results exhibited a strong correlation between weight loss and less oxygen consumption in the BLM group (bleomycin-induced) as compared to the SHAM group (control), which was confirmed by histological examination and protein marker analysis. The results suggest the potential use of oxygen consumption as an endpoint measurement in inhalation toxicity assessment tests without animal sacrifice, and the present study could be useful for providing valuable insights into disease progression and pharmacological interventions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Early evaluation of radiation sensitivity in lung cancer patients can facilitate the transition to personalized treatment strategies. To this end, we assessed the capability of 89 Zr-anti-γH2AX-TAT microPET imaging in determining the radiosensitivity of lung cancer xenograft models. We prepared and conducted quality control on 89 Zr-anti-γH2AX-TAT. The radiosensitivity of human non-small cell lung cancer cells (H460) and adenocarcinoma cells (A549) was analyzed through clonogenic survival experiments. Additionally, the role of γH2AX as a biomarker for radiosensitivity was validated by quantifying γH2AX foci via fluorescence staining. Subsequently, the H460 and A549 xenograft mouse models were subjected to irradiation, followed by 89 Zr-anti-γH2AX-TAT microPET imaging. Concurrently, we performed immunofluorescence staining for γH2AX in tumor tissues to establish a correlation between the uptake of 89 Zr-anti-γH2AX-TAT and γH2AX expression., Results: The surviving fraction 2 Gy (SF2) values of H460 and A549 indicating that A549 adenocarcinoma has higher radiosensitivity. The cell immunofluorescence experiment showed that the repair of γH2AX foci in H460 cells after irradiation was significantly higher than that in A549 cells, which also confirmed that A549 has higher radiosensitivity. The microPET imaging results showed the uptake of 89 Zr-anti-γH2AX-TAT in the tumor of the A549 models after radiotherapy was higher than H460 models. The immunofluorescence staining of tumor tissue confirmed that the expression level of γH2AX was higher and the correlation with microPET imaging uptake was good., Conclusion: 89 Zr-anti-γH2AX-TAT allows PET imaging of radiosensitivity in lung cancer xenograft models, and is expected to become an early evaluation method for lung cancer radiosensitivity., Competing Interests: Declarations Ethics approval and consent to participate All animal procedures in the in vivo study were performed in accordance with the 1986 UK Animals (Scientific Procedures) Act and approved by the ethics committee with the ethics approval number SBQDL-2022-077. Consent for publication Not applicable. Competing interests No potential conflicts of interest were disclosed., (© 2024. The Author(s).)

The ubiquity of microplastics (MP) in aquatic environments has been raising concerns. Although the μ-Fourier transform infrared spectroscopy (μ-FTIR) technique is commonly used to detect MPs, it is an expensive and time-consuming process that requires expert operation. Moreover, the mass concentration of MPs cannot be determined, thereby necessitating the development of an inexpensive and simple analytical technique for identifying and quantifying MPs in aquatic environments using thermal-based technologies. This study aimed to develop a method for identifying and quantifying MPs using differential scanning calorimetry (DSC), with six types of semi-crystalline polymers (polypropylene, low-density polyethylene, high-density polyethylene, polyamide, polyethylene terephthalate, and polytetrafluoroethylene) and four amorphous polymers (polyvinyl chloride, polystyrene, polycarbonate, and polymethyl methacrylate) as representative polymers. The melting point and glass transition temperature of each polymer were determined using the heating-cooling-heating method (20 °C/min), and Gaussian and asymmetry double sigmoidal models were chosen for peak deconvolution. As a case study, the effluent of a wastewater treatment plant in Chuncheon, South Korea, was analyzed using the established analysis protocol, and the results were compared with those from μ-FTIR analysis. The MP concentration was measured to be 0.70-0.79 μg/L using DSC, meaning that 105-117.75 g/d of MPs were discharged to Uiam Lake. This value differs from the 0.54-2.03 μg/L obtained by μ-FTIR analysis, which might be due to bias from the conversion method. This study demonstrates the feasibility of using DSC analysis as an economical and simple method for identifying and quantifying MPs in aquatic environments., 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.)

Over the past decade, metal oxide semiconductors have attracted considerable attention because of their transparency, high intrinsic charge carrier mobility, and charge carrier density. Metal oxide semiconductors also provide a promising route to develop resistive memory devices because of the tunability of their conductivity via the removal of oxygen ions, forming oxygen vacancies that can act as electron donors. Here, this paper reports the fabrication of a resistive random-access memory (ReRAM) device with TiO 2 and TiO 2- x layers and introduces a solution-processed In 2 O 3 -graphene oxide (GO) buffer layer from a water-based precursor solution to tune the switching characteristics. The devices were compared with a ReRAM device with no buffer layer, and the device composition was optimized by tuning the GO concentration in the layers. The devices showed hysteresis under cyclically scanned bias between positive and negative voltages with clear switching between the low resistance state (LRS) and the high resistance state (HRS). The optimized device also showed a more than 3 orders of magnitude difference in resistance between the LRS and HRS and a stable current retention. The devices also showed photoresponsive behaviors. In the LRS, the current increased significantly under illumination, while in the HRS, the current deteriorated slowly when constantly illuminated. These results highlight the dual role of the GO flakes in the buffer layer by increasing the resistance in the HRS and providing a photoresponsive switching capability. The ReRAM device was connected to a TFT device, and its feasibility as a memory component in a digital circuit was successfully demonstrated. These results provide a new avenue for developing metal-oxide-based ReRAM devices with GO-containing active layers.

This multicentre, prospective, single-arm study evaluated safinamide as add-on therapy to levodopa in Korean patients with Parkinson's disease (PD) with motor fluctuations with ≥ 1.5 h of "off" time daily, who took levodopa ≥ 3 times/day (n = 199). Baseline levodopa and dopamine agonist doses were maintained without escalation during the 18-week treatment period. Participants received safinamide 50 mg/day for 2 weeks and 100 mg/day thereafter. PD diaries and questionnaires (Parkinson's Disease Questionnaire, PDQ-39; Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale, MDS-UPDRS part 3 and part 4; King's Parkinson's Disease Pain Scale, KPPS; Mini-Mental State Examination, MMSE) were assessed at baseline and at week 18. Treatment-emergent adverse events (TEAEs) were recorded. Mean disease duration was 6.6 years, and mean levodopa equivalent daily dose was 721.1 mg/day. At week 18, significant improvements from baseline were seen for the co-primary endpoints, mean daily "off" time (- 1.3 ± 2.4 h, p < 0.001) and quality of life (QoL) based on PDQ-39 summary index (- 2.7 ± 10.3, p < 0.001), Moreover, significant improvements were seen in motor symptoms and motor complications (MDS-UPDRS part 3 and 4), daily "on" time without dyskinesia (all p < 0.001) and pain (KPPS; p = 0.013). TEAEs occurred in 40.2% of patients, with most being mild in severity. In conclusion, safinamide at a dosage of 100 mg/day significantly improved motor symptoms, QoL, and pain, and demonstrated a favourable safety profile without levodopa dosage escalation during the 18-week treatment period in Korean patients with PD.Trial registration number and date: NCT05312632, First Posted: April 5, 2022., Competing Interests: Declarations Conflict of interest Jieun Kim and Yoona Lee are employees of Eisai Korea Inc. All other authors have no relevant financial or non-financial interests to disclose. Ethical approval This study was performed in line with the principles of the Declaration of Helsinki 2013, and ICH Good Clinical Practice guidelines and Korean Good Clinical Practice guidelines. Approval was granted by the relevant Ethics Committees. Written informed consent was obtained from all study participants., (© 2024. The Author(s).)

Background: The choice of the deep inferior epigastric perforator (DIEP) flap for breast reconstruction has increased. Three-dimensional (3D) models of DIEP flaps have been introduced with advances in 3D technology to assist the tedious intramuscular dissection of the pedicle. This study presents the process of creating an ideal 3D model for a DIEP flap., Methods: Collaboration among various professionals, including surgeons, radiologists, and 3D-printing model makers, is essential for manufacturing suitable 3D-printing DIEP models. Our team facilitated the collaboration process by sharing the virtual 3D model via a uniform resource locator (URL) using an online platform accessible on mobile devices., Results: During collaboration in 3D DIEP model-making, we continuously upgraded the model to a better version. The model was modified according to the surgeon's preference from a 1:1 ratio size to a handheld size. Additionally, we achieved significant advancements over conventional methods, including improved visualization of detailed vessel pathways with separation of arteries and veins, tissue transparency, and superficial inferior epigastric vein (SIEV)., Conclusions: Through 3D model-making collaborations, our team successfully developed a 3D DIEP model with translucency and visualized arteries and veins separately with accentuation of the perforators, including SIEV tracing, which is more accurate. This ideal 3D model for the DIEP flap enables the selection of a perforator vessel that is safe and easy to dissect to lower complications and procedure time and will be of great help to less experienced surgeons., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Research concerning health literacy among migrant workers in South Korea has been limited, especially given the lack of validated instruments and the lack of focus on the cultural diversity of migrant workers., Objective: This study aimed to develop and validate a health literacy scale for unskilled migrant workers (HLS-MW) in South Korea., Methods: We first generated a pool of potential items based on a literature review and in-depth interviews with 23 migrant workers. Subsequently, we reviewed empirical referents from the first step to select relevant medical terminologies and passages, ultimately choosing 709 words. The study team initially generated 35 items with 709 health-related terms through empirical referent reviews. After content validity testing by an expert panel, 28 items comprising 89 terms on the 2 subscales of prose and documents were selected for psychometric testing. Overall, 402 unskilled migrant workers in South Korea completed a web-based survey between August and September 2021, with 334 responses included in the final analysis. We used multiple analytic approaches, including exploratory factor analysis, Rasch analysis (item response theory), and descriptive analysis, to examine the new scale's validity and reliability., Results: The final sample primarily included young male workers from South Asian countries. The HLS-MW yielded 2 factors: prose and documents. The item difficulty scores ranged from -1.36 to 2.56. The scale was reduced to 13 items (10 prose and 3 document items), with the final version exhibiting good internal reliability (Kuder-Richardson index=0.88; intraclass correlation coefficient=0.94, 95% CI 0.93-0.95) and test-retest reliability (r=0.74, 95% CI 0.57-0.92). HLS-MW scores differed significantly by Korean language proficiency (F2,331=3.54, P=.004)., Conclusions: The HLS-MW is a reliable and valid measure to assess health literacy among migrant workers in South Korea. Further studies are needed to test the psychometric properties of the HLS-MW in diverse migrant groups in South Korea while also establishing cutoffs to help identify those in need of health literacy support., (© Soo Jin Kang, Hye-Kyung Oh, Hae-Ra Han. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org).)

Background: Assessing the complex and multifaceted symptoms of patients with acute psychiatric disorders proves to be significantly challenging for clinicians. Moreover, the staff in acute psychiatric wards face high work intensity and risk of burnout, yet research on the introduction of digital technologies in this field remains limited. The combination of continuous and objective wearable sensor data acquired from patients with deep learning techniques holds the potential to overcome the limitations of traditional psychiatric assessments and support clinical decision-making., Objective: This study aimed to develop and validate wearable-based deep learning models to comprehensively predict patient symptoms across various acute psychiatric wards in South Korea., Methods: Participants diagnosed with schizophrenia and mood disorders were recruited from 4 wards across 3 hospitals and prospectively observed using wrist-worn wearable devices during their admission period. Trained raters conducted periodic clinical assessments using the Brief Psychiatric Rating Scale, Hamilton Anxiety Rating Scale, Montgomery-Asberg Depression Rating Scale, and Young Mania Rating Scale. Wearable devices collected patients' heart rate, accelerometer, and location data. Deep learning models were developed to predict psychiatric symptoms using 2 distinct approaches: single symptoms individually (Single) and multiple symptoms simultaneously via multitask learning (Multi). These models further addressed 2 problems: within-subject relative changes (Deterioration) and between-subject absolute severity (Score). Four configurations were consequently developed for each scale: Single-Deterioration, Single-Score, Multi-Deterioration, and Multi-Score. Data of participants recruited before May 1, 2024, underwent cross-validation, and the resulting fine-tuned models were then externally validated using data from the remaining participants., Results: Of the 244 enrolled participants, 191 (78.3%; 3954 person-days) were included in the final analysis after applying the exclusion criteria. The demographic and clinical characteristics of participants, as well as the distribution of sensor data, showed considerable variations across wards and hospitals. Data of 139 participants were used for cross-validation, while data of 52 participants were used for external validation. The Single-Deterioration and Multi-Deterioration models achieved similar overall accuracy values of 0.75 in cross-validation and 0.73 in external validation. The Single-Score and Multi-Score models attained overall R² values of 0.78 and 0.83 in cross-validation and 0.66 and 0.74 in external validation, respectively, with the Multi-Score model demonstrating superior performance., Conclusions: Deep learning models based on wearable sensor data effectively classified symptom deterioration and predicted symptom severity in participants in acute psychiatric wards. Despite lower computational costs, Multi models demonstrated equivalent or superior performance than Single models, suggesting that multitask learning is a promising approach for comprehensive symptom prediction. However, significant variations were observed across wards, which presents a key challenge for developing clinical decision support systems in acute psychiatric wards. Future studies may benefit from recurring local validation or federated learning to address generalizability issues., (©Minseok Hong, Ri-Ra Kang, Jeong Hun Yang, Sang Jin Rhee, Hyunju Lee, Yong-gyom Kim, KangYoon Lee, HongGi Kim, Yu Sang Lee, Tak Youn, Se Hyun Kim, Yong Min Ahn. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 13.11.2024.)

Alzheimer's disease (AD) is a degenerative brain disorder characterized by progressive cognitive decline and neuronal death due to extracellular deposition of amyloid β (Aβ) and intracellular deposition of tau proteins. Recently approved antibody drugs targeting Aβ have been shown to slow the progression of the disease, but they have minimal effects on cognitive improvement. Therefore, there is a need to develop drugs with cognitive-enhancing effects that can be used in conjunction with these antibody treatments. In this study, we investigated whether Polygala tenuifolia (PT), traditionally known for its cognitive-enhancing effects, can improve synaptic plasticity and identified its active components and mechanisms. PT demonstrated a dose-dependent effect in enhancing long-term potentiation (LTP), and among its components, 3,4,5-trimethoxycinnamic acid methyl ester (TMCA) showed a similar LTP-enhancing effect. TMCA increased the phosphorylation of the GluA1 subunit of the α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors and increased the amount of GluA1 on the synapse without affecting the amount of GluA2. Additionally, the increase in GluA1 induced by TMCA was inhibited by a PKA inhibitor. Consistent with these results, the enhancement of LTP by TMCA was inhibited by a GluA1 antagonist and a PKA inhibitor. In silico molecular docking experiments confirmed that TMCA binds to PKA. Finally, we confirmed the LTP-enhancing effect of TMCA in hippocampal slices from 5XFAD mice. These results suggest that PT and its active component, TMCA, can interact with PKA to enhance LTP, indicating the potential for improving cognitive function in AD patients., 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.)

Two-dimensional conductive metal-organic frameworks (2D cMOFs) stand at the forefront of chemiresistive sensing innovations due to their high surface areas, distinctive morphologies, and substantial electronic conductivity. Particularly, 2D cMOFs crafted using 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) and 2,3,6,7,10,11-hexaiminotriphenylene (HITP) organic ligands have garnered a large amount of attention due to their designable active sites and proper conductive characteristics. Nevertheless, a deeper exploration into their sensing mechanisms is imperative for a comprehensive understanding of the intrinsic chemistry, which is crucial for the intricate design of specialized 2D cMOF chemiresistive sensors. In this study, we fabricate six M-HXTP (M = Co, Ni, and Cu; X = H and I) chemiresistive sensors, focusing on the application of hydrogen sulfide (H 2 S) detection. Among these, the 2D cMOFs incorporating Cu metal manifested a remarkably enhanced response to H 2 S. A combination of experimental and computational studies unveils the mechanisms of sulfur oxidation and Cu reduction, wherein distortion of the reduced MX 4 cluster markedly amplifies the sensing response. Lastly, a real-time and portable wireless H 2 S sensing module has been demonstrated by using the Cu-HHTP composite material, highlighting the substantial practical significance and potential applicability.

Background: Well-being is a multidimensional construct comprising affective and non-affective components. Previous research has consistently linked personality traits to well-being, yet cultural variations in this association remain underexplored, particularly in collectivistic cultures such as Korea. Therefore, this study aims to identify universal and culture-specific characteristics of personality in relation to well-being., Methods: A sample of 527 Korean university students participated, providing data through the Korean version of the Temperament and Character Inventory-RS (TCI-RS), self-rated health (SRH), social support (SS), Satisfaction With Life Scale (SWLS), and positive and negative affect schedule (PANAS). Pearson correlation analysis and ANCOVA, with sex and age as covariates, were employed to examine linear associations. Multidimensional personality profiles were utilized to investigate non-linear associations among character dimensions on different aspects of well-being. All analysis was performed using jamovi 2.3.12., Results: Self-directedness and cooperativeness exhibited positive linear associations with both affective (positive and negative affect) and non-affective (SRH, SS, SWLS) components of well-being. Self-directedness emerged as a key predictor across various well-being aspects. Cooperativeness was strongly associated with perception of social support. Self-transcendence showed positive associations with both positive and negative affect, considering interactions with other character dimensions., Discussion: While self-directedness played a pivotal role universally, the impact of cooperativeness and self-transcendence appeared to be influenced by cultural factors, enhancing perception of social support and affecting both positive and negative affect in a collectivistic culture. This study illustrates the importance of considering cultural nuances in the relationship between personality and well-being. Future research should delve deeper into cultural differences, emphasizing the need for subtle interpretations of specific personality traits within diverse cultural contexts., Competing Interests: C. Robert Cloninger is an Academic Editor for PeerJ and is the Director of the Anthropedia Institute, a 501(c)(3) nonprofit organization that trains people to become certified professional health and wellness coaches specialized in promoting mental health and well-being., (©2024 Lee et al.)

Streptococcus pneumonia is a Gram-positive and facultative anaerobic bacterium that causes a number of diseases, including otitis media, community-acquired pneumonia, sepsis, and meningitis. With the emergence of antibiotic-resistant strains, there is an urgent need to develop antibiotics with a novel mechanism. The toxin-antitoxin (TA) system, which is primarily found in prokaryotes, consists of a toxin and its equivalent antitoxin genes. The YefM-YoeB module is a Type II TA system, where the YoeB toxin functions as a putative mRNA interferase upon activation, while the YefM antitoxin acts as a transcription repressor by binding to its promoter region along with YoeB. In this study, we determined the crystal structure of the YefM-YoeB complex from S. pneumoniae TIGR4 to comprehend the binding mechanism of the TA system. Furthermore, an in vitro ribonuclease activity assay was conducted to identify the ribonuclease activity of the YoeB toxin. Additionally, furthermore, the oligomeric state of the YefM-YoeB complex in solution was investigated, and a DNA-binding mode was proposed. These structural and functional insights into the YefM-YoeB complex could provide valuable information for the development of novel antibiotics targeting S. pneumonia-associated diseases., (© 2024 Wiley Periodicals LLC.)

Purpose: Intraoperative ultrasound was used to assess the flow velocity in the marginal vessel arch adjacent to the anastomosis, critical for evaluating the anastomotic blood supply. This technique also enabled us to investigate the potential effects of preserving the left colonic artery on the perfusion of the anastomosis., Methods: This prospective study included 40 rectal cancer patients who underwent laparoscopic anterior resection between January 2021 and January 2023. The length of the inferior mesenteric artery (IMA) was measured from its origin to the first branch, and the diameters of the mesenteric vessel IMA, left colonic artery (LCA), and marginal mesenteric artery (MMA) were recorded. Blood flow velocity and Doppler ultrasound waveforms of the MMA near the anastomosis were collected. Measurements were taken both before and after clamping the IMA using atraumatic forceps. The tardus parvus pattern of the MMA ultrasound waveforms was recorded to evaluate the hypoperfusion status of the anastomosis., Results: The mean velocities of MMA were 47.9 cm/s before clamping and 34.9 cm/s after atraumatic clamping, indicating significant differences (p < 0.05). Thirteen patients (32.5%) exhibited a Tardus parvus pattern after IMA atraumatic clamping. Multivariate analysis revealed older age and LCA diameter as independent clinical predictors of the hypoperfusion status after IMA clamping., Conclusions: Preservation of the LCA may improve perfusion near the anastomosis during rectal cancer surgery. Older age and LCA diameter can be considered useful predictors of the mesenteric hypoperfusion status after IMA ligation. Intraoperative ultrasound can evaluate the perfusion of the MMA near the anastomosis. Chinese Clinical Trial Registry-Registration number: ChiCTR2000041475., Competing Interests: Declarations Conflict of interest I declare that the authors have no competing interests that might be perceived to influence the results and discussion reported in this paper. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent Informed consent was obtained from all participants., (© 2024. The Author(s).)

A 77-year-old professional gold craftsman ingested a white powder used in goldsmithing, mistaking the powder for a health supplement. He detected a strange taste and immediately fell sick, reported the incident to 911, and was taken to the emergency room. He died approximately 8.5 h post-ingestion despite treatment. There were no significant findings in the autopsy, the victim's heart blood sample, gastric contents, and the white powder the victim had taken were submitted to the department of forensic toxicology. Using scanning electron microscopy energy dispersive X-ray analysis, potassium and gold (Au) were detected in the white powder. Ion chromatography analysis detected cyanide. Concentrations of cyanide were 0.5 mg/L in heart blood and 13.3 mg/L in gastric contents. Qualitative and quantitative analyses of Au in the heart blood sample and gastric contents using inductively coupled plasma-optical emission spectrometry detected concentrations of 79.8 mg/L and 2010.1 mg/L, respectively. Au and cyanide synergistically enhance cytotoxicity through inhibition of detoxification and increasing intracellular accumulation. In the present case, the detected blood cyanide concentration was sub or minimally lethal, and the blood Au concentration was high. The cause of the victim's death was the combined toxicity of Au and cyanide., (© 2024 American Academy of Forensic Sciences.)

Due to its significant bioconversion potential, the black soldier fly (BSF), Hermetia illucens, shows great promise as a cost-effective alternative for recycling biological waste. BSF larvae (BSFL) are constantly exposed high levels of pathogenic microorganisms, including bacteria and fungi, which endows BSFL with a robust immune system. Diptericin, a type of glycine-rich antimicrobial peptide (AMP) that exhibits activity against gram-negative bacteria, contains proline-rich domains (P-domains) and glycine-rich domains (G-domains); these domains are separated by a furin cleavage site. Although the presence and expression patterns of BSFL diptericins have been documented, their basic molecular properties remain unclear. To the best of our knowledge, in the present study, we report, for the first time, the molecular characteristics of seven full-length cDNA sequences of H. illucens diptericins and their expression patterns following challenges with gram-positive or gram-negative bacteria. Seven diptericin paralogs are located in tandem on chromosome 2, spanning a total length of 38.6 kb, with an average intergenic distance of approximately 5.5 kb. Sequence analysis revealed that three diptericins (HipDptA/B/C) are pseudogenized due to premature stop codons. In contrast, the other diptericins (HiDpt1/2/3/4) possess mature-sized G-domains rich in glycine at the C-terminus, which are essential for AMP activity, along with proline-rich domain (P-domain) in the N-terminal and either two (HiDpt1/2/3) or one (HiDpt4) putative furin cleavage sites (R-X-R/K-R) between these domains. These furin cleavage sites possibly produce a glycine-rich AMP and one or two additional peptides with unknown functions. Similar to other diptericins, the expression of HiDpt1/2/3/4 mRNAs is predominantly induced by gram-negative bacteria, increasing typically by ≥ 1,000-fold (up to 5,000-fold). Additionally, HiDpt1/3/4 show significant responses to gram-positive bacteria such as Micrococcus luteus, though not as strongly as to gram-negative bacteria. These findings suggest that HiDpts function as a rapid, effective, and broad-spectrum first-line defense mechanism in the BSFL immune system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To investigate the factors affecting visual field recovery in patients with pituitary adenoma following surgical removal, both eyes of 35 patients with pituitary adenoma who had been followed up for > six months post-surgery were retrospectively analyzed., Material and Methods: Pre- and post-operative visual acuity, visual field test, retinal nerve fiber layer (RNFL), and ganglion cell inner plexiform layer (GCIPL) thickness were investigated. The average age of the 35 patients was 58.3 ± 11.5 years. Preoperatively, 30 eyes (mean average RNFL thickness, 99.73 ± 5.89 μm) and 40 eyes (mean average RNFL thickness, 77.55 ± 8.35 μm) were included in the thick (≥ 90 μm) and thin RNFL group (< 90 μm), respectively., Results: In the thick RNFL group, pre- and post-operative mean deviation (MD) and pattern standard deviation (PSD) were favorable (all p < 0.001), and the proportion of eyes of postoperative MD change which were stable or improved was greater than in the thin RNFL group (p = 0.042). Preoperative MD, RNFL (except nasal quadrant) and GCIPL thickness were positively correlated to postoperative MD values (all, p < 0.05). Preoperative MD and temporal RNFL thickness were significantly correlated with postoperative MD change rate (p = 0.03 and 0.04, respectively). Preoperative GC IPL thickness and postoperative MD change rate were not significantly correlated (p = 0.61). Using univariate regression analysis, preoperative best corrected visual acuity (Odds ratio [OR], 0.050; p < 0.001), tumor volume (OR, 1.110, p = 0.002), higher preoperative MD values (OR, 0.858; p < 0.001), lower preoperative PSD values (OR, 1.169, p = 0.002), thick RNFL (OR, 0.215; p = 0.003) and thick GCIPL (OR, 0.305, p = 0.018) were significantly associated with a good visual field outcome following surgery. According to multivariate analysis, any other parameters were not significant. In patients with thick RNFL, postoperative MD values were better than in the thin RNFL group., Conclusions: Eyes with preoperative higher MD and thick temporal RNFL showed more improvement in their visual fields postoperative. Preoperative thick RNFL could be a potential predictor of visual field recovery following TSA-TR, while macular GCIPL thickness does not appear to be a reliable predictor., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Han 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.)

Purpose: The nProfiler 1 Stomach Cancer Assay (nProfiler1), designed to predict responses to fluorouracil-based adjuvant chemotherapy, measures the expression of four gastric cancer target genes (GZMB, WARS, SFRP4, and CDX1). The randomized phase III POST trial aimed to compare the efficacies of two adjuvant S-1-based doublet chemotherapies: S-1 plus cisplatin (SP) and S-1 plus docetaxel (DS). This study aimed to validate the nProfiler1 assay using a distinct cohort from the POST trial., Materials and Methods: The nProfiler1 assay stratifies patients into three groups (low-risk, intermediate-risk, and high-risk) using the prognostic single-patient classifier and two groups (chemotherapy-benefit and no-benefit) using the predictive single-patient classifier. The nProfiler1 assay was applied to formalin-fixed paraffin-embedded slides obtained from the POST trial. Disease-free survival (DFS) and overall survival (OS), including 5-year survival rates, were calculated for the enrolled patients., Results: Of the 153 patients in the POST trial, 118 were included in the post-hoc analysis. With a median follow-up of 57.9 months, no significant difference in DFS or OS was observed between the SP and DS groups. The prognostic single-patient classifier predicted the OS in the SP group (p=0.0425) but not in the DS group (p=0.5940). The chemotherapy-benefit group exhibited numerically longer DFS than the no-benefit group in the SP and DS groups., Conclusion: The nProfiler1 assay offers valuable insights into the prognosis and efficacy of adjuvant chemotherapy based on fluorouracil plus platinum doublet regimens but not docetaxel-containing regimens. Further validation with larger patient cohorts and different regimens is warranted.

Background: Although copper oxide nanoparticles (CuONPs) offer certain benefits to humans, they can be toxic to organs and exacerbate underlying diseases upon exposure. Chronic obstructive pulmonary disease (COPD), induced by smoking, can worsen with exposure to various harmful particles. However, the specific impact of CuONPs on COPD and the underlying mechanisms remain unknown. In this study, we investigated the toxic effects of CuONPs on the respiratory tract, the pathophysiology of CuONPs exposure-induced COPD, and the mechanism of CuONPs toxicity, focusing on thioredoxin-interacting protein (TXNIP) signaling using a cigarette smoke condensate (CSC)-induced COPD model., Results: In the toxicity study, CuONPs exposure induced an inflammatory response in the respiratory tract, including inflammatory cell infiltration, cytokine production, and mucus secretion, which were accompanied by increased TXNIP, NOD-like receptor protein 3 (NLRP3), caspase-1, and interleukin (IL)-1β. In the COPD model, CuONPs exposure induced the elevation of various indexes related to COPD, as well as increased TXNIP expression. Additionally, TNXIP-knockout (KO) mice showed a significantly decreased expression of NLRP3, caspase-1, and IL-1β and inflammatory responses in CuONPs-exposed COPD mice. These results were consistent with the results of an in vitro experiment using H292 cells. By contrast, TNXIP-overexpressed mice had a markedly increased expression of NLRP3, caspase-1, and IL-1β and inflammatory responses in CuONPs-exposed COPD mice., Conclusions: We elucidated the exacerbating effect of CuONPs exposure on the respiratory tract with underlying COPD, as well as related signaling transduction via TXNIP regulation. CuONPs exposure significantly increased inflammatory responses in the respiratory tract, which was correlated with elevated TXNIP-NLRP3 signaling., Competing Interests: Declarations Ethics approval and consent to participate This research was approved by the Institutional Animal Care Use Committee (IACUC) of Chonnam National University (CNU IACUC-YB-2021-146). Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Expanding the systemic treatment options for patients with psoriasis, deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor is approved in the United States, European Union, China, Japan, Taiwan, Korea, and other countries for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. Evidence suggests the comparative efficacy of systemic therapies may be different in Asian versus White patients. This systematic review and network meta-analysis (NMA) evaluated the clinical efficacy associated with deucravacitinib and other biologic or non-biologic systemic treatments for moderate to severe plaque psoriasis in Asian populations. Electronic databases were searched to identify randomized trials of the interventions of interest. Multinomial random effects models adjusting for baseline placebo risk were used to estimate Psoriasis Area and Severity Index (PASI) responses at weeks 10-16. Of 8596 studies identified, 20 were included in the NMA. The estimated PASI 75 and 90 (95% credible interval) response rates for deucravacitinib were estimated to be 66% (49%-80%) and 40% (24%-58%) in Asian populations, notably higher than placebo (6% [4%-9%] and 1% [0.8-2%]) and apremilast (24% [12%-40%] and 9% [4%-20%]). No statistically significant difference was observed in PASI 75 and 90 responses between deucravacitinib and adalimumab, certolizumab pegol, infliximab, ustekinumab, and tildrakizumab. Deucravacitinib demonstrated robust efficacy in the Asian population, with PASI 75 and 90 responses comparable to some biologics. Deucravacitinib provides a convenient oral therapy with efficacy similar to several biologic therapies., (© 2024 The Author(s). The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Background: Renal replacement therapy (RRT) is an important treatment option for sepsis-associated acute kidney injury (AKI); however, the optimal timing for its initiation remains controversial. Herein, we investigated the clinical outcomes of early continuous kidney replacement therapy (CKRT), defined as CKRT initiation within 6 hours of sepsis-associated AKI onset, which was earlier than the initiation time defined in previous studies., Methods: We used clinical data sourced from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. This study included patients aged ≥ 18 years who met the sepsis diagnostic criteria and received CKRT because of stage 2 or 3 AKI. Early and late CKRTs were defined as CKRT initiation within 6 hours and after 6 hours of the development of sepsis-associated AKI, respectively., Results: Of the 33,236 patients diagnosed with sepsis, 553 underwent CKRT for sepsis-associated AKI. After excluding cases of early mortality and patients with a dialysis history, 45 and 334 patients were included in the early and late CKRT groups, respectively. After propensity score matching, the 28-day mortality rate was significantly lower in the early CKRT group than in the late CKRT group (26.7% vs. 43.9%, P = 0.035). The early CKRT group also had a significantly greater number of days free of mechanical ventilation (median, 19; interquartile range [IQR], 3-25) and vasopressor administration (median, 21; IQR, 5-26) than the late CKRT group did (median, 10.5; IQR, 0-23; P = 0.037 and median, 13.5; IQR, 0-25; P = 0.028, respectively). The Kaplan-Meier curve also showed that early CKRT initiation was associated with an improved 28-day mortality rate (log-rank test, P = 0.040). In contrast, there was no significant difference in the 28-day mortality between patients who started CKRT within 12 hours and those who did not (log-rank test, P = 0.237)., Conclusion: Early CKRT initiation improved the survival of patients with sepsis-associated AKI. Initiation of CKRT should be considered as early as possible after sepsis-associated AKI onset, preferably within 6 hours., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Nostoxanthin, a yellow pigment, belongs to the xanthophyll group of carotenoids found in various species of bacteria and cyanobacteria. Several species of Sphingomonas can produce appropriate carotenoids for survive in various environments. This comprise nostoxanthin, a significant carotenoid. The study isolated the Sphingomonas species strain COS14-R2 from the Cosmos bipinnatus and identified it through the whole-genome sequence. The strain consists of a circular chromosome with a length of 3,677,457 base pairs.s ecThe genome consists of three carotenoid biosynthesis genes, specifically crtB (phytoene synthase), crtI (phytoene desaturase), and crtY (Lycopene beta-cyclase), which are involved in the synthesis of nostoxanthin. The strain has a circular, undulated colony morphology with a deep yellow color. It demonstrates optimal growth in liquid media at 25 to 35 °C and exhibits a high tolerance for pH levels between 5 and 11 and requires adequate quantities of carbon and nitrogen. We observed the highest concentration of nostoxanthin was recorded at 35 °C, pH of 7.5, glucose concentration of 40 g L -1 , and a yeast extract concentration of 5 g L -1 during dark incubation. The fed-batch fermentation process produced nostoxanthin at a concentration of 217.22 ± 9.60 mg L -1 , with a selectivity of 72.32% and a productivity of 2.59 g/L/h. The dry biomass extract was purified using column chromatography. The LC-MS/MS analysis of the purified fraction indicated that the molecular weight of nostoxanthin is 600.5098 m/z. The DPPH assay result of 75.5 ± 0.33% indicates nostoxanthin is highly effective in scavenging free radicals., Competing Interests: Declarations Conflict of interest The Authors declare that they do not have any conflict of interests. Ethical Approval Not applicable. Consent to Participate Not applicable. Consent for publication Not applicable., (© 2024. The Author(s).)