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Introduction: In this study, we compared the dentitional changes after Invisalign and conventional orthodontic treatment with 4 first premolar extractions., Methods: This retrospective study included 57 patients whose orthodontic treatment involved the extraction of 4 first premolars because of bialveolar protrusion. A total of 27 patients were treated with Invisalign (mean age, 25.5 ± 5.2 years) and 30 patients with the fixed appliance (mean age, 24.4 ± 5.8 years). The angular and linear changes of the maxillary and mandibular central incisors, second premolars, first molars, and second molars were measured from the recordings on the basis of the lateral cephalograms taken before and after treatment. The angular changes of the canines and second premolars were measured using panoramic radiographs., Results: The overbite and interincisal angle increased significantly in the Invisalign group compared with in the conventional fixed appliance group (P <0.05). The maxillary central incisors showed increased lingual tipping in the Invisalign group (P <0.05), whereas there was no statistically significant difference in the angular change of the mandibular incisors between groups (P >0.05). The maxillary first and second molars showed mesial tipping in the Invisalign group (P <0.05). The maxillary second premolars, first and second molars, and the mandibular second molars showed mesial movement in the Invisalign group (P <0.05)., Conclusions: The Invisalign group showed more statistically significant lingual tipping of the maxillary central incisors, distal tipping of the maxillary canines, and mesial tipping of the maxillary first and second molars after maximum retraction of the anterior teeth compared with the fixed appliance group., (Copyright © 2023 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Background: Rituximab is an essential induction immunosuppressant for ABO-incompatible kidney transplantation (KT) (ABOi-KT). However, studies on the optimal dose of rituximab are insufficient, and there are dosage differences between transplant centers and countries. Therefore, we conducted a study to determine the survival outcomes of patients receiving the most effective and safe dose of rituximab during ABOi-KT., Methods: Studies on rituximab dose were divided into four groups: ABO compatible, 1) placebo, 2) rituximab 200 mg, 3) rituximab 200-500 mg, and 4) rituximab 500 mg. We searched the CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded databases from 1970 to February 2022.9 . The inclusion criteria were adult patients (>18 years old). Reviews, observational studies, and clinical trials that did not clearly define outcomes or that did not have graft failure as an outcome were excluded. We performed direct and indirect network meta-analyses using Bayesian models and ranked different rituximab doses using a generation mixed treatment comparison (GeMTC) and Stata version 13. The NMA approach was evaluated using the GRADE framework, which specifies four levels of certainty for a given result: high, moderate, low, and very low. The outcomes included patient survival, graft failure, and bacterial and viral infections., Results: Twenty-five trials, including 5,378 subjects, were divided into the following four groups: 1) placebo, 2) rituximab 200 mg, 3) rituximab 200-500 mg, and 4) rituximab 500 mg. We focused on survival outcomes according to the dose of rituximab when patients received induction therapy for ABOi-KT. The mortality rate was significantly lower in the ABO-compatible and rituximab 200 mg groups (odds ratio [OR] 0.27, 95% CrI: 0.071-0.91 and OR 0.14, 95% CrI 0.036-0.47), compared with that in the placebo group., Conclusions: We found that low-dose rituximab in ABO-i KT was effective compared to the high-dose and placebo in maintaining the survival rate. However, large-scale and long-term data are necessary for further validation of our findings. Additionally, the use of smaller doses of rituximab will require further discussion., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This network meta-analysis was supported by grants from the Basic Science Research Program through the Bio & Medical Technology Development Program of the National Research Foundation (NRF) and funded by the Korean government (MSIT) (SDH: NRF-2019M3E5D1A02069619)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Tax-interacting protein 1 (TIP1) is a cancer-specific radiation-inducible cell surface antigen that plays a role in cancer progression and resistance to therapy. This study aimed to develop a novel anti-TIP1 human antibody for noninvasive PET imaging in patients with cancer., Experimental Design: A phage-displayed single-chain variable fragment (scFv) library was created from healthy donors' blood. High-affinity anti-TIP1 scFvs were selected from the library and engineered to human IgG1. Purified Abs were characterized by size exclusion chromatography high-performance liquid chromatography (SEC-HPLC), native mass spectrometry (native MS), ELISA, BIAcore, and flow cytometry. The labeling of positron emitter [89Zr]Zr to the lead Ab, L111, was optimized using deferoxamine (DFO) chelator. The stability of [89Zr]Zr-DFO-L111 was assessed in human serum. Small animal PET studies were performed in lung cancer tumor models (A549 and H460)., Results: We obtained 95% pure L111 by SEC-HPLC. Native MS confirmed the intact mass and glycosylation pattern of L111. Conjugation of three molar equivalents of DFO led to the optimal DFO-to-L111 ratio of 1.05. Radiochemical purity of 99.9% and specific activity of 0.37 MBq/μg was obtained for [89Zr]Zr-DFO-L111. [89Zr]Zr-DFO-L111 was stable in human serum over 7 days. The immunoreactive fraction in cell surface binding studies was 96%. In PET, preinjection with 4 mg/kg cold L111 before [89Zr]Zr-DFO-L111 (7.4 MBq; 20 μg) significantly (P < 0.01) enhanced the tumor-to-muscle standard uptake values (SUVmax) ratios on day 5 compared with day 2 postinjection., Conclusions: L111 Ab targets lung cancer cells in vitro and in vivo. [89Zr]Zr-DFO-L111 is a human antibody that will be evaluated in the first in-human study of safety and PET imaging., (©2024 American Association for Cancer Research.)

Nerves in patients with diabetic neuropathy (DN) show increased susceptibility to local anesthetics, potentially requiring a decreased dose. We investigated whether the minimum effective anesthetic concentration (MEAC) of mepivacaine for successful axillary block is lower in patients with DN than in those without. This prospective observational study included patients with DN ( n = 22) and without diabetes ( n = 22) at a tertiary care center. Patients received an ultrasound-guided axillary block with 30 mL of mepivacaine for anesthesia. The mepivacaine concentration used in each patient was calculated using Dixon's up-and-down method. A block was considered successful if all four sensory nerves had a score of 1 or 2 within 30 min with no pain during surgery. The primary outcome was the MEAC of mepivacaine, and the secondary outcomes included the minimal nerve stimulation intensity for the musculocutaneous nerve and the occurrence of adverse events. The MEAC 50 was 0.55% (95% CI 0.33-0.77%) in patients without diabetes and 0.58% (95% CI 0.39-0.77%) in patients with DN ( p = 0.837). The MEAC 90 was 0.98% (95% CI 0.54-1.42%) in patients without diabetes and 0.96% (95% CI 0.57-1.35%) in patients with DN ( p = 0.949). The stimulation threshold for the musculocutaneous nerve was significantly different between groups (0.49 mA vs. 0.19 mA for patients with vs. without diabetes; p = 0.002). In conclusion, the MEAC of mepivacaine for a successful axillary block is not lower in patients with DN.

Constipation is a highly prevalent gastrointestinal disorder in patients with chronic kidney disease (CKD). However, our understanding of its epidemiology and management in CKD is limited. We aimed to explore real-world data on constipation and laxative use in patients with CKD in a nationwide population-based cohort from the Korean Health Insurance Review and Assessment-National Patient Sample database. This study analyzed retrospective health claims data in Korea from 2012 to 2017 that were transformed into the Observational Medical Outcomes Partnership Common Data Model. The pooled proportion of constipation diagnoses was 30.5% in all patients with CKD and 15.9%, 16.5%, 17.4%, 29.9%, and 43.3% in patients with CKD stages 1-5, respectively, suggesting a higher prevalence in advanced CKD. Patients receiving peritoneal dialysis or hemodialysis had the highest prevalence of constipation, while transplant recipients showed a prevalence comparable to that of patients with early CKD. Patients with CKD had a significantly higher risk of constipation than age- and sex-matched non-CKD individuals (range of odds ratio [OR]:1.66-1.90). Laxative prescribing patterns differed by CKD severity. Osmotic agents were prescribed in more than half of patients with advanced CKD, while magnesium salts and bulking agents were prescribed less frequently. The CKD patients with constipation were more likely to be prescribed constipation-inducing medications, including antipsychotic and neurological medications. Our findings provide real-world constipation and laxative prescription status in the Korean CKD population, revealing a significantly higher risk of constipation and different laxative prescribing patterns in patients with CKD., (© 2024. The Author(s).)

Despite clinical and epidemiological evidence suggestive of a link between glioblastoma (GBM) and periodontitis (PD), the shared mechanisms of gene regulation remain elusive. In this study, we identify differentially expressed genes (DEGs) that overlap between the GEO datasets GSE4290 [GBM] and GSE10334 [PD]. Functional enrichment analysis was conducted, and key modules were identified using protein-protein interaction (PPI) network and weighted gene co-expression network analysis (WGCNA). The expression levels of CXCR4, LY96, and C3 were found to be significantly elevated in both the test dataset and external validation dataset, making them key crosstalk genes. Additionally, immune cell landscape analysis revealed elevated expression levels of multiple immune cells in GBM and PD compared to controls, with the key crosstalk genes negatively associated with Macrophages M2. FLI1 was identified as a potential key transcription factor (TF) regulating the three key crosstalk genes, with increased expression in the full dataset. These findings contribute to our understanding of the immune and inflammatory aspects of the comorbidity mechanism between GBM and PD., (© 2024. The Author(s).)

A hyperspectral push-broom imager has been designed, constructed, and tested. The narrow angular selectivity of a weakly index modulated volume Bragg grating is utilized to replace the objective lens, slit, and collimating lens of a conventional slit-based hyperspectral push-broom imager. The imager comprises a dispersion grating, an angular filter grating, a focusing lens, and an image sensor. The imager has a field of view (FOV) of 17 degrees in the spatial direction, a spectral range from 400 nm to 900 nm, and a spectral resolution of 2.1 nm. The acquired hyperspectral data cubes are presented, and the influence of wavelength-dependent incident angle errors is analyzed.

BACKGROUND The gut microbial metabolites demonstrate significant activity against metabolic diseases including osteoporosis (OP) and obesity, but active compounds, targets, and mechanisms have not been fully identified. Hence, the current investigation explored the mechanisms of active metabolites and targets against OP and obesity by using network pharmacology approaches. MATERIAL AND METHODS The gutMGene database was used to collect gut microbial targets-associated metabolites; DisGeNET and OMIM databases were used to identify targets relevant to OP and obesity. A total of 63 and 89 overlapped targets were considered the final OP and obesity targets after creating a Venn diagram of metabolites-related targets and disease-related targets. Furthermore, the top 20% of degrees, betweenness, and closeness were used to form the sub-network of protein-protein interaction of these targets. Finally, the biotransformation-increased receptors and biological mechanisms were identified and validated using ADMET properties analysis, molecular docking, and molecular dynamic simulation. RESULTS GO, KEGG pathway analysis, and protein-protein interactions were performed to establish metabolites and target networks. According to the enrichment analysis, OP and obesity are highly linked to the lipid and atherosclerosis pathways. Moreover, ADMET analysis depicts that the major metabolites have drug-likeliness activity and no or less toxicity. Following that, the molecular docking studies showed that compound K and TP53 target have a remarkable negative affinity (-8.0 kcal/mol) among all metabolites and targets for both diseases. Finally, the conformity of compound K against the targeted protein TP53 was validated by 250ns MD simulation. CONCLUSIONS Therefore, we summarized that compound K can regulate TP53 and could be developed as a therapy option for OP and obesity.

Evolvability is an emergent hallmark of cancer that depends on intra-tumor heterogeneity and genetic variation. Mutations generated by APOBEC3 contribute to genetic variation and tumor evolvability. However, the influence of APOBEC3 on the evolvability of the genome and its differential impact on cancer genes versus non-cancer genes remains unclear. Analyzing over 40,000 human protein-coding transcripts, we identified distinct distribution patterns of APOBEC3A/B TC motifs between cancer and non-cancer genes, suggesting unique associations with cancer. Studying a bat species with numerous APOBEC3 genes, we found distinct motif patterns in orthologs of cancer genes compared to non-cancer genes, as in humans, suggesting APOBEC3 evolution to reduce impacts on the genome rather than the converse. Simulations confirmed that APOBEC3-induced heterogeneity enhances cancer evolution through bimodal patterns of mutations in certain classes of genes. Our results suggest the bimodal distribution of APOBEC-induced mutations can significantly increase cancer heterogeneity., Competing Interests: The authors declare no competing interest.

Butyrate, a short-chain fatty acid (SCFA) produced by bacterial fermentation of fiber in the colon, is a source of energy for colonocytes. Butyrate is essential for improving gastrointestinal (GI) health since it helps colonocyte function, reduces inflammation, preserves the gut barrier, and fosters a balanced microbiome. Human colonic butyrate producers are Gram-positive firmicutes, which are phylogenetically varied. The two most prevalent subgroups are associated with Eubacterium rectale/Roseburia spp. and Faecalibacterium prausnitzii. Now, the mechanism for the production of butyrate from microbes is a very vital topic to know. In the present study, we discuss the genes encoding the core of the butyrate synthesis pathway and also discuss the butyryl-CoA:acetate CoA-transferase, instead of butyrate kinase, which usually appears to be the enzyme that completes the process. Recently, butyrate-producing microbes have been genetically modified by researchers to increase butyrate synthesis from microbes. The activity of butyrate as a histone deacetylase inhibitor (HDACi) has led to several clinical trials to assess its effectiveness as a potential cancer treatment. Among various significant roles, butyrate is the main energy source for intestinal epithelial cells, which helps maintain colonic homeostasis. Moreover, people with non-small-cell lung cancer (NSCLC) have distinct gut microbiota from healthy adults and frequently have dysbiosis of the butyrate-producing bacteria in their guts. So, with an emphasis on colon and lung cancer, this review also discusses how the microbiome is crucial in preventing the progression of certain cancers through butyrate production. Further studies should be performed to investigate the underlying mechanisms of how these specific butyrate-producing bacteria can control both colon and lung cancer progression and prognosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The present study aimed to analyze several aspects of the working conditions and health status of platform workers in the Republic of Korea, such as ergonomic and emotional hazards. We also compared the health status of the platform workers with that of the general population., Methods: A total of 1,000 platform workers participated in this survey from August 7 to August 17, 2022. The participants included 400 designated drivers, 400 food-delivery drivers, and 200 housekeeping managers. A face-to-face survey with a structured questionnaire was conducted by researchers who had received specific instructions. The focus of the survey extended to the work environment, encompassing factors such as workplace violence, as well as physical, chemical, and ergonomic hazards. Health-related data for the previous year were also collected, covering a range of issues such as hearing problems, skin problems, musculoskeletal symptoms, headaches, injuries, mental health issues, and digestive problems. Subsequently, we compared the health symptom data of the responders with those of the general population in the Republic of Korea., Results: Platform workers, including designated drivers, food-delivery drivers, and housekeeping managers, existed in the blind spot of social insurance, facing frequent exposure to physical and chemical hazards, ergonomic risk factors, and direct or indirect violence. The prevalence of health problems, including musculoskeletal symptoms, general fatigue, and depressive symptoms, in each occupational group was statistically higher than that in the general population after standardization for age and gender., Conclusion: The results revealed unfavorable working environment and inferior occupational health of platform workers compared with those of the general population., (© 2024 The Authors.)

Purpose: Venous thromboembolism (VTE) is a major complication for hip fracture patients, and may exist preoperatively. This study aimed to examine the prevalence of VTE after immediate screening in hip fracture patients., Materials and Methods: Hip fracture patients with an elevated level of D-dimer underwent screening for VTE using computed tomography (CT) angiography. Anticoagulation treatments were administered preoperatively to patients diagnosed with VTE, followed by administration of additional anticoagulation postoperatively. Medical records were reviewed to identify risk factors for preoperative VTE and determine the prognosis of the patients., Results: Among 524 hip fracture patients, 66 patients (12.6%) were diagnosed with VTE, including 42 patients with deep vein thrombosis (DVT), 17 patients with pulmonary thromboembolism (PTE), and 7 patients with both DVT and PTE. Of the patients with VTE, 68.2% were diagnosed within 24 hours of injury, and 33.3% of these patients had PTE. VTE patients showed a tendency toward being overweight ( P <0.01) and not on anticoagulant medication ( P =0.02) compared to patients without VTE. The risk of VTE was higher for femur shaft fractures (odds ratio [OR] 4.83, 95% confidence interval [CI] 2.18-10.69) and overweight patients (OR 2.12, 95% CI 1.17-3.85), and lower for patients who were previously on anticoagulants (OR 0.36, 95% CI 0.18-0.74). Patients with preoperatively diagnosed VTE were asymptomatic before and after surgery., Conclusion: Clinicians should be aware that VTE may be present within 24 hours of injury, and screening for VTE or prophylactic measures should be considered for high-risk patients.

Previous work shows that automatic attention biases toward recently selected target features transfer across action and perception and even across different effectors such as the eyes and hands on a trial-by-trial basis. Although these findings suggest a common neural representation of selection history across effectors, the extent to which information about recently selected target features is encoded in overlapping versus distinct brain regions is unknown. Using fMRI and a priming of pop-out task where participants selected unpredictable, uniquely colored targets among homogeneous distractors via reach or saccade, we show that color priming is driven by shared, effector-independent underlying representations of recent selection history. Consistent with previous work, we found that the intraparietal sulcus (IPS) was commonly activated on trials where target colors were switched relative to those where the colors were repeated; however, the dorsal anterior insula exhibited effector-specific activation related to color priming. Via multivoxel cross-classification analyses, we further demonstrate that fine-grained patterns of activity in both IPS and the medial temporal lobe encode information about selection history in an effector-independent manner, such that ROI-specific models trained on activity patterns during reach selection could predict whether a color was repeated or switched on the current trial during saccade selection and vice versa. Remarkably, model generalization performance in IPS and medial temporal lobe also tracked individual differences in behavioral priming sensitivity across both types of action. These results represent a first step to clarify the neural substrates of experience-driven selection biases in contexts that require the coordination of multiple actions., (© 2023 Massachusetts Institute of Technology.)

Objective: To analyze the clinical application value of a novel magnetic navigation ultrasound (MNU) combined with digital subtraction angiography (DSA) dual-guided percutaneous transhepatic biliary drainage (PTCD) through the right hepatic duct for the treatment of malignant obstructive jaundice. Methods: Randomized controlled trial. The clinical data of 64 patients with malignant obstructive jaundice requiring PTCD through the right hepatic duct at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province People's Hospital) from December 2018 to December 2021 were retrospectively analyzed. The MNU group ( n =32) underwent puncture guided by a novel domestic MNU combined with DSA, and the control group ( n =32) underwent puncture guided by traditional DSA. The operation time, number of punctures, X-ray dose after biliary stenting as shown by DSA, patients' tolerance of the operation, success rate of the operation, pre- and post-operative total bilirubin, and incidence of postoperative complications were compared between the two groups. Results: The operation time of the MNU group was significantly shorter than that of the control group [(17.8±7.3) vs. (31.6±9.9) min, t =-6.35, P =0.001]; the number of punctures in the MNU group was significantly lower [(1.7±0.6) vs. (6.3±3.9) times, t =-6.59, P =0.001]; and the X-ray dose after biliary stenting as shown by DSA in the MNU group was lower than that in the control group [(132±88) vs. (746±187) mGy, t =-16.81, P <0.001]; Five patients in the control group were unable to tolerate the operation, and two stopped the operation, however all patients in the MNU group could tolerate the operation, and all completed the operation, with a success rate of 100% (32/32) in the MNU group compared to 93.8%(30/32) in the control group; the common complications of PTCD were biliary bleeding and infection, and the incidence of biliary bleeding (25.0%, 8/32) and infection (18.8%, 6/32) in the MNU group was significantly lower than that in the control group, 53.1% (17/32) and 28.1% (9/32), respectively. Conclusion: Magnetic navigation ultrasound combined with DSA dual-guided PTCD through the right biliary system for the treatment of malignant obstructive jaundice is safe and feasible.

Various neurotransmitters are involved in regulating stress systems. In this study, we investigated the effects of gamma-aminobutyric acid-rich rice bran extract (GRBe) in mice stressed by forced swimming and tail suspension tests. Four weeks of oral administration of GRBe (500-2000 mg/kg) reduced the levels of dopamine and corticosterone in the blood and brain while increasing serotonin levels. GRBe was involved not only in stress but also in regulating sleep and obesity-related genes. Modern society experiences diverse and tense lives because of urbanization and informatization, which cause excessive stress due to complicated interpersonal relationships, heavy work burden, and fatigue from the organized society. High levels of stress cause psychological instability and disrupt the balance in the autonomic nervous system, which maintains the body's equilibrium, resulting in cardiovascular and cerebrovascular diseases, hormonal imbalances, and sleep disorders. Therefore, our results suggest that GRBe is a useful substance that can relieve tension by ultimately influencing a depressive-like state by lowering the levels of neuronal substances, hormones, and cytokines involved in stress and sleep disorders.

Advances in radiotherapy (RT) techniques, including intensity-modulated RT and image-guided RT, have allowed hypofractionation, increasing the fraction size over the conventional dose of 1.8-2.0 Gy. Hypofractionation offers advantages such as shorter treatment times, improved compliance, and under specific conditions, particularly in tumors with a low α/β ratio, higher efficacy. It was initially explored for use in RT for prostate cancer and adjuvant RT for breast cancer, and its application has been extended to various other malignancies. Hypofractionated RT (HFRT) may also be effective in patients who are unable to undergo conventional treatment owing to poor performance status, comorbidities, or old age. The treatment of brain tumors with HFRT is relatively common because brain stereotactic radiosurgery has been performed for over two decades. However, re-irradiation of recurrent lesions and treatment of elderly or frail patients are areas under investigation. HFRT for head and neck cancer has not been widely used because of concerns regarding late toxicity. Thus, we aimed to provide a comprehensive summary of the current evidence for HFRT for brain tumors and head and neck cancer and to offer practical recommendations to clinicians faced with the challenge of choosing new treatment options.

Metabolic abnormalities in the liver are closely associated with diverse metabolic diseases such as non-alcoholic fatty liver disease, type 2 diabetes, and obesity. The aim of this study was to evaluate the ameliorating effect of robinetin (RBN) on the significant pathogenic features of metabolic failure in the liver and to identify the underlying molecular mechanism. RBN significantly decreased triglyceride (TG) accumulation by downregulating lipogenesis-related transcription factors in AML-12 murine hepatocyte cell line. In addition, mice fed with Western diet (WD) containing 0.025% or 0.05% RBN showed reduced liver mass and lipid droplet size, as well as improved plasma insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values. CD38 was identified as a target of RBN using the BioAssay database, and its expression was increased in OPA-treated AML-12 cells and liver tissues of WD-fed mice. Furthermore, RBN elicited these effects through its anti-histone acetyltransferase (HAT) activity. Computational simulation revealed that RBN can dock into the HAT domain pocket of p300, a histone acetyltransferase, which leads to the abrogation of its catalytic activity. Additionally, knock-down of p300 using siRNA reduced CD38 expression. The chromatin immunoprecipitation (ChIP) assay showed that p300 occupancy on the promoter region of CD38 was significantly decreased, and H3K9 acetylation levels were diminished in lipid-accumulated AML-12 cells treated with RBN. RBN improves the pathogenic features of metabolic failure by suppressing the p300-CD38 axis through its anti-HAT activity, which suggests that RBN can be used as a new phytoceutical candidate for preventing or improving this condition.

Bisphenol A (BPA), an exogenous endocrine-disrupting chemical, is widely used to produce polycarbonate plastics. The widely used BPA has been detected in human urine samples, raising public anxiety about the detrimental effects of BPA on the bladder. In this study, we explored regulatory mechanisms for the adverse effects of BPA in human bladder BdFC and T24 cells. BPA induced extrinsic and intrinsic apoptosis and G2/M cell cycle arrest caused by the ATM-CHK1/CHK2-CDC25c-CDC2 signaling, which ultimately inhibited the growth of human bladder cells. We also found that BPA decreased the binding activity of AP-1 and NF-κB transcription factors in human bladder cells, which inhibited migration and invasion through matrix metallopeptidase-2 and -9 inactivation. Phosphorylation of MAPKs was implicated with BPA-mediated detrimental effects in human bladder cells. Collectively, our results provide a novel explanation for the underlying molecular mechanisms that BPA induces cytotoxicity in human bladder cells., (© 2024 Wiley Periodicals LLC.)

Administration of sedatives for post-resuscitation care can complicate the determination of the optimal timing to avoid inappropriate, pessimistic prognostications. This prospective study aimed to investigate the distribution and elimination kinetics of midazolam (MDZ) and its metabolites, and their association with awakening time. The concentrations of MDZ and its seven metabolites were measured immediately and at 4, 8, 12, and 24 h after the discontinuation of MDZ infusion, using liquid chromatography-tandem mass spectrometry. The area under the time-plasma concentration curve from 0 to 24 h after MDZ discontinuation (AUC last ) was calculated based on the trapezoidal rule. Of the 15 enrolled patients, seven awakened after the discontinuation of MDZ infusion. MDZ and three of its metabolites were major compounds and their elimination kinetics followed a first-order elimination profile. In the multivariable analysis, only MDZ was associated with awakening time (AUC last : R 2  = 0.59, p = 0.03; AUC inf : R 2  = 0.96, p < 0.001). Specifically, a 0.001% increase in MDZ AUC was associated with a 1% increase in awakening time. In the individual regression analysis between MDZ concentration and awakening time, the mean MDZ concentration at awakening time was 16.8 ng/mL. The AUC of MDZ is the only significant factor associated with the awakening time., (© 2024. The Author(s).)

Objective: To understand the infection status and molecular types of rhinovirus (RV) among cases of Acute Respiratory Infections (ARIs) in Luohe City, Henan Province, from 2017 to 2022. Methods: From October 2017 to June 2022, clinical and epidemiological data were collected from 2 270 cases of ARIs at Luohe Central Hospital in Henan Province. Throat swab specimens were obtained from these cases. Real-time quantitative polymerase chain reaction (qPCR) was used to screen for RV-positive specimens. Subsequently, the positive samples were subjected to nested reverse transcription polymerase chain reaction (nested RT-PCR) to amplify the full-length VP1 region. Using the MEGA software, along with 169 RV reference strains recommended by the International Committee on Taxonomy of Viruses, a phylogenetic tree was constructed to determine RV types. Results: Among the 2 270 cases of ARIs, there were 1 283 male cases (56.52%). The median age ( Q 1 , Q 3 ) was 3 (1, 6) years, with the population under 5 years old accounting for 68.59% (1 557/2 270). RV was detected in 137 cases (6.04%), of which 68 cases (49.64%) showed co-detection with other viruses, with the most common being co-detection with enterovirus, accounting for 14.60% (20/137). The RV detection rates in the age groups of 0~4 years, 5~14 years, 15~59 years, and≥60 years were 6.42% (100/1 557), 4.69% (21/448), 3.80% (6/158), and 9.35% (10/107), respectively, with no statistically significant differences ( χ 2 =5.310, P =0.150). The overall detection rates of RV before (2017-2019) and during (2020-2022) the COVID-19 pandemic showed no statistically significant difference ( χ 2 =1.823, P =0.177). A total of 109 VP1 sequences were obtained, including 62 types. Among them, RV-A, RV-B, and RV-C had 42, 3, and 17 types respectively. Conclusion: RV is one of the predominant pathogens in ARIs cases in Luohe City, Henan Province, from 2017 to 2022. Multiple types of RV co-circulate without any apparent dominant type.

Human breastmilk is an invaluable nutritional and pharmacological resource with a highly diverse metabolite profile, which can directly affect the metabolism of infants. Application of metabolomics can discriminate the complex relationship between such nutrients and infant health. As the most common biological fluid in metabolomic study, infant urinary metabolomics may provide the physiological impacts of different nutritional resources, namely human breastmilk and formulated milk. In this study, we aimed to identify possible differences in the urine metabolome of 30 infants (1-14 days after birth) fed with breast milk ( n = 15) or formulated milk ( n = 15). From metabolomic analysis with gas chromatography-mass spectrometry, 163 metabolites from single mass spectrometry (GC-MS), and 383 metabolites from tandem mass spectrometry (GC-MS/MS) were confirmed in urinary samples. Various multivariate statistical analysis were performed to discriminate the differences originating from physiological/nutritional variables, including human breastmilk/formulate milk feeding, sex, and duration of feeding. Both unsupervised and supervised discriminant analyses indicated that feeding resources (human breastmilk/formulated milk) gave marginal but significant differences in urinary metabolomes, while other factors (sex, duration of feeding) did not show notable discrimination between groups. According to the biomarker analyses, several organic acid and amino acids showed statistically significant differences between different feeding resources, such as 2-hydroxyhippurate.

There are little direct comparative evidences of strategies between ≥50% and the absolute target goal of low-density lipoprotein cholesterol (LDL-C) level <55 mg/100 ml for the patients who underwent percutaneous coronary intervention (PCI). This study aimed to investigate the clinical impact of different strategies between 2 groups of patients who underwent PCI. A total of 3,104 patients with previous PCI were retrospectively enrolled from 2014 to 2020 at Yeungnam University Medical Center. The study population was stratified into 2 groups based on whether the LDL-C level was <55 mg/100 ml at the 1-year mark or not. Furthermore, the 50% reduction rate of LDL-C was also categorized based on whether it had decreased by ≥50% from the initial LDL-C level at the 1-year mark. The primary end point was 3-year major adverse cardiovascular events (MACEs) which were defined as a composite of cardiovascular death, nonfatal myocardial infarction, target lesion revascularization, hospitalization for heart failure, or nonfatal stroke. There was no significant difference between the LDL <55 mg/100 ml group and the LDL ≥55 mg/100 ml group in the risk of MACEs (hazard ratio 1.06, 95% confidence interval 0.81 to 1.38, p = 0.690) after propensity score matching. However, the group that achieved ≥50% reduction of LDL-C from baseline LDL-C level showed a significant reduction in the occurrence of MACEs in the subgroup of LDL-C level ≥55 mg/100 ml (hazard ratio 0.41, 95% confidence interval 0.19 to 0.89, p = 0.025) compared with the group with <50% reduction of LDL-C. In all patients, the achievement rate of target LDL-C <55 mg/100 ml and more than 50% reduction from baseline was 17.2%. In conclusion, guideline-directed management strategy of ≥50% reduction of LDL-C from the baseline will be needed to reduce the incidence of MACEs in patients with LDL-C ≥55 mg/100 ml who underwent PCI. Additional efforts to increase the target goal achievement rate of LDL-C are warranted., Competing Interests: Declaration of Competing Interest The authors have no competing interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Uterine leiomyoma (UL), the most prevalent benign gynecologic tumor among reproductive-aged women, lacks sufficient research on the potential association between dietary intake and its occurrence in Korean women. Addressing this research gap, this study aims to evaluate the potential link between dietary intake and the prevalence of UL in Korean women., Methods: In this cross-sectional study, a cohort of 672 women, aged 23 to 73, were enrolled, with 383 (57%) being premenopausal. Dietary intake was assessed using a validated food frequency questionnaire (FFQ), and UL presence was determined through ultrasonography. The analysis focused exclusively on items within ten categories, including vegetables/fruit, vegetables, fruits, red meat, processed meat, poultry, fish, dairy product, milk, and alcohol. Multiple logistic regression models were employed to explore the relationship between dietary intake and the prevalence of UL, calculating odds ratios (ORs) and 95% confidence intervals (CIs) while adjusting for confounding factors., Results: Within the total cohort, 220 (32.7%) women were diagnosed with UL. High intakes of fish and poultry showed an association with higher UL prevalence. Odds ratios (95% CIs) for the upper quartiles compared to the lower quartiles were 1.68 (1.01-2.81; p trend = 0.05) for fish intake and 1.87 (1.11-3.17; p trend = 0.06) for poultry intake. Conversely, an inverse relationship emerged between dairy product intake and UL prevalence, with an odds ratio of 0.58 (95% CI 0.35-0.96; p trend = 0.05). Stratifying the analysis by menopausal status revealed a parallel pattern, with heightened UL prevalence with fish intake and reduced prevalence with dairy product intake. However, the link between poultry intake and UL prevalence was primarily observed among postmenopausal women. Among premenopausal women, elevated vegetable intake was linked to a decreased UL prevalence (OR 0.45, 95% CI 0.21-0.97 for top vs. bottom quartiles; p trend = 0.01)., Conclusion: We found that high consumption of fish and poultry, coupled with low intake of dairy products, correlated with an elevated prevalence of UL. Furthermore, vegetable intake exhibited an inverse relationship with UL prevalence, particularly among premenopausal women., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kim 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.)

O2-type lithium-rich layered oxides, known for mitigating irreversible transition metal migration and voltage decay, provide suitable framework for exploring the inherent properties of oxygen redox. Here, we present a series of O2-type lithium-rich layered oxides exhibiting minimal structural disordering and stable voltage retention even with high anionic redox participation based on the nominal composition. Notably, we observe a distinct asymmetric lattice breathing phenomenon within the layered framework driven by excessive oxygen redox, which includes substantial particle-level mechanical stress and the microcracks formation during cycling. This chemo-mechanical degradation can be effectively mitigated by balancing the anionic and cationic redox capabilities, securing both high discharge voltage (~ 3.43 V vs. Li/Li + ) and capacity (~ 200 mAh g -1 ) over extended cycles. The observed correlation between the oxygen redox capability and the structural evolution of the layered framework suggests the distinct intrinsic capacity fading mechanism that differs from the previously proposed voltage fading mode., (© 2024. The Author(s).)

Background: Graft tears are common postoperative findings in meniscal allograft transplant (MAT). Graft tear in medial MAT may be different from that of lateral MAT, considering the difference between medial meniscal tears and lateral meniscal tears. Moreover, medial MAT is frequently accompanied by ligament reconstruction, which is associated with graft tear. The effect of graft tear on the long-term survivorship of medial MAT has not been investigated., Hypothesis: Graft tear would adversely affect the survivorship of medial MAT and the effect would be different according to the timing of graft tear., Study Design: Cohort study; Level of evidence, 3., Methods: A total of 55 patients undergoing medial MAT between June 2019 and March 2000 were retrospectively reviewed. Postoperative magnetic resonance imaging (MRI) scans were reviewed to identify graft tears, and the timing of their occurrence was investigated. Postoperative MRI was performed routinely during the first postoperative year and every 2 years thereafter. The patients were classified into a no graft tear (NT) group, early graft tear (occurring within 1 year; ET) group, and late graft tear (occurring 1 year after surgery; LT) group. The survival rate of medial MAT was estimated according to graft tear, with a failure being defined as (1) reoperations including arthroplasty, realignment osteotomy, revision MAT, and meniscectomy (>50% of the graft or to the zone of the meniscocapsular junction) or (2) Lysholm score <65. Clinical scores were compared between the groups., Results: The mean follow-up duration was 8.6 ± 5.3 years. During that period, clinical failures occurred in 6 (10.9%) patients. The overall survival rate at 5 years was 94.0% (95% CI, 90.6%-97.4%). Graft tears were seen in 18 patients: 6 patients in the ET group and 12 patients in the LT group. The median time when the graft tear was noted on MRI scans was 5.5 months (range, 1-11 months) postoperatively in the ET group and 99.5 months (range, 19-264 months) postoperatively in the LT group. Five patients in the ET group had root tears, whereas 9 patients in the LT group had complex or horizontal tears. The 5-year survival rate of the ET group was 62.5% (95% CI, 41.2%-83.8%), which was significantly lower than that of the NT group (96.8%; 95% CI, 93.6%-99.9%) and the LT group (85.7%; 95% CI, 72.5%-98.9%; P = .002). The mean postoperative Lysholm scores were 85.6 ± 17.9 in the NT group, 93.0 ± 2.8 in the ET group, and 79.3 ± 11.6 in the LT group, showing no significant difference between the groups (Kruskal-Wallis test, P = .058)., Conclusion: Clinical relevance of graft tear that occurred after medial MAT was dependent upon its timing. ET was a risk factor for clinical failure, whereas LT did not adversely affect graft survivorship. Lysholm scores did not differ according to graft tear., Competing Interests: The authors declared that they have no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Based on the 'AT(N)' system, individuals with normal amyloid biomarkers but abnormal tauopathy or neurodegeneration biomarkers are classified as non-Alzheimer's disease (AD) pathologic change. This study aimed to assess the long-term clinical and cognitive trajectories of individuals with non-AD pathologic change among older adults without dementia, comparing them to those with normal AD biomarkers and AD pathophysiology. Analyzing Alzheimer's Disease Neuroimaging Initiative data, we evaluated clinical outcomes and conversion risk longitudinally using mixed effects models and multivariate Cox proportional hazard models. We found that compared to individuals with A-T-N-, those with abnormal tauopathy or neurodegeneration biomarkers (A-T + N-, A-T-N + , and A-T + N + ) had a faster rate of cognitive decline and disease progression. Individuals with A-T + N + had a faster rate of decline than those with A-T + N-. Additionally, in individuals with the same baseline tauopathy and neurodegeneration biomarker status, the presence of baseline amyloid could accelerate cognitive decline and clinical progression. These findings provide a foundation for future studies on non-AD pathologic change and its comparison with AD pathophysiology., Competing Interests: Declaration of Competing Interest We declare that all coauthors have seen and agree with the contents of the manuscript, that the ICMJE requirements for authorship have been met. We also confirm that neither the entire paper nor any part of its content has been published or has been accepted elsewhere. There are no financial or other relationships that might lead to a perceived conflict of interest. The principal author or guarantor takes full responsibility for the data, the analyses and interpretation, and the conduct of the research. The authors have full access to all of the data and have the right to publish any and all data separate and apart from any sponsor. JTY was supported by grants from the Science and Technology Innovation 2030 Major Projects (2022ZD0211600), National Natural Science Foundation of China (82001133, 92249305, 82271471, 82071201, 82071997), Shanghai Municipal Science and Technology Major Project (No.2018SHZDZX01) and ZHANGJIANG LAB, Tianqiao and Chrissy Chen Institute, and the State Key Laboratory of Neurobiology and Frontiers Center for Brain Science of Ministry of Education, Fudan University. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12–2–0012)., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background/objective: Laparoscopic surgery for rectal cancer is challenging for novice surgeons because it requires a sharp dissection in a narrow pelvis with visual limitations. Therefore, this study aimed to analyze the learning curve and clinical outcomes of laparoscopic surgery for rectal cancer performed by a novice surgeon en route to becoming an expert., Methods: In total, 119 patients who underwent laparoscopic surgery for rectal cancer performed by a single surgeon between June 2010 and December 2019 were analyzed. A single hybrid model based on the operative time, open conversion, complications, and resection margin involvement was generated to assess the success of laparoscopic surgery. Furthermore, the learning curve was evaluated using the risk-adjusted cumulative sum (RA-CUSUM) method., Results: The learning period was categorized into three phases according to the RA-CUSUM method (phase 1, 1st-33rd cases; phase 2, 34th-84th cases; and phase 3, 85th-119th cases). Tumor size (p = 0.004), distal resection margin (p = 0.003), and the number of harvested lymph nodes (p < 0.001) significantly increased with the learning period. The time to tolerable soft diet became shorter according to the learning period (p = 0.017). Advanced T stage (p = 0.024) and adjuvant chemotherapy (p = 0.012) were more common in phase 3., Conclusions: This study suggested that the initial technical competence of laparoscopic surgery for rectal cancer was acquired in the 33rd case. Technical mastery was achieved in the 84th case. After mastering the technique, the surgeon tended to challenge more advanced cases, however, the complication rates did not increase., Competing Interests: Declaration of competing interest All authors have no conflict of interest., (Copyright © 2024 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Objective: Human and preclinical studies of sulfur mustard (SM)-induced acute and chronic lung injuries highlight the role of unremitting inflammation. We assessed the utility of targeting the novel DAMP and TLR4 ligand, eNAMPT (extracellular nicotinamide phosphoribosyltransferase), utilizing a humanized mAb (ALT-100) in rat models of SM exposure., Methods: Acute (SM 4.2 mg/kg, 24 hrs), subacute (SM 0.8 mg/kg, day 7), subacute (SM 2.1 mg/kg, day 14), and chronic (SM 1.2 mg/kg, day 29) SM models were utilized., Results: Each SM model exhibited significant increases in eNAMPT expression (lung homogenates) and increased levels of phosphorylated NFkB and NOX4. Lung fibrosis (Trichrome staining) was observed in both sub-acute and chronic SM models in conjunction with elevated smooth muscle actin (SMA), TGFβ, and IL-1β expression. SM-exposed rats receiving ALT-100 (1 or 4 mg/kg, weekly) exhibited increased survival, highly significant reductions in histologic/biochemical evidence of lung inflammation and fibrosis (Trichrome staining, decreased pNFkB, SMA, TGFβ, NOX4), decreased airways strictures, and decreased plasma cytokine levels (eNAMPT, IL-6, IL-1β. TNFα)., Conclusion: The highly druggable, eNAMPT/TLR4 signaling pathway is a key contributor to SM-induced ROS production, inflammatory lung injury and fibrosis. The ALT-100 mAb is a potential medical countermeasure to address the unmet need to reduce SM-associated lung pathobiology/mortality., Competing Interests: COI Disclosures: Joe GN Garcia MD is CEO and Founder of Aqualung Therapeutics Corporation. All other authors report no conflict of interest.

Background: Soyo-san (Xiaoyao-san; SYS), a traditional herbal medicine formula, has been used for treating mood disorders, especially depression and anxiety. Modified SYS (mSYS) is formulated by adding or removing herbs to SYS, and is mainly used in cases of mood disorders with comorbid diseases such as diabetes, digestive disorders, and anorexia. However, there has been no detailed comparative analysis of the differences in efficacy and underlying neurological mechanisms between SYS and mSYS., Purpose: This review aimed to investigate the present scientific evidence regarding the effects of SYS and mSYS on depression and anxiety in animal models based on behavioral improvements and changes in biomarker levels., Methods: The PubMed, Embase, Scopus, and Medline databases were searched for all depression- and anxiety-model animal studies that used SYS and mSYS. The types of animals, methods for inducing depression or anxiety, publication trends, target diseases, types and proportions of herbs, and significant behavioral and biomolecular changes induced by SYS and mSYS treatment were analyzed., Results: A total of 1,120 studies were identified, of which 57 studies were finally included in this review. Behavioral or environmental stress was mainly used to induce depression or anxiety in rodent models. SYS treatment improved body weight, food intake, and depression- and anxiety-like behaviors. The proportions of the herbs in the original SYS formulation were mostly fixed, whereas the types and proportions of herbs used in mSYS formulations were quite diverse. mSYS had a wider range of target diseases than SYS, and it has been used not only for depression and anxiety, but also cancer and stroke. Changes in biomarker levels in the hippocampus of the brain have been studied most extensively for both SYS and mSYS. Both SYS and mSYS are reported to regulate 5-hydroxytryptamine, brain-derived neurotrophic factor, and hypothalamic-pituitary-adrenal axis-related biomolecules in the brain, as well as changes in micro-organisms and metabolite levels in the serum and intestinal environment., Conclusions: SYS and mSYS improved depression- and anxiety-like behaviors by regulating neurotransmission, neuronal survival, and inflammation. Further research is needed to elucidate the clinical value of mSYS through various uses-related in-depth mechanistic studies., 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 GmbH. All rights reserved.)

Despite six decades of the use of exogenous oxytocin for management of labor, little is known about its effects on the developing brain. Motivated by controversial reports suggesting a link between oxytocin use during labor and autism spectrum disorders (ASDs), we employed our recently validated rat model for labor induction with oxytocin to address this important concern. Using a combination of molecular biological, behavioral, and neuroimaging assays, we show that induced birth with oxytocin leads to sex-specific disruption of oxytocinergic signaling in the developing brain, decreased communicative ability of pups, reduced empathy-like behaviors especially in male offspring, and widespread sex-dependent changes in functional cortical connectivity. Contrary to our hypothesis, social behavior, typically impaired in ASDs, was largely preserved. Collectively, our foundational studies provide nuanced insights into the neurodevelopmental impact of birth induction with oxytocin and set the stage for mechanistic investigations in animal models and prospective longitudinal clinical studies., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Breastfeeding not only reduces infection-related morbidity, but also increases growth of preterm infants. Advantages of breast milk (BM) for preterm infants are significant. They continue to be studied. However, because not all preterm infants can receive breastfeeding, bovine-based infant formula (IF) is used as an alternative, which may increase the risk of several preterm complications. Exosomes isolated from biofluids are emerging as biomarkers in research of various diseases. Here, we characterized miRNA contents of exosomes in urine and serum samples of preterm infants who were BM and IF fed and performed transcriptomic analysis of small RNA libraries. We identified significantly up-regulated 6 miRNAs and 10 miRNAs, respectively. Gene Ontology (GO) analysis revealed that target genes of these miRNAs might participate in neuronal development, immunity modulation, detoxification of reactive oxygen species, and transmembrane exchange. Our data suggest that exosome-based systemic screening for preterm infants with breastfeeding might be a screening tool for identifying target molecules involved in therapy for preterm infants in neonatal intensive care unit (NICU) and for future application as nutraceutical formulations or pharmaceuticals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kim, Song, Le, Kim, Koh, Seo, Jeong, Kim and Ryu.)

Background: Dry eye disease (DED) is a common ocular disorder in which the tear film cannot maintain homeostasis. Acupuncture has been used to treat DED in Korean medicine. Particularly, intradermal acupuncture (IDA) is less painful and enables free movement after treatment. However, it can also provoke allergic reactions to metal. To overcome this, biodegradable microneedle acupuncture (BMA) has been developed. This study compared BMA with traditional IDA in terms of efficacy and safety in patients with DED., Methods: This study was designed as an investigator-initiated, assessor-blinded, single-center, parallel randomized controlled trial. Thirty patients with DED were enrolled and randomized to one of the treatments. One group was treated with BMA on the acupoints, including bilateral BL2, GB14, TE23, EX-HN5, and ST1. The other group was treated with traditional IDA at the same acupoints. Treatments were conducted 3 times a week for 4 weeks. The major endpoint was ocular surface disease index (OSDI). The minor endpoints were subjective symptoms visual analog scale (VAS), quality of life (QoL), and tear production measured by the Schirmer I test., Results: All enrolled participants successfully completed the trial, and all of their data was analyzed. Both treatments remarkably improved the OSDI score, VAS score, QoL score, and tear secretion after 4 weeks (P < .05). Except for tear production in the left eye (P < .05), there were no statistical differences between the 2 treatments on the final visit (P > .05). No adverse events were observed., Conclusion: BMA and IDA had the same therapeutic effect for improving DED and both were safe. BMA can be used in patients with DED as an alternative to traditional IDA., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

The serious impact of the Covid-19 pandemic underscores the need for rapid, reliable, and high-throughput diagnosis methods for infection. Current analytical methods, either point-of-care or centralized detection, are not able to satisfy the requirements of patient-friendly testing, high demand, and reliability of results. Here, we propose a two-point separation on-demand diagnostic strategy that uses laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF MS) and adopts a stable yet cleavable ionic probe as a mass reporter. The use of this reporter enables ultrasensitive, interruptible, storable, restorable, and high-throughput on-demand detection. We describe a demonstration of the concept whereby we (i) design and synthesize a laser-cleavable reporter (DTPA), (ii) conjugate the reporter onto an antibody and verify the function of the conjugate, (iii) detect with good turnaround and high sensitivity the conjugated reporter, (iv) analyze quantitatively by using a laser-cleavable internal standard, and (v) identify negative and positive samples containing the spike protein. The protocol has excellent sensitivity (amol for the SARS-CoV-2 Spike S1 subunit antibody) without any amplification. This strategy is also applicable for the detection of other disease antigens besides SARS-CoV-2.

Background: It is unknown whether the outcomes achieved in the early period after revision lateral meniscal allograft transplantation (RLMAT) are maintained through the midterm period., Purpose: To evaluate the midterm clinical and radiological results of patients who underwent RLMAT., Study Design: Case series; Level of evidence, 4., Methods: We reviewed the outcomes of 19 RLMATs in 18 patients with at least 5 years of follow-up data. The mean follow-up period was 6 ± 1.1 years (range, 5-8.5 years). Clinical outcomes were assessed using the modified Lysholm score, the International Knee Documentation Committee (IKDC) subjective score, and the Tegner activity level. Radiographic progression of arthritis was measured by the absolute and relative joint space widths on 45° of knee flexion posteroanterior radiographs preoperatively, 1 year postoperatively, and at the latest follow-up.Failure was defined as meniscocapsular separation, removal, or tear of more than half of the meniscal allograft on postoperative magnetic resonance imaging (MRI) or conversion to total knee arthroplasty. Of the 18 patients, 3 underwent ≥2 RLMATs. The survival rate was evaluated according to the number of revision surgeries., Results: For knees with an intact meniscus transplant at the final follow-up, the modified Lysholm and IKDC scores were significantly improved compared with preoperatively, but the Tegner activity level was unchanged. No significant differences were found in the absolute and relative joint space widths postoperatively. There were 6 failures within 3 years after RLMAT; the overall 5-year survival rate was 68.4% (13/19 knees). All failed knees showed bucket-handle tear patterns on MRI due to meniscocapsular healing failure. The survival rate decreased as the number of RLMATs increased-73.3% for a first RLMAT (n = 15 knees), 66.7% for a second RLMAT (n = 3 knees), and 0% for a third RLMAT (n = 1 knee). Midterm MRIs of 8 well-healed RLMATs showed evidence of meniscal degeneration; nonetheless, this did not affect clinical outcomes., Conclusion: The midterm results of RLMATs demonstrated a 5-year survival rate of 68.4% and positive clinical and radiological outcomes for failed MATs despite unimproved activity levels. Inadequate meniscocapsular healing was the leading cause of failure, and it needs to be carefully considered when performing RLMATs., Competing Interests: The authors have declared that there are no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto. Ethical approval for this study was obtained from Asan Medical Center (ref No. 2020-1813)., (© The Author(s) 2024.)

Introduction: The prevalence of dry eye disease (DED) has been consistently increasing yearly. However, the radical therapy has not yet been established. This study is to confirm the superiority of acupuncture over artificial tear drops (ATDs) in patients with DED., Methods and Analysis: This study is a single-centre, investigator-initiated, assessor-blinded, parallel randomised controlled trial. 30 participants will be enrolled. Over a period of 4 weeks, the experimental group would receive two kinds of acupuncture three times a week. First, body acupuncture would be performed on bilateral BL2, GB14, TE23, EX-HN5 and ST1 for 15 min. Thereafter, intradermal acupuncture would be performed on the same acupoints for 4 hours. On the other hand, the control group would apply the provided ATD at least four times a day. As a rescue medication for severe DED symptoms, both groups can additionally apply ATD. The frequency of ATD use would be recorded during the trial. The primary outcomes are the Ocular Surface Disease Index and tear film break-up time. The secondary outcomes are subjective symptom Visual Analogue Scale, quality of life, Schirmer I test, tear lactoferrin level, treatment satisfaction and safety. The outcomes would be mostly assessed at visits 1, 13 and 14., Ethics and Dissemination: This study was approved by the institutional review board of Naju Dongshin University Korean Medicine Hospital (Approval No. NJ-IRB-23-5). The obtained results will be disseminated through publication in a peer-reviewed journal., Trial Registration Number: KCT0008563., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We examined how 5- to 8-year-olds ( N = 51; M age = 83 months; 27 female, 24 male; 69% White, 12% Black/African American, 8% Asian/Asian American, 6% Hispanic, 6% not reported) and adults ( N = 18; M age = 20.13 years; 11 female, 7 male) accepted or rejected different distributions of resources between themselves and others. We used a reach-tracking method to track finger movement in 3D space over time. This allowed us to dissociate two inhibitory processes. One involved pausing motor responses to detect conflict between observed information and how participants thought resources should be divided; the other involved resolving the conflict between the response and the alternative. Reasoning about disadvantageous inequities involved more of the first system, and this was stable across development. Reasoning about advantageous inequities involved more of the second system and showed more of a developmental progression. Generally, reach tracking offers an on-line measure of inhibitory control for the study of cognition.

Agastache rugosa Kuntze (Lamiaceae; Labiatae), a medicinal and functional herb used to treat gastrointestinal diseases, grows well both on islands and inland areas in South Korea. Thus, we aimed to reveal the morphological and micromorphological differences between A. rugosa grown on island and inland areas and their pharmacological effects on gastritis in an animal model by combining morphological and mass spectrophotometric analyses. Morphological analysis showed that island A. rugosa had slightly smaller plants and leaves than inland plants; however, the density of all types of trichomes on the leaves, petioles, and stems of island A. rugosa was significantly higher than that of inland plants. The essential oil component analysis revealed that pulegone levels were substantially higher in island A. rugosa than in inland A. rugosa . Despite the differences between island and inland A. rugosa , treatment with both island and inland A. rugosa reduced gastric damages by more than 40% compared to the gastritis induction group. In addition, expression of inflammatory protein was reduced by about 30% by treatment of island and inland A. rugosa. The present study demonstrates quantitative differences in morphology and volatile components between island and inland plants; significant differences were not observed between the gastritis-inhibitory effects of island and inland A. rugosa , and the efficacy of island A. rugosa was found to be similar to that of A. rugosa grown in inland areas., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

The LEPR (leptin receptor) genotype is associated with obesity. Gut microbiome composition differs between obese and non-obese adults. However, the impact of LEPR genotype on gut microbiome composition in humans has not yet been studied. In this study, the association between LEPR single nucleotide polymorphism (rs1173100, rs1137101, and rs790419) and the gut microbiome composition in 65 non-obese Korean adults was investigated. Leptin, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels were also measured in all participants. Mean ± SD (standard deviation) of age, body mass index, and leptin hormone levels of participants was 35.2 ± 8.1 years, 21.4 ± 1.8 kg/m 2 , and 7989.1 ± 6687.4 pg/mL, respectively. Gut microbiome analysis was performed at the phylum level by 16S rRNA sequencing. Among the 11 phyla detected, only one showed significantly different relative abundances between LEPR genotypes. The relative abundance of Candidatus Saccharibacteria was higher in the G/A genotype group than in the G/G genotype group for the rs1137101 single nucleotide polymorphism ( p =0.0322). Participant characteristics, including body mass index, leptin levels, and other lipid levels, were similar between the rs1137101 G/G and G/A genotypes. In addition, the relative abundances of Fusobacteria and Tenericutes showed significant positive relationship with plasma leptin concentrations ( p =0.0036 and p =0.0000, respectively). In conclusion, LEPR genotype and gut microbiome may be associated even in normal-weight Korean adults. However, further studies with a greater number of obese adults are needed to confirm whether LEPR genotype is related to gut microbiome composition.

Dogs with sialocele often have concurrent hypercortisolism or are receiving long-term glucocorticoid treatment. However, their association has not been investigated. This retrospective matched case-control study investigated the association between hypercortisolism, long-term glucocorticoid treatment, and sialocele in dogs. We retrospectively reviewed the records from 1 January 2018 to 31 December 2022. Records of 19 dogs diagnosed with sialocele were investigated for hypercortisolism and long-term glucocorticoid treatment. Two age- and breed-matched controls for each sialocele dog (38 dogs) were investigated for the same concurrent diseases. Logistic regression analysis was used. The odds of sialocele in dogs with hypercortisolism were 15.56 times those of dogs without hypercortisolism ( p = 0.02; 95% CI: 1.54-156.79). The odds of sialocele in dogs with long-term glucocorticoid treatment (median, 8 months; range, 5-13) were 7.78 times those of dogs without long-term glucocorticoid treatment ( p = 0.03; 95% CI: 1.23-49.40). No associations were found between age, sex, body weight, and the presence of sialocele. The results indicate that sialocele was significantly associated with hypercortisolism and long-term glucocorticoid treatment in dogs. Therefore, dogs with hypercortisolism or receiving long-term glucocorticoid therapy should be screened for possible sialocele. Additionally, dogs with sialocele should be identified for concurrent hypercortisolism and prolonged glucocorticoid exposure., Competing Interests: The authors declare no conflicts of interest.

Caregiver sensitivity builds a basis for children's sense of security and effective emotion regulation during their development. Applying a cross-cultural lens, caregiver sensitivity can be divided into two subtypes, reactive and proactive, and its prevalence and meaning may differ across cultures. Guided by the theoretical frameworks of developmental niche and parental ethnotheories, the current study examines culture-specific meanings of caregiver sensitivity across five countries: India, Nepal, Korea, the United States of America (USA), and Germany. We examine the prevalence of maternal reactive and proactive sensitivity, children's emotional lability and regulation, and how mothers' sensitivity types are related to children's emotional characteristics. Participants included 472 mothers from the five countries with children aged between 6 and 7 years. Mothers reported their sensitivity preference in multiple vignettes and completed an emotion regulation checklist to report their children's emotional lability and regulation. A set of analyses of covariance (ANCOVAs) found cultural differences in mothers' preference for proactive and reactive sensitivity. Mothers in India and Nepal reported the highest preference for proactive sensitivity followed by Korea and the USA, while German mothers reported the lowest preference for proactive sensitivity. Consequent regression analyses revealed varying associations between proactive sensitivity and child emotional characteristics in all five countries either directly or as moderated by child sex. These results evidence that parental ethnotheories are part of the developmental niche embedded in a larger cultural context. Findings on the differential links between the types of sensitivity and child emotion regulation provide cultural models of parental emotion socialization and children's emotional functioning., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Song, Cho, Trommsdorff, Cole, Niraula and Mishra.)

Enterovirus A71 (EV71), coxsackievirus A16 (CVA16), and coxsackievirus B3 (CVB3) are pathogenic members of the Picornaviridae family that cause a range of diseases, including severe central nervous system complications, myocarditis, and pancreatitis. Despite the considerable public health impact of these viruses, no approved antiviral treatments are currently available. In the present study, we confirmed the potential of saucerneol, a compound derived from Saururus chinensis , as an antiviral agent against EV71, CVA16, and CVB3. In the in vivo model, saucerneol effectively suppressed CVB3 replication in the pancreas and alleviated virus-induced pancreatitis. The antiviral activity of saucerneol is associated with increased mitochondrial ROS (mROS) production. In vitro inhibition of mROS generation diminishes the antiviral efficacy of saucerneol. Moreover, saucerneol treatment enhanced the phosphorylation of STING, TBK-1, and IRF3 in EV71- and CVA16-infected cells, indicating that its antiviral effects were mediated through the STING/TBK-1/IRF3 antiviral pathway, which was activated by increased mROS production. Saucerneol is a promising natural antiviral agent against EV71, CVA16, and CVB3 and has potential against virus-induced pancreatitis and myocarditis. Further studies are required to assess its safety and efficacy, which is essential for the development of effective antiviral strategies against these viruses.

Introduction: We analyzed relationships among peripheral immunity markers, cognition, Alzheimer's disease (AD)-related biomarkers, and neuroimaging to understand peripheral immunity involvement in AD., Methods: Peripheral immunity markers were assessed in AD, non-AD neurodegenerative disorders, and controls, examining their connections with cognition, AD-related biomarkers, and neuroimaging using multiple regression models., Results: The study included 1579 participants. Higher levels of white blood cell, neutrophil, monocyte, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and lower lymphocyte-to-monocyte ratio (LMR) were associated with cognitive decline and more severe anxiety and depression. The impact of lower LMR, lymphocyte count, and higher NLR on cognitive decline is mediated through cerebrospinal fluid amyloid beta (Aβ) levels. Additionally, increased PLR, NLR, and SII were associated with brain atrophy and hippocampal Aβ deposition (amyloid positron emission tomography)., Discussion: Peripheral immunity markers offer a non-invasive and cost-effective means of studying AD-related pathophysiological changes, providing valuable insights into its pathogenesis and treatment., Highlights: Peripheral immunity markers linked to cognitive decline and anxiety/depression.Low LMR, LYM, and high NLR linked to reduced CSF Aβ, impacting cognition.High PLR, NLR, SII associated with brain atrophy and hippocampal Aβ deposition., Competing Interests: The authors declare no competing interests. Author disclosures are available in the supporting information., (© 2023 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

The regression relationship between water discharge rates and nutrient concentrations can provide a quick and straightforward way to estimate nutrient loads. However, recent studies indicated that the relationship might produce large biases in load estimates and, therefore, may not be applicable in certain types of cases. The goal of this study is to explore the theoretical reasons behind the selective applicability of the regression relationship between flow rates and nitrate + nitrite concentrations. For this study, we examined daily flow and nitrate + nitrite concentration observations made at the outlets of 22 watersheds monitored by the Heidelberg Tributary Loading Program (HTLP). The statistical relationship between the flow rates and concentrations was explored using regression equations offered by the LOAD ESTimator (LOADEST). Results demonstrated that the use of the regression equations provided nitrate + nitrite load estimates at acceptable accuracy levels ( N S E ≥ 0.35 and | P B I A S | ≤ 30.0 %) in 14 watersheds (64 % of 22 study watersheds). The regression relationships provided highly biased results at eight watersheds (36 %), implying their limited applicability. The heteroscedasticity of the residuals led to the high bias and resulting inaccurate regression, which was commonly found in watersheds where low flow had high nitrate + nitrite concentration variations. Conversely, the regression relationships provided acceptable accuracy for watersheds that had a relatively constant variance of the nitrate + nitrite concentrations. The results indicate that the homoscedasticity of residuals is the key assumption to be satisfied to estimate nitrate + nitrite loads from a statistical regression between flow discharge and nitrate + nitrite concentrations. The transport capacity (capacity-limited) concept implicitly assumed in the regression relationship between flow discharge and nitrate + nitrite concentrations is not always applicable, especially to agricultural areas in which nitrate + nitrite loads are highly variable depending on management practices (supply-limited). The findings suggest that the regression relationship should be carefully applied to areas in which intensive agricultural activities, including crop management and conservation practices, are implemented. Thus, the transport capacity concept is reasonably regarded to contribute to the homoscedasticity of residuals., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jung-Hun Song reports financial support was provided by 10.13039/501100003725National Research Foundation of Korea. Younggu Her reports financial support was provided by 10.13039/100005825National Institute of Food and Agriculture. The authors appreciate Dr. Jane Frankenber's constructive and valuable comments and suggestions that improved this manuscript and study., (© 2023 The Authors.)

Disease progression following androgen ablation was shown to be associated with upregulation of the glucocorticoid receptor (GR). Longitudinal monitoring of GR expression in circulating extracellular vesicles (EV) may reflect changes in the tumor cell and facilitates detection of acquired resistance. We utilized LNCaP, LREX cells and a patient-derived xenograft, MDA PDX 322-2-6a, for in vitro and in vivo experiments. Plasma-derived EVs were isolated from patients with localized high-risk prostate cancer undergoing androgen ablation. The mRNA levels of GR in EVs and their responsive genes were detected by transcriptome analysis, qRT-PCR and the protein levels by Western blot analysis. We detected changes in GR expression at mRNA and protein levels in EVs derived from LNCaP and LREX cells in in vitro studies. In in vivo experiments, LNCaP and the PDX MDA 322-2-6a-bearing mice were treated with enzalutamide. GR levels in plasma-derived EVs were increased only in those tumors that did not respond to enzalutamide. Treatment of mice bearing enzalutamide-resistant tumors with a GR inhibitor in combination with enzalutamide led to a transient pause in tumor growth in a subset of tumors and decreased GR levels intracellular and in plasma-derived EVs. In a subgroup of patients with high-risk localized prostate cancer treated with androgen signaling inhibition, GR was found upregulated in matching tissue and plasma EVs. These analyses showed that GR levels in plasma-derived EVs may be used for monitoring the transition of GR expression allowing for early detection of resistance to androgen ablation treatment., Significance: Longitudinal monitoring of GR expression in plasma-derived EVs from patients with prostate cancer treated with androgen signaling inhibitors facilitates early detection of acquisition of resistance to androgen receptor signaling inhibition in individual patients., (© 2023 The Authors; Published by the American Association for Cancer Research.)

Background: Prostate cancer (PCa) typically spreads to the bone, and this distribution is attributed to the central role of the microenvironment in progression. However, metastasis to the adrenal glands, while not as common, does occur. The biology that accounts for adrenal metastases may be attributed to the unique local steroid metabolome and co-clinical characterization may elucidate the role steroid biosynthesis plays in PCa progression., Methods: Three patients with metastatic PCa who had archived tumor tissue from an adrenalectomy were retrospectively identified, and one adrenal metastasis was developed into a xenograft (MDA-PCa-250). The adrenal metastases were characterized by performing somatic DNA whole exome sequencing (WES), RNA-Seq, immunohistochemistry (IHC), and steroid metabolite quantitation. The influence of steroid metabolites on adrenal metastasis cells and tumor growth was tested in vitro and in vivo., Results: Clinically, adrenalectomy was performed during castration-resistant oligometastatic disease, and two men experienced resensitization to leuprolide. Somatic DNA WES revealed heterogeneous alterations in tumor suppressor and DNA damage repair pathway genes. Adrenal metastases had active androgen receptor (AR) signaling by IHC, and RNA-Seq supported a potential role for adrenal androgen precursor metabolism in activating the AR. Steroid quantitation suggested the adrenal androgen precursors were converted into testosterone in these metastases, and stable isotope tracing of an organoid from MDA-PCa-250 confirmed the capability of adrenal metastases to biosynthesize testosterone from adrenal precursors. In vitro testing of a cell line derived from MDA-PCa-250 showed that testosterone and cortisol stimulated tumor cell growth. In vivo experiments demonstrated that MDA-PCa-250 grew in intact mice with circulating testosterone, but not in castrated mice., Conclusions: PCa adrenal metastases depend upon AR signaling driven by androgen precursors, androstenedione and dehydroepiandrosterone, available in the microenvironment, despite the presence of heterogeneous somatic DNA alterations. Moreover, MDA-PCa-250 provides a preclinical model that can recapitulate the unique androgen-dependence of adrenal metastases., Clinical Trial Registration: This study does not report the clinical results of a clinical trial, but it does use samples from a completed clinical trial that is registered with clinicaltrials.gov (NCT01254864)., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

A Gram-stain-negative, aerobic, non-flagellated and coccoid or ovoid bacterial strain, BSSL-BM11 T , was isolated from sand of coastal dunes along the Yellow Sea of the Korean peninsula. Strain BSSL-BM11 T grew optimally at 30 °C, at pH 7.0-8.0 and in the presence of 2.0-3.0 % (w/v) NaCl. Phylogenetic trees based on 16S rRNA gene sequences, the up-to-date bacterial core gene set and average amino acid identity (AAI) showed that strain BSSL-BM11 T forms a cluster with the type strains of Tianweitania sediminis and Corticibacterium populi . Strain BSSL-BM11 T showed 16S rRNA gene sequence similarities of 98.3 and 98.0 % to the type strains of T. sediminis and C. populi , respectively, and less than 96.4 % to the type strains of the other recognized species. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain BSSL-BM11 T and the type strains of T. sediminis and C. populi were 77.0-84.8 % and 20.0-28.1 %, respectively. The 16S rRNA gene similarity, AAI, ANI and dDDH values between T. sediminis Z8 T and C. populi KCTC 42249 T were 98.0, 77.4, 76.7 and 20.1 %, respectively. The DNA G+C content of strain BSSL-BM11 T from genomic sequence data was 61.3 mol%. Strain BSSL-BM11 T contained Q-10 as the predominant ubiquinone and C 18 : 1  ω 7 c , C 16 : 0 and cyclo C 19 : 0  ω 8 c as the major fatty acids. The major polar lipids of strain BSSL-BM11 T were phosphatidylcholine, phosphatidylglycerol and phosphatidylethanolamine. Based on the polyphasic data, it is proposed that C, populi be reclassified as a member of the genus Tianweitania . Phenotypic and phylogenetic analyses revealed that strain BSSL-BM11 T is separated from T. sediminis and C. populi . On the basis of the data presented here, strain BSSL-BM11 T (=KACC 21634 T =NBRC 114503 T ) is considered to represent a novel species of the genus Tianweitania , for which the name Tianweitania aestuarii sp. nov. is proposed.