Sulfur(VI) fluoride exchange (SuFEx) has emerged as an innovative click chemistry to harness the pivotal connectivity of sulfonyl fluorides. Synthesizing such alkylated S(VI) molecules through a straightforward process is of paramount importance, and their water-compatibility opens the door to a plethora of applications in biorelevant and materials chemistry. Prior aquatic endeavors have primarily focused on delivering catalysts involving ionic mechanisms, studies regarding visible-light photocatalytic transformation are unprecedented. Herein we report an on-water accelerated dearomative aquaphotocatalysis for heterocyclic alkyl SuFEx hubs. Notably, water exerts a pronounced accelerating effect on the [2 + 2] cycloaddition between (hetero)arylated ethenesulfonyl fluorides and inert heteroaromatics. This phenomenon is likely due to the high-pressure-like reactivity amplification at the water-oil interface. Conventional solvents proved totally ineffective, leading to the isomerization of the starting material.
This study aimed to assess the effects of microbial additives that produce antimicrobial and digestive enzymes on the growth performance, blood metabolites, fecal microflora, and carcass characteristics of growing-finishing pigs. A total of 180 growing-finishing pigs (Landrace × Yorkshire × Duroc; mixed sex; 14 weeks of age; 58.0 ± 1.00 kg) were then assigned to one of three groups with three repetitions (20 pigs) per treatment for 60 days of adaptation and 7 days of collection. Dietary treatments included 0, 0.5, and 1.0% microbial additives in the basal diet. For growth performance, no significant differences in the initial and final weights were observed among the dietary microbial additive treatments, except for the average daily feed intake, average daily gain, and feed efficiency. In terms of blood metabolites and fecal microflora, immunoglobulin G (IgG), blood urea nitrogen, blood glucose, and fecal lactic acid bacteria count increased linearly, and fecal E. coli counts decreased linearly with increasing levels of microbial additives but not growth hormones and Salmonella. Carcass quality grade was improved by the microbial additive. In addition, carcass characteristics were not influenced by dietary microbial additives. In conclusion, dietary supplementation with 1.0% microbial additive improved average daily gain, feed efficiency, IgG content, and fecal microflora in growing-finishing pigs.
BACKGROUND: While indirect comparison of infliximab (IFX) and vedolizumab (VDZ) in adults with Crohn's disease (CD) or ulcerative colitis (UC) shows that IFX has better effectiveness during induction, and comparable efficacy during maintenance treatment, comparative data specific to subcutaneous (SC) IFX (i.e., CT-P13 SC) versus VDZ are limited. AIM: Pooled analysis of randomised studies to compare efficacy and safety with IFX SC and VDZ in moderate-to-severe inflammatory bowel disease. METHODS: Parallel-group, randomised studies evaluating IFX SC and VDZ in patients with moderate-to-severe CD or UC were identified. Eligible studies reported ≥ 1 prespecified outcome of interest at Week 6 (reflecting treatment during the induction phase) and/or at 1 year (Weeks 50-54; reflecting treatment during the maintenance phase). Prespecified efficacy and safety outcomes considered in this pooled analysis included the proportions of patients achieving disease-specific clinical responses, clinical remission, or discontinuing due to lack of efficacy, and the proportions of patients experiencing adverse events (AEs), serious AEs, infections, serious infections, or discontinuing due to AEs. Data from multiple studies or study arms were extracted and pooled using a random-effect model; comparative analyses were performed separately for patients with CD and UC. RESULTS: We identified three eligible CD trials and four eligible UC trials that assigned over 1200 participants per disease cohort to either IFX SC or VDZ. In patients with CD, intravenous induction therapy with IFX demonstrated better efficacy (non-overlapping 95% confidence intervals [CIs]) compared with VDZ; during the maintenance phase, IFX SC showed numerically better efficacy (overlapping 95% CIs) than VDZ. A lower proportion of IFX SC-treated patients discontinued therapy due to lack of efficacy over 1 year. In patients with UC, efficacy profiles were similar with IFX SC and VDZ during the induction and maintenance phases, and a lower proportion of IFX SC-treated patients discontinued therapy due to lack of efficacy over 1 year. In both cohorts, safety profiles for IFX SC and VDZ were generally comparable during 1 year. CONCLUSION: IFX SC demonstrated better efficacy than VDZ in patients with CD, and similar efficacy to VDZ in patients with UC; 1-year safety was comparable with IFX SC and VDZ.
Antibodies, Monoclonal, Humanized , Colitis, Ulcerative , Crohn Disease , Adult , Humans , Colitis, Ulcerative/drug therapy , Infliximab/adverse effects , Crohn Disease/drug therapy , Gastrointestinal Agents/adverse effects , Remission Induction , Treatment Outcome , Randomized Controlled Trials as Topic
Background: To report a novel surgical technique for recurrent pupillary optic capture after flanged intraocular lens (IOL) fixation. Methods: In this retrospective case series, we detail our use of two parallel 7-0 polypropylene sutures passed between the iris plane and the optic of scleral-fixated IOL to address pupillary optic capture. Flanges were created using ophthalmic cautery to secure it to the sclera without suture. Results: Two eyes with pupillary optic capture underwent a sutureless surgical technique using 7-0 polypropylene flanges. No recurrences of pupillary optic capture were observed during the 1-year follow-up. Conclusion: Our sutureless surgical technique using a 7-0 polypropylene flange was an effective, efficient, and less invasive approach for treating recurrent pupillary optic capture.
BACKGROUND: Runaway youth without an adequate and safe place are vulnerable to sexual violence. Sexual violence is strongly associated with suicide risk, but peers and family are important factors in attenuating the negative outcomes of sexual violence; however, research on this relationship is insufficient because previous studies have focused only on runaway youth's problematic behavior. OBJECTIVE: This study's specific aims were as follows: 1) to verify the association between sexual violence and suicide risk among runaway youth, and 2) to assess whether peer and parental attachment moderated the association between sexual violence and suicide risk among runaway youth. PARTICIPANTS AND SETTING: The participants comprised 232 runaway youth (51.3 % girls); more than half were aged 17-19 years and approximately two-thirds of them had experienced child abuse. METHODS: Self-administered questionnaires were provided to the participating runaway youth in youth shelters in South Korea. The data were analyzed using a multiple additive moderating model that simultaneously included moderating and control variables. RESULTS: In total, 18.5 % of runaway youth were exposed to sexual violence (10.6 % boys, 26.1 % girls). Sexual violence victimization affected suicide risk among runaway youth. Peer attachment alleviated the negative relationship between sexual violence and suicide risk, and acted as a protective factor. Although the moderating effect of parental attachment was not significant, it significantly influenced suicide risk. CONCLUSION: Our findings demonstrate that runaway youth are vulnerable to sexual violence victimization, especially severe types of sexual violence. Our study verified the role of peer and parental attachment in the association between sexual violence and suicide risk among runaway youth. These findings suggest the need to improve positive peer and parent relationships to mitigate suicide risk among runaway youth.
Child Abuse , Crime Victims , Sex Offenses , Suicide , Male , Child , Female , Humans , Adolescent , Violence , Parents
BACKGROUND: Pharmacokinetic non-inferiority of subcutaneous (SC) to intravenous (IV) CT-P13 maintenance therapy was demonstrated in a randomized trial (NCT02883452). This post hoc analysis evaluated longitudinal clinical outcomes with the two infliximab treatment strategies. METHODS: Patients with Crohn's disease or ulcerative colitis received CTP13 IV loading doses (5â¯mg/kg; Week [W] 0 and W2) before randomization (1:1) to receive CT-P13 SC (body weight-based dosing every 2 weeks [Q2W]; W6-54; 'SC maintenance group') or CTP13 IV (5â¯mg/kg Q8W; W6-22) then CT-P13 SC (Q2W; W30-54; 'IV-to-SC switch group'). Paired W30/W54 patient-level data were analyzed. RESULTS: Fifty-three (IV-to-SC switch) and fifty-nine (SC maintenance) patients were analyzed. Median trough serum CT-P13 concentrations were significantly higher at W54 versus W30 in the IV-to-SC switch group (20.4 versus 2.3⯵g/mL; p < 0.00001), while remaining consistent in the SC maintenance group. Statistically significant improvements in pharmacokinetics, efficacy, fecal calprotectin levels, and quality of life were seen following switch to SC administration at W30 in the IV-to-SC switch group; safety findings were similar pre- and post-switch. CONCLUSION: Formulation switching from IV to SC infliximab maintenance therapy was well tolerated and may provide additional clinical improvements. Findings require confirmation in larger prospective studies.
Wire arc additive manufacturing (WAAM) is being extensively used in various industrial fields. In WAAM, if a bead is deposited without considering the central angle, its shape may collapse with increasing number of layers. To address this problem, a new method for optimizing the bead geometry using a support vector machine (SVM) classifier was established in this study. The ranges of the optimal deposition conditions were determined using the SVM classifier and verified by experiments. Geometric data of deposited beads were extracted using a laser profiler, and an SVM binary classifier was used to predict suitable ranges of the deposition conditions. Data were extracted through 20 single-layer basic experiments, classification was performed based on 4°, and the appropriateness of SVM classification was found through 8 single-layer and 3 multi-layer verification experiments. The results showed that the SVM classifier successfully selected the ranges of the optimal deposition conditions. Verification experiments revealed that the results in all cases were appropriately classified based on the boundary of the classification line. Moreover, the SVM classifier was efficient even when a small amount of input data was available. The contribution of this study is that the developed method can help build desired bead geometries in scenarios where deposition is required in the WAAM process, such as re-manufacturing. Thus, this method can be used in real-world industrial applications through further research on the bead shape with multi-layer deposition.
In underwater laser beam machining (ULBM), water provides a cooling effect by reducing the influence of the laser heat source, which makes ULBM more suitable for marking, cutting, and postprocessing than laser beam machining (LBM). Because the laser heat source not only affects the substrate temperature, but also heats the water, this study analyzes how the cooling effect occurs when water is heated. In this study, the heat-transformed zones in ULBM and heated underwater laser beam machining (HULBM) were improved by approximately 33% and 24%, respectively, compared to LBM at 400 W. In addition, the heat-affected zones in ULBM and HULBM improved by approximately 15% and 9%, respectively, compared to LBM. The hardness of ULBM and HULBM was higher than that of LBM. Based on these results, it was confirmed that water can reduce the effect of the laser heat source and improve the mechanical properties. Experiments will be conducted on the underwater laser beam machining of various substrates, such as Inconel718 and Ti-6Al-4V, in a future study. In addition, experiments will be conducted on the underwater laser beam machining of various substrates using a cooling system that can lower the temperature of water.
There has been significant research focused on the development of stretchable materials that can provide a large area with minimal material usage for use in solar cells and displays. However, most materials exhibit perpendicular shrinkage when stretched, which is particularly problematic for polymer-based substrates commonly used in stretchable devices. To address this issue, biaxial strain-controlled substrates have been proposed as a solution to increase device efficiency and conserve material resources. In this study, we present the design and fabrication of a biaxial strain-controlled substrate with a re-entrant honeycomb structure and a negative Poisson's ratio. Using a precisely machined mold with a shape error of less than 0.15%, we successfully fabricated polydimethylsiloxane substrates with a 500 µm thick re-entrant honeycomb structure, resulting in a 19.1% reduction in perpendicular shrinkage. This improvement translates to a potential increase in device efficiency by 9.44% and an 8.60% reduction in material usage for substrate fabrication. We demonstrate that this design and manufacturing method can be applied to the fabrication of efficient stretchable devices, such as solar cells and displays.
BACKGROUND: Although the development of BCR::ABL1 tyrosine kinase inhibitors (TKIs) rendered chronic myeloid leukemia (CML) a manageable condition, acquisition of drug resistance during blast phase (BP) progression remains a critical challenge. Here, we reposition FLT3, one of the most frequently mutated drivers of acute myeloid leukemia (AML), as a prognostic marker and therapeutic target of BP-CML. METHODS: We generated FLT3 expressing BCR::ABL1 TKI-resistant CML cells and enrolled phase-specific CML patient cohort to obtain unpaired and paired serial specimens and verify the role of FLT3 signaling in BP-CML patients. We performed multi-omics approaches in animal and patient studies to demonstrate the clinical feasibility of FLT3 as a viable target of BP-CML by establishing the (1) molecular mechanisms of FLT3-driven drug resistance, (2) diagnostic methods of FLT3 protein expression and localization, (3) association between FLT3 signaling and CML prognosis, and (4) therapeutic strategies to tackle FLT3+ CML patients. RESULTS: We reposition the significance of FLT3 in the acquisition of drug resistance in BP-CML, thereby, newly classify a FLT3+ BP-CML subgroup. Mechanistically, FLT3 expression in CML cells activated the FLT3-JAK-STAT3-TAZ-TEAD-CD36 signaling pathway, which conferred resistance to a wide range of BCR::ABL1 TKIs that was independent of recurrent BCR::ABL1 mutations. Notably, FLT3+ BP-CML patients had significantly less favorable prognosis than FLT3- patients. Remarkably, we demonstrate that repurposing FLT3 inhibitors combined with BCR::ABL1 targeted therapies or the single treatment with ponatinib alone can overcome drug resistance and promote BP-CML cell death in patient-derived FLT3+ BCR::ABL1 cells and mouse xenograft models. CONCLUSION: Here, we reposition FLT3 as a critical determinant of CML progression via FLT3-JAK-STAT3-TAZ-TEAD-CD36 signaling pathway that promotes TKI resistance and predicts worse prognosis in BP-CML patients. Our findings open novel therapeutic opportunities that exploit the undescribed link between distinct types of malignancies.
Blast Crisis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Animals , Mice , Humans , Blast Crisis/drug therapy , Blast Crisis/genetics , Blast Crisis/pathology , Fusion Proteins, bcr-abl/genetics , Drug Resistance, Neoplasm/genetics , Signal Transduction , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Protein Kinase Inhibitors/pharmacology , fms-Like Tyrosine Kinase 3/metabolism
PURPOSE: This study investigated the validity of introducing a clinical skills examination (CSE) to the Korean Oriental Medicine Licensing Examination through a mixed-method modified Delphi study METHODS: A 3-round Delphi study was conducted between September and November 2022. The expert panel comprised 21 oriental medicine education experts who were officially recommended by relevant institutions and organizations. The questionnaires included potential content for the CSE and a detailed implementation strategy. Subcommittees were formed to discuss concerns around the introduction of the CSE, which were collected as open-ended questions. In this study, a 66.7% or greater agreement rate was defined as achieving a consensus. RESULTS: The expert panel's evaluation of the proposed clinical presentations and basic clinical skills suggested their priorities. Of the 10 items investigated for building a detailed implementation strategy for the introduction of the CSE to the Korean Oriental Medicine Licensing Examination, a consensus was achieved on 9. However, the agreement rate on the timing of the introduction of the CSE was low. Concerns around 4 clinical topics were discussed in the subcommittees, and potential solutions were proposed. CONCLUSION: This study offers preliminary data and raises some concerns that can be used as a reference while discussing the introduction of the CSE to the Korean Oriental Medicine Licensing Examination.
Clinical Competence , Medicine, East Asian Traditional , Humans , Delphi Technique , Consensus , Republic of Korea
Background: Most commercial foot-and-mouth disease (FMD) vaccines have various disadvantages, such as low antibody titers, short-lived effects, compromised host defense, and questionable safety. Objectives: To address these shortcomings, we present a novel FMD vaccine containing Dectin-1 agonist, ß-D-glucan, as an immunomodulatory adjuvant. The proposed vaccine was developed to effectively coordinate innate and adaptive immunity for potent host defense against viral infection. Methods: We demonstrated ß-D-glucan mediated innate and adaptive immune responses in mice and pigs in vitro and in vivo. The expressions of pattern recognition receptors, cytokines, transcription factors, and co-stimulatory molecules were promoted via FMD vaccine containing ß-D-glucan. Results: ß-D-glucan elicited a robust cellular immune response and early, mid-, and long-term immunity. Moreover, it exhibited potent host defense by modulating host's innate and adaptive immunity. Conclusion: Our study provides a promising approach to overcoming the limitations of conventional FMD vaccines. Based on the proposed vaccine's safety and efficacy, it represents a breakthrough among next-generation FMD vaccines.
Foot-and-Mouth Disease , Vaccines , Animals , Mice , Swine , Adaptive Immunity , Glucans
The manufacturing process can modify the micromechanical structure, usefulness, and functionality of foams. Although one-step foaming is a simple process, controlling the morphology of the foams is difficult compared to the two-step processing method. In this study, we investigated the experimental differences in thermal and mechanical properties, particularly combustion behavior, between PET-PEN copolymers prepared by the two methods. With an increase in foaming temperature Tf, the PET-PEN copolymers became more fragile, and the breaking stress of the one-step PET-PEN foamed at the highest Tf was only 2.4% of that of the raw material. For the pristine PET-PEN, 24% of the mass was burned, leaving 76% as a molten sphere residue. The two-step MEG PET-PEN had only 1% of its mass remaining as a residue, whereas the one-step PET-PENs had between 41 and 55%. The actual mass burning rates were similar for all the samples except the raw material. The coefficient of thermal expansion of the one-step PET-PEN was about two orders of magnitude lower than that of the two-step SEG.
Rice bodies are commonly detected in adults with rheumatoid arthritis and rarely occur in children. An 11-year-old female adolescent who visited our hospital for evaluation of knee pain underwent a MRI scan, which revealed an intra-articular mass. Arthroscopic examination of the mass confirmed conglomerated rice bodies. We report a case of rice bodies that clinically presented as intra-articular masses.
The accessory tendon of the extensor hallucis longus is a common type of extensor hallucis longus variation. This is a case of a 38-year-old female patient who initially considered conservative treatment for a suspected partial rupture, but finally underwent surgery after being diagnosed with a complete rupture of the main tendon and accessory tendon medial to the main tendon on MRI scan.
The objective of this study was to investigate the effects of a traditional dry period (60 d) versus a no dry period (0 d) on the milk production, physiological response, and metabolic status of dairy cows exposed to heat stress during the transition period. Holstein dairy cows (n = 15) with similar expected calving dates were randomly assigned to two different dry period lengths: (1) no dry period (n = 7) and (2) a traditional dry period of 60 days (n = 8). All cows were studied from 8 weeks before expected calving to 10 weeks after calving and experienced heat stress during the transition period. The results showed that cows with no dry period decreased their milk yield in subsequent lactation, but compensated for the loss of milk yield accounted for by additional milk yield before calving. The energy balance at postpartum was improved in cows with no dry period compared to cows with a traditional dry period. There were no significant differences in the physiological response and blood metabolites at postpartum between the dry period lengths of dairy cows exposed to heat stress during the transition period. Taken together, our results showed that omitting the dry period improved the milk production and metabolic status of dairy cows exposed to heat stress during the transition period.
BACKGROUND AND OBJECTIVE: Whether benefits and risks of intravenous (IV) infliximab combotherapy with immunosuppressants versus infliximab monotherapy apply to subcutaneous (SC) infliximab is unknown. This post hoc analysis of a pivotal randomised CT-P13 SC 1.6 trial aimed to compare SC infliximab monotherapy with combotherapy in inflammatory bowel disease (IBD). METHODS: Biologic-naïve patients with active Crohn's disease or ulcerative colitis received CT-P13 IV 5 mg/kg at Week (W) 0 and 2 (dose-loading phase). At W6, patients were randomised (1:1) to receive CT-P13 SC 120 or 240 mg (patients < 80 or ≥ 80 kg) every 2 weeks until W54 (maintenance phase), or to continue CT-P13 IV every 8 weeks until switching to CT-P13 SC from W30. The primary endpoint-non-inferiority of trough serum concentrations-was assessed at W22. We report a post hoc analysis comparing pharmacokinetic, efficacy, safety and immunogenicity outcomes up to W54 for patients randomised to CT-P13 SC, stratified by concomitant immunosuppressant use. RESULTS: Sixty-six patients were randomised to CT-P13 SC (37 monotherapy, 29 combotherapy). At W54, there were no significant differences in the proportions of patients achieving target exposure (5 µg/mL; 96.6% monotherapy vs 95.8% combotherapy; p > 0.999) or meeting efficacy or biomarker outcomes including clinical remission (62.9% vs 74.1%; p = 0.418). Monotherapy and combotherapy groups had comparable immunogenicity (anti-drug antibodies [ADAs]: 65.5% vs 48.0% [p = 0.271], neutralising antibodies [in ADA-positive patients]: 10.5% vs 16.7% [p = 0.630], respectively). CONCLUSIONS: Pharmacokinetics, efficacy and immunogenicity were potentially comparable between SC infliximab monotherapy and combotherapy in biologic-naïve IBD patients. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02883452.
Biosimilar Pharmaceuticals , Inflammatory Bowel Diseases , Humans , Infliximab/adverse effects , Immunosuppressive Agents/adverse effects , Treatment Outcome , Biosimilar Pharmaceuticals/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Inflammatory Bowel Diseases/chemically induced , Gastrointestinal Agents/adverse effects
Kefir yeast, Kluyveromyces marxianus, has been evaluated for its potential probiotic properties-survivability, non-pathogenicity, and antioxidant and anti-microbial activities. However, host gut microbiota modulation of kefir yeasts remains unclear. Here, we compared kefir yeast strains K. marxianus A4 (Km A4) and K. marxianus A5 (Km A5) with Saccharomyces boulardii ATCC MYA-796 (Sb MYA-796) by investigating their adherence to colorectal adenocarcinoma (Caco-2) cells and gut microbiota modulation in BALB/c mice. The kefir yeast strains exhibited higher intestinal cell adhesion than Sb MYA-796 (p < 0.05). Bacteroidetes, Bacteroidales, and Bacteroides were more abundant in the 1 × 108 CFU/mL of Km A4 treatment group than in the control group (p < 0.05). Moreover, 1 × 108 CFU/mL of Km A5 increased Corynebacteriales and Corynebacterium compared to the 1 × 108 CFU/mL of Km A4 treatment group (p < 0.01). The results showed that Km A4 and Km A5 had good Caco-2 cell adhesion ability and modulated gut microbiota upon short-term administration in healthy mice. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01268-3.
PRCIS: Glaucoma surgeons are highly rated by the general public. Physicians with shorter wait times and who are younger are more likely to have higher ratings. Female glaucoma physicians are less likely to have higher ratings. PURPOSE: Find what characteristics of glaucoma physicians are associated with higher online ratings. METHODS: All American members of the American Glaucoma Society were queried on Healthgrades, Vitals, and Yelp. Ratings, medical school ranking, region of practice, sex, age, and wait times were recorded. RESULTS: One thousand one hundred six (78.2%) of American Glaucoma Society members had at least 1 review across the 3 platforms. The average score among glaucoma surgeons was 4.160 (0.898 SD). Female physicians were associated with lower online ratings [adjusted odds ratio (aOR): 0.536; 95% CI 0.354-0.808]. Physicians with <30 minutes of wait time had higher ratings: 15-30 minutes wait time (aOR: 2.273; 95% CI: 1.430-3.636) and <15 minutes wait time (aOR: 3.102; 95% CI: 1.888-5.146). Older physicians had lower ratings (aOR: 0.384; 95% CI: 0.255-0.572). CONCLUSIONS: Public online ratings of glaucoma specialists in the United States seem to favor those of younger age, men, and those with shorter wait times.
Surgeons , Waiting Lists , Male , Humans , Female , United States , Patient Satisfaction , Intraocular Pressure , Odds Ratio
The bacterial genus Enterococcus encompasses 38 species. Two of the most common species are E. faecalis and E. faecium. Recently, however, there has been an increase in clinical reports concerning less prevalent Enterococcus species, such as E. durans, E. hirae, and E. gallinarum. Rapid and accurate laboratory methods are needed to facilitate the identification of all these bacterial species. In the present study, we compared the relative accuracy of matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS), VITEK 2, and 16S rRNA gene sequencing using 39 enterococci isolates from dairy samples, and compared the resultant phylogenetic trees. We found that MALDI-TOF MS correctly identified all isolates at the species level except for one, whereas the VITEK 2 system, which is an automated identification system using biochemical characteristics of species, misidentified ten isolates. However, phylogenetic trees constructed from both methods showed all isolates in similar positions. Our results clearly showed that MALDI-TOF MS is a reliable and rapid tool for identifying Enterococcus species with greater discriminatory power than the biochemical assay method of VITEK 2.
