Shifts in Clinical Characteristics, Treatment, and Outcome for Rheumatic Mitral Stenosis: Insights From a 20-Year Multicentre Registry Study in Korea.

BACKGROUND: The rapid economic development of South Korea provides a unique model to study changes in the clinical characteristics, treatment approaches, and clinical outcomes of patients with rheumatic mitral stenosis (MS) relative to socioeconomic growth. METHODS: From the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, 2,337 patients diagnosed with moderate or severe rheumatic MS between January 2001 and December 2020 were analyzed. Patients were grouped into consecutive 5-year intervals based on their year of diagnosis. Clinical characteristics, echocardiographic data, and clinical outcomes were assessed. RESULTS: Over 20 years, the severity of mitral stenosis increased from 79.1% to 90.2%; similarly, the average age at diagnosis increased from 54.3 to 63.0 years (all P < 0.001). Comorbidities such as hypertension and atrial fibrillation increased (6.3% to 29.5% and 41.4% to 46.9%, respectively; all P for trend < 0.05). The rate of mitral intervention within five years after diagnosis increased from 31.2% to 47.4% (P for trend < 0.001). However, clinical outcomes of rheumatic mitral stenosis deteriorated over time in the composite outcomes (log-rank test, P < 0.001). Conversely, the incidence of stroke remained stable (60.6-73.7%; P < 0.001), which might be attributed to the increased use of anticoagulation therapy. CONCLUSION: This study observed an increase in patient age, comorbidities, and valve disease severity as the country transitioned from a developing to developed status. Despite a rise in mitral valve interventions, clinical outcomes deteriorated over 20 years, highlighting the need for modified treatment approaches to improve patient outcomes.

Validation of TRI-SCORE for Outcome Prediction After Isolated Tricuspid Valve Surgery in Asian Patients.

BACKGROUND: TRI-SCORE was recently developed in Europe as a risk model for predicting in-hospital death after isolated tricuspid valve surgery. We aimed to validate TRI-SCORE in an Asian population and investigate its value for predicting long-term outcomes. METHODS AND RESULTS: The TRI-SCORE was calculated for 202 patients (65±11 years, 61% women, 81% functional tricuspid regurgitation) who underwent isolated tricuspid valve surgery for severe tricuspid regurgitation at 2 Korean centers and was based on 8 parameters: age, New York Heart Association class, right-sided heart failure signs, furosemide daily dose, glomerular filtration rate, bilirubin, left ventricular ejection fraction, and moderate/severe right ventricular dysfunction. The primary outcome was all-cause death during follow-up; the secondary outcome was in-hospital death. During a median follow-up duration of 50 (interquartile range, 21-82) months after isolated tricuspid valve surgery, 23 (11.4%) patients experienced the primary outcome, and 7 (3.5%) patients experienced the secondary outcome. Observed all-cause death and in-hospital death increased by up to 50% in those with higher scores. Patients with the primary outcome had a higher TRI-SCORE (4.5±2.4 versus 2.9±2.1; P=0.001) than those without. The TRI-SCORE showed a significant association with the primary outcome (concordance index, 0.77, cutoff value, 4) and in-hospital death (area under the curve, 0.84; cutoff value, 3). Using the Kaplan-Meier analysis, patients with a high TRI-SCORE exhibited a poor outcome for all-cause death at follow-up (log-rank P<0.001) and in-hospital death (log-rank P=0.004). CONCLUSIONS: TRI-SCORE was validated in an Asian population and helped predict long-term outcomes after isolated tricuspid valve surgery.

Optimizing Percutaneous Mitral Valvuloplasty for Rheumatic Mitral Stenosis　- Clinical Significance of Changes in Mitral Valve Area.

BACKGROUND: Percutaneous mitral valvuloplasty (PMV) is a standard treatment for severe rheumatic mitral stenosis (RMS). However, the prognostic significance of the change in mitral valve area (∆MVA) during PMV is not fully understood.Methods and Results: This study analyzed data from the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, which included 3,140 patients with severe RMS. We focused on patients with severe RMS undergoing their first PMV. Changes in echocardiographic parameters, including MVA quantified before and after PMV, and composite outcomes, including mitral valve reintervention, heart failure admission, stroke, and all-cause death, were evaluated. An optimal result was defined as a postprocedural MVA ≥1.5 cm2without mitral regurgitation greater than Grade II. Of the 308 patients included in the study, those with optimal results and ∆MVA >0.5 cm² had a better prognosis (log-rank P<0.001). Patients who achieved optimal results but with ∆MVA ≤0.5 cm² had a greater risk of composite outcomes than those with optimal outcomes and ∆MVA >0.5 cm² (nested Cox regression analysis, hazard ratio 2.27; 95% confidence interval 1.09-4.73; P=0.028). CONCLUSIONS: Achieving an increase in ∆MVA of >0.5 cm2was found to be correlated with improved outcomes. This suggests that, in addition to achieving traditional optimal results, targeting an increase in ∆MVA of >0.5 cm2could be a beneficial objective in PMV treatment for RMS.

Sodium iodide symporter immunolabelling as a predictor of clinical iodide uptake in canine thyroid carcinoma: A preliminary study.

Thyroid follicular tumours may take up iodide via the sodium-iodide symporter. Knowledge of iodide uptake could then allow treatment with I-131 in dogs with high-risk tumours. The objective of this study was to determine the relationship between clinically detectable iodide uptake (as determined by scintigraphy and/or thyroxine concentrations) and sodium iodide symporter immunohistochemical labelling on histologically fixed thyroid tumours. Nineteen dogs were identified who were diagnosed with thyroid carcinoma and underwent surgery from November 2017 to July 2021. All had recorded thyroid hormone concentrations and were hyperthyroid and/or underwent preoperative nuclear imaging using planar scintigraphy (technetium-99m or I-123), or I-124 PET-CT. All dogs subsequently underwent surgery to remove the thyroid mass. Twenty-two tumours were submitted for histopathologic analysis immediately following surgery, which confirmed a diagnosis of thyroid carcinoma for each tumour. Images and/or thyroid hormone concentrations were reviewed for the included cases, and tumours were sorted into an avid/functional group (group 1) and a non-avid/functional group (group 2). The tumour tissues were re-examined histologically using sodium iodide symporter (NIS) immunohistochemistry (IHC). Group 1 contained 15 avid/functional tumours. Twelve of these tumours had membranous NIS IHC labelling. Group 2 contained 7 non-avid tumours. One of these tumours had membranous NIS IHC labelling. This resulted in an overall sensitivity and specificity for identification of avid/functional tumours with membranous NIS of 80.0% and 85.7%, respectively. NIS IHC may predict ion trapping in canine follicular thyroid tumours. Further studies using iodide-based imaging are warranted to better determine the clinical utility of this diagnostic modality.

Extracellular synthesis of silver nanoparticle using yeast extracts: antibacterial and seed priming applicationss.

The evolution and rapid spread of multidrug-resistant (MDR) bacterial pathogens have become a major concern for human health and demand the development of alternative antimicrobial agents to combat this emergent threat. Conventional intracellular methods for producing metal nanoparticles (NPs) using whole-cell microorganisms have limitations, including binding of NPs to cellular components, potential product loss, and environmental contamination. In contrast, this study introduces a green, extracellular, and sustainable methodology for the bio-materialization of silver NPs (AgNPs) using renewable resource cell-free yeast extract. These extracts serve as a sustainable, biogenic route for both reducing the metal precursor and stabilizing the surface of AgNPs. This method offers several advantages such as cost-effectiveness, environment-friendliness, ease of synthesis, and scalability. HR-TEM imaging of the biosynthesized AgNPs revealed an isotropic growth route, resulting in an average size of about ~ 18 nm and shapes ranging from spherical to oval. Further characterization by FTIR and XPS results revealed various functional groups, including carboxyl, hydroxyl, and amide contribute to enhanced colloidal stability. AgNPs exhibited potent antibacterial activity against tested MDR strains, showing particularly high efficacy against Gram-negative bacteria. These findings suggest their potential role in developing alternative treatments to address the growing threat of antimicrobial resistance. Additionally, seed priming experiments demonstrated that pre-sowing treatment with AgNPs improves both the germination rate and survival of Sorghum jowar and Zea mays seedlings. KEY POINTS: •Yeast extract enables efficient, cost-effective, and eco-friendly AgNP synthesis. •Biosynthesized AgNPs showed strong antibacterial activity against MDR bacteria. •AgNPs boost seed germination and protect against seed-borne diseases.

Outcomes of Severe Mitral Stenosis With the Revised Severity Criteria: Mitral Valve Replacement vs Percutaneous Mitral Valvuloplasty.

BACKGROUND: This study aimed to compare the outcomes, according to percutaneous mitral valvuloplasty (PMV) vs mitral valve replacement (MVR), of severe mitral stenosis (MS) with the updated criteria (MVA ≤ 1.5 cm2). METHODS: From the Multicenter Mitral Stenosis With Rheumatic Etiology (MASTER) registry of 3140 patients, we included patients with severe MS who underwent PMV or MVR between January 2000 and December 2021 except for previous valvular surgery/intervention, at least moderate other valvular dysfunction, and thrombus at the left atrium/appendage. Moderately severe MS (MS-MS) and very severe MS (VS-MS) were defined as 1.0 cm2 < MVA ≤ 1.5 cm2 and MVA ≤ 1.0 cm2, respectively. Primary outcomes were a composite of cardiovascular (CV) death and heart failure (HF) hospitalization. Secondary outcomes were a composite of primary outcomes and redo intervention. RESULTS: Among 442 patients (mean 56.5 ±11.9 years, women 77.1%), the MVR group (n = 260) was older, had more comorbidities, higher echoscore, larger left chambers, and higher right ventricular systolic pressure than the PMV group (n = 182). During a mean follow-up of 6.9 ± 5.2 years with inverse probability-weighted matching, primary outcomes did not differ, but the MVR group experienced fewer secondary outcomes (P = 0.010). In subgroup analysis of patients with MS-MS and VS-MS, primary outcomes did not differ. However, the MVR group in patients with VS-MS showed better secondary outcomes (P = 0.012). CONCLUSIONS: PMV or MVR did not influence CV mortality or HF hospitalization in both MS-MS and VS-MS. However, because of increased early redo intervention in the PMV group in VS-MS, MVR would be the preferable option without clear evidence of suitable morphology for PMV.

Alginic acid-functionalized silver nanoparticles: A rapid monitoring tool for detecting the technology-critical element tellurium.

The increasing global demand for tellurium, driven by its critical role in alloys, photovoltaic devices, and electronics, has raised concerns about its environmental pollution and neurotoxicity. In response, the potential of alginic acid (AA), a renewable, low-cost, and sustainable biopolymer, was explored for the biosynthesis of ultra-small silver nanoparticles (AgNPs) and their application in the detection of tellurium (Te(IV)). The effect of key synthesis parameters on desired physicochemical properties and yield of AgNPs was established to ensure high specificity and sensitivity towards Te(IV). The purified AgNPs with AA surface ligands were utilized to demonstrate a ratiometric absorbance sensor that exhibits excellent linearity and nanomolar-level affinity. This approach achieved a high correlation coefficient of ∼ 0.982, with a low detection limit of about 22 nM. Further investigations into the effect of pH, ionic strength, and organic molecules were conducted to elucidate detection performance and molecular understanding. The detection mechanism relies on the coordination between Te(IV) ions and the carboxylate groups of AA, which initiates aggregation-induced plasmon coupling in adjacent AgNPs. The capability of this analytical method to monitor Te(IV) in real-world water samples features its rapidity, user-friendliness, and suitability for point-of-care monitoring, making it a promising alternative to more complex techniques.

Production of transgenic first filial puppies expressing mutated human amyloid precursor protein gene.

Propagation of transgenic animals by germline transmission using assisted reproductive technologies such as in vitro fertilization (IVF) is the most efficient way to produce transgenic colonies for biomedical research. The objective of this study was to generate transgenic puppies from a founder dog expressing the mutated human amyloid precursor protein (mhAPP) gene. Experiment I assessed the characteristics of the semen prepared by freshly diluted, swim-up, and Percoll gradient methods using a computer-assisted semen analyzer (CASA). Motile and progressively motile sperm counts were higher in the Percoll gradient samples (p < 0.05) than in the swim-up and freshly diluted samples. In Experiment II, a total of 59, 70, and 65 presumptive zygotes produced by fresh, Percoll gradient, and swim-up methods, respectively, were transferred to surrogates (5 for each group); the Percoll gradient (27.27%) and swim-up samples (14.29%) showed the highest blastocyst formation rates, while fresh diluted semen did not produce any blastocyst. Experiment III examined the full-term developmental ability of embryos. Among the 5 surrogates in the Percoll gradient group, one (20.0%) became pregnant; it had 4 (6.15%) sacs and delivered 4 (6.15%; 2 males and 2 females) live puppies. Among the 4 puppies, 2 (50.0%) were found to transmit the transgene on their nail and toe under GFP fluorescence. Furthermore, the integration and expression of the mhAPP transgene were examined in the umbilical cords of all the IVF-derived puppies, and the presence of the transgene was only observed in the GFP-positive puppies. Thus, semen prepared by the Percoll method could generate transgenic puppies by male germline transmission using the IVF technique. Our result will help propagate transgenic dogs efficiently, which will foster human biomedical research.

Assessing of exercise intensity for a rhythmik exercise program based on cardiopulmonary functions.

This study investigated the determination of exercise intensity for a rhythmik exercise program based on cardiopulmonary functions. Nine female participants in their 20s to 40s performed a rhythmik exercise program for 60 min per session, three sessions weekly, for 8 weeks. All participants underwent a grade exercise test to measure their minute ventilation (VE), oxygen uptake (VO2), maximal volume of minute oxygen consumption (VO2max), heart rate (HR), and oxygen pulse (O2 pulse) at the time of anaerobic threshold (AT) and maximal exercise time (ETmax). To determine the exercise intensity of the rhythmik exercise program, the Polar Heart Monitor was used for quantification, and the Borg Scale was used to measure the rating of perceived exertion (RPE). We did not observe any significant effects on the reaching time of AT, VE, VO2, VO2max, HR, and O2 pulse at either AT or ETmax. However, maximal value of VE (VEmax) was significantly enhanced at ETmax. The exercise intensity of the rhythmik exercise program was found to be low at 62.85% of HRmax with an RPE of 12.22. Our results suggest that the rhythmik exercise program did not directly improve cardiopulmonary functions; however, considering the unstructured nature of the rhythmik exercise program, anticipated positive effects on cardiopulmonary fitness are achievable through changes in the program contents and exercise time according to the goals of the participants.

Thermostable Basic Fibroblast Growth Factor Enhances the Production and Activity of Human Wharton's Jelly Mesenchymal Stem Cell-Derived Extracellular Vesicles.

Wharton's jelly-derived mesenchymal stem cell (WJ-MSC)-derived exosomes contain a diverse cargo and exhibit remarkable biological activity, rendering them suitable for regenerative and immune-modulating functions. However, the quantity of secretion is insufficient. A large body of prior work has investigated the use of various growth factors to enhance MSC-derived exosome production. In this study, we evaluated the utilization of thermostable basic fibroblast growth factor (TS-bFGF) with MSC culture and exosome production. MSCs cultured with TS-bFGF displayed superior proliferation, as evidenced by cell cycle analysis, compared with wild-type bFGF (WT-bFGF). Stemness was assessed through mRNA expression level and colony-forming unit (CFU) assays. Furthermore, nanoparticle tracking analysis (NTA) measurements revealed that MSCs cultured with TS-bFGF produced a greater quantity of exosomes, particularly under three-dimensional culture conditions. These produced exosomes demonstrated substantial anti-inflammatory and wound-healing effects, as confirmed by nitric oxide (NO) assays and scratch assays. Taken together, we demonstrate that utilization of TS-bFGF for WJ-MSC-derived exosome production not only increases exosome yield but also enhances the potential for various applications in inflammation regulation and wound healing.

One-Pot Synthesis of 3,4-Dihydrocoumarins via C-H Oxidation/Conjugate Addition/Cyclization Cascade Reaction.

The 3,4-dihydrocoumarin derivatives were obtained from 2-alkyl phenols and oxazolones via C-H oxidation and cyclization cascade in the presence of silver oxide (Ag2O) and p-toluenesulfonic acid as a Brønsted acid catalyst. This approach provides a one-pot strategy to synthesize the multisubstituted 3,4-dihydrocoumarins with moderate to high yields (64-81%) and excellent diastereoselectivity (>20:1).

Cellulose graphitic carbon directed iron oxide interfaced polypyrrole electrode materials for high performance supercapacitors.

The rising demand for green and clean energy urges the enlargement of economical and proficient electrode materials for supercapacitors. Herein, we designed a novel electrode material by porous cellulose graphitic carbon (CC) derived from bio-waste cornhusk via the pyrolysis route, and α-Fe2O3 decorated nanostructure with CC (CCIO) was achieved in situ pyrolysis of corn-husk and Fe(NO3)3·9H2O metal salt followed by a coating of polypyrrole (CCIOP). The CC, CCIO, and CCIOP nanocomposite electrodes were characterized by XRD, Raman, FTIR, FE-SEM/EDX, FE-TEM, XPS, and BET analysis. The CCIOP nanocomposite electrode exhibits an enhanced specific capacitance (Csp) of 290.9 F/g, which is substantial to its pristine CC (128.3 F/g), PPy (140.3 F/g), and CCIO (190.7 F/g). The Csp of CCIOP in a three-electrode system, using 1 M Na2SO4 electrolyte exhibits excellent capacity retention of 79.1 % even at a high current density of 10 A/g. The as-fabricated asymmetric supercapacitor (ASC) delivered a remarkable capacity retention of 88.7 % with a coulombic efficiency of 98.8 % even after 3000 cycles. The study shows successful utilization of cellulose from bio-waste cornhusk into a substantial template applicable in future alternative energy storage devices.

Sequence tolerance of immunoglobulin variable domain framework regions to noncanonical intradomain disulfide linkages.

Most immunoglobulin (Ig) domains bear only a single highly conserved canonical intradomain, inter-ß-sheet disulfide linkage formed between Cys23-Cys104, and incorporation of rare noncanonical disulfide linkages at other locations can enhance Ig domain stability. Here, we exhaustively surveyed the sequence tolerance of Ig variable (V) domain framework regions (FRs) to noncanonical disulfide linkages. Starting from a destabilized VH domain lacking a Cys23-Cys104 disulfide linkage, we generated and screened phage-displayed libraries of engineered VHs, bearing all possible pairwise combinations of Cys residues in neighboring ß-strands of the Ig fold FRs. This approach identified seven novel Cys pairs in VH FRs (Cys4-Cys25, Cys4-Cys118, Cys5-Cys120, Cys6-Cys119, Cys22-Cys88, Cys24-Cys86, and Cys45-Cys100; the international ImMunoGeneTics information system numbering), whose presence rescued domain folding and stability. Introduction of a subset of these noncanonical disulfide linkages (three intra-ß-sheet: Cys4-Cys25, Cys22-Cys88, and Cys24-Cys86, and one inter-ß-sheet: Cys6-Cys119) into a diverse panel of VH, VL, and VHH domains enhanced their thermostability and protease resistance without significantly impacting expression, solubility, or binding to cognate antigens. None of the noncanonical disulfide linkages identified were present in the natural human VH repertoire. These data reveal an unexpected permissiveness of Ig V domains to noncanonical disulfide linkages at diverse locations in FRs, absent in the human repertoire, whose presence is compatible with antigen recognition and improves domain stability. Our work represents the most complete assessment to date of the role of engineered noncanonical disulfide bonding within FRs in Ig V domain structure and function.

Development of Novel Peptide-Modified Silver Nanoparticle-Based Rapid Biosensors for Detecting Aminoglycoside Antibiotics.

The detection and monitoring of aminoglycoside antibiotics (AGAs) have become of utmost importance due to their widespread use in human and animal therapy, as well as the associated risks of exposure, toxicity, and the emergence of antimicrobial resistance. In this study, we successfully synthesized casein hydrolysate peptides-functionalized silver nanoparticles (CHPs@AgNPs) and employed them as a novel colorimetric analytical platform to demonstrate remarkable specificity and sensitivity toward AGAs. The colorimetric and spectral response of the CHPs@AgNPs was observed at 405 and 520 nm, showing a linear correlation with the concentration of streptomycin, a representative AGA. The color changes from yellow to orange provided a visual indication of the analyte concentration, enabling quantitative determination for real-world samples. The AgNP assay exhibited excellent sensitivity with dynamic ranges of approximately 200-650 and 100-700 nM for streptomycin-spiked tap water and dairy whey with limits of detection found to be ∼98 and 56 nM, respectively. The mechanism behind the selective aggregation of CHPs@AgNPs in the presence of AGAs involves the amine groups of the target analytes acting as molecular bridges for electrostatic coupling with hydroxyl or carboxyl functionalities of adjacent NPs, driving the formation of stable NP aggregates. The developed assay offers several advantages, making it suitable for various practical applications. It is characterized by its simplicity, rapidity, specificity, sensitivity, and cost-effectiveness. These unique features make the method a promising tool for monitoring water quality, ensuring food safety, and dealing with emergent issues of antibiotic resistance.

Deep-learning model for predicting physical fitness in possible sarcopenia: analysis of the Korean physical fitness award from 2010 to 2023.

Introduction: Physical fitness is regarded as a significant indicator of sarcopenia. This study aimed to develop and evaluate a deep-learning model for predicting the decline in physical fitness due to sarcopenia in individuals with potential sarcopenia. Methods: This study used the 2010-2023 Korean National Physical Fitness Award data. The data comprised exercise- and health-related measurements in Koreans aged >65 years and included body composition and physical fitness variables. Appendicular muscle mass (ASM) was calculated as ASM/height2 to define normal and possible sarcopenia. The deep-learning model was created with EarlyStopping and ModelCheckpoint to prevent overfitting and was evaluated using stratified k-fold cross-validation (k = 5). The model was trained and tested using training data and validation data from each fold. The model's performance was assessed using a confusion matrix, receiver operating characteristic curve, and area under the curve. The average performance metrics obtained from each cross-validation were determined. For the analysis of feature importance, SHAP, permutation feature importance, and LIME were employed as model-agnostic explanation methods. Results: The deep-learning model proved effective in distinguishing from sarcopenia, with an accuracy of 87.55%, precision of 85.57%, recall of 90.34%, and F1 score of 87.89%. Waist circumference (WC, cm), absolute grip strength (kg), and body fat (BF, %) had an influence on the model output. SHAP, LIME, and permutation feature importance analyses revealed that WC and absolute grip strength were the most important variables. WC, figure-of-8 walk, BF, timed up-and-go, and sit-and-reach emerged as key factors for predicting possible sarcopenia. Conclusion: The deep-learning model showed high accuracy and recall with respect to possible sarcopenia prediction. Considering the need for the development of a more detailed and accurate sarcopenia prediction model, the study findings hold promise for enhancing sarcopenia prediction using deep learning.

A rapid, high-yield and bioinspired synthesis of colloidal silver nanoparticles using Glycyrrhiza glabra root extract and assessment of antibacterial and phytostimulatory activity.

Silver nanoparticles (AgNPs) have emerged as highly effective antimicrobial agents against multidrug-resistant (MDR) pathogens. This study aims to employ green chemistry principles for AgNP synthesis involving phytochemical-rich extract from Glycyrrhiza glabra roots. The approach highlights using renewable feedstocks, safer chemicals, minimum byproducts, and process scale-up. The synthesis of AgNPs was assessed using a surface plasmon resonance band at 420 nm, and structural properties were characterized using TEM, x-ray diffraction, Fourier-transform infrared spectroscopy, and X-ray photoelectron spectroscopy. This method enables the production of high-yield dispersions of AgNPs with desired physicochemical characteristics, including dark yellow solution, size (~20 nm), spherical to an oval shape, crystal structure, and stable colloidal properties. The antimicrobial activity of AgNPs was investigated against the MDR bacteria strains of gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli). This work reveals that the antimicrobial activity of AgNPs can be influenced by bacterial cell wall components. The results demonstrate the strong interaction between AgNPs and E. coli, exhibiting a dose-dependent antibacterial response. The green approach facilitated the safer, facile, and rapid synthesis of colloidal dispersions of AgNPs, providing a sustainable and promising alternative to conventional chemical and physical methods. Furthermore, the effect of AgNPs on various growth parameters, including seed germination, root and shoot elongation, and dry weight biomass, was assessed for mung bean seedlings. The results revealed phytostimulatory effects, suggesting the promising prospects of AgNPs in the nano-priming of agronomic seeds. RESEARCH HIGHLIGHTS: Glycyrrhiza glabra root extract enabled rapid, high-yield, and eco-friendly synthesis of silver nanoparticles (AgNPs). Spectrophotometric analysis examined the optical properties, scalability, and stability of AgNPs. Transmission electron microscopy provided insights into the size, shape, and dispersity of AgNPs. Scanning electron microscopy revealed significant damage to gram-negative bacterial cell morphology and membrane integrity. AgNPs were found to enhance seed germination, seedling growth, and biomass yield of Vigna radiata.

Rituximab plus multiagent chemotherapy for newly diagnosed CD20-positive acute lymphoblastic leukemia: a prospective phase II study.

BACKGROUND/AIMS: We performed a prospective study to determine the efficacy and safety of rituximab including chemotherapy in CD20-positive acute lymphoblastic leukemia (ALL). METHODS: Patients with newly diagnosed ALL, aged ≥ 15 years, were eligible for the study if their leukemic blast cells in bone marrow expressed CD20 ≥ 20% at the time of diagnosis. Patients received multiagent chemotherapy with rituximab. After achieving complete remission (CR), patients received five cycles of consolidation with concomitant rituximab. Rituximab was administered monthly from day 90 of transplantation for patients who received allogeneic hematopoietic cell transplantation. RESULTS: In patients with Philadelphia (Ph)-negative ALL, 39 of 41 achieved CR (95.1%), the 2- and 4-year relapse-free survival (RFS) rates were 50.4% and 35.7%, and the 2- and 4-year overall survival (OS) rates were 51.5% and 43.2%, respectively. In the group with Ph-positive ALL, all 32 patients achieved CR, the 2- and 4-year RFS rates were 60.7% and 52.1%, and the 2- and 4-year OS rates were 73.3% and 52.3%, respectively. In the Ph-negative ALL group, patients with higher CD20 positivity experienced more favorable RFS (p < 0.001) and OS (p = 0.06) than those with lower CD20 positivity. Patients who received ≥ 2 cycles of rituximab after transplantation had significantly improved RFS (hazard ratio [HR], 0.31; p = 0.049) and OS (HR, 0.29; p = 0.021) compared with those who received < 2 cycles. CONCLUSION: The addition of rituximab to conventional chemotherapy for CD20-positive ALL is effective and tolerable (Clinicaltrials. gov NCT01429610).

Thermostable Human Basic Fibroblast Growth Factor (TS-bFGF) Engineered with a Disulfide Bond Demonstrates Superior Culture Outcomes in Human Pluripotent Stem Cell.

Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) can differentiate into various tissues and are an essential source of various disease models and therapeutics. Various growth factors are required in order to culture pluripotent stem cells, among which basic fibroblast growth factor (bFGF) is essential for maintaining stem cell ability. However, bFGF has a short half-life (8 h) under normal mammalian cell culture conditions, and its activity decreases after 72 h, posing a serious problem in the production of high-quality stem cells. Here, we evaluated the various functions of pluripotent stem cells (PSCs) by utilizing an engineered thermostable bFGF (TS-bFGF) that is thermally stable and maintains activity longer under mammalian culture conditions. PSCs cultured with TS-bFGF showed better proliferation, stemness, morphology, and differentiation than cells cultured with wild-type bFGF. In light of the importance of stem cells in a wide range of applications in the medical and biotechnology fields, we anticipate that TS-bFGF, as a thermostable and long-acting bFGF, can play a key role in securing high-quality stem cells through various sets of stem cell culture processes.

Feasibility of Prompt Lumbar Drainage in Patients with Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Numerous studies have shown that continuous lumbar drainage (LD) reduces spontaneous subarachnoid hemorrhage (SAH)-related complications, decreasing the incidence of cerebral vasospasm, delayed cerebral ischemia , and hydrocephalus in patients treated with coiling or clipping, but performing LD before securing the aneurysm is still controversial. Our hospital has been implementing prompt LD for several years, and we present the results in this paper. METHODS: Between January 2014 and December 2020, a total of 438 patients with SAH were included in this retrospective study. The indication for prompt LD was aneurysmal SAH of modified Fisher grade III or higher without dense intraventricular hemorrhage with obstructive hydrocephalus requiring extraventricular drainage or large intracranial hemorrhage requiring immediate decompression. Prompt LD was performed for 229 patients with SAH, and the control group included 209 patients. We compared in-hospital mortality and vasospasm or hydrocephalus occurrence and procedure-related complications between the two groups. RESULTS: The in-hospital mortality rate was 7.4% for patients with prompt LD and 14.4% for patients without LD, and the difference was significant (P = 0.019). Vasospasm occurred in 10% of patients with prompt LD and 16.7% of controls (P = 0.039). Hydrocephalus requiring extraventricular drainage occurred in 10.9% of the LD group and 28.7% of the control group (P < 0.001). Rebleeding occurrence was 3.1% in the prompt LD group and 5.7% in the non-LD group (P = 0.168). Cerebrospinal fluid infection occurred in 0.4% of the prompt LD group and 1.4% of controls(P = 0.272). CONCLUSIONS: Prompt LD is a feasible option for treating patients with selective aneurysmal SAH.

Reclassification of moderate aortic stenosis based on data-driven phenotyping of hemodynamic progression.

The management and follow-up of moderate aortic stenosis (AS) lacks consensus as the progression patterns are not well understood. This study aimed to identify the hemodynamic progression of AS, and associated risk factors and outcomes. We included patients with moderate AS with at least three transthoracic echocardiography (TTE) studies performed between 2010 and 2021. Latent class trajectory modeling was used to classify AS groups with distinctive hemodynamic trajectories, which were determined by serial systolic mean pressure gradient (MPG) measurements. Outcomes were defined as all-cause mortality and aortic valve replacement (AVR). A total of 686 patients with 3093 TTE studies were included in the analysis. Latent class model identified two distinct AS trajectory groups based on their MPG: a slow progression group (44.6%) and a rapid progression group (55.4%). Initial MPG was significantly higher in the rapid progression group (28.2 ± 5.6 mmHg vs. 22.9 ± 2.8 mmHg, P < 0.001). The prevalence of atrial fibrillation was higher in the slow progression group; there was no significant between-group difference in the prevalence of other comorbidities. The rapid progression group had a significantly higher AVR rate (HR 3.4 [2.4-4.8], P < 0.001); there was no between-group difference in mortality (HR 0.7 [0.5-1.0]; P = 0.079). Leveraging longitudinal echocardiographic data, we identified two distinct groups of patients with moderate AS: slow and rapid progression. A higher initial MPG (≥ 24 mmHg) was associated with more rapid progression of AS and higher rates of AVR, thus indicating the predictive value of MPG in management of the disease.