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.

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.

Trash to Treasure: An Up-to-Date Understanding of the Valorization of Seafood By-Products, Targeting the Major Bioactive Compounds.

Fishery production is exponentially growing, and its by-products negatively impact industries' economic and environmental status. The large amount of bioactive micro- and macromolecules in fishery by-products, including lipids, proteins, peptides, amino acids, vitamins, carotenoids, enzymes, collagen, gelatin, chitin, chitosan, and fucoidan, need to be utilized through effective strategies and proper management. Due to the bioactive and healthy compounds in fishery discards, these components can be used as functional food ingredients. Fishery discards have inorganic or organic value to add to or implement in various sectors (such as the agriculture, medical, and pharmaceutical industries). However, the best use of these postharvest raw materials for human welfare remains unelucidated in the scientific community. This review article describes the most useful techniques and methods, such as obtaining proteins and peptides, fatty acids, enzymes, minerals, and carotenoids, as well as collagen, gelatin, and polysaccharides such as chitin-chitosan and fucoidan, to ensure the best use of fishery discards. Marine-derived bioactive compounds have biological activities, such as antioxidant, anticancer, antidiabetic, anti-inflammatory, and antimicrobial activities. These high-value compounds are used in various industrial sectors, such as the food and cosmetic industries, owing to their unique functional and characteristic structures. This study aimed to determine the gap between misused fishery discards and their effects on the environment and create awareness for the complete valorization of fishery discards, targeting a sustainable world.

Exploring Bioactive Compounds in Brown Seaweeds Using Subcritical Water: A Comprehensive Analysis.

In this study, we characterized the bioactive properties of three important brown seaweed species, Sargassum thunbergii, Undaria pinnatifida, and Saccharina japonica, by subcritical water extraction (SWE), as these species are well known for their beneficial health effects. Their physiochemical properties, including potential antioxidant, antihypertensive, and α-glucosidase inhibitory activity, and the antibacterial activity of the hydroysates were also analyzed. The highest total phlorotannin, total sugar content, and reducing sugar content in the S. thunbergii hydrolysates were 38.82 ± 0.17 mg PGE/g, 116.66 ± 0.19 mg glucose/g dry sample, and 53.27 ± 1.57 mg glucose/g dry sample, respectively. The highest ABTS+ and DPPH antioxidant activities were obtained in the S. japonica hydrolysates (124.77 ± 2.47 and 46.35 ± 0.01 mg Trolox equivalent/g, respectively) and the highest FRAP activity was obtained in the S. thunbergii hydrolysates (34.47 ± 0.49 mg Trolox equivalent/g seaweed). In addition, the seaweed extracts showed antihypertensive (≤59.77 ± 0.14%) and α-glucosidase inhibitory activity (≤68.05 ± 1.15%), as well as activity against foodborne pathogens. The present findings provide evidence of the biological activity of brown seaweed extracts for potential application in the food, pharmaceutical, and cosmetic sectors.

Characterization of SN38-resistant T47D breast cancer cell sublines overexpressing BCRP, MRP1, MRP2, MRP3, and MRP4.

BACKGROUND: Although several novel resistant breast cancer cell lines have been established, only a few resistant breast cancer cell lines overexpress breast cancer resistance proteins (BCRP). The aim of this study was to establish new resistant breast cancer cell lines overexpressing BCRP using SN38 (7-ethyl-10-hydroxycamptothecin), an active metabolite of irinotecan and was to discover genes and mechanisms associated with multidrug resistance. METHODS: SN38-resistant T47D breast cancer cell sublines were selected from the wild-type T47D cells by gradually increasing SN38 concentration. The sensitivity of the cells to anti-cancer drugs was assessed by 3-(4,5-methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Expression profiles of the resistance-related transporters were examined using RT-qPCR, and western blot analysis. Intracellular fluorescent dye accumulation in the resistant cells was determined using flow cytometry. RESULTS: The SN38-resistant T47D breast cancer cell sublines T47D/SN120 and T47D/SN150 were established after long-term exposure (more than 16 months) of wild-type T47D cells to 120 nM and 150 nM SN38, respectively. T47D/SN120 and T47D/SN150 cells were more resistant to SN38 (14.5 and 59.1 times, respectively), irinotecan (1.5 and 3.7 times, respectively), and topotecan (4.9 and 12 times, respectively), than the wild-type parental cells. Both T47D/SN120 and T47D/SN150 sublines were cross-resistant to various anti-cancer drugs. These resistant sublines overexpressed mRNAs of MRP1, MRP2, MRP3, MRP4, and BCRP. The DNA methylase inhibitor 5-aza-2'-deoxycytidine and the histone deacetylase inhibitor trichostatin A increased the expression levels of BCRP, MRP1, MRP2, MRP3, and MRP4 transcripts in T47D/WT cells. Fluorescent dye accumulation was found to be lower in T47D/SN120 and T47D/SN150 cells, compared to that in T47D/WT cells. However, treatment with known chemosensitizers increased the intracellular fluorescent dye accumulation and sensitivity of anti-tumor agents. CONCLUSION: T47D/SN120 and T47D/SN150 cells overexpressed MRP1, MRP2, MRP3, MRP4, and BCRP, which might be due to the suppression of epigenetic gene silencing via DNA hypermethylation and histone deacetylation. Although these resistant cells present a higher resistance to various anti-cancer drugs than their parental wild-type cells, multidrug resistance was overcome by treatment with chemosensitizers. These SN38 resistant T47D breast cancer cell sublines expressing resistance proteins can be useful for the development of new chemosensitizers.

Subcritical Water Hydrolysis of Comb Pen Shell (Atrina pectinata) Edible Parts to Produce High-Value Amino Acid Products.

Artina pectinata (Comb pen shell, CPS) is a high-protein source that contains a variety of essential amino acids. Subcritical water hydrolysis (SWH) was used to recover amino acids from the posterior adductor muscle (PAM), anterior adductor muscle (ADM), and mantle. The temperatures ranged from 120 °C to 200 °C, and the pressure and time of hydrolysis were 3 MPa and 30 min, respectively. Further characterization of the hydrolysates was performed to ascertain amino acid profiles and biofunctional properties. The hydrolysates contained more free amino acids than the untreated samples. Antioxidant activity of treated samples increased as SW temperatures increased. At 200 °C, those inhibiting ACE had a maximum antihypertensive activity of 200 °C in 1% PAM, ADM, and mantle with 85.85 ± 0.67, 84.55 ± 0.18, and 82.15 ± 0.85%, respectively, compared to 97.57 ± 0.67% in 1% standard captopril. Perhaps the most significant finding was the predominance of taurine in the three parts following SW treatment at 120 °C. The hydrolysates may be of considerable interest for use in food or energy drinks. SWH demonstrates efficacy in recovering amino acids, particularly taurine, from edible parts of A. pectinata.

Amino Acid Profiles and Biopotentiality of Hydrolysates Obtained from Comb Penshell (Atrina pectinata) Viscera Using Subcritical Water Hydrolysis.

The recovery of amino acids and other important bioactive compounds from the comb penshell (Atrina pectinata) using subcritical water hydrolysis was performed. A wide range of extraction temperatures from 140 to 290 °C was used to evaluate the release of proteins and amino acids. The amount of crude protein was the highest (36.14 ± 1.39 mg bovine serum albumin/g) at 200 °C, whereas a further increase in temperature showed the degradation of the crude protein content. The highest amount of amino acids (74.80 mg/g) was at 230 °C, indicating that the temperature range of 170-230 °C is suitable for the extraction of protein-rich compounds using subcritical water hydrolysis. Molecular weights of the peptides obtained from comb penshell viscera decreased with the increasing temperature. SDS-PAGE revealed that the molecular weight of peptides present in the hydrolysates above the 200 °C extraction temperature was ≤ 1000 Da. Radical scavenging activities were analyzed to evaluate the antioxidant activities of the hydrolysates. A. pectinata hydrolysates also showed a particularly good antihypertensive activity, proving that this raw material can be an effective source of amino acids and marine bioactive peptides.

Cardiac Imaging of Acute Myocarditis Following COVID-19 mRNA Vaccination.

Increasing rates of coronavirus disease 2019 (COVID-19) vaccination coverage will result in more vaccine-related side effects, including acute myocarditis. In Korea, we present a 24-year-old male with acute myocarditis following COVID-19 vaccination (BNT162b2). His chest pain developed the day after vaccination and cardiac biomarkers were elevated. Echocardiography showed minimal pericardial effusion but normal myocardial contractility. Electrocardiography revealed diffuse ST elevation in lead II, and V2-5. Cardiac magnetic resonance images showed the high signal intensity of T2- short tau inversion recovery image, the high value of T2 mapping sequence, and late gadolinium enhancement in basal inferior and inferolateral wall. It was presumed that COVID-19 mRNA vaccination was probably responsible for acute myocarditis. Clinical course of the patient was favorable and he was discharged without any adverse event.

Physician Confidence in Artificial Intelligence: An Online Mobile Survey.

BACKGROUND: It is expected that artificial intelligence (AI) will be used extensively in the medical field in the future. OBJECTIVE: The purpose of this study is to investigate the awareness of AI among Korean doctors and to assess physicians' attitudes toward the medical application of AI. METHODS: We conducted an online survey composed of 11 closed-ended questions using Google Forms. The survey consisted of questions regarding the recognition of and attitudes toward AI, the development direction of AI in medicine, and the possible risks of using AI in the medical field. RESULTS: A total of 669 participants completed the survey. Only 40 (5.9%) answered that they had good familiarity with AI. However, most participants considered AI useful in the medical field (558/669, 83.4% agreement). The advantage of using AI was seen as the ability to analyze vast amounts of high-quality, clinically relevant data in real time. Respondents agreed that the area of medicine in which AI would be most useful is disease diagnosis (558/669, 83.4% agreement). One possible problem cited by the participants was that AI would not be able to assist in unexpected situations owing to inadequate information (196/669, 29.3%). Less than half of the participants(294/669, 43.9%) agreed that AI is diagnostically superior to human doctors. Only 237 (35.4%) answered that they agreed that AI could replace them in their jobs. CONCLUSIONS: This study suggests that Korean doctors and medical students have favorable attitudes toward AI in the medical field. The majority of physicians surveyed believed that AI will not replace their roles in the future.

The flavonoid hesperidin exerts anti-photoaging effect by downregulating matrix metalloproteinase (MMP)-9 expression via mitogen activated protein kinase (MAPK)-dependent signaling pathways.

BACKGROUND: Hesperidin is a flavonoid with antioxidant, anti-inflammatory, and immune modulatory activities. Photoaging is a consequence of chronic exposure to the sun and ultraviolet (UV) radiation. This study was designed to evaluate the efficacy of hesperidin against photoaging of dorsal skin in hairless mice. METHODS: Hairless male mice (6-week-old) were divided into three groups (n = 7): control, UVB-treated vehicle, and UVB-treated hesperidin groups. UVB-irradiated mice from hesperidin group were orally administered 0.1 mL of water containing 100 mg/kg body weight per day hesperidin. RESULTS: The mean length and depth of wrinkles in the UVB-treated hesperidin group significantly improved after the oral administration of hesperidin, which significantly inhibited the increase in epidermal thickness and epidermal hypertrophy (P < 0.05). UVB irradiation of mice induced epidermal barrier dysfunction including an increase in the transepidermal water loss (TEWL); however, hesperidin decreased the TEWL. UVB irradiation increased the expression of MMP-9 and pro-inflammatory cytokines whereas UVB-treated hesperidin group showed reduced expression. These results indicate that hesperidin showed anti-photoaging activity in the UVB-irradiated hairless mice. In conclusion, hesperidin inhibited the UVB-induced increase in skin thickness, wrinkle formation, and collagen fiber loss in male hairless mice. CONCLUSIONS: These results suggest that hesperidin shows potent anti-photoaging activity by regulating MMP-9 expression through the suppression of MAPK-dependent signaling pathways.

Effects of Horse Meat Hydrolysate on Oxidative Stress, Proinflammatory Cytokines, and the Ubiquitin-Proteasomal System of C2C12 Cells.

Sarcopenia, the age-related muscle atrophy, is a serious concern as it is associated with frailty, reduced physical functions, and increased mortality risk. Protein supplementation is essential for preserving muscle mass, and horse meat can be an excellent source of proteins. Since sarcopenia occurs under conditions of oxidative stress, this study aimed to investigate the potential anti-muscle atrophy effect of horse meat hydrolysate using C2C12 cells. A horse meat hydrolysate less than 3 kDa (A4<3kDa) significantly increased the viability of C2C12 myoblasts against H2O2-induced cytotoxicity. Exposure of C2C12 myoblasts to lipopolysaccharide led to an elevation of cellular reactive oxygen species levels and mRNA expression of proinflammatory cytokines, including tumor necrosis factor-α and interleukin 6, and these effects were attenuated by A4<3kDa treatment. Additionally, A4<3kDa activated protein synthesis-related proteins through the protein kinase B/mechanistic target of rapamycin pathway, while decreasing the expression of activity and degradation-related proteins, such as Forkhead box O3, muscle RING finger protein-1, and Atrogin-1 in dexamethasone-treated C2C12 myotubes. Therefore, the natural material A4<3kDa has the potential ofprotecting against muscle atrophy, while further in vivo study is needed.

Physicochemical Features and Volatile Organic Compounds of Horse Loin Subjected to Sous-Vide Cooking.

The purpose of this study was to evaluate the effect of temperature and time of sous-vide cooking method on the characteristics of Thoroughbred horse loin. Sliced portions (200 ± 50 g) were cooked by boiling (control) and sous-vide (65 and 70 °C for 12, 18, and 24 h). The samples were analyzed for proximate composition, pH, color, texture, microstructure, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), microbiology, volatile organic compounds (VOCs), nucleotide content, and fatty acids composition. The color analysis showed decreased redness at elevated temperatures. Improved tenderness, demonstrated by reduced shear force values (36.36 N at 65 °C for 24 h and 35.70 N at 70 °C for 24 h). The micrographs indicated dense fiber arrangements at 70 °C. The SDS-PAGE revealed muscle protein degradation with extended sous-vide cooking. The VOC analysis identified specific compounds, potentially distinctive markers for sous-vide cooking of horse meat including 1-octen-3-ol, decanal, n-caproic acid vinyl ester, cyclotetrasiloxane, octamethyl, and 3,3-dimethyl-1,2-epoxybutane. This study highlights the cooking time's primary role in sous vide-cooked horse meat tenderness and proposes specific VOCs as potential markers. Further research should explore the exclusivity of these VOCs to sous-vide cooking.

Subcritical water-assisted fish gelatin hydrolysis for astaxanthin-loaded fish oil emulsion stability.

Though gelatin emulsifying properties have been intensively studied, how low-molecular-weight (LMW) fish gelatin affects astaxanthin (AST)-loaded fish oil emulsion stability remains elusive. In this study, subcritical water hydrolysis (SWH)-modified LMW fish gelatin (SWHG) was produced from 110 °C to 180 °C and used to enhance the AST steadiness in oil/water emulsions in the presence of an emulsifier, lecithin. In the prepared emulsions, the surface charge increased while droplet size decreased with the decrease in gelatin MW due to the reduced thickness of the adsorbed gelatin membrane. LMW gelatin and lecithin could form a firm-absorbed layer on the droplet surface by electrostatic interaction between amide groups of gelatin molecules and phosphate groups of lecithin, thus stabilizing the emulsions. SWHG improved the creaming stability of the emulsions and hindered the oxygen- and light-induced AST degradation for 11 months compared to high MW gelatin. Whereas, the control emulsion showed noticeable phase separation after two weeks of storage. These findings prove the advantage of the SWH approach and propose the use of SWHG in oil-in-water emulsions for AST stabilization.

Optimization and evaluation of Atrina pectinata polysaccharides recovered by subcritical water extraction: A promising path to natural products.

In this study, the recovery of Atrina pectinata posterior adductor polysaccharides (APP-PS) using subcritical water extraction (SWE) was optimized by response surface methodology (RSM) and the physicochemical and biological properties of the recovered APP-PS were evaluated. The optimal extraction conditions, which resulted in a maximum yield of 55.58 ± 1.12 %, were temperature, 152.08 °C; extraction time, 10 min; solid-liquid ratio, 30 g/600 mL. The obtained APP-PS was found to be 88.05 ± 0.17 % total sugar. Fourier transform infrared (FT-IR) and Nuclear magnetic resonance (NMR) analyses confirmed the presence of the α-coordination of D-glucan in the polymer sample. The analysis of monosaccharide composition, along with thermogravimetric analysis, revealed the typical structure of the sample, composed of glucose alone. Total phenolic contents of APP-PS were measured as 5.47 ± 0.01 mg Gallic acid/g of dry sample and total flavonoids contents were determined to be 0.78 ± 0.06 mg Quercetin/g of dry sample. For biological activities, ABTS+, DPPH and FRAP antioxidant activities were measured to be 20.00 ± 0.71, 2.35 ± 0.05 and 4.02 ± 0.07 µg Trolox equivalent/100 g of dry sample, respectively. Additionally ACE inhibitory was confirmed to be 87.02 ± 0.47 %. These results showed that SWE is an effective method to recover biofunctional materials from marine organisms.

Effect of cinnamon powder on quality attributes and off-flavor in fried chicken drumsticks made from long-term thawed Korean native chicken.

The effect of cinnamon powder on the quality and mitigation of off-flavor in fried chicken drumsticks made from long-term thawed Korean native chicken (Woorimatdag No. 1, WRMD1) was investigated. The WRMD1 drumsticks were categorized into 5 groups: conventional thawing (16 h, CT), long-term thawing (48 h, LT), cinnamon powder added into 'LT' as marinade (0.03%, CM) or incorporated into the batter (1.35%, CB), and long-term thawing with cinnamon powder incorporated both in the marinade and batter (0.03% + 1.35%, CMB). The crude fat content was significantly higher in the CT and CMB than that of the CB. The CM, CB, and CMB showed significantly lower levels of 2-thiobarbituric acid reactive substance compared with the CT and LT. The predominant fatty acids in all treatments were C18:1n9, C18:2n6, and C16:0. The LT displayed lower total unsaturated fatty acid content than the CT (P < 0.05). The CM effectively decreased lipid oxidative volatiles, such as 1-octanol, 1-octen-3-ol, and 2-octen-1-ol, (E), in the LT (P < 0.05). Both the CM and CB showed an inclination to increase specific pyrazines associated with pleasant notes compared with the LT, and showed higher levels of pyrazines, such as pyrazine, 2-ethyl-6-methyl-, and pyrazine, 3-ethyl-2,5-dimethyl-, than those of the CMB (P < 0.05). The CM contained higher levels of 2,3-butanedione when compared with the other groups (P < 0.05). Multivariate analysis demonstrated that cinnamon had an effect in discriminating the treatment groups with cinnamon addition from both the CT and LT, whereas the CM, CB, and CMB formed distinct clusters. The CM and CMB received significantly higher aroma scores from panelists in comparison to the other groups. These findings suggest that the CM (0.03% cinnamon powder) can be used to enhance the aroma in fried WRMD1 drumsticks by reducing or masking the off-flavor volatiles associated with long-term thawing.

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.

Expression of Three Clones of PD-L1 in Lung Cancer: A Single-center Experience.

BACKGROUND/AIM: Programmed cell death ligand 1 (PD-L1) is an immune checkpoint protein involved in immune evasion of malignant tumors. Confirmation of PD-L1 expression in non-small cell lung cancer (NSCLC) is necessary for the determination of immunotherapy using immune checkpoint inhibitors (ICIs). PDL-1 expression is currently analyzed by immunohistochemistry and is the only available biomarker that can guide the treatment of NSCLC using ICIs. The present study was conducted to compare the expression of three different commercial clones of PD-L1 in order for immunohistochemistry (IHC) for these clones to become more reliable for surgical pathologists. MATERIALS AND METHODS: This study examined the expression of PD-L1 in 76 cases of resected lung cancer using IHC. Three clones were examined: SP263, SP142, and 22C3PharmDx, which are commercially approved for quantifying PD-L1 expression in lung cancer. RESULTS: Of the 76 patients whose samples were evaluated for PD-L1 using the IHC 22C3pharmDx assay, 19 (25.0%) had a tumor proportion score (TPS) of ≥50% and 41 (53.9%) had a PD-L1 TPS of ≥1%. Furthermore, using the SP263, 48.7% had a TPS of ≥1% and 18.4% of >50%. The SP142 assay was used to evaluate tumor cells (TCs) and immune cells (ICs). Twenty (26.3%) cases were positive for TCs and 25 (32.9%) were reactive for ICs. CONCLUSION: These three commercial PD-L1 clones are comparable for detecting primary targets for anti-tumor immunotherapies. Careful evaluation by a pathologist is necessary to minimize misinterpretation errors.

Evaluation of the machinability and machining accuracy of polymer-based CAD/CAM blocks using merlon fracture test model.

The aims of this study were to estimate the machinability and machining accuracy of polymer-based CAM blocks using the merlon fracture test model specified in ISO 18675: 2022. Three hybrid disc blanks (MazicDuro, HC Disk, and Enamic) and three polymethyl methacrylate (PMMA) disc blanks (PMMA Disk, PMMA Block, and MazicTemp Hybrid) were tested in this study. The machinability was evaluated by assigning scores according to the fracture range of merlons with areas divided by ten vertical planes. The machining accuracy was evaluated by superimposing methods via CAD reference data and CAD specimen data. Within the limits of this study, a thickness of 0.3 mm is recommended for the clinical application of polymer-based CAD/CAM blocks in dental restorations that require superior machinability and accuracy. In addition, the machinability and machining accuracy tests of polymer-based CAM blocks are expected to provide guidelines for preparing accurate dental restorations.

Risk Factors and Outcomes With Progressive Mitral Annular Calcification.

Background Mitral annular calcification (MAC) is a chronic degenerative process that may progress. This study aimed to investigate associating factors and clinical implications of MAC progression. Methods and Results Among 560 patients with MAC identified by transthoracic echocardiography between January 2012 and June 2016, 138 patients (mean±SD age 72.7±10.2 years, 73 women) with mild or moderate MAC who received follow-up examination within 18 to 36 months were retrospectively analyzed. Progressive MAC was defined as hemodynamic or structural profiles that had worsened by more than 1 grade. Hemodynamic features were assessed by the transmitral mean diastolic pressure gradient (MDPG), and structural features were assessed by the MAC angle in the parasternal short-axis view. The clinical outcome was defined as a composite of all-cause mortality, hospitalization for heart failure, and occurrence of ischemic stroke. Forty-three patients (31.2%) showed progressive MAC. Patients with progressive MAC had higher systolic blood pressure, pulse pressure, MAC angle, and MDPG than those with stable MAC. Patients with progressive MAC had smaller left ventricular (LV) end-systolic dimensions and higher LV ejection fractions compared with those with stable MAC. In multivariate analysis, pulse pressure, LV ejection fraction, MAC angle, and MDPG at baseline were significantly associated with MAC progression. During a median of 39.2 months' follow-up, patients with progressive MAC showed poorer clinical outcomes than those with stable MAC (log-rank P=0.015). Conclusions MAC progression is not rare and is associated with structural substrate and hemodynamic loads that result in mechanical stress. Patients with progressive MAC have poor outcomes.