Evaluation of MCL-1 as a prognostic factor in canine mammary gland tumors.

Myeloid cell leukemia-1 (MCL-1), which belongs to the anti-apoptotic B cell lymphoma-2 family protein, is overexpressed in various cancers and is associated with cell immortality, malignant transformation, chemoresistance, and poor prognosis in humans. However, the significance of MCL-1 in canine mammary gland tumors (MGTs) remains unknown. This study aimed to examine MCL-1 expression in normal canine mammary glands and tumors and to assess its correlation with clinical and histologic variables. In total, 111 samples were examined, including 12 normal mammary gland tissues, 51 benign MGTs, and 48 malignant MGTs. Immunohistochemistry revealed that 53% of benign tumors and 75% of malignant tumors exhibited high MCL-1 expression, whereas only 8% of normal mammary glands exhibited high MCL-1 expression. High MCL-1 expression correlated with tumor malignancy (p < 0.001), large tumor size (> 3 cm) (p = 0.005), high Ki-67 expression (p = 0.046), and metastasis (p = 0.027). Survival curve analysis of dogs with malignant MGTs demonstrated a significant association between high MCL-1 expression and shorter median overall survival (p = 0.027) and progression-free survival (p = 0.014). Our study identified MCL-1 as a prognostic factor and potential therapeutic target in canine MGTs.

Clinical practice recommendations for the use of next-generation sequencing in patients with solid cancer: a joint report from KSMO and KSP.

In recent years, next-generation sequencing (NGS)-based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

The influence of social knowledge structures on hostile attribution bias in aggressive and nonaggressive individuals: An ERP study.

According to several social-cognitive models, social knowledge structures described as hostile scripts or schemas may explain why aggressive individuals are prone to attribute hostile intention to others' ambiguous behaviors, a cognitive bias called hostile attribution bias (HAB). The aggression-related concepts in aggressive individuals' semantic memory would be highly accessible, notably through the activation of hostile concepts in nonhostile social contexts, and such an activation would result in HAB. The aim of the study was to test this hypothesis using the N400 component with EEG measurements to assess objectively, in real time, the violation of hostile expectations following a nonhostile situation. To this end, scenarios with a clear nonhostile context (mismatch condition) vs. without nonhostile context (match condition) followed by a character's ambiguous provocative behavior were presented to readers, and ERPs to critical words that specified the hostile intent behind the behavior were analysed. Twelve aggressive and twelve nonaggressive individuals participated in the study. The presentation of a critical word (hostile intent) that violated nonhostile expectation caused an N400 response among nonaggressive whereas such an N400 effect was absent in aggressive individuals. The results suggest that, in nonaggressive individuals, a nonhostile social context activates nonhostile concepts, whereas in the same context, aggressive individuals activate nonhostile as well as hostile concepts. Numerous research applications of the Hostile Expectancy Violation paradigm in the field of HAB are discussed.

Deep learning based ECG segmentation for delineation of diverse arrhythmias.

Accurate delineation of key waveforms in an ECG is a critical step in extracting relevant features to support the diagnosis and treatment of heart conditions. Although deep learning based methods using segmentation models to locate P, QRS, and T waves have shown promising results, their ability to handle arrhythmias has not been studied in any detail. In this paper we investigate the effect of arrhythmias on delineation quality and develop strategies to improve performance in such cases. We introduce a U-Net-like segmentation model for ECG delineation with a particular focus on diverse arrhythmias. This is followed by a post-processing algorithm which removes noise and automatically determines the boundaries of P, QRS, and T waves. Our model has been trained on a diverse dataset and evaluated against the LUDB and QTDB datasets to show strong performance, with F1-scores exceeding 99% for QRS and T waves, and over 97% for P waves in the LUDB dataset. Furthermore, we assess various models across a wide array of arrhythmias and observe that models with a strong performance on standard benchmarks may still perform poorly on arrhythmias that are underrepresented in these benchmarks, such as tachycardias. We propose solutions to address this discrepancy.

Drug retention of biologic and targeted synthetic disease-modifying antirheumatic drugs in Korean patients with seropositive rheumatoid arthritis.

Background/Aims: The aim of this study was to compare the short- and long-term retention rates of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) in Korean patients with seropositive rheumatoid arthritis. Methods: This study was conducted with 1,538 treatment courses of 1,063 patients, including adalimumab (n = 332), etanercept (n = 369), infliximab (n = 146), abatacept (n = 152), tocilizumab (n = 299), tofacitinib (n = 136), and baricitinib (n = 104), in patients with seropositive rheumatoid arthritis who started b/tsDMARD treatment between 2008 and 2020 at Seoul St. Mary's Hospital. Discontinuation 1 and 3 years after the first prescription of each drug was investigated. Kaplan- Meier estimates of time to discontinuation were calculated to compare the difference in drug retention rate for each drug. Patient-level predictors of drug discontinuation were evaluated using a Cox proportional hazards model. Results: The overall 1-year drug retention rate was from 60.1% for adalimumab to 90.0% for tofacitinib in the b/tsDMARD-naïve group, and from 55.2% for infliximab to 84.8% for tofacitinib in the b/tsDMARD-experienced group. The 3-year drug retention rate was from 36.9% for infliximab to 86.5% for tofacitinib in the b/tsDMARD-naïve group, and from 31.0% for infliximab to 65.4% for tocilizumab in the b/tsDMARD-experienced group. Drug discontinuation appeared to be affected by specific types of b/tsDMARDs. Conclusions: Tocilizumab and tofacitinib are less commonly discontinued compared to tumor necrosis factor-α inhibitors at 1 and 3 years. Specifically, tofacitinib in the b/tsDMARD-naïve group and tocilizumab in the b/tsDMARD-experienced group showed the highest 3-year retention rates.

Impact of IL-1ß on lung pathology caused by Mycobacterium abscessus infection and its association with IL-17 production.

Mycobacterium abscessus (MAB), a non-tuberculous mycobacterium (NTM), causes chronic pulmonary inflammation in humans. The NLRP3 inflammasome is a multi-protein complex that triggers IL-1ß maturation and pyroptosis through the cleavage of caspase-1. In this study, we investigated the roles of NLRP3 and IL-1ß in the host's defense against MAB. The IL-1ß production by MAB was completely abolished in NLRP3, but not NLRC4, deficient macrophages. The NLRP3 inflammasome components, which are ASC and caspase-1 were also found to be essential for IL-1ß production in response to MAB. NLRP3 and IL-1ß deficiency did not affect the intracellular growth of MAB in macrophages, and the bacterial burden in lungs of NLRP3- and IL-1ß-deficient mice was also comparable to the burden observed in WT mice. In contrast, IL-1ß deficiency ameliorated lung pathology in MAB-infected mice. Notably, the lung homogenates of IL-1ß-deficient mice had reduced levels of IL-17, but not IFN-γ and IL-4 when compared with WT counterparts. Furthermore, in vitro co-culture analysis showed that IL-1ß signaling was essential for IL-17 production in response to MAB. Finally, we observed that the anti-IL-17 antibody administration moderately mitigated MAB-induced lung pathology. These findings indicated that IL-1ß production contribute to MAB-induced lung pathology via the elevation of IL-17 production.

Regioselective Syntheses of 2,3,5-Trisubstituted Pyridines via 5-Chloro-3-fluoro-2-(methylsulfonyl)pyridine.

We report the high-yielding, large-scale, one-pot synthesis of two versatile building blocks (1-Cl and 1-Br) for the regioselective synthesis of a variety of 2,3,5-trisubstituted pyridines from inexpensive materials. These molecules are readily derivatized at positions 2, 3, and 5. These building blocks can also be used for the synthesis of fused pyrido-oxazines and for the synthesis of 2,3,4,5-tetrasubstituted pyridines.

Serum and urine lipidomic profiles identify biomarkers diagnostic for seropositive and seronegative rheumatoid arthritis.

Objective: Seronegative rheumatoid arthritis (RA) is defined as RA without circulating autoantibodies such as rheumatoid factor and anti-citrullinated protein antibodies; thus, early diagnosis of seronegative RA can be challenging. Here, we aimed to identify diagnostic biomarkers for seronegative RA by performing lipidomic analyses of sera and urine samples from patients with RA. Methods: We performed untargeted lipidomic analysis of sera and urine samples from 111 RA patients, 45 osteoarthritis (OA) patients, and 25 healthy controls (HC). These samples were divided into a discovery cohort (n = 97) and a validation cohort (n = 84). Serum samples from 20 patients with systemic lupus erythematosus (SLE) were also used for validation. Results: The serum lipidome profile of RA was distinguishable from that of OA and HC. We identified a panel of ten serum lipids and three urine lipids in the discovery cohort that showed the most significant differences. These were deemed potential lipid biomarker candidates for RA. The serum lipid panel was tested using a validation cohort; the results revealed an accuracy of 79%, a sensitivity of 71%, and a specificity of 86%. Both seropositive and seronegative RA patients were differentiated from patients with OA, SLE, and HC. Three urinary lipids showing differential expression between RA from HC were identified with an accuracy of 84%, but they failed to differentiate RA from OA. There were five lipid pathways that differed between seronegative and seropositive RA. Conclusion: Here, we identified a panel of ten serum lipids as potential biomarkers that can differentiate RA from OA and SLE, regardless of seropositivity. In addition, three urinary lipids had diagnostic utility for differentiating RA from HC.

Characterizing Glomerular Barrier Dysfunction with Patient-Derived Serum in Glomerulus-on-a-Chip Models: Unveiling New Insights into Glomerulonephritis.

Glomerulonephritis (GN) is characterized by podocyte injury or glomerular filtration dysfunction, which results in proteinuria and eventual loss of kidney function. Progress in studying the mechanism of GN, and developing an effective therapy, has been limited by the absence of suitable in vitro models that can closely recapitulate human physiological responses. We developed a microfluidic glomerulus-on-a-chip device that can recapitulate the physiological environment to construct a functional filtration barrier, with which we investigated biological changes in podocytes and dynamic alterations in the permeability of the glomerular filtration barrier (GFB) on a chip. We also evaluated the potential of GN-mimicking devices as a model for predicting responses to human GN. Glomerular endothelial cells and podocytes successfully formed intact monolayers on opposite sides of the membrane in our chip device. Permselectivity analysis confirmed that the chip was constituted by a functional GFB that could accurately perform differential clearance of albumin and dextran. Reduction in cell viability resulting from damage was observed in all serum-induced GN models. The expression of podocyte-specific marker WT1 was also decreased. Albumin permeability was increased in most models of serum-induced IgA nephropathy (IgAN) and membranous nephropathy (MN). However, sera from patients with minimal change disease (MCD) or lupus nephritis (LN) did not induce a loss of permeability. This glomerulus-on-a-chip system may provide a platform of glomerular cell culture for in vitro GFB in formation of a functional three-dimensional glomerular structure. Establishing a disease model of GN on a chip could accelerate our understanding of pathophysiological mechanisms of glomerulopathy.

Multicomponent Intervention on Improving the Cognitive Ability of Older Adults with Mild Cognitive Impairment: A Pilot Randomized Controlled Trial.

This pilot randomized controlled trial aimed to evaluate the feasibility and potential outcomes of an innovative 16-session multicomponent intervention model to improve cognitive abilities in older adults with mild cognitive impairment (MCI) by promoting healthy lifestyle, cognitive skills, tai chi and mindfulness practices. This study was a multicentre, randomized controlled, two-arm, parallel-group, unblinded trial in Hong Kong. 57 Chinese older adults with MCI recruited from three local elderly centers were randomly assigned to either the control or intervention group. The study results support the feasibility and efficacy of the multicomponent intervention, and recommend future larger-scale randomized control trials.

Interferon-gamma signaling promotes cartilage regeneration after injury.

Osteoarthritis is a common chronic disease and major cause of disability and chronic pain in ageing populations. In this pathology, the entire joint is involved, and the regeneration of articular cartilage still remains one of the main challenges. Here, we investigated the molecular mechanisms underlying cartilage regeneration in young mice using a full-thickness cartilage injury (FTCI) model. FTCI-induced cartilage defects were created in the femoral trochlea of young and adult C57BL/6 mice. To identify key molecules and pathways involved in the early response to cartilage injury, we performed RNA sequencing (RNA-seq) analysis of cartilage RNA at 3 days after injury. Young mice showed superior cartilage regeneration compared to adult mice after cartilage injury. RNA-seq analysis revealed significant upregulation of genes associated with the immune response, particularly in the IFN-γ signaling pathway and qRT-PCR analysis showed macrophage polarization in the early phase of cartilage regeneration (3 days) in young mice after injury, which might promote the removal of damaged or necrotic cells and initiate cartilage regeneration in response to injury. IFN-γR1- and IFN-γ-deficient mice exhibited impaired cartilage regeneration following cartilage injury. DMM-induced and spontaneous OA phenotypes were exacerbated in IFN-γR1-/- mice than in wild-type mice. Our data support the hypothesis that IFN-γ signaling is necessary for cartilage regeneration, as well as for the amelioration of post-traumatic and age-induced OA.

Single-Centre Registry Analysis of Patients Who Underwent Percutaneous Coronary Intervention on Their Coronary Bypass Grafts.

Background: The study assessed the outcomes of patients undergoing percutaneous coronary intervention (PCI) to bypass grafts, focusing on all-cause mortality and target vessel failure (TVF) rates. Methods: A single-centre registry analysis included 364 patients who underwent PCI on coronary bypass grafts between 2008 and 2019. The study analyzed all-cause mortality and TVF, which encompassed target lesion revascularization, target vessel revascularization, and medically treated occluded target graft post-PCI. Results: The median age of the patients was 71 years (interquartile range: [IQR] 65-78), with 82.1% being male. Most patients (94.8%) received PCI on saphenous vein grafts, and the median graft age was 13.0 years (IQR: 8.4-17.6). Drug-eluting stents were used more frequently (54.4%) than bare-metal stents (45.6%), with a median stent diameter of 3.5 mm (IQR: 3-4) and length of 19 mm (IQR: 18-28). Outcome differences were not significant for PCI sites (aorto-ostial, graft body, anastomosis), use of drug-eluting stents, or use of protection devices. The 1-year mortality rate was 3.3%, whereas the combined rate of TVF or death was 20.3%. After 5 years, the mortality rate increased to 14.9%, and the combined TVF or death rate rose to 40.3%. Multivariable analyses revealed that chronic kidney disease was independently associated with mortality (hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.16-2.61, P = 0.007), whereas hypertension (HR 2.42, 95% CI 1.32-4.42, P = 0.004) and increased stent length (HR 1.01, 95% CI 1.00-1.02, P = 0.007) were independently associated with the TVF-or-mortality outcome. Conclusions: Patients undergoing PCI to bypass grafts experience considerable adverse outcomes over a 5-year period, highlighting the need for further strategies in managing this high-risk population.

Contexte: L'étude visait à évaluer l'issue des patients ayant subi une intervention coronarienne percutanée (ICP) sur un greffon coronarien, en mettant l'accent sur le taux de mortalité toutes causes confondues et le taux d'échecs de revascularisation du vaisseau cible (EVC). Méthodologie: Une analyse du registre d'un seul établissement a porté sur 364 patients ayant subi une ICP sur un greffon coronarien de 2008 à 2019. L'étude a analysé la mortalité toutes causes confondues et les EVC, qui comprenaient la revascularisation de la lésion cible, la revascularisation du vaisseau cible et le traitement médical de l'occlusion du greffon coronarien cible après l'ICP. Résultats: L'âge médian des patients était de 71 ans (intervalle interquartile [IIQ] de 65 à 78) et 82,1 % d'entre eux étaient de sexe masculin. La plupart des patients (94,8 %) avaient subi une ICP sur un greffon de veine saphène; l'âge médian des greffons était de 13,0 ans (IIQ de 8,4 à 17,6). Les endoprothèses médicamentées avaient été utilisées plus fréquemment (54,4 %) que les endoprothèses non médicamentées (45,6 %), le diamètre médian de l'endoprothèse étant de 3,5 mm (IIQ de 3 à 4) et sa longueur, de 19 mm (IIQ de 18 à 28). Les différences pour ce qui est de l'issue clinique n'étaient pas significatives à l'égard des sites d'ICP (aorto-ostial, corps du greffon, anastomose), de l'utilisation d'une endoprothèse médicamentée, ou encore de l'utilisation de dispositifs de protection. Le taux de mortalité à 1 an était de 3,3 %, alors que le taux combiné d'EVC ou de décès était de 20,3 %. Après 5 ans, le taux de mortalité avait augmenté à 14,9 %, alors que le taux combiné d'EVC ou de décès s'élevait à 40,3 %. Les analyses multivariables ont révélé que la néphropathie chronique était indépendamment associée au décès (rapport des risques instantanés [RRI] de 1,74, intervalle de confiance [IC] à 95 % de 1,16 à 2,61, p = 0,007), alors que l'hypertension (RRI de 2,42, IC à 95 % de 1,32 à 4,42, p = 0,004) et une longueur accrue de l'endoprothèse (RRI de 1,01, IC à 95 % de 1,00 à 1,02, p = 0,007) étaient indépendamment associées à une issue d'EVC ou de décès. Conclusions: Les patients qui ont subi une ICP sur un greffon coronarien présentent des complications considérables sur une période de 5 ans, ce qui souligne le besoin de mettre en place davantage de stratégies de prise en charge pour cette population à risque élevé.

The acute phase reactant orosomucoid-2 directly promotes rheumatoid inflammation.

Acute phase proteins involved in chronic inflammatory diseases have not been systematically analyzed. Here, global proteome profiling of serum and urine revealed that orosomucoid-2 (ORM2), an acute phase reactant, was differentially expressed in rheumatoid arthritis (RA) patients and showed the highest fold change. Therefore, we questioned the extent to which ORM2, which is produced mainly in the liver, actively participates in rheumatoid inflammation. Surprisingly, ORM2 expression was upregulated in the synovial fluids and synovial membranes of RA patients. The major cell types producing ORM2 were synovial macrophages and fibroblast-like synoviocytes (FLSs) from RA patients. Recombinant ORM2 robustly increased IL-6, TNF-α, CXCL8 (IL-8), and CCL2 production by RA macrophages and FLSs via the NF-κB and p38 MAPK pathways. Interestingly, glycophorin C, a membrane protein for determining erythrocyte shape, was the receptor for ORM2. Intra-articular injection of ORM2 increased the severity of arthritis in mice and accelerated the infiltration of macrophages into the affected joints. Moreover, circulating ORM2 levels correlated with RA activity and radiographic progression. In conclusion, the acute phase protein ORM2 can directly increase the production of proinflammatory mediators and promote chronic arthritis in mice, suggesting that ORM2 could be a new therapeutic target for RA.

Serum amyloid A expression in liver promotes synovial macrophage activation and chronic arthritis via NFAT5.

Nuclear factor of activated T-cells 5 (NFAT5), an osmo-sensitive transcription factor, can be activated by isotonic stimuli, such as infection. It remains unclear, however, whether NFAT5 is required for damage-associated molecular pattern-triggered (DAMP-triggered) inflammation and immunity. Here, we found that several DAMPs increased NFAT5 expression in macrophages. In particular, serum amyloid A (SAA), primarily generated by the liver, substantially upregulated NFAT5 expression and activity through TLR2/4-JNK signalling pathway. Moreover, the SAA-TLR2/4-NFAT5 axis promoted migration and chemotaxis of macrophages in an IL-6- and chemokine ligand 2-dependent (CCL2-dependent) manner in vitro. Intraarticular injection of SAA markedly accelerated macrophage infiltration and arthritis progression in mice. By contrast, genetic ablation of NFAT5 or TLR2/4 rescued the pathology induced by SAA, confirming the SAA-TLR2/4-NFAT5 axis in vivo. Myeloid-specific depletion of NFAT5 also attenuated SAA-accelerated arthritis. Of note, inflammatory arthritis in mice strikingly induced SAA overexpression in the liver. Conversely, forced overexpression of the SAA gene in the liver accelerated joint damage, indicating that the liver contributes to bolstering chronic inflammation at remote sites by secreting SAA. Collectively, this study underscores the importance of the SAA-TLR2/4-NFAT5 axis in innate immunity, suggesting that acute phase reactant SAA mediates mutual interactions between liver and joints and ultimately aggravates chronic arthritis by enhancing macrophage activation.

Usefulness of cordless ultrasonic cutting energy devices in endoscopic nipple-sparing mastectomy: a retrospective study.

Purpose: Endoscopic nipple-sparing mastectomy (E-NSM) is a minimally invasive surgical technique that shows good results in patients with breast cancer. The authors compared 3 different types of commercial energy devices to examine their efficacy and safety in E-NSM performed with breast reconstruction. Methods: A total of 36 cases of E-NSM were conducted with either Sonicision (S group, n = 11), Harmonic (H group, n = 6), or Thunderbeat (T group, n = 19). The clinicopathologic factors and postoperative complications, including nipple or skin necrosis and surgical site seroma volume, were evaluated for 3 months after surgery. Results: The surgical duration of E-NSM was significantly shorter in the S group than in the H group (P = 0.043) and T group (P = 0.037). However, the total surgical duration including E-NSM and breast reconstruction, and the total and daily drainage volume of postoperative seroma did not differ significantly among the 3 groups. Even when the energy devices were compared according to their working principle, i.e., ultrasonic (S and H) vs. hybrid (T), the total breast surgery duration and total and daily drainage volume of seroma showed no difference between the 2 groups. Although surgeon satisfaction did not significantly differ when using 3 devices for E-NSM (P = 0.428), surgeon's fatigue was found to be lowest in the S group, though it was not significant (P = 0.064). Conclusion: Any energy device can be safely used for E-NSM with breast reconstruction without causing any major complications. However, cordless ultrasonic energy devices allow greater mobility for the surgeon and, therefore, may shorten surgical time in breast surgery.

Cytokines, Vascular Endothelial Growth Factors, and PlGF in Autoimmunity: Insights From Rheumatoid Arthritis to Multiple Sclerosis.

In this review, we will explore the intricate roles of cytokines and vascular endothelial growth factors in autoimmune diseases (ADs), with a particular focus on rheumatoid arthritis (RA) and multiple sclerosis (MS). AD is characterized by self-destructive immune responses due to auto-reactive T lymphocytes and Abs. Among various types of ADs, RA and MS possess inflammation as a central role but in different sites of the patients. Other common aspects among these two ADs are their chronicity and relapsing-remitting symptoms requiring continuous management. First factor inducing these ADs are cytokines, such as IL-6, TNF-α, and IL-17, which play significant roles in the pathogenesis by contributing to inflammation, immune cell activation, and tissue damage. Secondly, vascular endothelial growth factors, including VEGF and angiopoietins, are crucial in promoting angiogenesis and inflammation in these two ADs. Finally, placental growth factor (PlGF), an emerging factor with bi-directional roles in angiogenesis and T cell differentiation, as we introduce as an "angio-lymphokine" is another key factor in ADs. Thus, while angiogenesis recruits more inflammatory cells into the peripheral sites, cytokines secreted by effector cells play critical roles in the pathogenesis of ADs. Various therapeutic interventions targeting these soluble molecules have shown promise in managing autoimmune pathogenic conditions. However, delicate interplay between cytokines, angiogenic factors, and PlGF has more to be studied when considering their complementary role in actual pathogenic conditions. Understanding the complex interactions among these factors provides valuable insights for the development of innovative therapies for RA and MS, offering hope for improved patient outcomes.

A Nationwide Study on HER2-low Breast Cancer in South Korea: Its Incidence of 2022 Real World Data and the Importance of Immunohistochemical Staining Protocols.

Purpose: Notable effectiveness of trastuzumab deruxtecan (T-DXd) in patients with HER2-low advanced breast cancer (BC) has focused pathologists' attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results. Materials and Methods: The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected. Results: Total 11,416 patients from twenty-five institutions included in this study. Of these patients, 40.7% (range: 6.0%-76.3%) were classified as HER2-zero, 41.7% (range: 10.5%-69.1%) as HER2-low, and 17.5% (range: 6.7%-34.0%) as HER2-positive. HER2-low tumors were associated with positive ER and PR statuses (p<0.001 and p<0.001, respectively). Antigen retrieval times (≥ 36 min vs. < 36 min) and antibody incubation times (≥ 12 min vs. < 12 min) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy (CNB) and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3259) of the patients. Conclusion: The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.

A parametric study regarding structural design of a bioprosthetic aortic valve by 3D fluid-structure interaction simulations.

Since the introduction of transcatheter aortic valve (AV) implantation as a viable option, surgical bioprosthetic AVs have recently started incorporating shorter struts considering future valve-in-valve procedures. However, the effect of leaflet coaptation geometry on the longevity of these valves remains unexplored. To address this gap, we performed a finite element analysis on bioprosthetic AVs with varying strut heights using a two-way fluid-structure interaction method. To establish a baseline, we used a standard height based on a rendered platform image of the CE PERIMOUNT Magna Ease valve from Edward Lifesciences in Irvine, CA. Bovine pericardium properties were assigned to the leaflets, while normal saline properties were used as the recirculating fluid in hemodynamic simulations. The physiological pressure profile of the cardiac cycle was applied between the aorta and left ventricle. We calculated blood flow velocity, effective orifice area (EOA), and mechanical stress on the leaflets. The results reveal that as the strut height increases, the stroke volume increases, leakage volume decreases, and EOA improves. Additionally, the maximum mechanical stress experienced by the leaflet decreases by 62% as the strut height increases to 1.2 times the standard height. This research highlights that a low-strut design in bioprosthetic AVs may negatively affect their durability, which can be useful in design of next-generation bioprosthetic AVs.