Anion Storing Boron Nitride Hybrid Nanosheets for High-Performance Dual Ion and Zinc Alkaline Full Cells.

Hexagonal boron nitride (BN), a well-known member of 2D materials, has a structure similar to graphene and is often referred to as white graphene. Despite its unique physical and chemical properties for energy storage applications, there have been very few studies on how BN stores anion carriers. Herein, the hybrid architecture and anion storage mechanism of BN nanosheets for high-performance hybrid energy storage full cells based on dual-ion and Zinc (Zn) alkaline systems is demonstrated. The chemical bonding between BN and reduced graphene oxide (rGO) is attributed to the formation of the heterointerface, which facilitates the charge transfer kinetics during an OH storing process. Based on the reversible surface redox reaction of BN and rGO hybrid (BN@rGO) confirmed by computational and spectroscopic analyses, the BN@rGO electrode is applied to both Na and OH dual-ion and Zn alkaline full cells. In the dual-ion system, Ti3C2‖BN@rGO full cells extended the operating voltage range up to 1.7 V, delivering a cell capacity of 49.4 mAh g-1 at 1000 mA g-1 and retaining 80% of its initial capacity after 40 000 cycles. In the Zn alkaline system, Zn‖BN@rGO full cells achieved a cell capacity of 58.1 mAh g-1 at 1000 mA g-1 and retained 80% capacity over 90 000 cycles.

Binding affinity screening of polyphenolic compounds in Stachys affinis extract (SAE) for their potential antioxidant and anti-inflammatory effects.

Free radical is a marker in various inflammatory diseases. The antioxidant effect protects us from this damage, which also plays an essential role in preventing inflammation. Inflammation protects the body from biological stimuli, and pro-inflammatory mediators are negatively affected in the immune system. Inflammation caused by LPS is an endotoxin found in the outer membrane of Gram-negative bacteria, which induces immune cells to produce inflammatory cytokines such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase. Based on this, the antioxidant and anti-inflammatory effects of plant extracts were investigated. First, the main phenolic compounds for the five peaks obtained from Stachys affinis extract (SAE) were identified. The antioxidant effect of each phenolic compound was confirmed through HPLC analysis before and after the competitive binding reaction between DPPH and the extract. Afterward, the anti-inflammatory effect of each phenolic compound was confirmed through competitive binding between COX2 and the extract in HPLC analysis. Lastly, the anti-inflammatory effect of SAE was confirmed through in vitro experiments and also confirmed in terms of structural binding through molecular docking. This study confirmed that phenolic compounds in SAE extract have potential antioxidant and anti-inflammatory effects, and may provide information for primary screening of medicinal plants.

Choroidal Thickening Induced by Pioglitazone in Diabetic Patients.

PURPOSE: This study aimed to determine the changes in choroidal thickness induced by pioglitazone in diabetic patients. METHODS: A total of 261 patients diagnosed with type 2 diabetes who had taken oral pioglitazone for more than 6 months were included in the study. After excluding patients who did not undergo regular eye examinations or who had ophthalmic surgery/interventions during the treatment period, a total of 40 eyes were included. The study examined the duration and dosage of pioglitazone, patient age, ocular axial length, refraction, glycated hemoglobin, systolic blood pressure, corrected visual acuity, macular thickness, choroidal thickness, and choroidal vascular index. Patients were categorized into a high-dose group if their pioglitazone dose was 30 mg or more per day, and a low-dose group if it was 15 mg or less. Choroidal thickness was measured below the subfovea and a 500 µm radius nasal and temporal to that location. RESULTS: Choroidal thickness significantly increased after 6 and 12 months of pioglitazone (6.70 and 13.65 µm, respectively) in all subjects. When stratified by pioglitazone dosage, choroidal thickness increased at 6 and 12 months in both high-dose group (4.48 and 0.84 µm, respectively) and low-dose groups (6.85 and 21.45 µm, respectively), with a greater change observed in the low-dose group (p < 0.05). Based on the location of choroidal thickness measurements, a significant increase in choroidal thickness was observed at 6 and 12 months of pioglitazone treatment in the subfoveal (7.00 and 13.15 µm, respectively) and nasal regions (6.43 and 19.24 µm, respectively), while a significant increase was only observed after 6 months of treatment in the temporal region (8.53 µm, p < 0.05). The largest increase in choroidal thickness was observed in the nasal side. CONCLUSIONS: This study found that choroidal thickness increased in diabetic patients after taking pioglitazone. Regular eye examinations are recommended for diabetic patients who are on pioglitazone.

Digital in-line holographic microscopy for label-free identification and tracking of biological cells.

Digital in-line holographic microscopy (DIHM) is a non-invasive, real-time, label-free technique that captures three-dimensional (3D) positional, orientational, and morphological information from digital holographic images of living biological cells. Unlike conventional microscopies, the DIHM technique enables precise measurements of dynamic behaviors exhibited by living cells within a 3D volume. This review outlines the fundamental principles and comprehensive digital image processing procedures employed in DIHM-based cell tracking methods. In addition, recent applications of DIHM technique for label-free identification and digital tracking of various motile biological cells, including human blood cells, spermatozoa, diseased cells, and unicellular microorganisms, are thoroughly examined. Leveraging artificial intelligence has significantly enhanced both the speed and accuracy of digital image processing for cell tracking and identification. The quantitative data on cell morphology and dynamics captured by DIHM can effectively elucidate the underlying mechanisms governing various microbial behaviors and contribute to the accumulation of diagnostic databases and the development of clinical treatments.

Subcutaneous Infliximab (CT-P13 SC) as Maintenance Therapy for Inflammatory Bowel Disease: Two Randomized Phase 3 Trials (LIBERTY).

BACKGROUND & AIMS: CT-P13 subcutaneous (SC), an SC formulation of the intravenous (IV) infliximab biosimilar CT-P13 IV, creates a unique exposure profile. The LIBERTY studies aimed to demonstrate superiority of CT-P13 SC vs placebo as maintenance therapy in patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Two randomized, placebo-controlled, double-blind studies were conducted in patients with moderately to severely active CD or UC and inadequate response or intolerance to corticosteroids and immunomodulators. All patients received open-label CT-P13 IV 5 mg/kg at weeks 0, 2, and 6. At week 10, clinical responders were randomized (2:1) to CT-P13 SC 120 mg or placebo every 2 weeks until week 54 (maintenance phase) using prefilled syringes. (Co-) primary end points were clinical remission and endoscopic response (CD) and clinical remission (UC) at week 54 (all-randomized population). RESULTS: Overall, 396 patients with CD and 548 patients with UC received induction treatment. At week 54 in the CD study, statistically significant higher proportions of CT-P13 SC-treated patients vs placebo-treated patients achieved clinical remission (62.3% vs 32.1%; P < .0001) and endoscopic response (51.1% vs 17.9%; P < .0001). In the UC study, clinical remission rates at week 54 were statistically significantly higher with CT-P13 SC vs placebo (43.2% vs 20.8%; P < .0001). Achievement of key secondary end points was significantly higher with CT-P13 SC vs placebo across both studies. CT-P13 SC was well tolerated, with no new safety signals identified. CONCLUSIONS: CT-P13 SC was more effective than placebo as maintenance therapy and was well tolerated in patients with moderately to severely active CD or UC who responded to CT-P13 IV induction. CLINICALTRIALS: gov, Numbers: NCT03945019 (CD) and NCT04205643 (UC).

Carbonized balsa wood-based photothermal evaporator for treating inorganic chemical wastewater.

Solar desalination provides a sustainable and eco-friendly solution for purifying wastewater, addressing environmental challenges associated with wastewater treatment. This study focuses on the purification of inorganic contaminants from laboratory chemical wastewater (ICWW) using a spherical solar still (SSS). To enhance the evaporation rate and overcome the impact of heavy metals on absorption efficiency, a carbonized balsa wood (CBW) solar evaporator was employed. Balsa wood pieces, carbonized at 250 °C for 15 min, were arranged in a SSS configuration. The CBW-integrated SSS demonstrated a remarkable freshwater productivity of 2.33 L/m2 for ICWW, surpassing the conventional SSS, which produced only 1.5 L/m2. The presence of heavy metal ions (Na+, Ca+, K+, and Mg2+) in ICWW significantly affected the evaporation rate, and the CBW solar evaporator exhibited an impressive removal efficiency of approximately 99%. Water quality parameters, including pH and chemical oxygen demand (COD), were investigated before and after treatment. The CBW-integrated SSS achieved an outstanding COD removal efficiency of about 99.77%, reducing the COD level from 229.51 to 0.521 mg/L. These results underscore the efficacy of the proposed solar desalination system in purifying ICWW, offering a promising approach to address environmental concerns associated with wastewater treatment.

Potential Tick Defense Associated with Skin and Hair Characteristics in Korean Water Deer (Hydropotes inermis argyropus).

The Korean water deer (WD), a predominant wildlife species in South Korea, is listed as vulnerable by the IUCN Red List. Despite belonging to the same family, Cervidae, WD show significantly fewer adult ixodid tick infestations compared to roe deer (RD). Ticks, which cannot fly, engage in questing behavior in natural environments to latch onto hosts. They detect signals like body temperature and host skin chemicals to navigate through the hair coat to the preferred epidermis. In light of this, we performed an extensive comparative study of the skin tissue and hair characteristics of both deer species, focusing on elements contributing to the reduced tick bite incidence in WD. Remarkably, WD exhibited more prominent blood vessels, sebaceous glands, and sweat glands, which are crucial for skin barrier functions (p < 0.005). Moreover, WD had irregular scale patterns on their hair cuticles and possessed hair that was significantly stiffer and 2.83 times thicker than that of RD (p < 0.001). These characteristics potentially impede ticks from reaching the epidermis hair in WD and RD in the context of tick bite prevention. Further investigations in this area could enhance our understanding of tick-host dynamics and contribute to developing preventive measures against tick-borne diseases in other deer species.

Potential Antioxidant and Anti-Inflammatory Properties of Polyphenolic Compounds from Cirsium japonicum Extract.

Cirsium japonicum is a medicinal plant that has been used due to its beneficial properties. However, extensive information regarding its therapeutic potential is scarce in the scientific literature. The antioxidant and anti-inflammatory potential of polyphenols derived from the Cirsium japonicum extracts (CJE) was systematically analyzed. High-performance liquid chromatography (HPLC) with mass spectrometry (MS) was used to examine the compounds in CJE. A total of six peaks of polyphenol compounds were identified in the extract, and their MS data were also confirmed. These bioactive compounds were subjected to ultrafiltration with LC analysis to assess their potential for targeting cyclooxygenase-2 (COX2) and DPPH. The outcomes showed which primary compounds had the highest affinity for binding both COX2 and DPPH. This suggests that components that showed excellent binding ability to DPPH and COX2 can be considered significant active substances. Additionally, in vitro analysis of CJE was carried out in macrophage cells after inducing inflammation with lipopolysaccharide (LPS). As a result, it downregulated the expression of two critical pro-inflammatory cytokines, COX2 and inducible nitric oxide synthase (iNOS). In addition, we found a solid binding ability through the molecular docking analysis of the selected compounds with inflammatory mediators. In conclusion, we identified polyphenolic compounds in CJE extract and confirmed their potential antioxidant and anti-inflammatory effects. These results may provide primary data for the application of CJE in the food and pharmaceutical industries with further analysis.

Artificial intelligence-based speckle featurization and localization for ultrasound speckle tracking velocimetry.

Deep learning-based super-resolution ultrasound (DL-SRU) framework has been successful in improving spatial resolution and measuring the velocity field information of a blood flows by localizing and tracking speckle signals of red blood cells (RBCs) without using any contrast agents. However, DL-SRU can localize only a small part of the speckle signals of blood flow owing to ambiguity problems encountered in the classification of blood flow signals from ultrasound B-mode images and the building up of suitable datasets required for training artificial neural networks, as well as the structural limitations of the neural network itself. An artificial intelligence-based speckle featurization and localization (AI-SFL) framework is proposed in this study. It includes a machine learning-based algorithm for classifying blood flow signals from ultrasound B-mode images, dimensionality reduction for featurizing speckle patterns of the classified blood flow signals by approximating them with quantitative values. A novel and robust neural network (ResSU-net) is trained using the online data generation (ODG) method and the extracted speckle features. The super-resolution performance of the proposed AI-SFL and ODG method is evaluated and compared with the results of previous U-net and conventional data augmentation methods under in silico conditions. The predicted locations of RBCs by the AI-SFL and DL-SRU for speckle patterns of blood flow are applied to a PTV algorithm to measure quantitative velocity fields of the flow. Finally, the feasibility of the proposed AI-SFL framework for measuring real blood flows is verified under in vivo conditions.

Clots reveal anomalous elastic behavior of fiber networks.

The adaptive mechanical properties of soft and fibrous biological materials are relevant to their functionality. The emergence of the macroscopic response of these materials to external stress and intrinsic cell traction from local deformations of their structural components is not well understood. Here, we investigate the nonlinear elastic behavior of blood clots by combining microscopy, rheology, and an elastic network model that incorporates the stretching, bending, and buckling of constituent fibrin fibers. By inhibiting fibrin cross-linking in blood clots, we observe an anomalous softening regime in the macroscopic shear response as well as a reduction in platelet-induced clot contractility. Our model explains these observations from two independent macroscopic measurements in a unified manner, through a single mechanical parameter, the bending stiffness of individual fibers. Supported by experimental evidence, our mechanics-based model provides a framework for predicting and comprehending the nonlinear elastic behavior of blood clots and other active biopolymer networks in general.

Efficient solar desalination for clean water production from different wastewaters.

Solar energy is one of the sustainable sources for many fruitful applications. Desalination of wastewater by solar power is a priority research focus and has attracted many researchers and scientists world-wide. However, handling industrial and other wastewater is typically a challenging task for effective treatment and re-use. The presence of contaminants in the effluent is hazardous to the environment and human health. In the present work, an attempt has been made to investigate different wastewaters including (i) garbage wastewater, (ii) waste vegetable water, (iii) landfill leachate, and (iv) pharmaceutical effluent fed into a solar distiller evaporated under natural solar illumination. Herein, different waste waters' pH, chemical oxygen demand (COD), ammoniacal-nitrogen (NH3-N), arsenic (As), Barium (Ba), Cobalt (CO), Chromium (Cr), Iron (Fe), Mercury (Hg), Potassium (K), Manganese (Mn), Magnesium (Mg), Sodium (Na), Nickel (Ni), Phosphate (P), and Zinc (Zn) were investigated by the inductively coupled plasma-atomic emission spectroscopy (ICP-AES). The concentration of NH3-N in the garbage wastewater, vegetables wastewater, landfill leachate, and pharmaceutical effluent were 157 mg/L, 142 mg/L, 161 mg/L, and 164 mg/L, respectively. The evaporated water output of garbage, waste-vegetable water, landfill leachate, and pharmaceutical effluents are 1.7 L/m2.day, 1.8 L/m2.day, 1.9 L/m2.day, and 1.65 L/m2.day, respectively. Finally, the test result reveals that the water quality is greatly improved after consecutive evaporation process by the solar distiller. This is one way to deal with the wastewater through a sustainable process for a better future.

Softening of PEO-LiTFSI/LLZTO Composite Polymer Electrolytes for Solid-State Batteries under Cyclic Compression.

Composite polymer electrolytes (CPEs) strike an effective balance between ionic conductivity and mechanical flexibility for lithium-ion solid-state batteries. Long-term performance, however, is limited by capacity fading after hundreds of charge and discharge cycles. The causes of performance degradation include multiple contributing factors such as dendrite formation, physicochemical changes in electrolytes, and structural remodeling of porous electrodes. Among the many factors that contribute to performance degradation, the effect of stress specifically on the composite electrolyte is not well understood. This study examines the mechanical changes in a poly(ethylene oxide) electrolyte with bis(trifluoromethane) sulfonimide. Two different sizes of Li6.4La3Zr1.4Ta0.6O12 particles (500 nm and 5 µm) are compared to evaluate the effect of the surface-to-volume ratio of the ion-conducting fillers within the composite. Cyclic compression was applied to mimic stress cycling in the electrolyte, which would be caused by asymmetric volume changes that occur during charging and discharging cycles. The electrolytes exhibited fatigue softening, whereby the compressive modulus gradually decreased with an increase in the number of cycles. When the electrolyte was tested for 500 cycles at 30% compressive strain, the compressive modulus of the electrolyte was reduced to approximately 80% of the modulus before cycling. While the extent of softening was similar regardless of particle size, CPEs with 500 nm particles exhibited a significant reduction in ionic conductivity after cyclic compression (1.4 × 10-7 ± 2.3 × 10-8 vs 1.1 × 10-7 ± 2.0 × 10-8 S/cm, mean ± standard deviation, n = 4), whereas there was no significant change in ionic conductivity for CPEs with 5 µm particles. These observations -performed deliberately in the absence of charge-discharge cycles -show that repetitive mechanical stresses can play a significant role in altering the performance of CPEs, thereby revealing another possible mechanism for performance degradation in all-solid-state batteries.

Metabolic transcriptomics dictate responses of cone photoreceptors to retinitis pigmentosa.

Most mutations in retinitis pigmentosa (RP) arise in rod photoreceptors, but cone photoreceptors, responsible for high-resolution daylight and color vision, are subsequently affected, causing the most debilitating features of the disease. We used mass spectroscopy to follow 13C metabolites delivered to the outer retina and single-cell RNA sequencing to assess photoreceptor transcriptomes. The S cone metabolic transcriptome suggests engagement of the TCA cycle and ongoing response to ROS characteristic of oxidative phosphorylation, which we link to their histone modification transcriptome. Tumor necrosis factor (TNF) and its downstream effector RIP3, which drive ROS generation via mitochondrial dysfunction, are induced and activated as S cones undergo early apoptosis in RP. The long/medium-wavelength (L/M) cone transcriptome shows enhanced glycolytic capacity, which maintains their function as RP progresses. Then, as extracellular glucose eventually diminishes, L/M cones are sustained in long-term dormancy by lactate metabolism.

What factors determine users' knowledge payment decisions? A mixed-method study.

Methods for obtaining valuable knowledge from the vast amount of mixed-quality information have become a top priority for knowledge demanders. As an online knowledge-sharing channel, the socialized question and answer (Q&A) platform provides important support services for knowledge payment. Based on the personal psychological dimensions of users and social capital theory, this paper aims to study the behavior mechanisms of knowledge payment users and examine the significant factors affecting user payment. Our research was conducted in two steps: a qualitative study to find these factors and a research model based on a quantitative study for testing the hypothesis. The results show that the three dimensions of individual psychology are not all positively correlated with cognitive and structural capital. Our results fill a gap in the literature on the formation of social capital in the knowledge payment environment by showing how individual psychological dimensions affect cognitive and structural capital differently. Thus, this study offers effective countermeasures for knowledge producers on social Q&A platforms to better amass their social capital. This research also makes practical recommendations for social Q&A platforms to strengthen the knowledge payment model.

A Postmortem Case Study-An Analysis of microRNA Patterns in a Korean Native Male Calf (Bos taurus coreanae) That Died of Fat Necrosis.

Korean native cattle are highly valued for their rich marbling and flavor. Nonetheless, endeavors to enhance marbling levels can result in obesity, a prevalent contributor to fat necrosis. Fat necrosis is characterized by the formation of necrotic fat masses in the abdominal cavity, which physically puts pressure on affected organs, causing physical torsion or obstruction, resulting in death and consequent economic loss. Pancreatic injuries or diabetes mellitus were reported as factors of fat necrosis in humans; however, the pathogenesis in animals has not been established. In this study, we identified fat necrosis in a 6-month-old Korean native cow and investigated its potential underlying causes. Serum samples were utilized for a microarray analysis of bovine miRNA. Comparative examination of miRNA expression levels between cattle afflicted with fat necrosis and healthy cattle unveiled notable variances in 24 miRNAs, such as bta-miR-26a, bta-miR-29a, bta-miR-30a-5p and bta-miR-181a. Upon conducting miRNA-mediated KEGG pathway analysis, several pathways including the prolactin signal pathway, insulin resistance, autophagy, the insulin-signaling pathway and the FoxO-signaling pathway were found to be significantly enriched in the calf affected by fat necrosis. As a result, this study potentially indicates a potential connection between fat necrosis and diabetes in Korean native cattle.

A Plant-Derived Maternal Vaccine against Porcine Epidemic Diarrhea Protects Piglets through Maternally Derived Immunity.

Newborn piglets are susceptible to a highly contagious enteritis caused by the porcine epidemic diarrhea virus (PEDV), associated with high levels of mortality worldwide. There is pressing need for a rapid, safe, and cost-effective vaccine to safeguard pigs from getting infected by PEDV. PEDV belongs to the coronavirus family and is characterized by high levels of mutability. The primary goal of a PEDV vaccine is to provide immunity to newborn piglets through vaccination of sows. Plant-based vaccines are becoming more popular because they have low manufacturing costs, are easily scalable, have high thermostability, and a long shelf life. This is in contrast to conventional vaccines which include inactivated, live, and/or recombinant types that can be expensive and have limited ability to respond to rapidly mutating viruses. The binding of the virus to host cell receptors is primarily facilitated by the N-terminal subunit of the viral spike protein (S1), which also contains several epitopes that are recognized by virus-neutralizing antibodies. As a result, we generated a recombinant S1 protein using a plant-based vaccine platform. We found that the recombinant protein was highly glycosylated, comparable to the native viral antigen. Vaccination of pregnant sows at four and two weeks before farrowing led to the development of humoral immunity specific to S1 in the suckling piglets. In addition, we noted significant viral neutralization titers in both vaccinated sows and piglets. When challenged with PEDV, piglets born from vaccinated sows displayed less severe clinical symptoms and significantly lower mortality rates compared to piglets born from non-vaccinated sows.

Optimization of bamboo-based photothermal interfacial solar evaporator for enhancing water purification.

Although solar desalination is a promising approach for obtaining freshwater, its practical application encounters challenges in achieving efficient photothermal evaporation. Recent research has focused on novel configurations of solar absorbers with unique structural features that can minimize heat loss. High-efficiency interfacial solar steam generation (SSG) can be achieved by optimizing the design of the absorber to harness incident heat energy on the top interfacial surface and ensuring a continuous water supply through microchannels. Artificially nanostructured absorbers might have high solar absorptivity and thermal stability. However, the manufacturing of absorbers is expensive, and the constituting materials are typically non-biodegradable. The unique structural configuration of natural plant-based solar absorbers provides a major breakthrough in SSG. Bamboo, as a natural biomass, possesses exceptional mechanical strength and excellent water transport through vertically oriented microchannels. This study aimed to enhance the performance of SSG with a carbonized bamboo-based solar absorber (CBSA). To achieve this goal, we optimized the carbonization thickness of the absorber by varying the carbonization time. Furthermore, the height of the CBSA was varied from 5 to 45 mm to determine the optimal height for effective solar evaporation. Accordingly, the highest evaporation rate of 3.09 kg m-2 h-1 was achieved for the CBSA height of 10 mm and top-layer carbonization thickness of 5 mm. The cost-effectiveness, simple fabrication, and superior desalination performance of the CBSA demonstrate a strong potential for practical applications.

AI-based analysis of 3D position and orientation of red blood cells using a digital in-line holographic microscopy.

The morphological and mechanical characteristics of red blood cells (RBCs) largely vary depending on the occurrence of hematologic disorders. Variations in the rheological properties of RBCs affect the dynamic motions of RBCs, especially their rotational behavior. However, conventional techniques for measuring the orientation of biconcave-shaped RBCs still have some technical limitations, including complicated optical setups, complex post data processing, and low throughput. In this study, we propose a novel image-based technique for measuring 3D position and orientation of normal RBCs using digital in-line holographic microscopy (DIHM) and artificial intelligence (AI). Formaldehyde-fixed RBCs are immobilized in coagulated polydimethylsiloxane (PDMS). Holographic images of RBCs positioned at various out-of-plane angles are acquired by precisely manipulating the PDMS-trapped RBC sample attached to a 4-axis optical stage. With the aid of deep learning algorithms for data augmentation and regression analysis, the out-of-plane angle of RBCs is directly predicted from the captured holographic images. The 3D position and in-plane angle of RBCs are acquired by employing numerical reconstruction and ellipse detection methods. Combining these digital image processing techniques, the 3D positional and orientational information of each RBC recorded in a single holographic image is measured within 23.5 and 3.07 s, respectively. The proposed AI-based DIHM technique that can extract the 3D position, orientation, and morphology of individual RBCs would be utilized to analyze the dynamic translational and rotational motions of abnormal RBCs with hematologic disorders in shear flows through further research.

Six-Year Survival Outcomes for Patients with HER2-Positive Early Breast Cancer Treated with CT-P6 or Reference Trastuzumab: Observational Follow-Up Study of a Phase 3 Randomised Controlled Trial.

BACKGROUND: The Phase 3 CT-P6 3.2 study demonstrated equivalent efficacy and comparable safety between CT-P6 and reference trastuzumab in patients with human epidermal growth factor receptor-2 (HER2)-positive early breast cancer after up to 3 years' follow-up. OBJECTIVE: To investigate long-term survival with CT-P6 and reference trastuzumab. METHODS: In the CT-P6 3.2 study, patients with HER2-positive early breast cancer were randomised to neoadjuvant chemotherapy with CT-P6 or reference trastuzumab, surgery, and adjuvant CT-P6 or reference trastuzumab before a 3-year post-treatment follow-up. Patients who completed the study could enter a 3-year extension (CT-P6 4.2 study). Data were collected every 6 months to assess overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). RESULTS: Of 549 patients enrolled in the CT-P6 3.2 study, 216 (39.3%) patients continued in the CT-P6 4.2 study (CT-P6, 107; reference trastuzumab, 109) (intention-to-treat extension set). Median follow-up was 76.4 months for both groups. Medians were not reached for time-to-event parameters; estimated hazard ratios (95% confidence intervals) for CT-P6 versus reference trastuzumab were 0.59 (0.17-2.02) for OS, 1.07 (0.50-2.32) for DFS, and 1.08 (0.50-2.34) for PFS. Corresponding 6-year survival rates in the CT-P6 and reference trastuzumab groups, respectively, were 0.96 (0.90-0.99) and 0.94 (0.87-0.97), 0.87 (0.78-0.92) and 0.89 (0.81-0.94), and 0.87 (0.78-0.92) and 0.89 (0.82-0.94). CONCLUSIONS: Data from this extended follow-up of the CT-P6 3.2 study demonstrate the comparable long-term efficacy of CT-P6 and reference trastuzumab up to 6 years. EUDRACT NUMBER: 2019-003518-15 (retrospectively registered 10 March 2020).