Initial Studies Research Articles

Consensus-Based Development of a Pediatric Echocardiography Complexity Score: Design, Rationale, and Results of a Quality Improvement Collaborative.

The complexity of congenital heart disease has been primarily stratified on the basis of surgical technical difficulty, specific diagnoses, and associated outcomes. We report on the refinement and validation of a pediatric echocardiography complexity (PEC) score. The American College of Cardiology Quality Network assembled a panel from 12 centers to refine a previously published PEC score developed in a single institution. The panel refined complexity categories and included study modifiers to account for complexity related to performance of the echocardiogram. Each center submitted data using the PEC scoring tool on 15 consecutive inpatient and outpatient echocardiograms. Univariate and multivariate analyses were performed to assess for independent predictors of longer study duration. Among the 174 echocardiograms analyzed, 68.9% had underlying congenital heart disease; 44.8% were outpatient; 34.5% were performed in an intensive care setting; 61.5% were follow-up; 46.6% were initial or preoperative; and 9.8% were sedated. All studies had an assigned PEC score. In univariate analysis, longer study duration was associated with several patient and study variables (age <2 years, PEC 4 or 5, initial study, preoperative study, junior or trainee scanner, and need for additional imaging). In multivariable analysis, a higher PEC score of 4 or 5 was independently associated with longer study duration after controlling for study variables and center variation. The PEC scoring tool is feasible and applicable in a variety of clinical settings and can be used for correlation with diagnostic errors, allocation of resources, and assessment of physician and sonographer effort in performing, interpreting, and training in pediatric echocardiography.

Palladium-Catalyzed Annulative π-Extension of Bay-Iodinated Triphenylenes to Access Polycyclic Aromatic Compounds.

A palladium-catalyzed annulative π-extension reaction of bay-iodinated triphenylenes with aryl iodides/o-chloroaromatic carboxylic acids was developed. This approach enabled the synthesis of diverse polycyclic aromatic compounds, including dibenzo[fg,op]tetracenes, azadibenzo[fg,op]tetracenes, and tribenzo[a,g,m]coronenes. Initial studies indicate that the resulting product, 2,3,8,9,14,15-hexakis(decyloxy)tribenzo[a,g,m]coronene, exhibits good liquid-crystalline properties.

Mecp2 knock-out astrocytes affect synaptogenesis by interleukin 6 dependent mechanisms

Synaptic abnormalities are a hallmark of several neurological diseases, and clarification of the underlying mechanisms represents a crucial step toward the development of therapeutic strategies. Rett syndrome (RTT) is a rare neurodevelopmental disorder, mainly affecting females, caused by mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene, leading to a deep derangement of synaptic connectivity. Although initial studies supported the exclusive involvement of neurons, recent data have highlighted the pivotal contribution of astrocytes in RTT pathogenesis through non-cell autonomous mechanisms. Since astrocytes regulate synapse formation and functionality by releasing multiple molecules, we investigated the influence of soluble factors secreted by Mecp2 knock-out (KO) astrocytes on synapses. We found that Mecp2 deficiency in astrocytes negatively affects their ability to support synaptogenesis by releasing synaptotoxic molecules. Notably, neuronal inputs from a dysfunctional astrocyte-neuron crosstalk lead KO astrocytes to aberrantly express IL-6, and blocking IL-6 activity prevents synaptic alterations.

Exploring the effects of Dasatinib, Quercetin, and Fisetin on DNA methylation clocks: a longitudinal study on senolytic interventions.

Senolytics, small molecules targeting cellular senescence, have emerged as potential therapeutics to enhance health span. However, their impact on epigenetic age remains unstudied. This study aimed to assess the effects of Dasatinib and Quercetin (DQ) senolytic treatment on DNA methylation (DNAm), epigenetic age, and immune cell subsets. In a Phase I pilot study, 19 participants received DQ for 6 months, with DNAm measured at baseline, 3 months, and 6 months. Significant increases in epigenetic age acceleration were observed in first-generation epigenetic clocks and mitotic clocks at 3 and 6 months, along with a notable decrease in telomere length. However, no significant differences were observed in second and third-generation clocks. Building upon these findings, a subsequent investigation evaluated the combination of DQ with Fisetin (DQF), a well-known antioxidant and antiaging senolytic molecule. After one year, 19 participants (including 10 from the initial study) received DQF for 6 months, with DNAm assessed at baseline and 6 months. Remarkably, the addition of Fisetin to the treatment resulted in non-significant increases in epigenetic age acceleration, suggesting a potential mitigating effect of Fisetin on the impact of DQ on epigenetic aging. Furthermore, our analyses unveiled notable differences in immune cell proportions between the DQ and DQF treatment groups, providing a biological basis for the divergent patterns observed in the evolution of epigenetic clocks. These findings warrant further research to validate and comprehensively understand the implications of these combined interventions.

Long-range optical coherence tomography of pediatric airway during drug induced sleep endoscopy: A preliminary report

ObjectiveDrug induced sleep endoscopy (DISE) is often performed for pediatric obstructive sleep apnea (OSA) when initial diagnostic studies do not provide adequate information for therapy. However, DISE scoring is subjective and with limitations. This proof-of-concept study demonstrates the use of a novel long-range optical coherence tomography (LR-OCT) system during DISE of two pediatric patients. MethodsLR-OCT was used to visualize the airway of pediatric patients during DISE. At the conclusion of DISE, the OCT probe was guided in the airway under endoscopic visual guidance, and cross-sectional images were acquired at the four VOTE locations. Data processing involved image resizing and alignment, followed by rendering of three-dimensional (3D) volumetric models of the airways. ResultsTwo patients were included in this study. Patient one had 18.4%, 20.9%, 72.3%, and 97.3% maximal obstruction at velum, oropharynx, tongue base, and epiglottis, while patient two had 40.2%, 41.4%, 8.0%, and 17.5% maximal obstruction at these regions, respectively. Three-dimensional reconstructions of patients’ airways were also constructed from the OCT images. ConclusionThis proof-of-concept study demonstrates the successful evaluation of pediatric airway during DISE using LR-OCT, which accurately identified sites and degrees of obstruction with respective 3D airway reconstruction.

On the formation of ammonia from the thermal decomposition of hydroxylammonium nitrate vapor

The ionic liquid hydroxylammonium nitrate (HAN) is a promising propellant for various types of spacecraft propulsion systems. With respect to combustion and plasma-based electric propulsion, the thermal decomposition of HAN into gas phase species provides a convenient feed gas supply. While the decomposition of HAN in the liquid phase has been extensively studied, little is known about the decomposition chemistry of HAN vapor interacting with heated surfaces. The ability to decompose HAN vapor on a reactive surface could provide a means to control the feed gas composition and enhance the performance of spacecraft propulsion systems.In this initial qualitative study, HAN was vaporized and thermally decomposed using porous 316-stainless-steel and quartz disks under vacuum conditions. Decomposition products with low vapor pressures would condense on an in-line quartz tube which was subsequently collected and analyzed with Raman spectroscopy, NMR spectroscopy, and FT-IR spectroscopy. At temperatures above 440 K the 316-stainless-steel system produced significant quantities of ammonia which reacted with vaporized nitric acid to form ammonium nitrate. Temperatures below 440 K yielded partial HAN decomposition which resulted in a binary mixture of HAN and ammonium nitrate. The degree to which HAN was consumed was determined by analysis of the 1008 cm−1N-OH asymmetric Raman band of HAN and the 1049 cm−1 symmetric stretching Raman band of the nitrate ion, NO3−. The quartz system yielded significantly different results with no ammonium nitrate detected at temperatures above 440 K. Reformed HAN was the primary product detected at lower temperatures. The difference in reported measurements and visual observations highlights the distinct differences in HAN vapor decomposition chemistry from the two materials examined.

Ruptured basilar artery perforator aneurysm mimicking superior cerebellar artery aneurysm

Background and importanceThe diagnosis of basilar artery perforator aneurysm is difficult due to their small size, with high rates of negative angiography. Furthermore, due to the considerable variation of basilar artery perforator (BAP), even if an aneurysm originates from a BAP, it is often difficult to clearly identify its origin on angiography. Clinical presentationA 46-female patient presented with World Federation of Neurological Surgeons Scale 1 subarachnoid hemorrhage. Initial imaging study, including digital subtraction angiography (DSA), revealed no vascular lesions. Two-week after admission, DSA revealed an aneurysm arising from the left superior cerebellar artery (SCA). Endovascular coil embolization was planned first. However, aneurysm selection using microcatheter was failed. Then, surgical approach was done via pre-temporal approach. We identified SCA, but there was no aneurysm. Further dissection revealed an aneurysm arising from basilar artery perforator, which was overlapped by SCA. The parent artery of the aneurysm arose from juxtaproximal to the orifice of left SCA, and crossed SCA at the juxtadistal to the aneurismal sac. Complete clip occlusion was done preserving BAP. After the surgery, the patient developed diplopia without extraoccular movement limitations. Two-month after the surgery, she was fully recovered without any neurologic deficits. ConclusionIt is crucial to adequately consider the possibility of open surgery as a viable option in case that endovascular treatment of aneurysms originated from the distal segment of basilar artery proves unsuccessful.

A mixed methods experience sampling study of a posttraumatic growth model for addiction recovery

Problematic substance use and addiction is a growing crisis in the United States. As a result, identifying factors that effectively promote addiction recovery is, currently, of particular societal importance. Informed by evidence that—while addiction can be perpetuated by stress-related impulsivity and decreased self-regulation—perceived social support is protective against addiction, we test a model for addiction recovery as a form of posttraumatic growth (PTG), focused specifically on close relationships and personal strength—two domains of PTG. In an initial study, we found that perceived social support and impulsivity predicted number of relapses in individuals in a substance use disorder recovery program. Using experience sampling, we then observed that experiencing a stressful event predicted impulsive behavior. However, experiencing closeness with others—a domain of PTG—was directly associated with perceived social support, and both predicted positive emotional states, which were, in turn, inversely associated with experiencing a stressful event. Further, when experiencing a stressful event, personal strength—also a domain of PTG—was inversely associated with impulsive behavior and was predicted by both perceived social support and positive emotional states. Finally, in a follow-up experiment, we found that an ecological momentary intervention targeting perceived social support decreased impulsivity and increased self-regulation—an aspect of personal strength—in a dose-dependent fashion. Taken together, our findings: (1) support a PTG model for recovery; (2) provide evidence for processes by which close supportive relationships are protective against addiction and relapse; and (3) indicate that self-regulation is responsive to a short in-the-moment perceived social support intervention. We suggest that these findings support the theory that addiction is a social disease in the sense that close personal interactions and supportive relationships: (a) buffer against stress-related impulsivity, thereby protecting against addiction and relapse; and (b) increase personal strength, thereby decreasing the probability of impulsive—including addictive—behavior and promoting recovery.

Unveiling Three Interconvertible Redox States of Boraphenalene.

Neutral 1-boraphenalene displays the isoelectronic structure of the phenalenyl carbocation and is expected to behave as an attractive organoboron multi-redox system. However, the isolation of new redox states have remained elusive even though the preparation of neutral boron(III)-containing phenalene compounds have been extensively studied. Herein, we have adopted an N-heterocyclic carbene ligand stabilization approach to achieve the first isolation of the stable and ambipolar 1-boraphenalenyl radical 1•. The 1-boraphenalenyl cation 1+ and anion 1- have also been electrochemically observed and chemically isolated, representing new redox forms of boraphenalene for the study of non-Kekulé polynuclear benzenoid molecules. Experimental and theoretical investigations suggest that the interconvertible three-redox-state species undergo reversible electronic structure modifications, which primarily take place on the polycyclic framework of the molecules, exhibiting atypical behavior compared to known donor-stabilized organoboron compounds. Initial reactivity studies, aromaticity evaluations, and photophysical studies show redox-state-dependent trends. While 1+ is luminescent in both the solution and solid states, 1• exhibits boron-centered reactivity and 1- undergoes substitution chemistry on the boraphenalenyl skeleton and serves as a single-electron transfer reductant.

Diagnosis and Treatment Patterns of Chronic Thromboembolic Pulmonary Hypertension in Russia, Kazakhstan, Turkey, Lebanon, and Saudi Arabia: A Registry Study.

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) in countries with limited resources have, to date, been poorly represented in registries. This work assesses the epidemiology, diagnosis, hemodynamic and functional parameters, and treatment of CTEPH in Russia, Kazakhstan, Turkey, Lebanon, and Saudi Arabia. A prospective, cohort, phase IV, observational registry with 3-year follow-up (n = 212) in patients aged ≥ 18 years diagnosed with CTEPH was created. Clinical, hemodynamic, and functional parameters were obtained at an initial visit, follow-up visits, and a final visit at the end of 3years' observation or end of follow-up. Data were recorded on electronic case report forms. Parameters evaluated included 6-minute walking distance (6MWD), use of pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA), pulmonary hypertension (PH)-targeted therapy, and survival. All statistical analyses were exploratory and descriptive, and were performed in the overall population. The most common symptoms were typical of those expected for CTEPH. Almost 90% of patients underwent right heart catheterization at diagnosis or initial study visit. In total, 66 patients (31%) underwent PEA before the initial visit; 95 patients (45%) were considered operable, 115 (54%) were inoperable, and two (1%) had no operability data. Only 26 patients (12%) had been assessed for BPA at their initial visit. PH-targeted therapy was documented at diagnosis for 77 patients (36%), most commonly a phosphodiesterase type 5 inhibitor (23%). Use of PH-targeted therapy increased to 142patients (67%) at the initial visit, remaining similar after 3 years. Use of riociguat increased from 6% of patients at diagnosis to 38% at 3 years. Between baseline and end of observation, results for patients with paired data showed an increase in 6MWD. Survival at the end of observation was 88%. These data highlight the current diagnosis and management of CTEPH in the participating countries. They show that early CTEPH diagnosis remains challenging, and use of off-label PH-targeted therapy is common. gov: NCT02637050; registered December 2015.

Usefulness of fat-containing agents: an initial study on estimating fat content for magnetic resonance imaging.

This initial study aimed at testing whether fat-containing agents can be used for the fat mass estimation methods using magnetic resonance imaging (MRI). As an example for clinical application, fat-containing agents (based on soybean oil, 10% and 20%), 100% soybean oil, and saline as reference substances were placed outside the proximal femurs obtained from 14 participants and analyzed by 0.3T MRI. Fat content was the estimated fat fraction (FF) based on signal intensity (SIeFF, %). The SIeFF values of the femoral bone marrow, including the femoral head, neck, shaft, and trochanter area, were measured. MRI data were compared in terms of bone mineral content (BMC) and bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) in the proximal femur. Twelve pig femurs were also used to confirm the correlation between FF by the DIXON method and SIeFF. According to Pearson's correlation coefficient, the SIeFF and total BMC and BMD data revealed strong and moderate negative correlations in the femoral head (r < - 0.74) and other sites (r = - 0.66 to - 0.45). FF and SIeFF showed a strong correlation (r = 0.96). This study was an initial investigation of a method for estimating fat mass with fat-containing agents and showed the potential for use in MRI. SIeFF and FF showed a strong correlation, and SIeFF and BMD and BMC showed correlation; however, further studies are needed to use SIeFF as a substitute for DXA.

Capacitive immunosensing at gold nanoparticle-decorated reduced graphene oxide electrodes fabricated by one-step laser nanostructuration

Nanostructured electrochemical biosensors have ushered in a new era of diagnostic precision, offering enhanced sensitivity and specificity for clinical biomarker detection. Among them, capacitive biosensing enables ultrasensitive label-free detection of multiple molecular targets. However, the complexity and cost associated with conventional fabrication methods of nanostructured platforms hinder the widespread adoption of these devices. This study introduces a capacitive biosensor that leverages laser-engraved reduced graphene oxide (rGO) electrodes decorated with gold nanoparticles (AuNPs). The fabrication involves laser-scribed GO-Au3+ films, yielding rGO-AuNP electrodes, seamlessly transferred onto a PET substrate via a press-stamping methodology. These electrodes have a remarkable affinity for biomolecular recognition after being functionalized with specific bioreceptors. For example, initial studies with human IgG antibodies confirm the detection capabilities of the biosensor using electrochemical capacitance spectroscopy. Furthermore, the biosensor can quantify CA-19-9 glycoprotein, a clinical cancer biomarker. The biosensor exhibits a dynamic range from 0 to 300 U mL−1, with a limit of detection of 8.9 U mL−1. Rigorous testing with known concentrations of a pretreated CA-19-9 antigen from human fluids confirmed their accuracy and reliability in detecting the glycoprotein. This study signifies notable progress in capacitive biosensing for clinical biomarkers, potentially leading to more accessible and cost-effective point-of-care solutions.

Reptile Identification for Endemic and Invasive Alien Species Using Transfer Learning Approaches.

The Canary Islands are considered a hotspot of biodiversity and have high levels of endemicity, including endemic reptile species. Nowadays, some invasive alien species of reptiles are proliferating with no control in different parts of the territory, creating a dangerous situation for the ecosystems of this archipelago. Despite the fact that the regional authorities have initiated actions to try to control the proliferation of invasive species, the problem has not been solved as it depends on sporadic sightings, and it is impossible to determine when these species appear. Since no studies for automatically identifying certain species of reptiles endemic to the Canary Islands have been found in the current state-of-the-art, from the Signals and Communications Department of the Las Palmas de Gran Canaria University (ULPGC), we consider the possibility of developing a detection system based on automatic species recognition using deep learning (DL) techniques. So this research conducts an initial identification study of some species of interest by implementing different neural network models based on transfer learning approaches. This study concludes with a comparison in which the best performance is achieved by integrating the EfficientNetV2B3 base model, which has a mean Accuracy of 98.75%.

Synthesis, preclinical, and initial clinical evaluation of integrin αVβ3 and gastrin-releasing peptide receptor (GRPR) dual-targeting radiotracer [68Ga]Ga-RGD-RM26-03.

LNC1015 was designed and synthesized by linking cyclic RGD and the RM26 peptide. Preclinical pharmacokinetics were detected in a PC3 xenograft model using microPET and biodistribution studies. The clinical feasibility of [68Ga]Ga-LNC1015 PET/CT was performed in patients with breast cancer, and the results were compared with those of 18F-fluorodeoxyglucose (FDG). [68Ga]Ga-LNC1015 had good stability in saline for at least 2h, and favorable binding affinity and specificity were demonstrated in vitro and in vivo. The tumor uptake and retention of [68Ga]Ga-LNC1015 during PET imaging were improved compared with its monomeric counterparts [68Ga]Ga-RGD and [68Ga]Ga-RM26 at all the time points examined. In our initial clinical studies, the tumor uptake and tumor-to-background ratio (TBR) of primary and metastatic lesions in [68Ga]Ga-LNC1015 PET/CT were significantly higher than those in [18F]FDG PET/CT, resulting in high lesion detection rate and tumor delineation. The dual targeting radiotracer [68Ga]Ga-LNC1015 showed significantly improved tumor uptake and retention, as well as lower liver uptake than [68Ga]Ga-RGD and [68Ga]Ga-RM26 monomer. The first-in-human study showed high TBRs in patients, suggesting favorable pharmacokinetics and high clinical feasibility for PET/CT imaging of cancer.

A Silicon-Photo-Multiplier-Based Camera for the Terzina Telescope on Board the Neutrinos and Seismic Electromagnetic Signals Space Mission

NUSES is a pathfinder satellite project hosting two detectors: Ziré and Terzina. Ziré focuses on the study of protons and electrons below 250 MeV and MeV gamma rays. Terzina is dedicated to the detection of Cherenkov light produced by ultra-high-energy cosmic rays above 100 PeV and ultra-high-energy Earth-skimming neutrinos in the atmosphere, ensuring a large exposure. This work mainly concerns the description of the Cherenkov camera, composed of SiPMs, for the Terzina telescope. To increase the data-taking period, the NUSES orbit will be Sun-synchronous (with a height of about 550 km), thus allowing Terzina to always point toward the dark side of the Earth’s limb. The Sun-synchronous orbit requires small distances to the poles, and as a consequence, we expect an elevated dose to be received by the SiPMs. Background rates due to the dose accumulated by the SiPM would become a dominant contribution during the last two years of the NUSES mission. In this paper, we illustrate the measured effect of irradiance on SiPM photosensors with a variable-intensity beam of 50 MeV protons up to a 30 Gy total integrated dose. We also show the results of an initial study conducted without considering the contribution of solar wind protons and with an initial geometry with Geant4. The considered geometry included an entrance lens as one of the options in the initial design of the telescope. We characterize the SiPM output signal shape with different μ-cell sizes. We describe the developed parametric SiPM simulation, which is a part of the full Terzina simulation chain.

Evaluating short- and long-term investment strategies: development and validation of the investment strategies scale (ISS)

PurposeIn response to the growing importance of understanding individual investment strategies, the present study aimed to develop a new scale for measuring both the short- and long-term investment strategies of individuals.Design/methodology/approachThe study assessed the psychometric properties of the investment strategies scale (ISS) using data collected from 1428 individual investors. In the initial study, an exploratory factor analysis (EFA) was conducted to investigate the factor structure of the proposed scale (N = 700). The EFA results yielded a two-factor structure, and Cronbach’s alpha values for short- and long-term investment strategies were 0.90 and 0.88, respectively. A confirmatory factor analysis was performed to validate the factor structure of the scale in the second study (N = 728).FindingsThe results demonstrated that the two-factor model fit the data well. In the third study, the correlation between Hofstede’s long-term orientation and the two dimensions of the scale was investigated. The results indicated that long-term investment strategies significantly predict long-term orientation, thus confirming the concurrent validity of the scale.Research implicationsThese findings demonstrate that the proposed ISS is a reliable and valid instrument for measuring individuals’ short- and long-term investment strategies, contributing to a deeper understanding of investment decision-making processes.Originality/valueThis study introduces a novel measurement tool—ISS—specifically designed to comprehensively assess both short- and long-term investment strategies among individual investors.

Mesenchymal Stem Cell Applications in Graft Versus Host Disease

Allogeneic hematopoietic stem cell transplantation stands as a promising cure for a variety of diseases. However, the potential of acute or chronic graft-versus-host disease (GvHD), which leads to significant morbidity and mortality, remains a cause for concern. GvHD occurs due to the complex interactions of immune cells from the graft and the host cells. Despite the existence of prophylactic treatments, GvHD may still occur, and the resistance to conventional therapies necessitates novel approaches and treatments. Mesenchymal stem cells, which are pluripotent stem cells capable of self-renewal and multilineage differentiation, have gained attention for their low immunogenicity and ability to be sourced from various origins. They have shown promise as therapeutic tools for the cell-based treatment of inflammatory, immune-mediated, and degenerative diseases owing to their remarkable abilities in immunomodulation, immunosuppression, and tissue regeneration. In GvHD, MSCs have demonstrated therapeutic potential through paracrine activity and organelle transfer via nanotubes, microvesicles, or exosomes. The emergence of MSCs as a treatment for severe steroid-resistant GvHD gained attention in the early 2000s. While initial studies have demonstrated encouraging results in the use of MSCs for the prevention of GvHD, there is still a need for further investigation. Therefore, in this current review, we aim to delve deeper into MSC’s features and their clinical applications in the case of GvHD treatment.

Skin lightening properties of zerumbone cream: A placebo-controlled study.

Despite the demonstrated anti-melanogenic and UV protective effects of Zerumbone (ZER) invitro, there is a lack of clinical trials that have been done to assess these properties. The primary objective of this study was to assess the effectiveness of ZER in lightening the skin tone of human participants with a single-blind approach. Twenty-six participants were randomly assigned to two groups to investigate the application location (left or right volar forearm) for the placebo and ZER creams. Both creams were topically administered to the volar forearms twice daily over a duration of 4 weeks. Initial skin irritation was assessed before and 30 min after applying creams. The melanin and erythema levels were quantified with Mexameter MX 18. Twenty participants were included in the analysis. The cream formulation had excellent physical properties and was well-received by the participants. The initial skin irritation study results indicated that neither of the creams elicited an allergic reaction. The administration of ZER cream resulted in a statistically significant reduction in melanin levels (p < 0.05) after 1 week compared to the initial baseline. Furthermore, after 2 weeks of application, ZER cream demonstrated significant differences in melanin levels compared to placebo (p < 0.05). No adverse effects were observed in the group using ZER cream. ZER demonstrated significant potential as a skin-lightening agent.

Hormone replacement therapy and breast cancer incidence in Korean women

ObjectivesAfter the 2002 Women's Health Initiative (WHI) study, the global use of menopausal hormone therapy (MHT) declined, and despite subsequent studies indicating a low risk of breast cancer, concerns about MHT usage persist. We examined the relationship between changes in MHT use and changes in the incidence of breast cancer from 2002 to 2020 in South Korea. Study designThis study used tumor registry information from 2002 to 2020 from the Korean Statistical Information Service and analyzed the incidence rate of invasive breast cancer in women, who were divided into two age groups: <50 and >50 years. The numbers of MHT prescriptions in Korea between 2002 and 2020 was determined from pharmacy data. ResultsThe incidence of breast cancer per 100,000 women in South Korea increased from 34.3 in 2002 to 96.4 in 2020. Breast cancer incidence rates increased annually in both groups of women (those aged under and over 50 years), with no significant difference between the two (p = 0.614). Prescriptions for estrogen therapy (ET) in 2020 were 52.7 % lower than those in 2002. Prescriptions for estrogen-progesterone therapy (EPT) decreased by 27.9 % over the same period. Conversely, tibolone prescriptions, which had initially decreased by 25.4 % in 2004, subsequently showed a steady increase and were 93.6 % higher in 2020 than in 2002. ConclusionThe incidence of breast cancer increased annually in Korean women of all ages; however, the use of ET and EPT for MHT has declined since 2002, particularly the use of EPT after 2010. MHT, especially EPT, did not significantly increase the incidence of breast cancer in Korean women.

Biofabrication's Contribution to the Evolution of Cultured Meat.

Cultured Meat (CM) is a growing field in cellular agriculture, driven by the environmental impact of conventional meat production, which contributes to climate change and occupies ≈70% of arable land. As demand for meat alternatives rises, research in this area expands. CM production relies on tissue engineering techniques, where a limited number of animal cells are cultured in vitro and processed to create meat-like tissue comprising muscle and adipose components. Currently, CM is primarily produced on a small scale in pilot facilities. Producing a large cell mass based on suitable cell sources and bioreactors remains challenging. Advanced manufacturing methods and innovative materials are required to subsequently process this cell mass into CM products on a large scale. Consequently, CM is closely linked with biofabrication, a suite of technologies for precisely arranging cellular aggregates and cell-material composites to construct specific structures, often using robotics. This review provides insights into contemporary biomedical biofabrication technologies, focusing on significant advancements in muscle and adipose tissue biofabrication for CM production. Novel materials for biofabricating CM are also discussed, emphasizing their edibility and incorporation of healthful components. Finally, initial studies on biofabricated CM are examined, addressing current limitations and future challenges for large-scale production.