Impact of 18F-FES PET/CT on Clinical Decisions in the Management of Recurrent or Metastatic Breast Cancer.

The clinical impact of 16α-18F-fluoro-17ß-estradiol (18F-FES) PET/CT on patient management has not been well investigated. The aim of this study was to assess the clinical impact of 18F-FES PET/CT on the management of patients with recurrent or metastatic breast cancer. Methods: Study subjects were identified retrospectively from a database of a prospective trial for postmarketing surveillance of 18F-FES between 2021 and 2023. Patients who were suspected or known to have recurrent or metastatic estrogen receptor-positive breast cancer based on a routine standard workup were included. Planned management before and actual management after 18F-FES PET/CT were assessed by 2 experienced medical oncologists via medical chart review. A 5-point questionnaire was provided to evaluate the value of 18F-FES PET/CT for management planning. The rate of intention-to-treat and interdisciplinary changes, and the impact of 18F-FES PET/CT according to PET/CT result or clinical indication, were examined. Results: Of the 344 included patients, 120 (35%) experienced a change in management after 18F-FES PET/CT. In 139 (40%) patients,18F-FES PET/CT supported the existing management decision without a change in management. Intention-to-treat and interdisciplinary changes accounted for 64% (77/120) and 68% (82/120) of all changes, respectively. A higher rate of change was observed when lesions were 18F-FES-negative (44% [36/81]) than 18F-FES-positive (30% [51/172]) or mixed 18F-FES-positive/negative (36% [33/91]). Regarding clinical indications, the highest rate of change was shown when evaluating the origins of metastasis of double primary cancers (64% [9/14]). Conclusion: 18F-FES PET/CT modified the management of recurrent or metastatic breast cancer, serving as an impactful imaging modality in clinical practice.

Cryoprotective Ice-Philic Black Phosphorus Nanosheets for Augmented Thawing of Frozen Cells.

Controlling ice formation is critical in fields such as atmospheric science and biological cryopreservation. However, thermal heterogeneity during freezing and thawing in cryopreservation causes uneven ice crystallization and melting, leading to mechanical and thermal stress-induced damage. This study introduces biocompatible and biodegradable black phosphorus (BP)-polyethylene glycol-amine nanosheets (NS) to address this issue. BP NS primarily localize at ice grain boundaries, while amine groups of NH2-PEG-NH2 form hydrogen bonds with H2O molecules, penetrating ice crystals. In situ cross-sectional observations confirmed that BP-PEG-NH2 NS promotes uniform melting and facilitates ice cracks and boundaries. Heat transfer analysis using a bidirectional heating system revealed that the internal heat energy varies based on BP dispersion within the ice crystals. When applied to the cryopreservation of human tongue squamous cell carcinoma cells, BP-PEG-NH2 NSs significantly improved post-thaw viability. It presents a promising strategy for designing thawing materials after cryopreservation of cells, tissues, and organs.

A brief guide to analyzing expression quantitative trait loci.

Molecular quantitative trait locus (molQTL) mapping has emerged as an important approach for elucidating the functional consequences of genetic variants and unraveling the causal mechanisms underlying diseases or complex traits. However, the variety of analysis tools and sophisticated methodologies available for molQTL studies can be overwhelming for researchers with limited computational expertise. Here, we provide a brief guideline with a curated list of methods and software tools for analyzing expression quantitative trait loci (eQTL), the most widely studied type of molQTL.

The potential influences of COVID-19 and social vulnerability measures on child maltreatment in the United States: Spatial temporal cluster analysis and negative binomial regression.

BACKGROUND: Although existing research has reported the impacts of COVID-19 on child abuse and neglect (CAN), little attention was paid to the relationship between spatial patterns in the trends of COVID-19 cases and their effects on the prevalence of CAN cases. OBJECTIVE: This study examined the associations between trends of confirmed cases of COVID-19 and child removal due to physical abuse and neglect at the county level in the U.S while taking the social vulnerability into account. PARTICIPANTS AND SETTING: This study utilized three secondary data sets nationally collected. METHODS: Spatial-temporal cluster analysis was used to classify and assign trends in confirmed cases of COVID-19 into their distinctive clusters. These spatial-temporal clusters were then used as independent variables in the negative binomial regression (NBR) models. RESULTS: Average cases of physical abuse and neglect increased as the growth rates of confirmed cases of COVID-19 were accelerated except for the counties assigned to the cluster characterized by moderately low increase and very high increases. NBR found social vulnerability measures have no effects on child removal due to physical abuse and neglect after controlling spatial-temporal clusters of the confirmed cases of COVID-19. CONCLUSIONS: Our study indicates that concentration of disaster has certain effects on child maltreatment. This suggests that child welfare pay special attention to the areas that undergo steep increases in confirmed cases under public health crises.

Spatially resolved analysis of pancreatic cancer identifies therapy-associated remodeling of the tumor microenvironment.

In combination with cell-intrinsic properties, interactions in the tumor microenvironment modulate therapeutic response. We leveraged single-cell spatial transcriptomics to dissect the remodeling of multicellular neighborhoods and cell-cell interactions in human pancreatic cancer associated with neoadjuvant chemotherapy and radiotherapy. We developed spatially constrained optimal transport interaction analysis (SCOTIA), an optimal transport model with a cost function that includes both spatial distance and ligand-receptor gene expression. Our results uncovered a marked change in ligand-receptor interactions between cancer-associated fibroblasts and malignant cells in response to treatment, which was supported by orthogonal datasets, including an ex vivo tumoroid coculture system. We identified enrichment in interleukin-6 family signaling that functionally confers resistance to chemotherapy. Overall, this study demonstrates that characterization of the tumor microenvironment using single-cell spatial transcriptomics allows for the identification of molecular interactions that may play a role in the emergence of therapeutic resistance and offers a spatially based analysis framework that can be broadly applied to other contexts.

Efficacy of postoperative radioactive iodine therapy for patients with low and intermediate risk papillary thyroid carcinoma.

PURPOSE: This study aimed to evaluate the efficacy of postoperative radioactive iodine (RAI) and its impact on recurrence rates and survival benefits in low- to intermediate-risk papillary thyroid carcinoma (PTC). METHODS: This retrospective study involved the examination of 1286 patients diagnosed with low- to intermediate-risk PTC who underwent total thyroidectomy with or without neck dissection, supplemented with postoperative RAI therapy or not between the years 2000 and 2021. RESULTS: From the patient pool, 589 (45%) were classified as low-risk and 697 (55%) as intermediate-risk according to the 2015 American Thyroid Association guidelines. Among the low-risk group, 375 (63.7%) underwent postoperative RAI, while in the intermediate-risk group, 566 (82.2%) underwent the procedure. The overall survival and disease-free survival rates were not statistically different between the groups that received RAI and those that did not, in both the low- and intermediate-risk categories. In a subgroup analysis, within the intermediate-risk category, postoperative RAI was significantly correlated with decreased recurrence in two subgroups: patients over 55 years with pN1b disease (hazard ratio 0.043, 95% confidence interval 0.004-0.500, p = 0.012) and patients over 55 years with five or more metastatic lymph nodes (hazard ratio 0.060, 95% confidence interval 0.005-0.675, p = 0.023). CONCLUSION: Our findings suggest that, while post-total thyroidectomy RAI does not substantially influence recurrence or survival rates in most low-risk and intermediate-risk PTC patients, it may be beneficial in specific subgroups, particularly patients over 55 with pN1b disease or those presenting with five or more metastatic lymph nodes.

L-Fucose-Rich Sulfated Glycans from Edible Brown Seaweed: A Promising Functional Food for Obesity and Energy Expenditure Improvement.

The global obesity epidemic, exacerbated by the sedentary lifestyle fostered by the COVID-19 pandemic, presents a growing socioeconomic burden due to decreased physical activity and increased morbidity. Current obesity treatments show promise, but they often come with expensive medications, frequent injections, and potential side effects, with limited success in improving obesity through increased energy expenditure. This study explores the potential of a refined sulfated polysaccharide (SPSL), derived from the brown seaweed Scytosiphon lomentaria (SL), as a safe and effective anti-obesity treatment by promoting energy expenditure. Chemical characterization revealed that SPSL, rich in sulfate and L-fucose content, comprises nine distinct sulfated glycan structures. In vitro analysis demonstrated potent anti-lipogenic properties in adipocytes, mediated by the downregulation of key adipogenic modulators, including 5' adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor γ (PPARγ) pathways. Inhibiting AMPK attenuated the anti-adipogenic effects of SPSL, confirming its involvement in the mechanism of action. Furthermore, in vivo studies using zebrafish models showed that SPSL increased energy expenditure and reduced lipid accumulation. These findings collectively highlight the therapeutic potential of SPSL as a functional food ingredient for mitigating obesity-related metabolic dysregulation by promoting energy expenditure. Further mechanistic and preclinical investigations are warranted to fully elucidate its mode of action and evaluate its efficacy in obesity management, potentially offering a novel, natural therapeutic avenue for this global health concern.

Accumulated in-situ spectral information analysis of room-temperature phosphorescence with time-gated bioimaging.

This study introduces the time-gated analysis of room-temperature phosphorescence (RTP) for the in-situ analysis of the visible and spectral information of photons. Time-gated analysis is performed using a microscopic system consisting of a spectrometer, which is advantageous for in-situ analysis since it facilitates the real-time measurement of luminescence signal changes. An RTP material hybridized with a DNA aptamer that targets a specific protein enhances the intensity and lifetime of phosphorescence after selective recognition with the target protein. In addition, time-gated analysis allows for the millisecond-scale imaging of phosphorescence signals, excluding autofluorescence, and improves the signal-to-background ratio (SBR) through the accumulation of signals. While collecting the time-gated images and spectra of RTP and autofluorescent materials simultaneously, we develop a method for obtaining phosphorescence signals by means of selective exclusion of autofluorescence signals in simulated or real cell conditions. It is confirmed that the accumulated time-gated analysis can provide ample information about luminescence signals for bioimaging and biosensing applications.

Quality Characteristics of Meat Analogs through the Incorporation of Textured Vegetable Protein and Tenebrio molitor Larvae in the Presence of Transglutaminase.

Alternative protein sources with greater nutritional value and a lower environmental footprint have recently attracted interest in the production of meat substitutes. However, it is required that these alternatives mimic the texture and structure of meat. This study investigated varying ratios of textured vegetable proteins (TVP) to Tenebrio molitor larvae (brown mealworm; TM) with the addition of transglutaminase (TG) to determine the quality characteristics of these emulsions. The results demonstrated low protein solubility of the emulsions as TVP content increased. Furthermore, when the proportion of TM was high, the TG-treated emulsion had a low pH. Additionally, when there was a high TM ratio to TVP in the TG treatment, the emulsions demonstrated better thermal stability and water holding capacity. Regarding the rheological properties of the emulsion, both the frequency-dependent storage modulus (G') and loss modulus (G'') increased as the proportion of TVP in the emulsion increased with and without the addition of TG. Differential scanning calorimetry analyses demonstrated two protein denaturation peaks in all treatments, with high peak temperatures for both treatments with a high proportion of TM. The hardness and chewiness of the emulsion were highest in the treatment (T6 and T8) with TG, and the gumminess of the emulsion was greatest when TM only or when equal ratios of TVP and TM were treated with TG, respectively. In conclusion, the addition of TM to TVP with TG improves the overall texture of the protein mixture, making it a suitable meat alternative.

The influence of spatial distribution and transcriptional regulation of secondary metabolites on the bioactivities of Adenophora triphylla (Japanese lady bell).

The distribution of secondary metabolites in plant tissues plays a crucial role in determining their pharmacological properties. In this study, we investigated the dynamics of the bioactive compounds in Adenophora triphylla, a medicinal herb with diverse therapeutic applications. The anti-inflammatory properties of the EtOAc fraction from the aerial part extract (A_ EtF) exhibited an IC50 value of 27.2 ± 2.3 µg/mL, significantly surpassing that of the EtOAc fraction from the root extract (R_EtF) with an IC50 of 38.9 ± 2.9 µg/mL. Similarly, the anti-melanogenic activity of A_EtF (IC50 = 68.9 ± 2.3 µg/mL) outperformed that of R_EtF (IC50 = 90.0 ± 5.5 µg/mL). Analysis of the distinct chemical profiles of these tissues using UPLC-ESI-Q-TOF-MS revealed that the distribution of secondary metabolites contributes to the observed variations in pharmacological properties between the aerial parts and roots. Transcriptome analysis further elucidated spatially regulated genes associated with secondary metabolism, highlighting the role of AbtYABBYs as potential regulators of phenylpropanoid biosynthesis. To validate their function, these genes were transiently expressed in tobacco leaves via agro-infiltration, confirming their role in modulating polyphenolic compound biosynthesis. Our findings underscore the importance of understanding spatial gene expression patterns for harnessing the complete pharmacological potential of medicinal plants. This study provides valuable insights into the spatial regulation of secondary metabolism and lays the groundwork for targeted manipulation of plant bioactivity for therapeutic and industrial applications.

The influence of exercise intensity on comorbid anxious behavior in psychiatric conditions.

Many experts have extensively studied the potential of exercise as a treatment option for psychiatric conditions, including depression and autism spectrum disorder (ASD). Despite their core symptoms, these conditions exhibits comparable component traits, an anxiety. In this study, we explored the effect of exercise on behavioral abnormalities in psychiatric conditions, focusing on its intensity and emotional resilience. Shank3B knockout (KOSED) mice displaying self-injurious repetitive behavior and C57BL/6J mice, susceptible to stress as ASD and depression model, respectively, were subjected to moderate-intensity exercise (ME) for 2 weeks. ME mitigated the core symptoms (excessive grooming traits and behavioral despair) but did not exert a significant anxiolytic effect. Notably, exercise intensity has emerged as a critical determinant of its efficacy, as evidenced by a lower ventilation threshold and anxiolytic effect mediated by low-intensity exercise. The findings substantiate the notion that exercise is promising as a disease-modifying treatment, but intensity matters for emotional resilience.

Longitudinal dynamics of circulating tumor DNA for treatment monitoring in patients with breast cancer recurrence.

The prevalence and dynamics of circulating tumor DNA (ctDNA) in patients with breast cancer recurrence or de novo metastatic cancer were examined in a retrospective analysis of a prospective observational cohort. Twenty-three recurrent/metastatic breast cancer cases (8 locoregional, 15 distant metastasis) were enrolled, and sequential plasma samples were obtained. Anchor mutations were selected from the target sequencing of each patient's primary and/or metastatic tumor. An in-house developed assay (UHS assay) was employed for a tumor-informed ctDNA assay during treatment and follow-up. A median of three (range 1-5) anchor mutations per case were applied for ctDNA detection. ctDNA was detected in 14 (63.6%, 14/22) cases at the time of enrollment and 18 (78.5%, 18/23) cases during follow-up. More anchor mutations and higher tumor burden were significantly related to higher ctDNA positive rates (p-value 0.036, 0.043, respectively). The mean enriched variant allele frequency (eVAF) at each time point was significantly higher for stable or progressive disease responses (ANOVA test p-value < 0.001). Eight patients showed an increase in their ctDNA eVAF prior to clinical progression with a mean lead time of 6.2 months (range 1.5-11 months). ctDNA dynamics measured using personalized assay reflected the clinical course of breast cancer recurrence.

Interfacial Engineering for Controlled Crystal Mosaicity in Single-Crystalline Perovskite Films.

Organic-inorganic hybrid perovskites have attracted significant attention for optoelectronic applications due to their efficient photoconversion properties. However, grain boundaries and irregular crystal orientations in polycrystalline films remain issues. This study presents a method for producing crystalline-orientation-controlled perovskite single-crystal films using retarded solvent evaporation. It is shown that single-crystal films, grown via inverse temperature crystallization within a confined space, exhibit enhanced optoelectronic property. Using interfacial polymer layer, this method produces high-quality perovskite single-crystalline films with varying crystal orientations. Density functional theory calculations confirm favorable adsorption energies for (110) surfaces with methylammonium iodide and PbI2 terminations on poly(3-hexylthiophene), and stronger adsorption for (224) surfaces with I and methylammonium terminations on polystyrene, influenced by repulsive forces between the thiophene group and the perovskite surface. The correlation between charge transport characteristics and perovskite single-crystalline properties highlights potential advancements in perovskite optoelectronics, improving device performance and reliability.

A Mediating Effect of Public Service Motivation on Retention Intention Among Child Welfare Students: Task Self-Efficacy.

PURPOSE: This study investigates the role of Public Service Motivation (PSM) in retaining highly skilled and qualified child welfare graduates within the public child welfare sector. MATERIALS AND METHODS: Three entire cohorts of child welfare student social workers over three years (N = 125) in BSW and MSW child welfare programs at seven universities in a Southern state were surveyed to examine the effects of task self-efficacy achieved through the curriculum and public service motivation on retention intention among social work students specializing in child welfare practice at both the baccalaureate and master's levels. Mediation analysis was conducted to estimate the indirect effect of self-efficacy on students' retention intention. RESULTS: The self-efficacy of child welfare students, operationalized as their confidence in performing competencies, significantly influences their intention to remain in the field of child welfare. Furthermore, self-efficacy among child welfare students has a statistically significant effect on their PSM. PSM, in turn, significantly impacts their intention to persist in child welfare work. DISCUSSION: The findings indicate that PSM partially mediates the relationship between students" self-efficacy and their intent to remain in child welfare work, even when controlling for educational background. We recommend that child welfare agencies recognize and nurture workers" PSM by incorporating practices that promote PSM.

The Effect of Irradiation on Meat Products.

The effects of irradiation on meat constituents including water, proteins, and lipids are multifaceted. Irradiation leads to the decomposition of water molecules, resulting in the formation of free radicals that can have both positive and negative effects on meat quality and storage. Although irradiation reduces the number of microorganisms and extends the shelf life of meat by damaging microbial DNA and cell membranes, it can also accelerate the oxidation of lipids and proteins, particularly sulfur-containing amino acids and unsaturated fatty acids. With regard to proteins, irradiation affects both myofibrillar and sarcoplasmic proteins. Myofibrillar proteins, such as actin and myosin, can undergo depolymerization and fragmentation, thereby altering protein solubility and structure. Sarcoplasmic proteins, including myoglobin, undergo structural changes that can alter meat color. Collagen, which is crucial for meat toughness, can undergo an increase in solubility owing to irradiation-induced degradation. The lipid content and composition are also influenced by irradiation, with unsaturated fatty acids being particularly vulnerable to oxidation. This process can lead to changes in the lipid quality and the production of off-odors. However, the effects of irradiation on lipid oxidation may vary depending on factors such as irradiation dose and packaging method. In summary, while irradiation can have beneficial effects, such as microbial reduction and shelf-life extension, it can also lead to changes in meat properties that need to be carefully managed to maintain quality and consumer acceptability.

Evaluation of safety and operative time in tumescent-free robotic nipple-sparing mastectomy: a retrospective single-center cohort study.

Purpose: Tumescent in nipple-sparing mastectomy (NSM) has been reported to increase the risk of necrosis by impairing blood flow to the skin flap and nipple-areolar complex. At our institution, we introduced a tumescent-free robotic NSM using the da Vinci single-port system (Intuitive Surgical, Inc.). Methods: We conducted a retrospective analysis of patients who underwent tumescent-free robotic NSM between October 2020 and March 2023 at Asan Medical Center (Seoul, Korea). Clinicopathological characteristics, adverse events, and operative time were evaluated. Results: During the study period, 118 patients underwent tumescent-free robotic NSM. Thirty-one patients (26.3%) experienced an adverse event. Five patients (4.2%) were classified as grade III based on the Clavien-Dindo classification and required surgery. The mean total operative time was 467 minutes for autologous tissue reconstruction (n = 49) and 252 minutes for implants (n = 69). No correlation was found between the cumulative number of surgical cases and the breast operative time (P = 0.30, 0.52, 0.59 for surgeons A, B, C) for the 3 surgeons. However, a significant linear relationship (P < 0.001) was observed, with the operative time increasing by 13 minutes for every 100-g increase in specimen weight. Conclusion: Tumescent-free robotic NSM is a safe procedure with a feasible operative time and few adverse events.

Structure-Activity Relationship Study of Tris-Benzamides as Estrogen Receptor Coregulator Binding Modulators.

Estrogen receptor coregulator binding modulators (ERXs) are a novel class of molecules targeting the interaction between estrogen receptor α (ERα) and its coregulator proteins, which has proven to be an attractive strategy for overcoming endocrine resistance in breast cancer. We previously reported ERX-11, an orally bioavailable tris-benzamide, that demonstrated promising antitumor activity against ERα-positive breast cancer cells. To comprehend the significance of the substituents in ERX-11, we carried out structure-activity relationship studies. In addition, we introduced additional alkyl substituents at either the N- or C-terminus to improve binding affinity and biological activity. Further optimization guided by conformational restriction led to the identification of a trans-4-phenylcyclcohexyl group at the C-terminus (18h), resulting in a greater than 10-fold increase in binding affinity and cell growth inhibition potency compared to ERX-11. Tris-benzamide 18h disrupted the ERα-coregulator interaction and inhibited the ERα-mediated transcriptional activity. It demonstrated strong antiproliferative activity on ERα-positive breast cancer cells both in vitro and in vivo, offering a promising potential as a therapeutic candidate for treating ERα-positive breast cancer.

Association of residual ductal carcinoma in situ with breast cancer treatment outcomes after neoadjuvant chemotherapy according to hormone receptor status.

PURPOSE: This research aimed to clarify the impact of residual ductal carcinoma in situ(DCIS) in surgical specimens obtained after neoadjuvant chemotherapy(NAC) for breast cancer on the associated prognosis outcomes. METHODS: This retrospective study was performed on a cohort of 1,009 patients who achieved pCR following NAC for breast cancer and underwent subsequent breast surgery at a single institution between January 2008 and December 2019. Overall survival, local recurrence-free survival, distant metastasis-free survival, and disease-free survival of the residual and non-residual DCIS groups were the outcomes compared, with further subgroup analysis performed according to hormone receptor status. RESULTS: 260 individuals (25.8%) presented with residual DCIS. Based on a median follow-up of 54.0 months, no significant differences in outcomes were observed between the two groups. Patients with residual DCIS and hormone receptor-negative (HR-) breast cancer demonstrated a significant decrease in distant metastasis-free survival (p = 0.030) compared to those without residual DCIS. In the HR + cohort, no significant difference was observed between the two groups. Multivariate analysis of the HR- cohort demonstrated a significant association between residual DCIS and an elevated risk for distant recurrence (hazard ratio = 2.3, 95% confidence interval = 1.01-5.20, p = 0.047). CONCLUSIONS: Residual DCIS following NAC may impact breast cancer outcomes, particularly with respect to the occurrence of distant metastasis in HR- patients. Therefore, clinicians must vigilantly monitor patients with residual DCIS after NAC, and further research is needed to expand our understanding of the clinical implications of residual DCIS.