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This study uncovers a dynamic shift in estrogen receptor expression during granulosa cell (GC) differentiation in the ovary, highlighting a transition from estrogen receptor alpha (ESR1) to estrogen receptor beta (ESR2). Using a transgenic mouse model with Esr1- iCre-mediated Esr2 deletion, we demonstrate that ESR2 expression is absent in GCs derived from ESR1-expressing ovarian surface epithelium (OSE) cells. Single-cell analysis of the OSE-GC lineage reveals a developmental trajectory from Esr1 -expressing OSE cells to Foxl2 -expressing pre-GCs, culminating in GCs exclusively expressing Esr2. Transcriptome analyses identified vasculature-derived TGFβ1 ligands as key regulators of this transition. Supporting this, TGFβ1 treatment of cultured embryonic ovaries reduced Esr1 expression while promoting Esr2 expression. This study underscores the capability of GCs to switch from ESR1 to ESR2 expression as a fundamental aspect of normal differentiation. [ABSTRACT FROM AUTHOR]

This guideline outlines the use of 3,4-dihydroxy-6-18F-fluoro-L-phenylalanine positron emission tomography / computed tomography for the diagnosis and management of neuroendocrine tumors, brain tumors, and other tumorous conditions. It provides detailed recommendations on patient preparation, imaging procedures, and result interpretation. Based on international standards and adapted to local clinical practices, the guideline emphasizes safety, quality control, and the effective application of 3,4-dihydroxy-6-18F-fluoro-L-phenylalanine positron emission tomography / computed tomography for various tumors such as insulinomas, pheochromocytomas, and medullary thyroid carcinoma. It also addresses the use of premedication with carbidopa, fasting protocols, and optimal imaging techniques. The aim is to assist nuclear medicine professionals in delivering precise diagnoses, improving patient outcomes, and accommodating evolving medical knowledge and technology. This comprehensive document serves as a practical resource to enhance the accuracy, quality, and safety of 3,4-dihydroxy-6-18F-fluoro-L-phenylalanine positron emission tomography / computed tomography in oncology. [ABSTRACT FROM AUTHOR]

This guideline outlines the use of 18F-fluoro-2-deoxyglucose positron emission tomography / computed tomography for the diagnosis and management of infectious and inflammatory diseases. It provides detailed recommendations for healthcare providers on patient preparation, imaging procedures, and the interpretation of results. Adapted from international standards and tailored to local clinical practices, the guideline emphasizes safety, quality control, and effective use of the technology in various conditions, including spinal infections, diabetic foot, osteomyelitis, vasculitis, and cardiac inflammation. The aim is to assist nuclear medicine professionals in delivering accurate diagnoses and improving patient outcomes while allowing flexibility to adapt to individual patient needs, technological advancements, and evolving medical knowledge. This document is a comprehensive resource for enhancing the quality and safety of 18F-fluoro-2-deoxyglucose positron emission tomography / computed tomography for the evaluation of infectious and inflammatory diseases. Preamble: The Korean Society of Nuclear Medicine (KSNM) was established in 1961 to promote the clinical and technological advancement of nuclear medicine in South Korea, with members that include nuclear medicine physicians and associated scientists. The KSNM regularly formulates and revises procedural guidelines for nuclear medicine examinations to enhance the field and improve the quality of patient care. These guidelines are designed to support healthcare professionals in providing appropriate medical care to patients. However, they are not immutable rules or mandatory requirements for conducting examinations. Therefore, KSNM states that these guidelines should not be used in legal actions challenging a healthcare professional's medical decisions. The ultimate judgment regarding specific procedures or appropriate measures should be made by nuclear medicine physicians, considering the unique circumstances of each case. Deviation from these guidelines does not imply substandard medical practice. Rather, reasonable judgments differing from the guidelines can be made based on the patient's condition, available resources, and advancements in knowledge or technology. Due to the diversity and complexity of patients, it is often challenging to predict the most appropriate diagnostic and accurate therapeutic responses. Thus, adherence to these guidelines does not always guarantee an exact diagnosis or successful outcomes. The purpose of this guideline is to assist healthcare providers in making reasonable decisions and conducting effective and safe examinations based on current medical knowledge, available resources, and patient needs when performing 18F-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) examinations for infectious/inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background: The phase angle (PhA) in bioelectrical impedance analysis (BIA) reflects the cell membrane integrity or body fluid equilibrium. We examined how the PhA aligns with previously known markers of acute heart failure (HF) and assessed its value as a screening tool. Methods: PhA was measured in 50 patients with HF and 20 non-HF controls along with the edema index (EI), another BIA parameter suggestive of edema. Chest computed tomography-measured lung fluid content (LFC) was used to assess pulmonary congestion. A correlation analysis was conducted to evaluate the relationships between PhA and EI, NT-proBNP, and LFC. Receiver operating characteristic (ROC) curve analysis was used to determine the cut-off values for PhA and EI for classifying patients with HF. The area under the curve (AUC) was compared using the DeLong test to evaluate the performance of PhA and EI compared to that of LFC in correctly classifying HF. Results: The PhA levels were significantly lower in the HF group. Whole-body PhA was 4.49° in the HF group and 5.68° in the control group. Moderate and significant correlation was observed between PhA measured at 50-kHz and both NT-proBNP (-0.56 to -0.27, all p-values<0.05) and LFC (-0.52 to -0.41, all p-values <0.05). The AUC for whole-body PhA was 0.827 (confidence interval [CI] 0.724–0.931, p<0.01) and was 0.883 (CI 0.806–0.961, p<0.01) for EI, and the optimal cutoffs were estimated as 5° (sensitivity 0.84, specificity 0.80) and 0.394 (sensitivity 0.78, specificity 0.95), respectively. When both PhA and EI were included in the model, the AUC increased to 0.905, and this was comparable to that of LFC (AUC = 0.913, p = 0.857). Conclusions: PhA exhibited a correlation with known markers of HF and demonstrated its potential as a non-invasive screening tool for the early detection of HF exacerbation. The combined use of PhA and EI can provide a robust alternative for routine self-monitoring in patients with HF, thereby enhancing early intervention. [ABSTRACT FROM AUTHOR]

Deuteronomy 19:16–21 states that a false accuser should face the same punishment intended for the accused. In Deut 22:20–21, if the groom’s charge is true, his bride’s penalty would be death. However, if his charge is false, in Deut 22:18–19, instead of the death penalty, the groom receives three penalties: 1) flogging, 2) payment, and 3) inability of divorcing her. Thus, most scholars have suggested that there is an apparent discrepancy of penalties between the groom and the bride in Deut 22:13–21. This article argues that the most essential element to satisfy the requirements of Deut 19:16–21 is intentionality, and that Deut 22:13–21 is not about the husband’s false accusation with evil intent to harm his wife; rather, it is a legitimate accusation of the husband concerning the wife’s virginity. Thus, the emphasis shifts from punitive measures to the intention behind the accusation, elucidating the underlying principles governing these laws. [ABSTRACT FROM AUTHOR]

Background: This study aimed to establish the optimal cutoff values for visual amyloid positivity using standardized uptake value ratios (SUVRs) in [18F]flutemetamol (FMM) positron emission tomography (PET) imaging. Given the variability in amyloid assessment, our goal was to determine cutoff values that enhance diagnostic accuracy and assist clinicians in reliably identifying amyloid positivity. Results: The identified cutoff values for visual amyloid positivity were > 1.6 for the cerebellar gray matter, > 1.38 for the whole cerebellum, and > 0.63 for the pons, yielding high sensitivity (95.5%, 94.5%, and 95.8%, respectively) and specificity (91.2%, 94.3%, and 95.2%, respectively). Conclusions: The SUVR cutoff values demonstrated excellent diagnostic performance, supporting their clinical use in assessing visual amyloid positivity in [18F]FMM PET imaging. [ABSTRACT FROM AUTHOR]

Chronic stress disrupts gut microbiota homeostasis, contributing to anxiety and depression. This study explored the effects of Limosilactobacillus reuteri fermented brown rice (FBR) on anxiety using an ICR mouse chronic mild stress (CMS) model. Anxiety was assessed through body weight, corticosterone levels, neurotransmitter profiles, and behavioral tests. A four-week FBR regimen reduced corticosterone, restored neurotransmitters like gamma-aminobutyric acid (GABA) and serotonin, and improved anxiety-related behaviors. Metagenomic (16S rRNA) and metabolomic analyses revealed enhanced amino acid metabolism, energy metabolism, and short-chain fatty acid (SCFA) production in FBR-treated mice. FBR-enriched beneficial gut bacteria, aligning the microbiota profile with that of non-stressed mice. FBR also modulated GABA receptor-related gene expression, promoting relaxation. Network pharmacology identified quercetin, GABA, glutamic acid, phenylalanine, and ferulic acid as bioactive compounds with neuroprotective potential. These findings highlight FBR's potential as a gut-brain axis-targeted therapeutic for anxiety and stress-related disorders. [ABSTRACT FROM AUTHOR]

Background/Objectives: Taxanes, including paclitaxel and docetaxel, are widely used in cancer treatment but frequently cause hypersensitivity reactions (HSRs), disrupting treatment continuity. This meta-analysis aimed to identify consistent risk factors for taxane-induced HSRs to support personalized risk assessments and optimize therapeutic outcomes. Methods: This systematic review and meta-analysis followed the PRISMA guidelines and was registered with PROSPERO (CRD42023476738). Comprehensive literature searches were conducted up to 30 June 2024. The quality of the studies was assessed using the Newcastle-Ottawa Scale. Data were synthesized to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs), using fixed or random effects models. Results: A total of 18 studies of moderate or higher quality were included, involving 8333 patients. The incidence of HSRs ranged from 3.0% to 33.1%. Risk factors assessed included history of allergy, obesity, postmenopausal state, ovarian cancer, and H2 receptor antagonist (H2RA) premedication. A history of allergy was identified as a potential risk factor with marginal significance (OR 1.85, 95% CI 0.97–3.54, p = 0.06), while H2RA premedication, ovarian cancer, and female sex were not significantly associated with HSR risk. Substantial heterogeneity was observed for obesity (I2 = 57.71%, p = 0.069) and postmenopausal status (I2 = 78.98%). Conclusions: This study highlights the complex nature of taxane-induced HSRs and emphasizes the need for personalized risk assessments. While a history of allergy is a potential risk factor, heterogeneity across other factors underscores the importance of individualized approaches. Clinicians should tailor strategies to balance the benefits of taxane therapy with patient-specific risks to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Motivated by the resource-based view (RBV) of the firm, this study explores whether mergers and acquisitions (M&As) can facilitate or impede a firm's marketing capabilities. Furthermore, this study also examines whether the influence of M&As on a firm's marketing capabilities is conditional to the type of deals, that is, domestic versus cross-border acquisitions. Using the difference-in-differences research design with a large sample of 15,509 firm-year observations for 898 US public acquirers, this study tests the postacquisition changes in a firm's marketing capabilities as reflected in the sensitivity of sales revenue to marketing-related expenditure. The results of the empirical tests show a postacquisition increase in sales sensitivity, suggesting that firms can enhance their marketing capabilities through M&As. However, it is also found that the enhancement in marketing capabilities is limited to domestic M&As and disappears for cross-border acquisitions. This result suggests that more salient differences in a firm's marketing environment attributable to cross-border acquisitions may disrupt a firm's marketing capabilities and dampen the positive effect of M&As. Fields of Specialization : Strategic management, marketing JEL CLASSIFICATION: G34; L25; M30 [ABSTRACT FROM AUTHOR]

Background: Multiple factors, such as muscle fatty infiltration (FI), tendon collagen content, and collagen arrangement, determine bone-tendon interface (BTI) healing after rotator cuff (RC) repair. Purpose: To evaluate the effects of systemic administration of ezetimibe-atorvastatin (EZE/ATZ) combination on muscle FI and tendon collagen density and arrangement in an RC repair rat model. Study design: Controlled laboratory study. Methods: A total of 26 male Sprague-Dawley rats were randomly divided equally into control and EZE/ATZ groups and subjected to RC tendon repair surgery. Postoperatively, the EZE/ATZ group rats received a combination of EZE (10 mg/kg/d) and ATZ (20 mg/kg/d) for 4 weeks, after which they were sacrificed. Oil Red O staining was used to assess FI in the supraspinatus muscle. The expression of biomarkers related to muscle atrophy and FI was measured using quantitative real-time polymerase chain reaction. For the qualitative and quantitative analysis of FI-related biomarkers, immunohistochemical staining was performed. Biomechanical and histological analyses were performed to evaluate the quality of BTI healing after RC repair. Results: The EZE/ATZ group showed significantly lower FI compared with the control group (P <.001) and significantly downregulated expression of gene markers related to muscle atrophy and FI. On histological analysis, the EZE/ATZ group exhibited increased collagen type I contents, consistent collagen arrangement (P =.005), and significantly higher collagen density (P =.003) compared with the control group. Biomechanical analysis of the BTI healing revealed that the EZE/ATZ group had significantly increased ultimate strength (P =.006) compared with the control group. Conclusion: Systemic EZE/ATZ administration suppressed supraspinatus FI by downregulating muscle atrophy–related and FI-related genes after RC repair. Additionally, EZE/ATZ use improved collagen biosynthesis, density, and arrangement at the BTI and significantly increased tensile strength. Clinical Relevance: The results of the current study strongly advocate the use of EZE/ATZ to improve shoulder function and tendon healing after RC repair. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to evaluate the treatment approaches and locoregional patterns for adenoid cystic carcinoma (ACC) in the breast, which is an uncommon malignant tumor with limited clinical data. Materials and Methods: A total of 93 patients diagnosed with primary ACC in the breast between 1992 and 2022 were collected from multi-institutions. All patients underwent surgical resection, including breast-conserving surgery (BCS) or total mastectomy (TM). Recurrence patterns and locoregional recurrence-free survival (LRFS) were assessed. Results: Seventy-five patients (80.7%) underwent BCS, and 71 of them (94.7%) received post-operative radiation therapy (PORT). Eighteen patients (19.3%) underwent TM, with five of them (27.8%) also receiving PORT. With a median follow-up of 50 months, the LRFS rate was 84.2% at 5 years. Local recurrence (LR) was observed in five patients (5.4%) and four cases (80%) of the LR occurred in the tumor bed. Three of LR (3/75, 4.0%) had a history of BCS and PORT, meanwhile, two of LR (2/18, 11.1%) had a history of mastectomy. Regional recurrence occurred in two patients (2.2%), and both cases had a history of PORT with (n=1) and without (n=1) irradiation of the regional lymph nodes. Partial breast irradiation (p=0.35), BCS (p=0.96) and PORT in BCS group (p=0.33) had no significant association with LRFS. Conclusion: BCS followed by PORT was the predominant treatment approach for ACC of the breast and LR mostly occurred in the tumor bed. The findings of this study suggest that partial breast irradiation might be considered for PORT in primary breast ACC. [ABSTRACT FROM AUTHOR]

The emergence of multidrug‐resistant (MDR) and extensively drug‐resistant (XDR) strains of Mycobacterium tuberculosis (Mtb) poses a significant threat to health globally. During searching for new chemical entities regulating MDR‐ and XDR‐Mtb, chemical investigation of the black oil beetle gut bacterium Micromonospora sp. GR10 led to the discovery of eight new members of arenicolides along with the identification of arenicolide A (Ar−A, 1), which was a previously reported macrolide with incomplete configuration. Genomic analysis of the bacterial strain GR10 revealed their putative biosynthetic pathway. Quantum mechanics‐based computation, chemical derivatizations, and bioinformatic analysis established the absolute stereochemistry of Ar−A and arenicolides D−K (Ar−D−K, 2–9) completely for the first time. Biological studies of 1–9 revealed their antimicrobial activity against MDR and XDR strains of Mtb. Ar−A had the most potent in vitro antimicrobial efficacy against MDR‐ and XDR‐Mtb. Mechanistically, Ar−A induced ATP depletion and destabilized Mtb cell wall, thereby inhibiting growth. Notably, Ar−A exerted a significant antimicrobial effect against Mtb in macrophages, was effective in the treatment of Mtb infections, and showed a synergistic effect with amikacin (AMK) in a mouse model of MDR‐Mtb lung infection. Collectively, our findings indicate Ar−A to be a promising drug lead for drug‐resistant tuberculosis. [ABSTRACT FROM AUTHOR]

Aim: This study examined the efficacy of AST‐001 for the core symptoms of autism spectrum disorder (ASD) in children. Methods: This phase 2 clinical trial consisted of a 12‐week placebo‐controlled main study, a 12‐week extension, and a 12‐week follow‐up in children aged 2 to 11 years with ASD. The participants were randomized in a 1:1:1 ratio to a high‐dose, low‐dose, or placebo‐to‐high‐dose control group during the main study. The placebo‐to‐high‐dose control group received placebo during the main study and high‐dose AST‐001 during the extension. The a priori primary outcome was the mean change in the Adaptive Behavior Composite (ABC) score of the Korean Vineland Adaptive Behavior Scales II (K‐VABS‐II) from baseline to week 12. Results: Among 151 enrolled participants, 144 completed the main study, 140 completed the extension, and 135 completed the follow‐up. The mean K‐VABS‐II ABC score at the 12th week compared with baseline was significantly increased in the high‐dose group (P = 0.042) compared with the placebo‐to‐high‐dose control group. The mean CGI‐S scores were significantly decreased at the 12th week in the high‐dose (P = 0.046) and low‐dose (P = 0.017) groups compared with the placebo‐to‐high‐dose control group. During the extension, the K‐VABS‐II ABC and CGI‐S scores of the placebo‐to‐high‐dose control group changed rapidly after administration of high‐dose AST‐001 and caught up with those of the high‐dose group at the 24th week. AST‐001 was well tolerated with no safety concern. The most common adverse drug reaction was diarrhea. Conclusions: Our results provide preliminary evidence for the efficacy of AST‐001 for the core symptoms of ASD. [ABSTRACT FROM AUTHOR]

Background Understanding the attachment patterns of the corrugator supercilii (CS) muscle is vital for treatments designed to improve facial symmetry and functionality. Objectives The aim of this research was to elucidate the anatomical trajectory and intricate relationships of the CS within the upper face and midface, specifically focusing on its connections with the frontalis (FT) and orbicularis oculi (OOc) muscles. Methods The CS was examined in 41 specimens of embalmed adult Korean cadavers with microdissection, histological analyses, and microcomputed tomography, performing an in-depth exploration of its anatomical positioning and the intricate interactions with adjacent muscles. Results Some lower fibers of the CS extended to the upper orbital part of the OOc in 59.5% of cases, while the CS interdigitated or blended exclusively with the FT in 40.5% of cases. The fibers of the CS demonstrated diverse extensions toward the upper face and midface, exhibiting varied trajectories and lengths. Additionally, lower fibers of the CS extended to significant anatomical landmarks such as the OOc, malaris muscle, and the superficial musculoaponeurotic system (SMAS). Conclusions In this study, we demonstrate that precise understanding of the CS and its relationship with the FT and OOc is crucial for optimizing invasive or noninvasive treatment like botulinum toxin injection, SMAS lifting, and browplasty surgery. The extension of lower fibers of the CS to significant anatomical landmarks indicates complex interactions with adjacent facial structures, highlighting the necessity of detailed anatomical knowledge for clinical applications. [ABSTRACT FROM AUTHOR]