Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome is a rare paraneoplastic disorder associated with plasma cell dyscrasia and multisystem involvement. This report describes a case of splanchnic venous thrombosis presenting as the initial clinical manifestation. A 38-year-old woman presented with acute abdominal pain associated with progressive polyneuropathy. Imaging studies revealed extensive thrombosis of the superior mesenteric vein with extension into the portal vein, moderate ascites, hepatosplenomegaly, and diffuse osteosclerotic bone lesions. Laboratory investigations demonstrated an immunoglobulin A (IgA) lambda monoclonal gammopathy. Positron emission tomography-computed tomography showed widespread hypermetabolic osteosclerotic lesions, hypermetabolic axillary lymphadenopathy, and increased cardiac uptake. Transthoracic echocardiography revealed right ventricular dilation with an intermediate probability of pulmonary hypertension. The overall clinical, radiological, and laboratory findings were consistent with disseminated POEMS syndrome. This case illustrates a rare initial presentation of POEMS syndrome manifesting as splanchnic venous thrombosis. It emphasizes the importance of considering POEMS syndrome in patients with unexplained portal hypertension or atypical venous thrombosis in the presence of systemic manifestations.
The geyser phenomenon is a rare complication of chronic rotator cuff disease in which synovial fluid passes from the glenohumeral joint through a rotator cuff defect into the acromioclavicular (AC) joint, resulting in a cystic swelling over the shoulder. Because these lesions can enlarge over time and exhibit atypical imaging features, they may be mistaken for soft tissue tumors. We report the case of a 78-year-old Saudi man with diabetes mellitus, hypertension, and rheumatoid disease who presented with a slowly enlarging left shoulder mass that had been present for 1.5 years. Magnetic resonance imaging (MRI) demonstrated a 5.7-cm complex cyst communicating with the AC joint, associated with massive full-thickness rotator cuff tears and advanced degenerative changes. Follow-up imaging showed interval enlargement of the lesion, hemorrhagic contents, and a new lytic lesion in the lateral clavicle, raising concern for infection or malignancy. The patient underwent surgical excision of the lesion with distal clavicle resection. Histopathological examination revealed a benign inflammatory pseudocyst with no evidence of malignancy. This case illustrates an unusual presentation of the geyser phenomenon that clinically and radiologically mimicked a soft tissue neoplasm. Awareness of this entity may help avoid unnecessary investigations and facilitate the establishment of the correct diagnosis.
Enhancements in crop resilience strategies that maintain production are essential to address the challenges posed by climate change and increasing food consumption. Calcium-dependent signaling networks are essential for plant responses to abiotic and biotic stressors, with calmodulin-binding transcription activator (CAMTA) transcription factors serving as crucial regulators within this framework, as these factors govern gene expression through specific cis-regulatory elements located in promoter regions. Recent investigations have expanded to include CAMTA-binding motifs as the stress-responsive cis-regulatory modules across several plant species under examination. These findings indicate that CAMTA-associated cis-elements, comprising CGCG motifs and ABA-responsive regions, facilitate the integration of environmental signals that influence transcription. Cis-regulatory elements (CREs), such as promoters, enhancers, silencers, and insulators, control the exact timing and location of stress-responsive gene expression in plants. Recent breakthroughs in genome editing have enabled the direct manipulation of these cis-regulatory areas, facilitating precise control over gene expression. This work presents an overview of CAMTA structures, their interaction with promoter cis-regulatory regions, and the potential for promoter cis-element engineering to enhance agricultural performance under diverse settings. It emphasizes CRISPR-based strategies for precise CRE modifications and highlights the role of CAMTA in identifying stress-responsive regions. This establishes the foundation for the advancement of next-generation stress-resilient crops, which will ensure food security.
X-linked hypophosphatemic rickets (XLH) is the most common form of hereditary vitamin-resistant rickets, caused by inactivating mutations of the PHEX (phosphate-regulating endopeptidase homolog, X-linked) gene, leading to elevated fibroblast growth factor 23 (FGF23) and chronic hypophosphatemia secondary to renal phosphate wasting. We report the case of a 3.5-year-old boy presenting with bilateral varus deformity of the lower limbs, frontal bossing, rachitic rosary, and growth retardation (-2.5 SD). Laboratory investigations revealed hypophosphatemia (0.88 mmol/L) with severely reduced urinary phosphate excretion (196.8 mg/24 h), elevated alkaline phosphatase (521 IU/L), and normal serum calcium and vitamin D levels. Exome sequencing identified a hemizygous pathogenic variant in PHEX: c.2192T>G (p.Phe731Cys), confirming the diagnosis of XLH. This case illustrates the decisive contribution of exome sequencing in confirming vitamin-resistant rickets and the importance of early diagnosis to prevent irreversible orthopedic sequelae.
Older men with HIV (MWH) experience a higher burden of frailty than age-matched men without HIV, but the biological mechanisms underlying this vulnerability are not completely understood. Testosterone (T) deficiency may contribute to frailty through effects on muscle mass and physical function. To evaluate the associations of free (T), total T, and sex hormone-binding globulin (SHBG) with incident frailty among men with HIV. Prospective cohort study. The MACS/WIHS Combined Cohort Study. 306 non-frail MWH (129 robust, 177 prefrail) with longitudinal frailty assessments. Incident frailty defined using the Fried frailty phenotype. Free T, Total T and SHBG were measured, with free T assessed by equilibrium dialysis. Marginal structural models were used to estimate associations with frailty outcomes while accounting for time and related covariates. Over a mean follow-up of 9.0 years, low free T (<54 pg/mL) and low total T (<300 ng/dL) were associated with higher risk of incident frailty compared with higher concentrations (HR: 2.49, 95%CI:1.21-5.11; HR: 3.31, 95%CI: 1.26-8.68, respectively). SHBG concentrations were not consistently associated with frailty outcomes. Low T levels predict incident frailty in men with HIV. Assessment of androgen status may help identify men at increased frailty risk. Further investigations are warranted to assess the role of T therapy in frailty prevention.
Piper crocatum Ruiz & Pav. (Piperaceae), commonly known as red betel, is a medicinal plant widely used in Southeast Asian traditional medicine and has attracted increasing interest due to its diverse pharmacological properties. However, the relationship between its phytochemical constituents, biological activities, molecular mechanisms, and drug discovery potential remains insufficiently integrated. This Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided review aimed to summarize the phytochemical constituents and pharmacological activities of P. crocatum and evaluate their relevance as potential lead structures for drug development. Literature published between 2000 and 2026 was retrieved from Scopus and PubMed. A total of 180 records were identified, and 102 eligible original studies reporting phytochemical and/or biological investigations of P. crocatum were included in the final analysis. Forty compounds have been reported from P. crocatum, including phenolic compounds, neolignans, flavonoids, terpenoids, and phytosterols. These constituents are associated with antimicrobial, antibiofilm, antioxidant, anti-inflammatory, antidiabetic, hepatoprotective, anticancer, and immunomodulatory activities. Mechanistic evidence suggests that these effects involve modulation of oxidative stress, inflammatory signaling, microbial sterol biosynthesis, biofilm-related proteins, and metabolic enzymes such as α-glucosidase and pancreatic lipase. Among the reported compounds, pachypodol, crocatin derivatives, β-sitosterol, and stigmasterol show promising pharmacological profiles and may serve as lead structures for further development. Overall, the chemical diversity and multitarget activities of P. crocatum support its potential as a source of drug discovery candidates. Future studies should prioritize bioassay-guided isolation, molecular target validation, pharmacokinetic evaluation, and structure-activity relationship analysis.
Randomized clinical trials are a mainstay of medical research, but have drawbacks including time and cost. Bayesian adaptive trials can improve the speed and efficiency of clinical trials and are an increasingly common trial design in critical care. However, the complexity of Bayesian adaptive trials may prevent clinicians from easily interpreting their results. Do intensivist physicians perceive, understand, and accept results from Bayesian adaptive clinical trials differently than results from traditional frequentist trials when presented with otherwise identical data? We surveyed US intensivists from March through April 2022 about their perceptions of Bayesian adaptive trials. Within the survey, participants were randomized to read an abstract for a hypothetical new sepsis drug trial that used either Bayesian adaptive methods or traditional frequentist methods, with both abstracts based on the same simulated trial data. Participants then were asked about perceived understanding, validity, and general acceptance of the trial's methods and results. Survey responses were compared between experimental groups using Mann-Whitney U tests and ordinal logistic regressions. We received complete results from 273 of 592 eligible physicians (response rate, 46.1%). Participants in the Bayesian group reported lesser understanding of the methods (mean rating in frequentist vs Bayesian groups, 3.18 vs 2.85; P < .001) and the results of the trial (mean rating, 3.36 vs 3.00; P < .001) compared with the frequentist group. Participants in the Bayesian group also expressed greater concerns about trial validity (eg, mean rating about the risk of type 1 error, 2.70 vs 2.99; P = .001) compared with the frequentist group. Participants in both groups reported similar beliefs about acceptance of trial results (eg, mean rating in frequentist vs Bayesian group about the effectiveness of the study drug, 3.87 vs 3.86; P = .47). Our results show that despite lower perceived understanding of Bayesian trials and skepticism about elements of their validity, no substantive differences were found in intensivist physician acceptance of Bayesian trial results compared with frequentist trial results. CHEST Critical Care 2026; 4(2):100264.
Multicultural adolescents in South Korea may face unique challenges related to acculturation that can affect their mental health over time. This study examined developmental trajectories of depression among multicultural adolescents in South Korea over a 9-year period and investigated how acculturation strategies and contextual factors influence these trajectories. Participants were 1,500 multicultural adolescents (50.7% female; Mage = 10.98 years at baseline) from the Multicultural Adolescents Panel Study (2012-2020). The sample included adolescents with mothers from various countries (Japan 33.4%, Philippines 25.1%, Chinese Korean 19.1%, China 7.3%, others 15.1%). Using latent class growth analysis, we examined depression trajectories and their associations with individual factors (acculturation strategies, self-esteem, acculturative stress), parental acculturative stress, and friend support. We identified three distinct depression trajectories (low-level: 38.7%, mid-level: 44.9%, and high-level: 16.4%). Integration acculturation strategy showed advantages over assimilation in predicting more favorable depression trajectories. However, contrary to traditional expectations, results tentatively suggest that marginalization may not necessarily be associated with worse outcomes compared to separation strategies, although this finding should be interpreted with caution given the dichotomized measurement of acculturation strategies. Higher self-esteem, lower acculturative stress, and stronger friend support significantly predicted membership in more favorable trajectory groups. These findings challenge assumptions about uniform vulnerability to depression among multicultural adolescents and suggest more complex relationships between acculturation strategies and mental health than previously recognized.
Background The optimal choice of polyethylene insert in total knee arthroplasty (TKA) continues to cause contention. Rotating platform bearings (RP) have theoretical advantages but have failed to demonstrate a functional difference compared to fixed bearings (FB) in clinical studies. No studies have analysed the effect of body mass index (BMI) on functional scores between RP and FB TKA. No studies have investigated RP and FB TKA using the new Patient Knee Implant Performance (PKIP) patient-reported outcome measure (PROM). Methods This was a post-hoc analysis of the data from two prospective, non-randomised, multi-centre studies conducted across centres in Australia, the United Kingdom, and the United States by DePuy Synthes (West Chester, Pennsylvania, United States). Functional outcomes between RP TKA and FB TKA were compared. Baseline and two-year follow-up data were compared across multiple PROMs in both groups, including PKIP. The analysis included adjustment for BMI between groups. Results A total of 1,718 patients across 27 centres were included in the study. Of this, 959 participants underwent FB TKA and 759 participants underwent RP TKA. No significant difference was found between RP and FB in the change from baseline at two years across any parameter in all PROMs. When adjusted for BMI, statistical differences were seen between RP TKA and FB TKA at two years in several PROMs. Conclusion Both FB and RB showed excellent results at two years. Our data does not demonstrate a significant difference in RP TKA over FB TKA at two years in any PROM. Advantages were seen in some PROMs for RP when adjusted for BMI alone at two years.
Introduction The use of generative artificial intelligence (GenAI) has been widely adopted across multiple fields and is beginning to be integrated into research, specifically in qualitative and mixed-methods designs. Currently, GenAI can be used for data familiarization and analysis. However, approaches that integrate GenAI with human analysis are still relatively new, and no studies in medical education have explored this approach. The overarching purpose of this study is to compare GenAI-led and human-led thematic analyses of qualitative data and to explore strategies that can enhance GenAI-led thematic analysis, thereby providing insights into how GenAI and human-led analyses can complement each other. Methods  A GenAI platform (Microsoft 365 Copilot; Microsoft Corporation, Redmond, Washington, USA) was used to conduct reflexive thematic analysis and generate themes through a qualitative research dataset that includes 23 interview transcripts, whereby data were collected in 2024. The GenAI analysis was conducted through an iterative process of exploring the functions of Copilot, optimizing data input, and investigating prompting strategies. The quality of the GenAI analysis was explored by comparing its output to the human-led analysis. Results Overall, we found that, through effective prompting strategies, Copilot was able to create a thematic table, providing a comprehensive view and summary of the data. However, at times, Copilot could not use the entirety of a large prompt. Additionally, through examining the Copilot-generated and human-generated codebooks, it was found that Copilot took a more interpretive analytical approach compared to the human-led analysis, which utilized a qualitative descriptive approach. Conclusion In conclusion, since the use of GenAI to support qualitative analysis is new, we caution readers to explore the functions of the GenAI platform they use and understand the prompting strategies that yield the optimal analytical approach and output for their objectives. Specifically, it is important to reflect on the types of qualitative analysis that GenAI can support and to consider reflexivity and potential biases throughout the research process.
The aim of the present investigation was to observe the effects of different energy densities of ultraviolet A photobiomodulation (UVA PBM) on human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs). The hESC-MSCs were cultured and irradiated with UVA PBM at energy densities ranging from 0.5 to 5.0 J/cm2 at a wavelength of 355 nm. Key biological parameters, including proliferation, viability, and migration, were evaluated at 72 h postirradiation. Compared with the control, the UVA PBM significantly increased cell proliferation and viability at energy densities ranging from 0.5 to 2.0 J/cm2 and 0.5 to 3.0 J/cm2, respectively. Further, UVA PBM notably increased the migratory capacity of hESC-MSCs within the 0.5-2.0 J/cm2 range. Interestingly, higher energy densities beyond this threshold were found to be ineffective in promoting these cellular responses. In addition to examining proliferation, viability, and migration, this study explored the role of UVA PBM in osteogenic differentiation. Following irradiation, hESC-MSCs were induced toward osteogenesis, and differentiation was assessed through Alizarin Red S staining to evaluate calcium deposition. The results indicated that UVA PBM at optimal low-energy densities not only enhanced early proliferation but also supported osteogenic potential, as evidenced by increased mineralization in treated cells. To further understand the molecular mechanisms underlying these effects, quantitative PCR (qPCR) was performed to analyze the expression of key osteogenic markers, including RUNX2, Alkaline phosphatase, and Osteocalcin (OCN). Gene expression analysis revealed significant upregulation of these markers in the UVA PBM-treated groups, suggesting that UVA PBM promotes osteogenesis at the transcriptional level. UVA PBM at low energy densities significantly enhances the proliferation, viability, migration, and osteogenic differentiation of hESC-MSCs, potentially through the modulation of osteogenic gene expression. These findings highlight the therapeutic potential of UVA PBM in regenerative medicine and bone tissue engineering, particularly dentistry.
Investigating how the auditory system processes harmonics is essential for advancing our understanding of sound segregation mechanisms and for guiding the development of technologies that support speech and music perception in complex listening environments, particularly for aging populations and individuals with hearing loss. Previous studies have investigated the extent of mistuning required for a harmonic to be perceived as distinct from a complex tone and how factors like modulation patterns, onset timing and ear of presentation can influence this threshold. However, the effect of a missing fundamental frequency on mistuned harmonic separation thresholds remains unexplored. This pilot study, conducted using an adjustment method developed in our lab for this specific application, investigated mistuning thresholds for the first harmonic in complex tones with and without F0 at 125, 200 and 440 Hz. Because the F0 helps define the harmonic structure of a sound, its removal was expected to impair the perceptual framework used to detect pitch deviations, thereby increasing mistuning thresholds, as predicted by current models of pitch perception. Contrary to expectations, the results revealed a significant overall improvement in performance when the F0 was missing. These results have important implications for understanding pitch processing as it suggests that the auditory system may more effectively detect pitch irregularities by relying on the harmonic structure of a sound rather than on the presence, or relationship with, its fundamental frequency.
Respiratory syncytial virus (RSV) is the leading cause of acute respiratory infections globally, with particularly severe implications for infants and the elderly population. Despite the substantial burden on public health, effective therapeutic options for the treatment of RSV infections remain limited. The pathogenesis of RSV is characterized by complex inflammatory responses, while high-mobility group box 1 (HMGB1), a damage-associated molecular pattern protein, is known to play a role in amplifying inflammation. However, the specific role of HMGB1 in RSV infection has not been thoroughly investigated. This study aims to elucidate the role of HMGB1 in RSV replication and to evaluate its potential as a target for antiviral therapy. The interaction between the RSV nucleocapsid (N) protein and HMGB1 was demonstrated through co-immunoprecipitation and mass spectrometry. Knockdown or overexpression of HMGB1 by small interfering RNA or pCMV-HA-HMGB1 resulted in a significant reduction or induction in RSV replication in vitro, thereby confirming the critical role of HMGB1 in viral propagation. Moreover, structure-based molecular docking analyses identified glycyrrhizic acid (GA) and amlexanox (AMX) as high-affinity ligands for HMGB1. In cellular studies, both GA and AMX effectively inhibited RSV replication in a dose-dependent manner while selectively suppressing HMGB1's secretion to the cytoplasm or extracellular space from RSV-infected cells. AMX was found to down-regulate HMGB1 expression while GA did not. In experiments using lethal murine RSV infection models, treatment with GA and AMX significantly improved survival rates and reduced lung pathology. In conclusion, these findings suggest that HMGB1 is a promising therapeutic target for RSV infection and highlight GA and AMX as potential antiviral candidates that can modulate HMGB1-mediated immunopathology.
Acute liver failure disrupts cerebral glucose homeostasis and contributes to neurological manifestations of hepatic encephalopathy (HE). Neurons, which partly rely on the insulin-sensitive glucose transporter GLUT4, may be particularly vulnerable to systemic metabolic disturbances. Transforming growth factor beta 1 (TGF-β1), implicated in HE pathogenesis, is known to modulate insulin signaling in peripheral tissues; however, its role in neuronal glucose handling remains poorly defined. In this study, we investigated whether reduction of peripheral TGF-β1 in HE impairs the neuronal GLUT4 status and whether this effect can be reproduced by systemic TGF-β1 neutralization (sTGF-β1n) in healthy mice. Both HE and sTGF-β1n increased GLUT4 immunoreactivity in MAP2-positive neurons and promoted its accumulation within the neuronal cytoplasm. Together with unaltered GLUT4 membrane levels, this suggests defective cytosol-to-membrane translocation or mobilization of the transporter. These changes were accompanied by altered PI3K/Akt/PKCζ signaling in HE only, but decreased AMPK phosphorylation in both model treatments, indicating the latter route to be the common mediator of impaired regulation of GLUT4 trafficking. While hypoglycemia and hyperinsulinemia were observed only in the HE model, selective sTGF-β1n reproduces alterations in neuronal GLUT4 distribution in the absence of hypoglycemia and hyperinsulinemia accompanying HE in the present model, indicating that TGF-β1 deficiency per se may contribute to this deficit. Our findings highlight TGF-β1 availability as a previously underappreciated modulator of neuronal glucose metabolism, and peripheral reduction of TGF-β1 as a factor potentially aggravating energy deficit in HE.
Background and objective Febrile seizures are the most common seizure disorder in children under five years of age. Although typically benign, their recurrence and atypical presentations warrant a deeper understanding of underlying risk factors. This study aims to explore the clinical, biochemical, and genetic factors associated with febrile seizures in young children. Methodology A hospital-based case-control investigation was conducted at a tertiary care teaching hospital in Uttar Pradesh. A total of 106 children aged six months to five years were enrolled, including 53 cases with febrile seizures and 53 age- and sex-matched febrile controls without seizures. KCC2 gene polymorphism analysis (rs2297201) was performed in children with atypical or recurrent febrile seizures and in matched controls. Comparative analyses were performed using the chi-squared test and Student's t-test (two-tailed), with a p-value of < 0.05 regarded as statistically significant. Results A total of 40 patients out of 53 (75.47%) experienced simple seizures, while 13 (24.53%) had complex seizures. Recurrence was reported in 19 (35.85%) cases out of 53. Electrolyte and biochemical analysis revealed significantly lower sodium, ionized calcium, magnesium, iron, vitamin B12, and vitamin D levels in the case group. Hemoglobin and mean corpuscular volume (MCV) were also significantly lower in the case group (p < 0.0001). Genotype analysis of the KCC2 rs2297201 polymorphism revealed a higher frequency of the CC genotype in the case group (p = 0.0318). Conclusion This study identifies significant clinical, biochemical, and genetic differences between children with febrile seizures and febrile controls. These findings may contribute to understanding the underlying mechanisms of febrile seizures and help identify potential biomarkers for early detection.
This brief research report investigates how racial and socioeconomic segregation shape spatial inequalities in health outcomes and healthcare access across Boston, Massachusetts. It examines the spatial clustering of race, poverty, and poor health, and analyzes how these patterns align with the locations of major hospitals in the city. We integrated data from the 2018-2022 American Community Survey, CDC PLACES, and the Massachusetts Center for Health Information and Analysis (CHIA) for all non-specialized acute care hospitals in Boston. Spatial autocorrelation was assessed using Global Moran's I statistics and Bivariate Local Indicators of Spatial Association (BiLISA) maps to identify co-clustering of non-White population, poverty, and poor health at the census tract level. All three measures showed statistically significant positive spatial autocorrelation (p < 0.001), confirming moderate-strong spatial clustering across Boston. Bivariate maps show racial composition, poverty, and poor health outcomes to have significant spatial clustering around hospitals. Historical segregation patterns still exist to this day and shape how people receive healthcare in the city. Patterns around recently closed Carney Hospital further underscored the spatial burden of care redistribution. Safety-net hospitals disproportionately serve neighborhoods with the greatest health and economic vulnerabilities while wealthier hospitals are embedded in healthier areas. These findings highlight the need for interhospital collaboration, equitable resource distribution, and policy interventions that explicitly address the spatial legacy of structural racism in healthcare delivery in American cities.
Direct electrical stimulation (DES) has long been used in patients undergoing epilepsy surgery for two key purposes: functional brain mapping and seizure triggering. In this review, the findings from DES applications to the opercula are synthesized, with the aim of mapping opercular functions and investigating seizure induction. Clinical responses to opercular DES are frequent and diverse, showing a partial segregation with spatial overlap, and exhibiting topographical differences: Emotion is evoked in the most anterior part of frontal operculum, expressive aphasia is the mid-posterior part, followed by oropharyngeal, dysarthria, and gustatory in the central opercula, somatosensory and vestibular in the posterior opercula, and auditory (or rarely visual) in the temporal opercula. No studies have specifically looked at DES-induced seizures from the opercula. Only a small number of studies about insulo-opercular epilepsy have mentioned that DES of the opercula induced seizures. Overall, opercular DES studies converge on the view that the opercula comprise a complex multimodal cortex integrating especially sensorial perception. Each subdivision had a different dominant response to DES, whose organization helps understand the different subgroups of opercular epilepsy.
Diabetes mellitus is an emerging global health concern, with its prevalence rising at an alarming rate. Cardiovascular complications are significantly more pronounced in diabetic individuals, underscoring the urgent need for effective therapeutic interventions. Significant efforts and investments have been dedicated to developing pharmacological treatments for diabetes. While each therapy offers its own advantages and disadvantages, their effectiveness in slowing disease progression remains limited. In contrast, exercise has gained recognition as a potent therapeutic strategy for diabetes and its complications, exerting metabolic and cardioprotective effects through various physiological and molecular mechanisms. Engaging in regular physical activity reduces cellular stress and inflammation, inhibits cardiomyocyte apoptosis and myocardial fibrosis, and improves endothelial and mitochondrial function, thereby maintaining cardiomyocyte homeostasis. Additionally, recent studies have investigated the potential synergistic effects of combining exercise with novel pharmacological agents, emphasizing its complementary role in managing diabetic heart failure. This review aims to discuss the mechanistic pathways through which structured physical exercise alleviates diabetic cardiomyopathy with additional consideration of its synergistic effects when combined with antidiabetic pharmacotherapies.
This study aims to determine phenolic contents, antioxidant capacity, and enzyme inhibition activity of Vitex agnus-castus L. extracts and three vinegars of Vitex Agnus-Castus L. (VAC Vinegar 1, 2, and 3). Quinic acid, gallic acid, protocatechuic acid, gentisic acid, chlorogenic acid, protocatechuic aldehyde, 4-OH benzoic acid, caffeic acid, salicylic acid, cyranoside, luteolin, and apigenin were detected in VAC Vinegar 1. VAC Vinegar 1 exhibited the highest phenolic (219.95 ± 4.57 µg PEs/mg) and flavonoid (121.71 ± 2.43 µg QEs/mg) contents. VAC Vinegar 3 demonstrated exceptional radical scavenging (ABTS IC50: 3.20 ± 0.01 µg/mL). VAC Vinegar 1 and 3 exhibited potent α-glucosidase inhibition and strong α-amylase inhibition. VAC vinegar 1 achieved the highest cholinesterase (93.12% AChE; 84.18% BChE), and urease (98.67%) inhibition, and all vinegars showed superior elastase and tyrosinase inhibition. Results highlight the functional potential of Vitex agnus-castus L. vinegars with potential applications related to anti-aging, neuroprotective, and glycemic regulatory effects.
Neoadjuvant chemotherapy (NAC) exerts selective pressure on tumor biology, frequently altering the expression of ER, PR, and HER2 in residual disease. While guidelines mandate re-biopsy to guide adjuvant therapy, whether these biomarker conversions represent a true prognostic deterioration or a manageable adaptation remains controversial. This study investigates the relative prognostic weight of biomarker conversion and proliferative dynamics (Ki-67) in determining patient survival. We retrospectively analyzed 338 patients with invasive breast cancer who had residual disease following standard NAC and curative surgery. Paired biomarker status (pre-NAC vs. post-NAC) for ER, PR, HER2, and Ki-67 was evaluated. Adjuvant therapy was adapted according to the residual tumor profile, including targeted therapy for patients acquiring HER2 positivity. Survival outcomes were analyzed using Cox regression models. Biomarker conversion was substantial, with conversion rates of 13.9% for ER, 18% for PR, and 27% for HER2. However, despite this high frequency of receptor conversion, changes in receptor status (loss or gain) did not translate into statistically significant differences in disease-free survival (DFS) or overall survival (OS) (all p > 0.05). In sharp contrast, Ki-67 dynamics emerged as the significant independent prognostic factor. Patients who converted from high-to-low proliferation (Ki-67 < 18%) achieved significantly superior DFS (HR: 0.45, 95% CI: 0.24-0.84, p = 0.011) and OS (HR: 0.36, 95% CI: 0.15-0.85, p = 0.020) compared to those with persistent high expression. While biomarker conversion is a frequent event in residual breast cancer, it does not compromise survival outcomes when adjuvant treatment is adjusted according to the post-NAC immunohistochemical (IHC) profile. Instead, prognosis is predominantly driven by the tumor's proliferative response. These findings suggest that persistent high Ki-67, rather than biomarker conversion, should be the primary marker for escalating adjuvant therapy and risk stratification.