Categories
Nevin Manimala Statistics

Clinical Utility of Targeted Next-Generation Sequencing for Determining Human Epidermal Growth Factor Receptor 2 Status and Optimizing Targeted Therapy in Breast Cancer

World J Oncol. 2025 Jul 8;16(4):347-356. doi: 10.14740/wjon2583. eCollection 2025 Aug.

ABSTRACT

BACKGROUND: The development of targeted next-generation sequencing (NGS) technologies has contributed to precision medicine, as evidenced by the growing interest in evaluating human epidermal growth factor receptor 2 (HER2) expression status to treat unresectable/metastatic HER2-low breast cancer (BC). However, the concordance between erb-b2 receptor tyrosine kinase 2 (ERBB2) copy number alteration (CNA) and HER2 immunohistochemistry (IHC) has never been determined. The aim of this study was to evaluate the utility of targeted NGS for determining HER2 status and optimizing targeted therapies for BC.

METHODS: ERBB2 CNAs were examined by targeted NGS in 41 formalin-fixed paraffin-embedded (FFPE) BC tissues. ERBB2 CNA was compared with HER2 status evaluated by IHC in tissue sections, which were identical to those subjected to targeted NGS, using the Ventana 4B5 antibody.

RESULTS: The median fold changes (FCs) for ERBB2 CNAs in tumors with an IHC score of 3+, 2+, 1+, and 0 were 4.81, 1.49, 1.00, and 1.00, respectively. The difference in the FC for ERBB2 CNA according to HER2 status was statistically significant (P < 0.001). An FC greater than 1.0 for ERBB2 CNA was established as the cutoff value to differentiate between tumors with an IHC score of 3+, 2+, or 1+ and tumors with an IHC score of 0, on the basis of receiver operating characteristic curve analysis. The overall percent agreement, positive percent agreement, negative percent agreement, and Cohen’s kappa between ERBB2 CNA and HER2 status were 68.3%, 57.7%, 86.7%, and 0.39, respectively. The numbers of patients with mutations in ERBB2, estrogen receptor 1 (ESR1), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), serine/threonine kinase 1 (AKT1), and phosphatase and tensin homolog (PTEN) were 7, 3, 6, 1, and 5, respectively. Targeted NGS detected additional gene mutations and presented treatment options for seven of 22 patients (31.8%) with an FC of ERBB2 CNA = 1.00.

CONCLUSIONS: Targeted NGS has the potential in distinguishing HER2 IHC 3+, 2+, and 1+ tumors from IHC 0 in patients with BC; however, differentiating between HER2 IHC 1+ and 0 remains challenging. Additionally, targeted NGS may aid in the identification of actionable mutations, thereby contributing to the selection of optimal treatment strategies in BC management.

PMID:40810081 | PMC:PMC12339287 | DOI:10.14740/wjon2583

Categories
Nevin Manimala Statistics

Can the MMP-9/NGAL ratio be a diagnostic biomarker for the diagnosis of endometrioma in infertile patients?

Front Endocrinol (Lausanne). 2025 Jul 30;16:1624717. doi: 10.3389/fendo.2025.1624717. eCollection 2025.

ABSTRACT

OBJECTIVE: In this study, we aimed to investigate whether serum NGAL, MMP-9 and the MMP-9/NGAL ratio, which are inflammatory markers used for the diagnosis and follow-up of some diseases, can be used as diagnostic and follow-up markers for the diagnosis of endometriomas in infertile patients.

METHODS: Forty-five patients with unexplained infertility and 45 infertile patients with endometriomas were included in the study. Patients with endometriomas of at least 3 cm in size were included in the study. NGAL and MMP-9 levels in venous blood samples and the MMP-9/NGAL ratios of the unexplained infertility and endometrioma groups and the preoperative and postoperative results of the endometrioma group were compared.

RESULTS: The mean blood NGAL and MMP-9 levels in the endometrioma and unexplained groups were 22.0 ± 4.0 ng/ml and 25.4 ± 4.9 ng/ml and 43.7 ± 8.0 ng/ml and 39.3 ± 10.7 ng/ml, respectively, and all the results were statistically significant (p=0.001; p=0.012). The mean blood levels of NGAL and MMP-9 in endometriomas and the same patients at three months after surgery were 24.9 ± 4.9 ng/ml and 27.0 ± 4.9 ng/ml and 43.9 ± 7.3 ng/ml and 36.7 ± 8.7 ng/ml, respectively (p=0.179; p=0.006). The mean ratios of MMP-9/NGAL in the endometrioma, unexplained and postoperative groups were 2.0 ± 0.2, 1.5 ± 0.2 and 1.4 ± 0.2, respectively. All these results were significantly different between the endometrioma-unexplained group and the endometrioma-postoperative group (p=0.001; p=0.001). When we performed a ROC curve analysis for the presence of endometrioma, an MMP-9/NGAL ratio greater than 1.75 had 86.1% sensitivity and 84% specificity in indicating the presence of endometrioma (AUC=0.898). There was a positive correlation between the VAS score and the MMP-9/NGAL ratio.

CONCLUSIONS: Interestingly, the NGAL blood NGAL level was lower in the endometrioma group than in the control group. The MMP-9/NGAL ratio can be useful in the diagnosis of endometrioma, and this ratio reflects the clinical findings of the disease.

PMID:40810077 | PMC:PMC12343217 | DOI:10.3389/fendo.2025.1624717

Categories
Nevin Manimala Statistics

The Impact of Critical Care Quarantine on the Residual Risk of Unexpected Organ Donor Blood-borne Virus Infection

Transplant Direct. 2025 Aug 13;11(9):e1843. doi: 10.1097/TXD.0000000000001843. eCollection 2025 Sep.

ABSTRACT

BACKGROUND: The transmission of undetected infections from organ donors to recipients is a persistent concern in transplantation medicine. Despite nucleic acid testing, some infections, especially those acquired recently, may evade detection. This study aimed to model the effects of critical care interval before screening on the residual risk of undetected infections in organ donors.

METHODS: We modeled the risk of blood-borne virus acquisition in donors using a Poisson process, assuming that the critical care interval carries negligible risk. A continuous probability function was developed using estimates of HIV, hepatitis C virus, and hepatitis B virus incidence, viral doubling rates, and assay performance characteristics from a commonly used triplex nucleic acid screening test.

RESULTS: Our quarantine-adjusted window period model showed that longer critical care intervals resulted in a decreased quarantine-adjusted residual risk of undetected infections. This relationship was linear for most assay window periods. For example, a typical critical care interval of 2.7 d reduces the residual risk by 43.5% for hepatitis C virus, 22.9% for HIV, and 7.4% for hepatitis B virus. In some clinical situations, the critical care quarantine effect may outweigh intragroup variations in risk behavior. The model also enabled comparisons of different blood collection times.

CONCLUSIONS: The quarantine-adjusted window period model indicates that the critical care interval further reduces the risk of undetected infections in deceased organ donors. This supports and quantifies the impact of screening organ donors as close to retrieval surgery as possible, rather than delaying surgery solely based on the risk of residual infection.

PMID:40810059 | PMC:PMC12348399 | DOI:10.1097/TXD.0000000000001843

Categories
Nevin Manimala Statistics

Health Promotion and Digital Tools: Analysis of Consumer Demands

Yonago Acta Med. 2025 Jul 9;68(3):187-196. doi: 10.33160/yam.2025.08.003. eCollection 2025 Aug.

ABSTRACT

BACKGROUND: A survey was conducted to determine the demand for the use of digital health content for health promotion, both among those interested in using digital tools and those interested in health promotion.

METHODS: This study targeted smartphone owners who attended a class on how to use a smartphone (CS) and/or a class on advancements in health (CH) held in Nanbu Town. The main questionnaire items included questions on age, gender, frailty, subjective cognitive decline (SCD), smartphone usage, and interest in health promotion using digital technology. An analysis was conducted on 33 participants in the CS and 33 participants from the CH who provided complete responses to the questionnaire.

RESULTS: The percentages of interest in using smartphones for accessing content on exercise, cognitive training, and nutrition management were 97.0%, 97.0%, and 87.9%, respectively, among CS participants and 69.7%, 78.8%, and 81.8%, respectively, among CH participants. The percentage of responses regarding interest in exercise content was significantly different between the two groups. Furthermore, some individuals responded that they were interested but concerned about how to use the services. No statistically significant differences were found with respect to the comparison of the percentages of responses by age group, frailty determination results, and SCD determination results among the participants of the CS and CR groups.

CONCLUSION: Regardless of age or the risk of developing health problems, there is demand for content related to health promotion using digital tools for those who want to master digital tools and who want to improve their health. However, support should be provided to them to ensure that they correctly use those tools. Notably, some individuals who want to improve their health are not interested in using digital tools.

PMID:40810047 | PMC:PMC12343190 | DOI:10.33160/yam.2025.08.003

Categories
Nevin Manimala Statistics

Words Matter with Age: Instructions Dictate Self-Selected Walking Speed in Young and Older Adults

bioRxiv [Preprint]. 2025 Jul 22:2025.07.18.665559. doi: 10.1101/2025.07.18.665559.

ABSTRACT

Background Our previous work demonstrated that in young adults, 61% of gait speed variance was attributable to instruction type. However, no study has investigated whether verbal instructions differentially influence older adults.

RESEARCH QUESTION: This study investigated how walking prompts contribute to gait speed variability across age groups.

METHODS: Thirty-four young adults (21±2 years) and twenty-eight older adults (70±5 years) performed walking trials responding to 24 different instructions.

RESULTS: Average walking speed was 1.23±0.30 m/s. Between-subject variance accounted for 25.3% of the total variance, while between subject and instruction variance components accounted for 76.1% of the total variance. When analyzed separately, variance due to instructions accounted for similar amounts of total variance within older adults (56.9%) and young adults (55.7%), a statistically non-significant difference (p = 0.85). A significant age-instruction interaction (χ 2 =76.84, df = 23. p<0.001) revealed that the age differences between average gait speed depended on which instruction was given. Complex instructions elicited the largest between group differences (β:-0.24 to -0.32 m/s), while simple tasks showed minimal differences (β:-0.03 to -0.06 m/s).

SIGNIFICANCE: Instructions explain similar variance within each age group (~56%), but the model treating instructions as fixed effects captures how different age groups respond to the same instructions. These findings highlight the critical importance of instruction standardization in gait assessment protocols, as systematic age-related differences in instruction interpretation can significantly impact measured outcomes. Instructions that produce minimal between-group differences may be most appropriate for standardized clinical assessments, while those showing larger age effects may be valuable for detecting age-related changes in gait control.

PMID:40810011 | PMC:PMC12346562 | DOI:10.1101/2025.07.18.665559

Categories
Nevin Manimala Statistics

Neural network models of autonomous adaptive intelligence and artificial general intelligence: how our brains learn large language models and their meanings

Front Syst Neurosci. 2025 Jul 30;19:1630151. doi: 10.3389/fnsys.2025.1630151. eCollection 2025.

ABSTRACT

This article describes a biological neural network model that explains how humans learn to understand large language models and their meanings. This kind of learning typically occurs when a student learns from a teacher about events that they experience together. Multiple types of self-organizing brain processes are involved, including content-addressable memory; conscious visual perception; joint attention; object learning, categorization, and cognition; conscious recognition; cognitive working memory; cognitive planning; neural-symbolic computing; emotion; cognitive-emotional interactions and reinforcement learning; volition; and goal-oriented actions. The article advances earlier results showing how small language models are learned that have perceptual and affective meanings. The current article explains how humans, and neural network models thereof, learn to consciously see and recognize an unlimited number of visual scenes. Then, bi-directional associative links can be learned and stably remembered between these scenes, the emotions that they evoke, and the descriptive language utterances associated with them. Adaptive resonance theory circuits control model learning and self-stabilizing memory. These human capabilities are not found in AI models such as ChatGPT. The current model is called ChatSOME, where SOME abbreviates Self-Organizing MEaning. The article summarizes neural network highlights since the 1950s and leading models, including adaptive resonance, deep learning, LLMs, and transformers.

PMID:40810002 | PMC:PMC12343567 | DOI:10.3389/fnsys.2025.1630151

Categories
Nevin Manimala Statistics

Dietary Protein Hydrolysate From Calanus finmarchicus Reduces Oxidative Stress and Increases Intestinal Health in European Sea Bass (Dicentrarchus labrax) Juveniles

Aquac Nutr. 2025 Aug 6;2025:5531437. doi: 10.1155/anu/5531437. eCollection 2025.

ABSTRACT

The aquaculture industry is in dire need of novel feed ingredients that can improve the health and welfare of farmed fish and shrimp. Zooplankton are natural and underutilized marine resources with the potential to be part of a nutritional solution. The aim of this study was to determine the health effects for European sea bass juveniles fed diets with a protein hydrolysate from the zooplankton species Calanus finmarchicus, a novel raw material for feed ingredients. Calanus hydrolysate (CH) was benchmarked using fish hydrolysates as controls at inclusion rates of 3%-4%, depending on the protein content for each of the hydrolysates to allow equivalent protein levels in the diets. The initial feeding trial was 84 days, with an additional week to perform an inflammatory challenge with a UV-inactivated bacterium. Fish receiving diets with CH inclusion were associated with lower levels of hepatic protein carbonyls, a lower level of calprotectin and higher levels of mucins compared to the control hydrolysate diets. No statistically significant differences among the diets for the biomarkers related to the inflammatory challenge were observed. The study showed that dietary inclusion of CH has the potential to reduce oxidative stress and increase intestinal health, thus, improving the health of European sea bass juveniles. These health-promoting effects, combined with the sustainable origin of C. finmarchicus highlight the potential of CH as a novel functional ingredient for future aquaculture feeds. Its use could contribute to reduced reliance on traditional fishmeal sources, thereby, supporting more sustainable and resilient aquaculture practices.

PMID:40809997 | PMC:PMC12349996 | DOI:10.1155/anu/5531437

Categories
Nevin Manimala Statistics

Association between Reusable Anesthesia Circuits and Hospital Waste Reduction, Cost Savings, and Environmental Impact: A Quality Improvement Study

Perioper Care Oper Room Manag. 2025 Sep;40:100518. doi: 10.1016/j.pcorm.2025.100518. Epub 2025 Jun 28.

ABSTRACT

BACKGROUND: Anesthesia services are a major contributor to healthcare sector greenhouse gas emissions. Interventions aimed to reduce waste are necessary. Reusable anesthesia circuits offer a sustainable alternative to single-use circuits. Their adoption in the United States remains limited. The objective of this project was to evaluate the feasibility, cost-effectiveness, and environmental impact of using FDA-approved reusable anesthesia circuits.

METHODS: Supported by the SMART QI framework, we evaluated the impact of switching to reusable circuits on elective electroconvulsive therapy (ECT) procedures. We measured waste generation, room preparation times, material costs, and projected system wide financial and greenhouse gas emissions impact. Greenhouse gas emissions were estimated using the Practice Greenhealth Scope 3 Emissions Accounting Tool. Descriptive statistics compared pre- and post-intervention outcomes, with statistical significance at p < 0.05.

RESULTS: We compared 185 ECT procedures: 98 single-use from pre-intervention and 87 reusable circuits from post-intervention. Preparation times did not change. Daily waste from reusable circuits was significantly lower than single-use circuits (99.2g vs. 357.2g, p < 0.001). Cost analysis revealed 40% reduction in median per-case expenditures with reusable circuits ($4.30 vs. $8.50 per patient, p < 0.001).Scope 3 greenhouse gas emissions per procedure decreased nearly 50% (1.09 kgCO2 vs. 2.57 kgCO2, p < 0.001). Modeling of institutional-level data projected an annual cost savings of $108,860 and a reduction of 45,062.4 kgCO2 if reusable circuits were implemented across all hospitals in the network.

DISCUSSION: Reusable anesthesia circuits can significantly reduce hospital waste, lower costs, and decrease carbon emissions without compromising procedural efficiency.

PMID:40809989 | PMC:PMC12341448 | DOI:10.1016/j.pcorm.2025.100518

Categories
Nevin Manimala Statistics

The use of parenteral application of ferric carboxymaltose in the prevention of iron deficiency anaemia in suckling piglets

Vet Med (Praha). 2025 Jul 25;70(7):242-246. doi: 10.17221/22/2025-VETMED. eCollection 2025 Jul.

ABSTRACT

This study aimed to evaluate the effectiveness of ferric carboxymaltose injection in the prevention of anaemia in suckling piglets. In group A (n = 8), piglets were administered iron in the form of iron carboxymaltose complex (Ferinject®) at a dose of 200 mg i.m. (neck muscle) at the age of 3 days. In group B (n = 8), piglets were given iron in the form of iron dextran (Ferribion®) at a dose of 200 mg i.m. (neck muscle) at the age of 3 days. In group C (n = 8, anaemic control group), iron was not administered until the age of 10 days. During the study, no statistically significant differences were observed in the parameters of red blood cell count or blood plasma iron concentration between the group that received iron carboxymaltase and the group that received iron dextran. The results of haematological and biochemical examinations achieved in our study show that the application of iron carboxymaltase was successful in preventing iron deficiency anaemia in piglets. The results indicate comparable efficacy of iron carboxymaltase and iron dextran.

PMID:40809948 | PMC:PMC12342125 | DOI:10.17221/22/2025-VETMED

Categories
Nevin Manimala Statistics

Biosynthesis of zinc oxide nanoparticles using Sideritis akmanii plant and evaluation of its biological activity

Toxicol Res (Camb). 2025 Aug 6;14(4):tfaf115. doi: 10.1093/toxres/tfaf115. eCollection 2025 Aug.

ABSTRACT

In this study, zinc oxide nanoparticles (ZnONPs) were synthesized by green synthesis technique using the extract obtained from Sideritis akmanii plant and the obtained ZnONPs were characterized by Ultraviolet-Visible Spectrophotometry (UV-VIS), X-Ray Diffraction (XRD) spectrophotometer, Scanning Electron Microscopy (SEM) and Fourier Transform Infrared Spectroscopy (FT-IR) techniques. Cytotoxic effects of both ZnONPs and Sideritis akmanii plant extract on A549 cells were investigated by MMT assay and genotoxic effects by Comet assay method. It was observed that the cytotoxic activity of ZnONP doses was higher than Sideritis akmanii plant extracts. In the comet test, the highest DNA damage (62.25 ± 10.15) was observed in the 10 mg/mL ZnONP application at 48 h of application, DNA damage did not exceed the negative control group at 3 different plant extract doses. Moreover, the genotoxic effects of 4 different concentrations of ZnONPs (0.1, 1, 5, 10 mM) were evaluated on Drosophila melonagaster with the SMART test. The results obtained as a result of ZnONP application were found to be close to the control group and it was determined that no statistically significant genotoxic effect was observed. The antimicrobial activity of ZnONPs on Escherichia coli (ATCC 25922), Staphylococcus aureus (ATCC 29213), Salmonella enteritidis (ATCC 13076), Klebsiella pneumoniae (ATCC 700603) and Candida albicans (ATCC 90028) microorganisms was analyzed using disk diffusion method. According to the antimicrobial and antifungal activity data, it was determined that the synthesized ZnONPs were effective on all microorganism strains used in the study and the inhibition zone diameters ranged from 8 to 13.67 mm.

PMID:40809917 | PMC:PMC12341928 | DOI:10.1093/toxres/tfaf115