Categories
Nevin Manimala Statistics

STAT5B Suppresses Ferroptosis by Promoting DCAF13 Transcription to Regulate p53/xCT Pathway to Promote Mantle Cell Lymphoma Progression

Biologics. 2024 Jul 4;18:181-193. doi: 10.2147/BTT.S461287. eCollection 2024.

ABSTRACT

OBJECTIVE: The purpose of this study was to analyze the mechanism by which STAT5B inhibits ferroptosis in mantle cell lymphoma (MCL) by promoting DCAF13 transcriptional regulation of p53/xCT pathway.

METHODS: The correlations between STAT5B, DCAF13 and ferroptosis in MCL were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA, http://gepia.cancer-pku.cn/index.html). The expression levels and pairwise correlations of STAT5B, DCAF13, p53 and xCT in MCL patients were detected, respectively. STAT5B was silenced to confirm their criticality in MCL ferroptosis. the effects of blocking necrosis, apoptosis and ferroptosis on the anti-MCL effects of STAT5B were examined. Cells with STAT5B overexpression and/or DCAF13 silencing were constructed to confirm the involvement of DCAF13 in the STAT5B-regulated p53/xCT pathway. The regulation of p53 ubiquitination was confirmed by DCAF13 overexpression and MG132. The effects of silencing DCAF13 and MG132 on STAT5B overexpression on MCL was clarified by a tumor-bearing nude mouse model.

RESULTS: DCAF13 was overexpressed in MCL and positively correlated with STAT5B, negatively correlated with p53, and positively correlated with xCT. Inhibition of ferroptosis alleviated the inhibitory effects of siSTAT5B on MCL, while inhibition of necrosis and apoptosis had few effects. Silencing of DCAF13 led to the blocking of STAT5B regulation of p53/xCT and ferroptosis. The changes in DCAF13 and the addition of MG132 did not have statistically significant effects on p53 mRNA. Elevation of DCAF13 resulted in downregulation of p53 protein levels, and this inhibition was reversed by MG132. In animal models, the promotion of MCL and the inhibition of ferroptosis by STAT5B. Silencing of DCAF13 blocked STAT5B inhibition of p53 and induction of xCT, GPX4, and GSH.

CONCLUSION: STAT5B suppresses ferroptosis by promoting DCAF13 transcription to regulate p53/xCT pathway to promote MCL progression.

PMID:38979130 | PMC:PMC11229983 | DOI:10.2147/BTT.S461287

Categories
Nevin Manimala Statistics

Measuring the Overall Development of Patient Safety in a New Hospital Using Trigger Tools

Int J Qual Health Care. 2024 Jul 8:mzae064. doi: 10.1093/intqhc/mzae064. Online ahead of print.

ABSTRACT

BACKGROUND: The new building of the Hospital in Lichtenfels (Germany) was put into operation in mid-July 2018. Neither the medical personnel nor medical departments have been changed. We want to evaluate how “safe” or “insecure” the new hospital or department in the beginning might have been. Our objective is to investigate if safety decreases at the beginning in a new hospital, despite modern environments and conditions.

METHODS: Adverse events associated with treatment were included to evaluate the total number of adverse events resulting from medical care and medications. Patients records had to be closed and completed, the length of stay had to be at least 24 hours, the patient had to have been formally admitted to the hospital (Institute for Healthcare Improvement IHI GTT “Global Trigger Tool” recommendation). The identified adverse events were grouped into 27 categories of the Institute for Healthcare Improvement “Global Trigger Tool.” We randomly reviewed 40 patient records per month 6 months before and 6 months after moving to the new hospital.

RESULTS: Statistical analysis showed that there was no significant difference in individual adverse events. The sum of adverse events was statistically higher after moving into a new hospital. Complete number of harms did reach statistical significance (χ2=6.62; df=1; p<.05; Cramer’s V=0.12), indicating that new environments “triggers” significantly more potential errors (50%) in comparison to the old environments (38.33%).

CONCLUSION: According to our results, the new hospital is slightly insecure in the first period (6 months) after its founding.

PMID:38978150 | DOI:10.1093/intqhc/mzae064

Categories
Nevin Manimala Statistics

Cytotoxic T-lymphocyte-associated 4 protein expression is associated with a high international prognostic score in advanced-stage classical Hodgkin lymphoma

BMC Res Notes. 2024 Jul 8;17(1):190. doi: 10.1186/s13104-024-06853-1.

ABSTRACT

OBJECTIVE: Twenty percent of all classical Hodgkin lymphoma (CHL) cases relapse and recur, especially in advanced stages with a high International Prognostic Score (IPS). Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a regulatory molecule that can inhibit the immune response and is related to tumor aggressiveness. This study aimed to determine the relationship between CTLA-4 expression in advanced-stage CHL and IPS, identifying it as a potential therapy target.

RESULTS: In advanced-stage CHL, the group with a high IPS exhibited significantly higher mean CTLA-4 expression compared to the group with a low IPS (p = 0.003).The group with Hb level < 10.5 g/dl, leukocyte count > 15,000/µL, lymphocyte count < 8%, albumin level < 4 g/dl, and stage 4 exhibited higher CTLA-4 expression than the other group, although only leukocyte count and stage showed statistical significance (p = 0.004 and p = 0.020). Mean CTLA-4 expression was 239.84 ± 76.36 for nodular sclerosis, 293.95 ± 147.94 for mixed cellularity, 271.4 ± 23.56 for lymphocyte depleted, and 225.2 for lymphocyte-rich subtypes. The results suggest that CTLA-4 expression is associated with adverse prognostic factors in the IPS for advanced-stage CHL, supporting the notion that immune checkpoints play a role in cancer progression.

PMID:38978137 | DOI:10.1186/s13104-024-06853-1

Categories
Nevin Manimala Statistics

Survival, mortality and epidemic risk status of COVID-19: a population-based Study in Golestan province, Iran

Arch Public Health. 2024 Jul 8;82(1):105. doi: 10.1186/s13690-024-01330-4.

ABSTRACT

BACKGROUND: Appreciating the various dimensions of the coronavirus disease 2019 (COVID-19) pandemic can improve health systems and prepare them to deal better with future pandemics and public health events. This study was conducted to investigate the association between the survival of hospitalized patients with COVID-19 and the epidemic risk stratification of the disease in Golestan province, Iran.

METHODS: In this study, all patients with COVID-19 who were hospitalized in the hospitals of Golestan province of Iran from February 20, 2020, to December 19, 2022, and were registered in the Medical Care Monitoring Center (MCMC) system (85,885 individuals) were examined.The community’s epidemic risk status (ERS) was determined based on the daily incidence statistics of COVID-19. The survival distribution and compare Survival in different subgroups was investigated using Kaplan-Meier and log-rank test and association between the survival and ERS by multiple Cox regression modeling.

RESULTS: Out of 68,983 individuals whose data were correctly recorded, the mean age was 49 (SD = 23.98) years, and 52.8% were women. In total, 11.1% eventually died. The length of hospital stay was varying significantly with age, gender, ERS, underlying diseases, and COVID-19 severity (P < 0.001 for all). The adjusted hazard ratio of death for the ERS at medium, high, and very high-risk status compared to the low-risk status increased by 19%, 26%, and 56%, respectively (P < 0.001 for all).

CONCLUSIONS: Enhancing preparedness, facilitating rapid rises in hospital capacities, and developing backup healthcare capacities can prevent excessive hospital referrals during health crises and further deaths.

PMID:38978085 | DOI:10.1186/s13690-024-01330-4

Categories
Nevin Manimala Statistics

Impact of Active learning model and prior knowledge on discovery time of elusive relevant papers: a simulation study

Syst Rev. 2024 Jul 8;13(1):175. doi: 10.1186/s13643-024-02587-0.

ABSTRACT

Software that employs screening prioritization through active learning (AL) has accelerated the screening process significantly by ranking an unordered set of records by their predicted relevance. However, failing to find a relevant paper might alter the findings of a systematic review, highlighting the importance of identifying elusive papers. The time to discovery (TD) measures how many records are needed to be screened to find a relevant paper, making it a helpful tool for detecting such papers. The main aim of this project was to investigate how the choice of the model and prior knowledge influence the TD values of the hard-to-find relevant papers and their rank orders. A simulation study was conducted, mimicking the screening process on a dataset containing titles, abstracts, and labels used for an already published systematic review. The results demonstrated that AL model choice, and mostly the choice of the feature extractor but not the choice of prior knowledge, significantly influenced the TD values and the rank order of the elusive relevant papers. Future research should examine the characteristics of elusive relevant papers to discover why they might take a long time to be found.

PMID:38978084 | DOI:10.1186/s13643-024-02587-0

Categories
Nevin Manimala Statistics

Implementation factors of tuberculosis control program in primary healthcare settings in China: a mixed-methods using the Consolidated Framework for Implementation Research framework

Infect Dis Poverty. 2024 Jul 8;13(1):52. doi: 10.1186/s40249-024-01222-3.

ABSTRACT

BACKGROUND: Tuberculosis (TB) is a major cause of death worldwide, and Chinese TB burden ranked the second globally. Chinese primary healthcare (PHC) sectors implement the TB Control Program (TCP) to improve active case finding, referral, treatment adherence, and health education. This study aimed to identify barriers and enablers of TCP implementation in high TB burden regions of West China.

METHODS: We conducted a representative study using mixed-methods in 28 counties or districts in Chongqing Municipality and Guizhou Province of West China from October 2021 to May 2022. Questionnaire surveys and semi-structured in-depth interviews were conducted with 2720 TB healthcare workers (HCWs) and 20 interviewees in PHC sectors. Descriptive statistical analysis was used to investigate TB HCWs’ characteristics, and path analysis model was utilized to analyze the impact of associated factors on TCP implementation. Thematic framework analysis was developed with the guide of the adapted Consolidated Framework for Implementation Research (CFIR) on factors of TCP implementation.

RESULTS: This study found that 84.6% and 94.1% of community and village HCWs had low professional titles. Based on the results of multiple regression analysis and correlation analysis, lower TB core knowledge scores (-0.09) were identified as barriers for TCP implementation in community PHC sectors, and low working satisfaction (-0.17) and low working willingness (-0.10) are barriers for TPC implementation in village PHC sectors. The results of in-depth interviews reported barriers in all domains and enablers in four domains of CFIR. There were identified 19 CFIR constructs associated with TCP implementation, including 22 barriers such as HCWs’ heavy workload, and 12 enablers such as HCWs’ passion towards TCP planning.

CONCLUSIONS: With the guide of the CFIR framework, complex factors (barriers and enablers) of TCP implementation in PHC sectors of West China were explored, which provided important evidences to promote TB program in high TB burden regions. Further implementation studies to translate those factors into implementation strategies are urgent needed.

PMID:38978081 | DOI:10.1186/s40249-024-01222-3

Categories
Nevin Manimala Statistics

Exploring the effects of post operative hyperoxic intermittent stimuli on reticulocyte levels in cancer patients: a randomized controlled study

J Anesth Analg Crit Care. 2024 Jul 8;4(1):43. doi: 10.1186/s44158-024-00179-x.

ABSTRACT

BACKGROUND: Anemia is common among hospitalized critically ill and surgical oncological patients. The rising incidence of cancer and aggressive treatments has increased the demand for blood products, further strained by a dwindling donor pool. The normobaric oxygen paradox (NOP) has emerged as a potential avenue to increase EPO levels. While some studies support its efficacy, research remains limited in clinical settings. This study aims to assess the effectiveness of a NOP protocol in stimulating erythropoiesis, as measured by changes in reticulocyte counts, in cancer patients undergoing abdominal surgeries.

METHODS: This is a post hoc analysis of a prospective, single-center, controlled, randomized study. A total of 49 patients undergoing abdominal surgery were analyzed at the Institut Jules Bordet. Adult patients admitted to the intensive care unit (ICU) for at least 24 h were enrolled, excluding those with severe renal insufficiency or who received transfusions during the study period. Participants were randomized into two groups: a normobaric oxygen paradox (OXY) group who received 60% oxygen for 2 h on days 1, 3, and 5 post-surgery and a control (CTR) group who received standard care. Data on baseline characteristics, surgical details, and laboratory parameters were collected. Statistical analysis included descriptive statistics, chi-square tests, t-tests, Mann-Whitney tests, and linear and logistic regression.

RESULTS: The final analysis included 33 patients (median age 62 [IQR 58-66], 28 (84.8%) males, with no withdrawals or deaths during the study period. No significant differences were observed in baseline surgical characteristics or perioperative outcomes between the two groups. In the OXY group (n = 16), there was a significant rise (p = 0.0237) in the percentage of reticulocyte levels in comparison to the CTR group (n = 17), with median values of 36.1% (IQR 20.3-57.8) versus – 5.3% (IQR – 19.2-57.8), respectively. The increases in hemoglobin and hematocrit levels did not significantly differ between the groups when compared to their baselines’ values.

CONCLUSIONS: This study provides preliminary evidence supporting the potential of normobaric oxygen therapy in stimulating erythropoiesis in cancer patients undergoing abdominal surgeries. While the OXY group resulted in increased reticulocyte counts, further research with larger sample sizes and multi-center trials is warranted to confirm these findings.

TRIAL REGISTRATION: The study was retrospectively registered under NCT number 06321874 on The 10th of April 2024.

PMID:38978080 | DOI:10.1186/s44158-024-00179-x

Categories
Nevin Manimala Statistics

Standard medical ethnobotany of Kohistan, North Pakistan

J Ethnobiol Ethnomed. 2024 Jul 8;20(1):64. doi: 10.1186/s13002-024-00704-w.

ABSTRACT

BACKGROUND: This study was exclusively focused on the documentation and cross-cultural evaluation of ethnomedicinal knowledge (EMK) within the diverse linguistic groups of Kohistan situated between the Himalayan and Hindukush Mountain ranges in the north Pakistan.

METHODS: Data were gathered during the field survey (May 2022 to July 2023) through group conversations, semi-structured interviews, and on-site observation. Venn diagrams were employed to illustrate the comparative assessment of EMK, and different ethnobotanical indices were utilized to examine the data.

RESULTS: A total of 96 wild medicinal plant species (MPs) belonging to 74 genera and 52 botanical families were documented. The most reported MPs belong to the family Polygonaceae (11 species), followed by Asteraceae (9 species) and Lamiaceae (8 species). The ethnomedicinal uses of Leontopodium himalayanum, Pedicularis oederi, Plocama brevifolia, Polypodium sibiricum, Pteridium esculentum, Sambucus wightiana, Solanum cinereum, Teucrium royleanum, Rhodiola integrifolia, Aconitum chasmanthum were reported for the first time in this region. Among the reported taxa herbaceous species were dominated (72%), followed by trees and shrubs (17% and 10%, respectively). Digestive problems (40 taxa and 114 use reports) and skin disorders (19 taxa and 549 use reports) were the most cited disease categories, whereas M. communis, M. longifolia, Ajuga integrifolia, Ziziphus jujuba, and Clematis grata exhibited the highest percentage fidelity levels. Out of 109 documented medicinal uses, a mere 12 were shared across all linguistic groups, and Bateri emerges as a notable outlier with the highest number of medicinal uses. In addition, a significant homogeneity was noted in the reported botanical taxa (61 species) among different linguistic groups. However, since the last decade biocultural heritage of Kohistan is facing multifaceted risks that need urgent attention.

CONCLUSION: Our findings could be valuable addition to the existing stock of ethnomedicinal knowledge and may provide ethnopharmacological basis to novel drug discovery for preexisting and emerging diseases prioritizing detailed phytochemical profiling and the evaluation of bioactive potential.

PMID:38978072 | DOI:10.1186/s13002-024-00704-w

Categories
Nevin Manimala Statistics

Smart decision support system for keratoconus severity staging using corneal curvature and thinnest pachymetry indices

Eye Vis (Lond). 2024 Jul 8;11(1):28. doi: 10.1186/s40662-024-00394-1.

ABSTRACT

BACKGROUND: This study proposes a decision support system created in collaboration with machine learning experts and ophthalmologists for detecting keratoconus (KC) severity. The system employs an ensemble machine model and minimal corneal measurements.

METHODS: A clinical dataset is initially obtained from Pentacam corneal tomography imaging devices, which undergoes pre-processing and addresses imbalanced sampling through the application of an oversampling technique for minority classes. Subsequently, a combination of statistical methods, visual analysis, and expert input is employed to identify Pentacam indices most correlated with severity class labels. These selected features are then utilized to develop and validate three distinct machine learning models. The model exhibiting the most effective classification performance is integrated into a real-world web-based application and deployed on a web application server. This deployment facilitates evaluation of the proposed system, incorporating new data and considering relevant human factors related to the user experience.

RESULTS: The performance of the developed system is experimentally evaluated, and the results revealed an overall accuracy of 98.62%, precision of 98.70%, recall of 98.62%, F1-score of 98.66%, and F2-score of 98.64%. The application’s deployment also demonstrated precise and smooth end-to-end functionality.

CONCLUSION: The developed decision support system establishes a robust basis for subsequent assessment by ophthalmologists before potential deployment as a screening tool for keratoconus severity detection in a clinical setting.

PMID:38978067 | DOI:10.1186/s40662-024-00394-1

Categories
Nevin Manimala Statistics

Combined expert-in-the-loop-random forest multiclass segmentation U-net based artificial intelligence model: evaluation of non-small cell lung cancer in fibrotic and non-fibrotic microenvironments

J Transl Med. 2024 Jul 8;22(1):640. doi: 10.1186/s12967-024-05394-2.

ABSTRACT

BACKGROUND: The tumor microenvironment (TME) plays a key role in lung cancer initiation, proliferation, invasion, and metastasis. Artificial intelligence (AI) methods could potentially accelerate TME analysis. The aims of this study were to (1) assess the feasibility of using hematoxylin and eosin (H&E)-stained whole slide images (WSI) to develop an AI model for evaluating the TME and (2) to characterize the TME of adenocarcinoma (ADCA) and squamous cell carcinoma (SCCA) in fibrotic and non-fibrotic lung.

METHODS: The cohort was derived from chest CT scans of patients presenting with lung neoplasms, with and without background fibrosis. WSI images were generated from slides of all 76 available pathology cases with ADCA (n = 53) or SCCA (n = 23) in fibrotic (n = 47) or non-fibrotic (n = 29) lung. Detailed ground-truth annotations, including of stroma (i.e., fibrosis, vessels, inflammation), necrosis and background, were performed on WSI and optimized via an expert-in-the-loop (EITL) iterative procedure using a lightweight [random forest (RF)] classifier. A convolution neural network (CNN)-based model was used to achieve tissue-level multiclass segmentation. The model was trained on 25 annotated WSI from 13 cases of ADCA and SCCA within and without fibrosis and then applied to the 76-case cohort. The TME analysis included tumor stroma ratio (TSR), tumor fibrosis ratio (TFR), tumor inflammation ratio (TIR), tumor vessel ratio (TVR), tumor necrosis ratio (TNR), and tumor background ratio (TBR).

RESULTS: The model’s overall classification for precision, sensitivity, and F1-score were 94%, 90%, and 91%, respectively. Statistically significant differences were noted in TSR (p = 0.041) and TFR (p = 0.001) between fibrotic and non-fibrotic ADCA. Within fibrotic lung, statistically significant differences were present in TFR (p = 0.039), TIR (p = 0.003), TVR (p = 0.041), TNR (p = 0.0003), and TBR (p = 0.020) between ADCA and SCCA.

CONCLUSION: The combined EITL-RF CNN model using only H&E WSI can facilitate multiclass evaluation and quantification of the TME. There are significant differences in the TME of ADCA and SCCA present within or without background fibrosis. Future studies are needed to determine the significance of TME on prognosis and treatment.

PMID:38978066 | DOI:10.1186/s12967-024-05394-2