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Nevin Manimala Statistics

Multi-layer Bundling as a New Approach for Determining Multi-scale Correlations Within a High-Dimensional Dataset

Bull Math Biol. 2024 Jul 12;86(9):105. doi: 10.1007/s11538-024-01335-8.

ABSTRACT

The growing complexity of biological data has spurred the development of innovative computational techniques to extract meaningful information and uncover hidden patterns within vast datasets. Biological networks, such as gene regulatory networks and protein-protein interaction networks, hold critical insights into biological features’ connections and functions. Integrating and analyzing high-dimensional data, particularly in gene expression studies, stands prominent among the challenges in deciphering these networks. Clustering methods play a crucial role in addressing these challenges, with spectral clustering emerging as a potent unsupervised technique considering intrinsic geometric structures. However, spectral clustering’s user-defined cluster number can lead to inconsistent and sometimes orthogonal clustering regimes. We propose the Multi-layer Bundling (MLB) method to address this limitation, combining multiple prominent clustering regimes to offer a comprehensive data view. We call the outcome clusters “bundles”. This approach refines clustering outcomes, unravels hierarchical organization, and identifies bridge elements mediating communication between network components. By layering clustering results, MLB provides a global-to-local view of biological feature clusters enabling insights into intricate biological systems. Furthermore, the method enhances bundle network predictions by integrating the bundle co-cluster matrix with the affinity matrix. The versatility of MLB extends beyond biological networks, making it applicable to various domains where understanding complex relationships and patterns is needed.

PMID:38995438 | DOI:10.1007/s11538-024-01335-8

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Nevin Manimala Statistics

Consumers’ knowledge and experiences of adverse drug reaction reporting in Australia: a national survey

Eur J Clin Pharmacol. 2024 Jul 12. doi: 10.1007/s00228-024-03729-y. Online ahead of print.

ABSTRACT

This study aimed to investigate the current knowledge and experiences of consumers in Australia on adverse drug reaction (ADR) reporting and their reasons for reporting or not reporting ADRs, with a focus on the use of digital tools for ADR reporting.

METHODS: A cross-sectional online survey was conducted among adults who had taken medicine in Australia. A structured questionnaire with multiple choice or Likert scale responses with an option for participants to provide free-text responses and pretested for face validity was used. Consumer characteristics, knowledge, and ADR reporting practices were analyzed using descriptive statistics and the chi-square test or Fisher’s exact test.

RESULTS: A total of 544 survey responses were included in the analysis. The majority of respondents were women (68%), and 22% were aged between 65 and 74 years. Fifty-eight percent (n = 317) of respondents knew that they could report ADRs to either the Therapeutic Goods Administration (TGA), state or territory government health department, or healthcare professionals. Three-quarters (n = 405) of respondents stated that they had experienced an ADR; of these, 36% reported an ADR to either the TGA, state or territory government health department, or healthcare professionals. Among those who reported ADRs, 58% were unaware that they could use digital tools to report ADRs. The main reason for not reporting was that they did not think the ADR was serious enough to report (39%).

CONCLUSION: Over half of consumers knew that they could report ADR; however, improved consumer awareness about using digital tools for ADR reporting and increased ADR reporting is needed.

PMID:38995427 | DOI:10.1007/s00228-024-03729-y

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Nevin Manimala Statistics

SARS-CoV-2-Spike T-cell response after receiving one or two Wuhan-Hu-1-based mRNA COVID-19 vaccine booster doses in elderly nursing home residents

J Med Virol. 2024 Jul;96(7):e29790. doi: 10.1002/jmv.29790.

ABSTRACT

The effect of COVID-19 booster vaccination on SARS-CoV-2 T-cell mediated immune responses in elderly nursing home residents has not been explored in depth. Thirty-nine elderly nursing home residents (median age, 91 years) were included, all fully vaccinated with mRNA vaccines. The frequency of and the integrated mean fluorescence (iMFI) for peripheral blood SARS-CoV-2-Spike reactive IFN-γ-producing CD4+ or CD8+ T cells before and after the first (Pre-3D and Post-3D) and second (Pre-4D and Post-4D) vaccine booster doses was determined using flow cytometry for an intracellular staining method. 3D increased significantly (p = 0.01) the percentage of participants displaying detectable SARS-CoV-2-T-cell responses compared with pre-3D (97% vs. 74%). The magnitude of the increase was statistically significant for CD8+ T cells (p = 0.007) but not for CD4+ T cells (p = 0.77). A trend towards higher frequencies of peripheral blood SARS-CoV-2-CD8+ T cells was observed post-3D compared with pre-3D (p = 0.06). The percentage of participants with detectable SARS-S-CoV-2 CD4+ T-cell responses decreased post-4D (p = 0.035). Following 4D, a nonsignificant decrease in the frequencies of both T cell subsets was noticed (p = 0.94 for CD8+ T cells and p = 0.06 for CD4+ T cells). iMFI data mirrored that of T-cell frequencies. The kinetics of SARS-CoV-2 CD8+ and CD4+ T cells following receipt of 3D and 4D were comparable across SARS-CoV-2-experienced and -naïve participants and between individuals receiving a homologous or heterologous vaccine booster. 3D increased the percentage of elderly nursing home residents displaying detectable SARS-CoV-2 T-cell responses but had a marginal effect on T-cell frequencies. The impact of 4D on SARS-CoV-2 T-cell responses was negligible; whether this was due to suboptimal priming or rapid waning could not be ascertained.

PMID:38994662 | DOI:10.1002/jmv.29790

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Nevin Manimala Statistics

Absolute risk from double nested case-control designs: cause-specific proportional hazards models with and without augmented estimating equations

Biometrics. 2024 Jul 1;80(3):ujae062. doi: 10.1093/biomtc/ujae062.

ABSTRACT

We estimate relative hazards and absolute risks (or cumulative incidence or crude risk) under cause-specific proportional hazards models for competing risks from double nested case-control (DNCC) data. In the DNCC design, controls are time-matched not only to cases from the cause of primary interest, but also to cases from competing risks (the phase-two sample). Complete covariate data are available in the phase-two sample, but other cohort members only have information on survival outcomes and some covariates. Design-weighted estimators use inverse sampling probabilities computed from Samuelsen-type calculations for DNCC. To take advantage of additional information available on all cohort members, we augment the estimating equations with a term that is unbiased for zero but improves the efficiency of estimates from the cause-specific proportional hazards model. We establish the asymptotic properties of the proposed estimators, including the estimator of absolute risk, and derive consistent variance estimators. We show that augmented design-weighted estimators are more efficient than design-weighted estimators. Through simulations, we show that the proposed asymptotic methods yield nominal operating characteristics in practical sample sizes. We illustrate the methods using prostate cancer mortality data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Study of the National Cancer Institute.

PMID:38994640 | DOI:10.1093/biomtc/ujae062

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Nevin Manimala Statistics

Optimal refinement of strata to balance covariates

Biometrics. 2024 Jul 1;80(3):ujae061. doi: 10.1093/biomtc/ujae061.

ABSTRACT

What is the best way to split one stratum into two to maximally reduce the within-stratum imbalance in many covariates? We formulate this as an integer program and approximate the solution by randomized rounding of a linear program. A linear program may assign a fraction of a person to each refined stratum. Randomized rounding views fractional people as probabilities, assigning intact people to strata using biased coins. Randomized rounding is a well-studied theoretical technique for approximating the optimal solution of certain insoluble integer programs. When the number of people in a stratum is large relative to the number of covariates, we prove the following new results: (i) randomized rounding to split a stratum does very little randomizing, so it closely resembles the linear programming relaxation without splitting intact people; (ii) the linear relaxation and the randomly rounded solution place lower and upper bounds on the unattainable integer programming solution; and because of (i), these bounds are often close, thereby ratifying the usable randomly rounded solution. We illustrate using an observational study that balanced many covariates by forming matched pairs composed of 2016 patients selected from 5735 using a propensity score. Instead, we form 5 propensity score strata and refine them into 10 strata, obtaining excellent covariate balance while retaining all patients. An R package optrefine at CRAN implements the method. Supplementary materials are available online.

PMID:38994639 | DOI:10.1093/biomtc/ujae061

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Nevin Manimala Statistics

CircDUSP22 Attenuates the Ferroptosis of Prostate Cancer Cells via miR-18a-5p/SLC7A11/GPX4 Signaling

Comb Chem High Throughput Screen. 2024 Jul 11. doi: 10.2174/0113862073324077240624094140. Online ahead of print.

ABSTRACT

BACKGROUND: According to current worldwide cancer data, Prostate Cancer (PC) ranks as the second most common type of cancer and is the fifth leading cause of cancer-related mortality among men worldwide. PC in China has the 10th highest number of new cases and the 13th highest fatality rate, both of which show an ongoing annual increase. One of the significant challenges with prostate cancer is the difficulty in early detection, often resulting in diagnosis at intermediate or late stages, complicating treatment. Although hormonal therapy is initially successful in controlling the progression of prostate cancer, almost all tumors that respond to hormones eventually transform into Castration-resistant Prostate Cancer (CRPC) within 18-24 months of hormonal therapy. This poses clinical difficulties due to an absence of successful therapeutic approaches. Therefore, understanding the fundamental mechanisms of prostate cancer development, identifying effective therapeutic targets, and discovering reliable molecular biomarkers are crucial objectives.

METHODS: CircRNA expression in plasma was assessed in 4 samples obtained from patients with Benign Prostatic Hyperplasia (BPH), and PC was detected through microarray probes. Statistical analysis of the expression of circDUSP22 and clinicopathological features was conducted. The investigation of target genes was conducted using luciferase reporter assays and bioinformatics analysis. The expression levels of circDUSP22, miR-18a-5p, and Solute Carrier Family 7 member 11 (SLC7A11) were assessed using a quantitative Real-time Polymerase Chain Reaction (qRT-PCR) assay. Cell invasion, migration, colony formation, and proliferation were evaluated using Transwell, wound healing, colony formation, and CCK-8 assays, respectively. RNA Immunoprecipitation (RIP) and dual-luciferase reporter assays were used to examine the connections among circDUSP22, miR-18a-5p, and SLC7A11. The impact of circDUSP22 on the expression of ferroptosis-related proteins, specifically SLC7A11, as well as its effects on Fe2+ and ROS were also examined.

RESULTS: In both plasma samples and PCa cell lines, there was a substantial elevation of circDUSP22 and SLC7A11 expression and a decline in miR-18a-5p expression. Suppression of circDUSP22 significantly impeded the migration, invasion, and proliferation of PC cells in vitro. The target gene of miR-18a-5p, SLC7A11, was found to be upregulated as an effect of circDUSP22’s competitive binding to miR-18a-5p. Cellular experiments demonstrated that interference with circDUSP22 expression in DU145 and PC-3 cells led to increased ferroptosis and decreased SLC7A11 expression. The modulation of prostate cancer cell proliferation was reversed by either overexpressing SLC7A11 or inhibiting miR-18a-5p in response to the silencing of circDUSP22.

CONCLUSION: The circDUSP22 has been found to have a substantial effect on the development of ferroptosis in PC. It has been observed to influence the formation and evolution of this disorder by affecting the miR-18a-5p/SLC7A11 signaling pathway.

PMID:38994627 | DOI:10.2174/0113862073324077240624094140

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Nevin Manimala Statistics

miR-584-5p is a New Potential Prognostic Biomarker in Head and Neck Squamous Cell Carcinoma

Curr Comput Aided Drug Des. 2024 Jul 11. doi: 10.2174/0115734099305382240704071258. Online ahead of print.

ABSTRACT

BACKGROUND: MicroRNA-584-5p (miR-584-5p) plays an important role in certain types of cancer. However, its precise role in head and neck squamous cell carcinoma (HNSC) remains unknown.

OBJECTIVE: Our aim was to investigate how miR-584-5p influences HNSC.

METHODS: The Cancer Genome Atlas (TCGA) provided samples for the study. We use statistical methods to evaluate the diagnostic value, the prognostic value, and the correlation with the clinical features of miR-584-5p. We analyze the target genes and the regulatory network of miR- 584-5p. Quantitative reverse transcriptase PCR (qRT-PCR) confirmed the expression of miR- 584-5p in HNSC cell lines.

RESULTS: MiR-584-5p expression of miR-584-5p varied significantly among different types of cancer. A notable correlation was observed between elevated miR-584-5p expression and gender (p < 0.001) and histological grade (p < 0.001). Furthermore, high levels of miR-584-5p were found to be associated with a decrease in overall survival (HR: 1.44; 95% CI: 1.10-1.88; p = 0.007), progression-free survival (HR: 1.35; 95% CI: 1.02-1.79; p = 0.035) and disease-specific survival (HR: 1.54; 95% CI: 1.09-2.18; p = 0.016) in the context of HNSC. miR-584-5p demonstrated independent prognostic significance in HNSC and potentially contributes to disease progression through multiple pathways, such as dilated cardiomyopathy and hypertrophic cardiomyopathy. In particular, HNSC cell lines exhibited a substantial upregulation of miR-584-5p compared to normal epithelial cells.

CONCLUSIONS: It is possible that miR-584-5p could serve as a promising patent for a therapeutic target and prognostic biomarker for people with HNSC.

PMID:38994617 | DOI:10.2174/0115734099305382240704071258

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Nevin Manimala Statistics

The impact of the COVID-19 vaccination programme on symptomatic and severe SARS-CoV-2 infection during a period of Omicron variant dominance in Ireland, December 2021 to March 2023

Euro Surveill. 2024 Jul;29(28). doi: 10.2807/1560-7917.ES.2024.29.28.2300697.

ABSTRACT

BackgroundAs Ireland prepared for an autumn 2023 COVID-19 vaccination booster campaign, there was concern that vaccine fatigue would affect uptake, which has been abating.AimThis study aimed to quantify the direct impact of the COVID-19 vaccination programme in Ireland on averted COVID-19-related outcomes including symptomatic presentations to primary care/community testing centres, emergency department (ED) presentations, hospitalisations, intensive care unit (ICU) admissions and deaths, in individuals aged ≥ 50 years, during Omicron dominance.MethodsWe conducted a retrospective observational COVID-19 vaccine impact study in December 2021-March 2023 in Ireland. We used national data on notified outcomes and vaccine coverage, as well as vaccine effectiveness (VE) estimates, sourced from the World Health Organization’s live systematic review of VE, to estimate the count and prevented fraction of outcomes in ≥ 50-year-olds averted by the COVID-19 vaccination programme in this age group.ResultsThe COVID-19 vaccination programme averted 48,551 symptomatic COVID-19 presentations to primary care/community testing centres (36% of cases expected in the absence of vaccination), 9,517 ED presentations (53% of expected), 102,160 hospitalisations (81% of expected), 3,303 ICU admissions (89% of expected) and 15,985 deaths (87% of expected).ConclusionsWhen Omicron predominated, the COVID-19 vaccination programme averted symptomatic and severe COVID-19 cases, including deaths due to COVID-19. In line with other international vaccine impact studies, these findings emphasise the benefits of COVID-19 vaccination for population health and the healthcare system and are relevant for informing COVID-19 booster vaccination programmes, pandemic preparedness and communicating the reason for and importance of COVID-19 vaccination in Ireland and internationally.

PMID:38994604 | DOI:10.2807/1560-7917.ES.2024.29.28.2300697

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Nevin Manimala Statistics

Marked increase in cryptosporidiosis cases, Spain, 2023

Euro Surveill. 2024 Jul;29(28). doi: 10.2807/1560-7917.ES.2024.29.28.2300733.

ABSTRACT

BackgroundBy mid-September 2023, several event notifications related to cryptosporidiosis had been identified from different regions in Spain. Therefore, a request for urgent notification of cryptosporidiosis cases to the National Surveillance Network was launched.AimWe aimed at assessing the extent of the increase in cases, the epidemiological characteristics and the transmission modes and compared to previous years.MethodsWe analysed data on case notifications, outbreak reports and genotypes focusing on June-October 2023 and compared the results to 2016-2022.ResultsIn 2023, 4,061 cryptosporidiosis cases were notified in Spain, which is an increase compared to 2016-2022. The cumulative incidence was 8.3 cases per 100,000 inhabitants in 2023, sixfold higher than the median of 1.4 cases per 100,000 inhabitants 2016-2022. Almost 80% of the cases were notified between June and October. The largest outbreaks were related to contaminated drinking water or swimming pools. Cryptosporidium hominis was the most common species in the characterised samples (115/122), and the C. hominis IfA12G1R5 subtype, previously unusual in Spain, was detected from 76 (62.3%) of the 122 characterised samples.ConclusionsA substantial increase in cryptosporidiosis cases was observed in 2023. Strengthening surveillance of Cryptosporidium is essential for prevention of cases, to better understand trends and subtypes circulating and the impact of adverse meteorological events.

PMID:38994603 | DOI:10.2807/1560-7917.ES.2024.29.28.2300733

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Nevin Manimala Statistics

Efficacy and safety analysis of sodium zirconium cyclosilicate and calcium polystyrene sulfonate on rapid reduction of potassium in moderate to severe hyperkalemia patients with chronic kidney disease without dialysis

Clin Nephrol. 2024 Jul 12. doi: 10.5414/CN111226. Online ahead of print.

ABSTRACT

BACKGROUND: Hyperkalemia is a common complication of chronic kidney disease (CKD). This study aims to investigate the efficacy and safety of sodium zirconium cyclosilicate and calcium polystyrene sulfonate in reducing potassium in patients with acute and severe hyperkalemia in CKD who are not undergoing dialysis.

MATERIALS AND METHODS: A retrospective real-world study was conducted among 73 patients with non-dialysis chronic kidney disease who were hospitalized in the First Affiliated Hospital of Chengdu Medical College from June 2020 to June 2022. 33 patients treated with sodium zirconium cyclosilicate were categorized as SZC group, and the other 40 patients treated with calcium polystyrene sulfonate were categorized as CPS group. Serum potassium, serum sodium, magnesium, calcium, and phosphorus levels were examined. Adverse reactions were recorded during medication.

RESULTS: Significantly decreased serum potassium was observed in both groups, whereas the potassium reduction was higher in the SZC group than in the CPS group at 2, 4, 24, and 48 hours after medication while there was no statistically significant difference in the serum potassium level between the two groups at 72 hours. For those people whose initial potassium exceeded 6 mmol/L, the potassium reduction was more obvious in the SZC group than in the CPS group at 2 and 4 hours after medication. The control rate of hyperkalemia in the SZC group was significantly higher than in the CPS group at 4, 24, and 48 hours. No distinct change was observed in serum sodium, calcium, magnesium, and phosphorus before and 72 hours after medication. No severe adverse reactions occurred.

CONCLUSION: Sodium zirconium cyclosilicate has a more obvious effect on reducing potassium particularly for those patients with moderate to severe hyperkalemia who need rapid potassium reduction.

PMID:38994592 | DOI:10.5414/CN111226