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1.
Front Neurosci ; 18: 1392002, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39099634

RESUMO

Background: Acupuncture, as an alternative and complementary therapy recommended by the World Health Organization for stroke treatment, holds potential in ameliorating neurofunctional deficits induced by ischemic stroke (IS). Understanding the immediate and long-term effects of acupuncture and their interrelation would contribute to a better comprehension of the mechanisms underlying acupuncture efficacy. Methods: Activation likelihood estimation (ALE) meta-analysis was used to analyze the brain activation patterns reported in 21 relevant functional neuroimaging studies. Among these studies, 12 focused on the immediate brain activation and 9 on the long-term activation. Single dataset analysis were employed to identify both immediate and long-term brain activation of acupuncture treatment in IS patients, while contrast and conjunction analysis were utilized to explore distinctions and connections between the two. Results: According to the ALE analysis, immediately after acupuncture treatment, IS patients exhibited an enhanced cluster centered around the right precuneus (PCUN) and a reduced cluster centered on the left middle frontal gyrus (MFG). After long-term acupuncture treatment, IS patients showed an enhanced cluster in the left PCUN, along with two reduced clusters in the right insula (INS) and hippocampus (HIP), respectively. Additionally, in comparison to long-term acupuncture treatment, the right angular gyrus (ANG) demonstrated higher ALE scores immediately after acupuncture, whereas long-term acupuncture resulted in higher scores in the left superior parietal gyrus (SPG). The intersecting cluster activated by both of them was located in the left cuneus (CUN). Conclusion: The findings provide initial insights into both the immediate and long-term brain activation patterns of acupuncture treatment for IS, as well as the intricate interplay between them. Both immediate and long-term acupuncture treatments showed distinct patterns of brain activation, with the left CUN emerging as a crucial regulatory region in their association. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, CRD42023480834.

2.
Heliyon ; 10(14): e33598, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39100465

RESUMO

Recently, a novel improved adaptive Type-II progressive censoring strategy has been suggested in order to obtain adequate data from trials that require a lengthy amount of time. Considering this scheme, this paper focuses on various classical and Bayesian estimation challenges for parameter and some reliability metrics for the XLindley distribution. Two classical estimation methods are considered from the classical perspective to get the point and interval estimations of the model parameter as well as reliability and hazard rate functions. In addition to the usual approaches, the Bayesian methodology is looked at by leveraging the squared error loss function and the Markov chain Monte Carlo technique. The Bayes point and credible intervals are obtained based on two forms of the posterior distribution. A simulation examination is implemented adopting multiple circumstances to distinguish between the conventional and Bayesian estimations. The simulation results demonstrate that the Bayesian approach using the likelihood function is superior for estimating the model parameter when compared with the other methods. In contrast, when estimating reliability metrics, it is advisable to utilize the Bayesian method with the spacings function. Two real-world data sets are analyzed to integrate the proposed approaches into practice, and the ideal progressive censoring strategy is chosen using some optimality criteria.

3.
Commun Stat Theory Methods ; 53(17): 6038-6054, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39100716

RESUMO

Phase IV clinical trials are designed to monitor long-term side effects of medical treatment. For instance, childhood cancer survivors treated with chest radiation and/or anthracycline are often at risk of developing cardiotoxicity during their adulthood. Often the primary focus of a study could be on estimating the cumulative incidence of a particular outcome of interest such as cardiotoxicity. However, it is challenging to evaluate patients continuously and usually, this information is collected through cross-sectional surveys by following patients longitudinally. This leads to interval-censored data since the exact time of the onset of the toxicity is unknown. Rai et al. computed the transition intensity rate using a parametric model and estimated parameters using maximum likelihood approach in an illness-death model. However, such approach may not be suitable if the underlying parametric assumptions do not hold. This manuscript proposes a semi-parametric model, with a logit relationship for the treatment intensities in two groups, to estimate the transition intensity rates within the context of an illness-death model. The estimation of the parameters is done using an EM algorithm with profile likelihood. Results from the simulation studies suggest that the proposed approach is easy to implement and yields comparable results to the parametric model.

4.
Am J Hum Genet ; 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39106865

RESUMO

Mendelian randomization (MR) utilizes genome-wide association study (GWAS) summary data to infer causal relationships between exposures and outcomes, offering a valuable tool for identifying disease risk factors. Multivariable MR (MVMR) estimates the direct effects of multiple exposures on an outcome. This study tackles the issue of highly correlated exposures commonly observed in metabolomic data, a situation where existing MVMR methods often face reduced statistical power due to multicollinearity. We propose a robust extension of the MVMR framework that leverages constrained maximum likelihood (cML) and employs a Bayesian approach for identifying independent clusters of exposure signals. Applying our method to the UK Biobank metabolomic data for the largest Alzheimer disease (AD) cohort through a two-sample MR approach, we identified two independent signal clusters for AD: glutamine and lipids, with posterior inclusion probabilities (PIPs) of 95.0% and 81.5%, respectively. Our findings corroborate the hypothesized roles of glutamate and lipids in AD, providing quantitative support for their potential involvement.

5.
BMC Genomics ; 25(1): 764, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39107741

RESUMO

BACKGROUND: Chemoreception is crucial for insect fitness, underlying for instance food-, host-, and mate finding. Chemicals in the environment are detected by receptors from three divergent gene families: odorant receptors (ORs), gustatory receptors (GRs), and ionotropic receptors (IRs). However, how the chemoreceptor gene families evolve in parallel with ecological specializations remains poorly understood, especially in the order Coleoptera. Hence, we sequenced the genome and annotated the chemoreceptor genes of the specialised ambrosia beetle Trypodendron lineatum (Coleoptera, Curculionidae, Scolytinae) and compared its chemoreceptor gene repertoires with those of other scolytines with different ecological adaptations, as well as a polyphagous cerambycid species. RESULTS: We identified 67 ORs, 38 GRs, and 44 IRs in T. lineatum ('Tlin'). Across gene families, T. lineatum has fewer chemoreceptors compared to related scolytines, the coffee berry borer Hypothenemus hampei and the mountain pine beetle Dendroctonus ponderosae, and clearly fewer receptors than the polyphagous cerambycid Anoplophora glabripennis. The comparatively low number of chemoreceptors is largely explained by the scarcity of large receptor lineage radiations, especially among the bitter taste GRs and the 'divergent' IRs, and the absence of alternatively spliced GR genes. Only one non-fructose sugar receptor was found, suggesting several sugar receptors have been lost. Also, we found no orthologue in the 'GR215 clade', which is widely conserved across Coleoptera. Two TlinORs are orthologous to ORs that are functionally conserved across curculionids, responding to 2-phenylethanol (2-PE) and green leaf volatiles (GLVs), respectively. CONCLUSIONS: Trypodendron lineatum reproduces inside the xylem of decaying conifers where it feeds on its obligate fungal mutualist Phialophoropsis ferruginea. Like previous studies, our results suggest that stenophagy correlates with small chemoreceptor numbers in wood-boring beetles; indeed, the few GRs may be due to its restricted fungal diet. The presence of TlinORs orthologous to those detecting 2-PE and GLVs in other species suggests these compounds are important for T. lineatum. Future functional studies should test this prediction, and chemoreceptor annotations should be conducted on additional ambrosia beetle species to investigate whether few chemoreceptors is a general trait in this specialized group of beetles.


Assuntos
Receptores Odorantes , Animais , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Besouros/genética , Filogenia , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo
6.
J Exp Child Psychol ; 247: 106037, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39137505

RESUMO

Since the COVID-19 pandemic, both the public and researchers have raised questions regarding the potential impact of protective face-mask wearing on infants' development. Nevertheless, limited research has tested infants' response to protective face-mask wearing adults in real-life interactions and in neurodiverse populations. In addition, scarce attention was given to changes in interactive behavior of adults wearing a protective face-mask. The aims of the current study were (1) to examine differences in 12-month-old infants' behavioral response to an interactive parent wearing a protective face-mask during face-to-face interaction, (2) to investigate potential differences in infants at higher likelihood for autism (HL-ASD) as compared with general population (GP) counterparts, and (3) to explore significant differences in parents' behaviors while wearing or not wearing a protective face-mask. A total of 50 mother-infant dyads, consisting of 20 HL-ASD infants (siblings of individuals with autism) and 30 GP infants, participated in a 6-min face-to-face interaction. The interaction was videotaped through teleconferencing and comprised three 2-min episodes: (a) no mask, (b) mask, and (c) post-mask. Infants' emotionality and gaze direction, as well as mothers' vocal production and touching behaviors, were coded micro-analytically. Globally, GP infants exhibited more positive emotionality compared with their HL-ASD counterparts. Infants' negative emotionality and gaze avoidance did not differ statistically across episodes. Both groups of infants displayed a significant increase in looking time toward the caregiver during the mask episode. No statistically significant differences emerged in mothers' behaviors. These findings suggest that the use of protective face-masks might not negatively affect core dimensions of caregiver-infant interactions in GP and HL-ASD 12-month-old infants.

7.
Protein Sci ; 33(9): e5134, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39145435

RESUMO

Function and structure are strongly coupled in obligated oligomers such as Triosephosphate isomerase (TIM). In animals and fungi, TIM monomers are inactive and unstable. Previously, we used ancestral sequence reconstruction to study TIM evolution and found that before these lineages diverged, the last opisthokonta common ancestor of TIM (LOCATIM) was an obligated oligomer that resembles those of extant TIMs. Notably, calorimetric evidence indicated that ancestral TIM monomers are more structured than extant ones. To further increase confidence about the function, structure, and stability of the LOCATIM, in this work, we applied two different inference methodologies and the worst plausible case scenario for both of them, to infer four sequences of this ancestor and test the robustness of their physicochemical properties. The extensive biophysical characterization of the four reconstructed sequences of LOCATIM showed very similar hydrodynamic and spectroscopic properties, as well as ligand-binding energetics and catalytic parameters. Their 3D structures were also conserved. Although differences were observed in melting temperature, all LOCATIMs showed reversible urea-induced unfolding transitions, and for those that reached equilibrium, high conformational stability was estimated (ΔGTot = 40.6-46.2 kcal/mol). The stability of the inactive monomeric intermediates was also high (ΔGunf = 12.6-18.4 kcal/mol), resembling some protozoan TIMs rather than the unstable monomer observed in extant opisthokonts. A comparative analysis of the 3D structure of ancestral and extant TIMs shows a correlation between the higher stability of the ancestral monomers with the presence of several hydrogen bonds located in the "bottom" part of the barrel.


Assuntos
Triose-Fosfato Isomerase , Triose-Fosfato Isomerase/química , Triose-Fosfato Isomerase/genética , Triose-Fosfato Isomerase/metabolismo , Animais , Evolução Molecular , Multimerização Proteica , Modelos Moleculares , Estabilidade Enzimática
8.
Sci Rep ; 14(1): 18191, 2024 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-39107402

RESUMO

Cobas EGFR mutation Test v2 was FDA-approved as qualitative liquid biopsy for actionable EGFR variants in non-small cell lung cancer (NSCLC). It generates semiquantitative index (SQI) values that correlate with mutant allele levels, but decision thresholds for clinical use in NSCLC surveillance are lacking. We conducted long-term ctDNA monitoring in 20 subjects with EGFR-mutated NSCLC; resulting in a 155 on-treatment samples. We defined optimal SQI intervals to predict/rule-out progression within 12 weeks from sampling and performed orthogonal calibration versus deep-sequencing and digital PCR. SQI showed significant diagnostic power (AUC 0.848, 95% CI 0.782-0.901). SQI below 5 (63% of samples) had 93% (95% CI 87-96%) NPV, while SQI above 10 (25% of samples) had 69% (95% CI 56-80%) PPV. Cobas EGFR showed perfect agreement with sequencing (Kappa 0.860; 95% CI 0.674-1.00) and digital PCR. SQI values strongly (r: 0.910, 95% 0.821-0.956) correlated to mutant allele concentrations with SQI of 5 and 10 corresponding to 6-9 (0.2-0.3%) and 64-105 (1.1-1.6%) mutant allele copies/mL (VAF) respectively. Our dual-threshold classifier of SQI 0/5/10 yielded informative results in 88% of blood draws with high NPV and good overall clinical utility for patient-centric surveillance of metastatic NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Mutação , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Biópsia Líquida/métodos , DNA Tumoral Circulante/genética , DNA Tumoral Circulante/sangue , Análise Mutacional de DNA/métodos , Metástase Neoplásica
9.
Forensic Sci Int Genet ; 73: 103111, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39128429

RESUMO

This study evaluates the performance of analysing surface DNA samples using massively parallel sequencing (MPS) compared to traditional capillary electrophoresis (CE). A total of 30 samples were collected from various surfaces in an office environment and were analysed with CE and MPS. These were compared against 60 reference samples (office inhabitants). To identify contributors, likelihood ratios (LRs) were calculated for MPS and CE data using the probabilistic genotyping software MPSproto and EuroForMix respectively. Although a higher number of sequences/peaks were observed per DNA profile in MPS compared to CE, LR values were found to be lower for MPS data formats. This might be the result of the increased complexity of MPS data, along with a possible elevation of unknown alleles and/or artefacts. The study highlights avenues for improving MPS data quality and analysis to facilitate more robust interpretation of challenging casework-like samples.

10.
Biom J ; 66(6): e202300185, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39101657

RESUMO

There has been growing research interest in developing methodology to evaluate the health care providers' performance with respect to a patient outcome. Random and fixed effects models are traditionally used for such a purpose. We propose a new method, using a fusion penalty to cluster health care providers based on quasi-likelihood. Without any priori knowledge of grouping information, our method provides a desirable data-driven approach for automatically clustering health care providers into different groups based on their performance. Further, the quasi-likelihood is more flexible and robust than the regular likelihood in that no distributional assumption is needed. An efficient alternating direction method of multipliers algorithm is developed to implement the proposed method. We show that the proposed method enjoys the oracle properties; namely, it performs as well as if the true group structure were known in advance. The consistency and asymptotic normality of the estimators are established. Simulation studies and analysis of the national kidney transplant registry data demonstrate the utility and validity of our method.


Assuntos
Biometria , Pessoal de Saúde , Análise por Conglomerados , Funções Verossimilhança , Humanos , Pessoal de Saúde/estatística & dados numéricos , Biometria/métodos , Transplante de Rim , Algoritmos
11.
Biostatistics ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39142660

RESUMO

Immune response decays over time, and vaccine-induced protection often wanes. Understanding how vaccine efficacy changes over time is critical to guiding the development and application of vaccines in preventing infectious diseases. The objective of this article is to develop statistical methods that assess the effect of decaying immune responses on the risk of disease and on vaccine efficacy, within the context of Cox regression with sparse sampling of immune responses, in a baseline-naive population. We aim to further disentangle the various aspects of the time-varying vaccine effect, whether direct on disease or mediated through immune responses. Based on time-to-event data from a vaccine efficacy trial and sparse sampling of longitudinal immune responses, we propose a weighted estimated induced likelihood approach that models the longitudinal immune response trajectory and the time to event separately. This approach assesses the effects of the decaying immune response, the peak immune response, and/or the waning vaccine effect on the risk of disease. The proposed method is applicable not only to standard randomized trial designs but also to augmented vaccine trial designs that re-vaccinate uninfected placebo recipients at the end of the standard trial period. We conducted simulation studies to evaluate the performance of our method and applied the method to analyze immune correlates from a phase III SARS-CoV-2 vaccine trial.

12.
Front Public Health ; 12: 1416750, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38947345

RESUMO

Background: Internet hospitals, online health communities, and other digital health APPs have brought many changes to people's lives. However, digital health resources are experiencing low continuance intention due to many factors, including information security, service quality, and personal characteristics of users. Methods: We used cross-sectional surveys and structural equation modeling analysis to explore factors influencing user willingness to continue using digital health resources. Results: Information quality (ß = 0.31, p < 0.05), service quality (ß = 0.19, p < 0.05), platform reputation (ß = 0.34, p < 0.05), and emotional support (ß = 0.23, p < 0.05) have significant positive effects on user value co-creation behavior. Additionally, user trust and perceived usefulness could mediate the association between user value co-creation behavior and continuance intention, with mediation effects of 0.143 and 0.125, respectively. User involvement can positively moderate the association between user value co-creation behavior and user trust (ß = 0.151, t = 2.480, p < 0.001). Also, user involvement can positively moderate the association between value co-creation behavior and perceived usefulness (ß = 0.103, t = 3.377, p < 0.001). Conclusion: The keys to solving the problem of low continuance intention are improving the quality and service level of digital health resources, and promoting users' value co-creation behavior. Meanwhile, enterprises should build a good reputation, create a positive communication atmosphere in the community, and enhance user participation and sense of belonging.


Assuntos
Intenção , Análise de Classes Latentes , Humanos , Estudos Transversais , Masculino , Feminino , Adulto , Inquéritos e Questionários , Pessoa de Meia-Idade , Confiança , Recursos em Saúde , Adulto Jovem
13.
World J Clin Cases ; 12(18): 3285-3287, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38983426

RESUMO

Intensive care unit-acquired weakness (ICU-AW) significantly hampers patient recovery and increases morbidity. With the absence of established preventive strategies, this study utilizes advanced machine learning methodologies to unearth key predictors of ICU-AW. Employing a sophisticated multilayer perceptron neural network, the research methodically assesses the predictive power for ICU-AW, pinpointing the length of ICU stay and duration of mechanical ventilation as pivotal risk factors. The findings advocate for minimizing these elements as a preventive approach, offering a novel perspective on combating ICU-AW. This research illuminates critical risk factors and lays the groundwork for future explorations into effective prevention and intervention strategies.

14.
IUCrJ ; 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38989800

RESUMO

Stimulated by informal conversations at the XVII International Small Angle Scattering (SAS) conference (Traverse City, 2017), an international team of experts undertook a round-robin exercise to produce a large dataset from proteins under standard solution conditions. These data were used to generate consensus SAS profiles for xylose isomerase, urate oxidase, xylanase, lysozyme and ribonuclease A. Here, we apply a new protocol using maximum likelihood with a larger number of the contributed datasets to generate improved consensus profiles. We investigate the fits of these profiles to predicted profiles from atomic coordinates that incorporate different models to account for the contribution to the scattering of water molecules of hydration surrounding proteins in solution. Programs using an implicit, shell-type hydration layer generally optimize fits to experimental data with the aid of two parameters that adjust the volume of the bulk solvent excluded by the protein and the contrast of the hydration layer. For these models, we found the error-weighted residual differences between the model and the experiment generally reflected the subsidiary maxima and minima in the consensus profiles that are determined by the size of the protein plus the hydration layer. By comparison, all-atom solute and solvent molecular dynamics (MD) simulations are without the benefit of adjustable parameters and, nonetheless, they yielded at least equally good fits with residual differences that are less reflective of the structure in the consensus profile. Further, where MD simulations accounted for the precise solvent composition of the experiment, specifically the inclusion of ions, the modelled radius of gyration values were significantly closer to the experiment. The power of adjustable parameters to mask real differences between a model and the structure present in solution is demonstrated by the results for the conformationally dynamic ribonuclease A and calculations with pseudo-experimental data. This study shows that, while methods invoking an implicit hydration layer have the unequivocal advantage of speed, care is needed to understand the influence of the adjustable parameters. All-atom solute and solvent MD simulations are slower but are less susceptible to false positives, and can account for thermal fluctuations in atomic positions, and more accurately represent the water molecules of hydration that contribute to the scattering profile.

15.
Heliyon ; 10(12): e32500, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38994043

RESUMO

As the population of Somaliland continues to grow rapidly, the demand for electricity is anticipated to rise exponentially over the next few decades. The provision of reliable and cost-effective electricity service is at the core of the economic and social development of Somaliland. Wind energy might offer a sustainable solution to the exceptionally high electricity prices. In this study, a techno-economic assessment of the wind energy potential in some parts of the western region of Somaliland is performed. Measured data of wind speed and wind direction for three sites around the capital city of Hargeisa are utilized to characterize the resource using Weibull distribution functions. Technical and economic performances of several commercial wind turbines are examined. Out of the three sites, Xumba Weyne stands out as the most favorable site for wind energy harnessing with average annual power and energy densities at 80 m hub height of 317 kW/m2 and 2782 kWh/m2, respectively. Wind turbines installed in Xumba Weyne yielded the lowest levelized cost of electricity (LCOE) of not more than 0.07 $/kWh, shortest payback times (i.e., less than 7.2 years) with minimum return on investment (ROI) of approximately 150%.

16.
J Appl Stat ; 51(9): 1689-1708, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957179

RESUMO

In competing risks data, in practice, there may be lack of information or uncertainty about the true failure type, termed as 'missing failure type', for some subjects. We consider a general pattern of missing failure type in which we observe, if not the true failure type, a set of possible failure types containing the true one. In this work, we focus on both parametric and non-parametric estimation based on current status data with two competing risks and the above-mentioned missing failure type. Here, the missing probabilities are assumed to be time-dependent, that is, dependent on both failure and monitoring time points, in addition to being dependent on the true failure type. This makes the missing mechanism non-ignorable. We carry out maximum likelihood estimation and obtain the asymptotic properties of the estimators. Simulation studies are conducted to investigate the finite sample properties of the estimators. Finally, the methods are illustrated through a data set on hearing loss.

17.
Bull Math Biol ; 86(9): 106, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38995457

RESUMO

Maximum likelihood estimation is among the most widely-used methods for inferring phylogenetic trees from sequence data. This paper solves the problem of computing solutions to the maximum likelihood problem for 3-leaf trees under the 2-state symmetric mutation model (CFN model). Our main result is a closed-form solution to the maximum likelihood problem for unrooted 3-leaf trees, given generic data; this result characterizes all of the ways that a maximum likelihood estimate can fail to exist for generic data and provides theoretical validation for predictions made in Parks and Goldman (Syst Biol 63(5):798-811, 2014). Our proof makes use of both classical tools for studying group-based phylogenetic models such as Hadamard conjugation and reparameterization in terms of Fourier coordinates, as well as more recent results concerning the semi-algebraic constraints of the CFN model. To be able to put these into practice, we also give a complete characterization to test genericity.


Assuntos
Conceitos Matemáticos , Modelos Genéticos , Mutação , Filogenia , Funções Verossimilhança , Algoritmos
18.
Int J Mol Sci ; 25(13)2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-39000413

RESUMO

Our study aims to address the methodological challenges frequently encountered in RNA-Seq data analysis within cancer studies. Specifically, it enhances the identification of key genes involved in axillary lymph node metastasis (ALNM) in breast cancer. We employ Generalized Linear Models with Quasi-Likelihood (GLMQLs) to manage the inherently discrete and overdispersed nature of RNA-Seq data, marking a significant improvement over conventional methods such as the t-test, which assumes a normal distribution and equal variances across samples. We utilize the Trimmed Mean of M-values (TMMs) method for normalization to address library-specific compositional differences effectively. Our study focuses on a distinct cohort of 104 untreated patients from the TCGA Breast Invasive Carcinoma (BRCA) dataset to maintain an untainted genetic profile, thereby providing more accurate insights into the genetic underpinnings of lymph node metastasis. This strategic selection paves the way for developing early intervention strategies and targeted therapies. Our analysis is exclusively dedicated to protein-coding genes, enriched by the Magnitude Altitude Scoring (MAS) system, which rigorously identifies key genes that could serve as predictors in developing an ALNM predictive model. Our novel approach has pinpointed several genes significantly linked to ALNM in breast cancer, offering vital insights into the molecular dynamics of cancer development and metastasis. These genes, including ERBB2, CCNA1, FOXC2, LEFTY2, VTN, ACKR3, and PTGS2, are involved in key processes like apoptosis, epithelial-mesenchymal transition, angiogenesis, response to hypoxia, and KRAS signaling pathways, which are crucial for tumor virulence and the spread of metastases. Moreover, the approach has also emphasized the importance of the small proline-rich protein family (SPRR), including SPRR2B, SPRR2E, and SPRR2D, recognized for their significant involvement in cancer-related pathways and their potential as therapeutic targets. Important transcripts such as H3C10, H1-2, PADI4, and others have been highlighted as critical in modulating the chromatin structure and gene expression, fundamental for the progression and spread of cancer.


Assuntos
Neoplasias da Mama , Regulação Neoplásica da Expressão Gênica , Metástase Linfática , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Metástase Linfática/genética , Feminino , RNA-Seq/métodos , Perfilação da Expressão Gênica/métodos , Linfonodos/patologia , Axila , Biomarcadores Tumorais/genética , Análise de Sequência de RNA/métodos
19.
medRxiv ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38947001

RESUMO

Network meta-analysis, also known as mixed treatments comparison meta-analysis or multiple treatments meta-analysis, extends conventional pairwise meta-analysis by simultaneously synthesizing multiple interventions in a single integrated analysis. Despite the growing popularity of network metaanalysis within comparative effectiveness research, it comes with potential challenges. For example, within-study correlations among treatment comparisons are rarely reported in the published literature. Yet, these correlations are pivotal for valid statistical inference. As demonstrated in earlier studies, ignoring these correlations can inflate mean squared errors of the resulting point estimates and lead to inaccurate standard error estimates. This paper introduces a composite likelihood-based approach that ensures accurate statistical inference without requiring knowledge of the within-study correlations. The proposed method is computationally robust and efficient, with substantially reduced computational time compared to the state-of-the-science methods implemented in R packages. The proposed method was evaluated through extensive simulations and applied to two important applications including a network meta-analysis comparing interventions for primary open-angle glaucoma, and another comparing treatments for chronic prostatitis and chronic pelvic pain syndrome.

20.
MethodsX ; 13: 102816, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39040216

RESUMO

Wildfire is an important natural disturbance agent in Canadian forests, but it has also caused significant economic damage nationwide. Spatial fire growth models have emerged as important tools for representing wildfire dynamics across diverse landscapes, enabling the mapping of key wildfire hazard metrics such as location-specific burn probabilities or likelihoods of fire ignition. While these summary metrics have gained popularity, they often fall short in capturing the directional spread of wildfires and their potential spread distances. The metrics depicting the directional spread of wildfire can be derived from raw outputs generated with fire growth models, such as the perimeters and ignition locations of individual fires, but extracting this information requires complex data processing. To address this data gap, we present PostBP, an open-source Python package designed for post-processing the raw outputs of fire growth models - the ignition locations and perimeters of individual fires simulated over multiple stochastic iterations - into a matrix of fire spread likelihoods between all pairs of forest patches in a landscape. The PostBP also generates several other summary outputs, such as the source-sink ratio and the fire spread rose diagram. We provide an overview of PostBP's capabilities and demonstrate its practical application to a forested landscape.•Wildfire growth models generate large amounts of outputs, which are hard to summarize for practical decision-making.•The PostBP package calculates the summary metrics characterizing the directional spread of wildfires.•The fire risk summaries generated with PostBP can support the assessments of wildfire risk and mitigation measures.

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