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Nevin Manimala Statistics

Gene Co-expression Network Analysis and Linking Modules to Phenotyping Response in Plants

Methods Mol Biol. 2022;2539:261-268. doi: 10.1007/978-1-0716-2537-8_20.

ABSTRACT

Environmental factors, including different stresses, can have an impact on the expression of genes and subsequently the phenotype and development of plants. Since a large number of genes are involved in response to the perturbation of the environment, identifying groups of co-expressed genes is meaningful. The gene co-expression network models can be used for the exploration, interpretation, and identification of genes responding to environmental changes. Once a gene co-expression network is constructed, one can determine gene modules and the association of gene modules to the phenotypic response. To link modules to phenotype, one approach is to find the correlated eigengenes of given modules or to integrate all eigengenes in regularized linear model. This manuscript describes the method from construction of co-expression network, module discovery, association between modules and phenotypic data, and finally to annotation/visualization.

PMID:35895209 | DOI:10.1007/978-1-0716-2537-8_20

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Nevin Manimala Statistics

Experimental Design for Controlled Environment High-Throughput Plant Phenotyping

Methods Mol Biol. 2022;2539:57-68. doi: 10.1007/978-1-0716-2537-8_7.

ABSTRACT

It is essential that the scientific community develop and deploy accurate and high-throughput techniques to capture factors that influence plant phenotypes if we are to meet the projected demands for food and energy. In recognition of this fact, multiple research institutions have invested in automated high-throughput plant phenotyping (HTPP) systems designed for use in controlled environments. These systems can generate large amounts of data in relatively short periods of time, potentially allowing researchers to gain insights about phenotypic responses to environmental, biological, and management factors. Reliable inferences about these factors depends on the use of proper experimental design when planning phenotypic studies in order to avoid issues such as lack of power and confounding. In this chapter, the topic of experimental design will be discussed, from basic principles to examples specific to controlled environment plant phenotyping. Examples will be provided based on the package agricolae in the R statistical language.

PMID:35895196 | DOI:10.1007/978-1-0716-2537-8_7

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Nevin Manimala Statistics

[18F]ROStrace detects oxidative stress in vivo and predicts progression of Alzheimer’s disease pathology in APP/PS1 mice

EJNMMI Res. 2022 Jul 27;12(1):43. doi: 10.1186/s13550-022-00914-x.

ABSTRACT

BACKGROUND: Oxidative stress is implicated in the pathogenesis of the most common neurodegenerative diseases, such as Alzheimer’s disease (AD). However, tracking oxidative stress in the brain has proven difficult and impeded its use as a biomarker. Herein, we investigate the utility of a novel positron emission tomography (PET) tracer, [18F]ROStrace, as a biomarker of oxidative stress throughout the course of AD in the well-established APP/PS1 double-mutant mouse model. PET imaging studies were conducted in wild-type (WT) and APP/PS1 mice at 3 different time points, representing early (5 mo.), middle (10 mo.), and advanced (16 mo.) life (n = 6-12, per sex). Semi-quantitation SUVRs of the plateau phase (40-60 min post-injection; SUVR40-60) of ten brain subregions were designated by the Mirrione atlas and analyzed by Pmod. Statistical parametric mapping (SPM) was used to distinguish brain regions with elevated ROS in APP/PS1 relative to WT in both sexes. The PET studies were validated by ex vivo autoradiography and immunofluorescence with the parent compound, dihydroethidium.

RESULTS: [18F]ROStrace retention was increased in the APP/PS1 brain compared to age-matched controls by 10 mo. of age (p < 0.0001) and preceded the accumulation of oxidative damage in APP/PS1 neurons at 16 mo. (p < 0.005). [18F]ROStrace retention and oxidative damages were higher and occurred earlier in female APP/PS1 mice as measured by PET (p < 0.001), autoradiography, and immunohistochemistry (p < 0.05). [18F]ROStrace differences emerged midlife, temporally and spatially correlating with increased Aβ burden (r2 = 0.36; p = 0.0003), which was also greatest in the female brain (p < 0.001).

CONCLUSIONS: [18F]ROStrace identifies increased oxidative stress and neuroinflammation in APP/PS1 female mice, concurrent with increased amyloid burden midlife. Differences in oxidative stress during this crucial time may partially explain the sexual dimorphism in AD. [18F]ROStrace may provide a long-awaited tool to stratify at-risk patients who may benefit from antioxidant therapy prior to irreparable neurodegeneration.

PMID:35895177 | DOI:10.1186/s13550-022-00914-x

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Nevin Manimala Statistics

Health-related quality of life analysis in ovarian cancer clinical trials involving PARP inhibitors: a critical methodological perspective

Qual Life Res. 2022 Jul 27. doi: 10.1007/s11136-022-03193-0. Online ahead of print.

ABSTRACT

The poly (ADP-ribose) polymerase inhibitors (PARPi) have yielded significant clinical benefits as maintenance therapy in women with newly diagnosed and relapsed platinum-sensitive advanced ovarian cancer. These drugs were approved based on progression-free survival, the primary endpoint of their respective pivotal trials. Health-related quality of life (HRQoL) and/or patient-reported outcomes were included in these trials as a secondary exploratory endpoint. Nevertheless, many weaknesses in the analysis of HRQoL across these trials can be noticed. Heterogeneity and suboptimal HRQoL analysis in oncology trials contribute to misconceptions about this endpoint among oncologists and prevent quality of life as being an endpoint used for approvals. In this article, we discuss these HRQoL results from a methodological perspective and propose some solutions for improvement that could be used by regulatory and academic institutions running ovarian cancers trials. Notably, we suggest to measure and analyze HRQoL data after disease progression, to focus dedicated papers on the statistical analyses of HRQoL recommended by the SISAQOL consortium (linear mixed model for repeated measures and time-to-event approaches) and to communicate on available guidelines to ensure compliance with best international practices regarding the measurement and analysis of HRQoL.

PMID:35895164 | DOI:10.1007/s11136-022-03193-0

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Nevin Manimala Statistics

Social needs and health-related quality of life among hematologic cancer survivors

Support Care Cancer. 2022 Jul 27. doi: 10.1007/s00520-022-07281-2. Online ahead of print.

ABSTRACT

OBJECTIVES: Recent studies have examined social needs (social determinants of health) among cancer survivors, but studies have not specifically focused on patients with leukemia or lymphoma. We examined food insecurity and other social needs among hematologic cancer survivors, including individuals who had completed primary therapy for leukemia, lymphoma, or multiple myeloma. A particular focus of the study was on the relationship between social needs and health-related quality of life.

METHODS: We conducted a postal survey of a multiethnic cohort of hematologic cancer survivors who reside in Augusta, GA, or the surrounding area and who had been treated at the Georgia Cancer Center.

RESULTS: A total of 53 patients with a history of hematologic cancer (leukemia, lymphoma, or multiple myeloma) completed the survey (10.6% response rate). The mean age was 62.6 years. The participants were diverse according to annual household income and employment status. About two-thirds were white and almost one-third were African American. Five of 52 participants (9.6%) experienced food insecurity. Patients with food insecurity had poorer HRQOL compared with those who were food secure (63.3 vs. 87.33, p = 0.0308). A similar pattern was seen for those who had difficulty paying utility bills, those who had housing insecurity, and those who had to go without health care because of a lack of transportation. Overall, there was a statistically significant inverse association between HRQOL and number of social needs (p = 0.004).

CONCLUSION: When caring for cancer survivors, social needs such as food insecurity and housing insecurity are important considerations for oncologists and primary care providers, especially when caring for patients with lower socioeconomic status and racial/ethnic minorities.

PMID:35895158 | DOI:10.1007/s00520-022-07281-2

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Nevin Manimala Statistics

Prognostic value of lymph node involvement in oral squamous cell carcinoma

Clin Oral Investig. 2022 Jul 27. doi: 10.1007/s00784-022-04630-7. Online ahead of print.

ABSTRACT

OBJECTIVES: Different parameters have been identified in patients with oral squamous cell carcinomas (OSCC) that have a serious impact on survival, including residual tumour and extracapsular spread. Moreover, other factors, including the lymph node ratio (LNR) and lymph node yield (LNY), have been suggested as prognostic markers.

MATERIAL AND METHODS: This retrospective study included patients diagnosed with OSCC and cervical lymph node metastases during the years 2010-2020. Patients’ records were evaluated regarding lymph node status, final therapy regime, tumour recurrence, time to death, tumour association with death, disease-free survival (DSF), and overall survival (OS).

RESULTS: In 242 patients with a mean age of 63.57 ± 11.24 years, treated either by selective neck dissection (SND; n = 70) or by modified radical neck dissection (MRND; n = 172), 5772 lymph nodes were detected. The LNR and LNY were identified as independent risk factors in OS and DFS. The optimal cut-off point for the LNY was ≥ 17 lymph nodes in the SND and ≥ 27 lymph nodes in the MRND group. The metastatic lymph node clearance (MLNC) was established as a score to relate the LNR and LNY to the extent of lymph node removal. Survival analysis showed statistically significant differences among score levels.

CONCLUSIONS: As information about the extent of nodal dissection is excluded from LNR and LNY, we propose the use of a new scoring system comprising individual cut-off values for LNY and LNR with regard to the extent of neck dissection.

CLINICAL RELEVANCE: MLNC might help to identify high-risk OSCC patients with metastatic lymph nodes.

PMID:35895143 | DOI:10.1007/s00784-022-04630-7

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Nevin Manimala Statistics

What lies on macroalgal surface: diversity of polysaccharide degraders in culturable epiphytic bacteria

AMB Express. 2022 Jul 27;12(1):98. doi: 10.1186/s13568-022-01440-8.

ABSTRACT

Macroalgal surface constitutes a peculiar ecological niche and an advantageous substratum for microorganisms able to degrade the wide diversity of algal glycans. The degrading enzymatic activities of macroalgal epiphytes are of paramount interest for the industrial by-product sector and biomass resource applications. We characterized the polysaccharide hydrolytic profile of bacterial isolates obtained from three macroalgal species: the red macroalgae Asparagopsis taxiformis and Sphaerococcus coronopifolius (Rhodophyceae) and the brown Halopteris scoparia (Phaeophyceae), sampled in South Portugal. Bacterial enrichment cultures supplemented with chlorinated aliphatic compounds, typically released by marine algae, were established using as inoculum the decaying biomass of the three macroalgae, obtaining a collection of 634 bacterial strains. Although collected from the same site and exposed to the same seawater seeding microbiota, macroalgal cultivable bacterial communities in terms of functional and phylogenetic diversity showed host specificity. Isolates were tested for the hydrolysis of starch, pectin, alginate and agar, exhibiting a different hydrolytic potential according to their host: A. taxiformis showed the highest percentage of active isolates (91%), followed by S. coronopifolius (54%) and H. scoparia (46%). Only 30% of the isolates were able to degrade starch, while the other polymers were degraded by 55-58% of the isolates. Interestingly, several isolates showed promiscuous capacities to hydrolyze more than one polysaccharide. The isolate functional fingerprint was statistically correlated to bacterial phylogeny, host species and enrichment medium. In conclusion, this work depicts macroalgae as holobionts with an associated microbiota of interest for blue biotechnologies, suggesting isolation strategies and bacterial targets for polysaccharidases’ discovery.

PMID:35895126 | DOI:10.1186/s13568-022-01440-8

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Nevin Manimala Statistics

Quantitative and qualitative assessments of deep learning image reconstruction in low-keV virtual monoenergetic dual-energy CT

Eur Radiol. 2022 Jul 27. doi: 10.1007/s00330-022-09018-5. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate a novel deep learning image reconstruction (DLIR) technique for dual-energy CT (DECT) derived virtual monoenergetic (VM) images compared to adaptive statistical iterative reconstruction (ASIR-V) in low kiloelectron volt (keV) images.

METHODS: We analyzed 30 venous phase acute abdominal DECT (80/140 kVp) scans. Data were reconstructed to ASIR-V and DLIR-High at four different keV levels (40, 50, 74, and 100) with 1- and 3-mm slice thickness. Quantitative Hounsfield unit (HU) and noise assessment were measured within the liver, aorta, fat, and muscle. Subjective assessment of image noise, sharpness, texture, and overall quality was performed by two board-certified radiologists.

RESULTS: DLIR reduced image noise by 19.9-35.5% (p < 0.001) compared to ASIR-V in all reconstructions at identical keV levels. Contrast-to-noise ratio (CNR) increased by 49.2-53.2% (p < 0.001) in DLIR 40-keV images compared to ASIR-V 50 keV, while no significant difference in noise was identified except for 1 and 3 mm in aorta and for 1-mm liver measurements, where ASIR-V 50 keV showed 5.5-6.8% (p < 0.002) lower noise levels. Qualitative assessment demonstrated significant improvement particularly in 1-mm reconstructions (p < 0.001). Lastly, DLIR 40 keV demonstrated comparable or improved image quality ratings when compared to ASIR-V 50 keV (p < 0.001 to 0.22).

CONCLUSION: DLIR significantly reduced image noise compared to ASIR-V. Qualitative assessment showed that DLIR significantly improved image quality particularly in thin sliced images. DLIR may facilitate 40 keV as a new standard for routine low-keV VM reconstruction in contrast-enhanced abdominal DECT.

KEY POINTS: • DLIR enables 40 keV as the routine low-keV VM reconstruction. • DLIR significantly reduced image noise compared to ASIR-V, across a wide range of keV levels in VM DECT images. • In low-keV VM reconstructions, improvements in image quality using DLIR were most evident and consistent in 1-mm sliced images.

PMID:35895120 | DOI:10.1007/s00330-022-09018-5

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Nevin Manimala Statistics

Evaluation of IOL power calculation with the Kane formula for pediatric cataract surgery

Graefes Arch Clin Exp Ophthalmol. 2022 Jul 27. doi: 10.1007/s00417-022-05779-3. Online ahead of print.

ABSTRACT

PURPOSE: To assess the accuracy of the Kane formula for intraocular lens (IOL) power calculation in the pediatric population.

METHODS: The charts of pediatric patients who underwent cataract surgery with in-the-bag IOL implantation with one of two IOL models (SA60AT or MA60AC) between 2012 and 2018 in The Hospital for Sick Children, Toronto, Ontario, CanFada, were retrospectively reviewed. The accuracy of IOL power calculation with the Kane formula was evaluated in comparison with the Barrett Universal II (BUII), Haigis, Hoffer Q, Holladay 1, and Sanders-Retzlaff-Kraff Theoretical (SRK/T) formulas.

RESULTS: Sixty-two eyes of 62 patients aged 6.2 (IQR 3.2-9.2) years were included. The SD values of the prediction error obtained by Kane (1.38) were comparable with those by BUII (1.34), Hoffer Q (1.37), SRK/T (1.40), Holaday 1 (1.41), and Haigis (1.50), all p > 0.05. A significant difference was observed between the Hoffer Q and Haigis formulas (p = 0.039). No differences in the median and mean absolute errors were found between the Kane formula (0.54 D and 0.91 ± 1.04 D) and BUII (0.50 D and 0.88 ± 1.00 D), Hoffer Q (0.48 D and 0.88 ± 1.05 D), SRK/T (0.72 D and 0.97 ± 1.00 D), Holladay 1 (0.63 D and 0.94 ± 1.05 D), and Haigis (0.57 D and 0.98 ± 1.13 D), p = 0.099.

CONCLUSION: This is the first study to investigate the Kane formula in pediatric cataract surgery. Our results place the Kane among the noteworthy IOL power calculation formulas in this age group, offering an additional means for improving IOL calculation in pediatric cataract surgery. The heteroscedastic statistical method was first implemented to evaluate formulas’ predictability in children.

PMID:35895106 | DOI:10.1007/s00417-022-05779-3

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Nevin Manimala Statistics

Perspectives on Hyperthermic Intraperitoneal Chemotherapy for Advanced Ovarian Cancer-Reply

JAMA Surg. 2022 Jul 27. doi: 10.1001/jamasurg.2022.2941. Online ahead of print.

NO ABSTRACT

PMID:35895070 | DOI:10.1001/jamasurg.2022.2941