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Nevin Manimala Statistics

MRI volumetry and diffusion tensor imaging for diagnosis and follow-up of late post-traumatic injuries

Ann Phys Rehabil Med. 2023 Dec 25;67(2):101783. doi: 10.1016/j.rehab.2023.101783. Online ahead of print.

ABSTRACT

BACKGROUND: Traumatic Brain Injury (TBI) is a major cause of acquired disability and can cause devastating and progressive post-traumatic encephalopathy. TBI is a dynamic condition that continues to evolve over time. A better understanding of the pathophysiology of these late lesions is important for the development of new therapeutic strategies.

OBJECTIVES: The primary objective was to compare the ability of fluid-attenuated reversion recovery (FLAIR) and diffusion tensor imaging (DTI) magnetic resonance imaging (MRI) markers to identify participants with a Glasgow outcome scale extended (GOS-E) score of 7-8, up to 10 years after their original TBI. The secondary objective was to study the brain regionalization of DTI markers. Finally, we analyzed the evolution of late-developing brain lesions using repeated MRI images, also taken up to 10 years after the TBI.

METHODS: In this retrospective study, participants were included from a cohort of people hospitalized following a severe TBI. Following their discharge, they were followed-up and clinically assessed, including a DTI-MRI scan, between 2012 and 2016. We performed a cross-sectional analysis on 97 participants at a median (IQR) of 5 years (3-6) post-TBI, and a further post-TBI longitudinal analysis over 10 years on a subpopulation (n = 17) of the cohort.

RESULTS: Although the area under the curve (AUC) of FLAIR, fractional anisotropy (FA), and mean diffusivity (MD) were not significantly different, only the AUC of FA was statistically greater than 0.5. In addition, only the FA was correlated with clinical outcomes as assessed by GOS-E score (P<10-4). On the cross-sectional analysis, DTI markers allowed study post-TBI white matter lesions by region. In the longitudinal subpopulation analysis, the observed number of brain lesions increased for the first 5 years post-TBI, before stabilizing over the next 5 years.

CONCLUSIONS: This study has shown for the first time that post-TBI lesions can present in a two-phase evolution. These results must be confirmed in larger studies. French Data Protection Agency (Commission nationale de l’informatique et des libertés; CNIL) study registration no: 1934708v0.

PMID:38147704 | DOI:10.1016/j.rehab.2023.101783

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Nevin Manimala Statistics

A model to assess the environmental and economic impacts of municipal waste management in Europe

Waste Manag. 2023 Dec 25;174:605-617. doi: 10.1016/j.wasman.2023.12.029. Online ahead of print.

ABSTRACT

The Monitoring Framework proposed in the EU27 New Circular Economy Action Plan comprises two mass-based indicators, namely overall recycling rate and recycling rate for specific waste streams. Yet, to monitor and assess the impacts of circular economy, indicators cannot be limited to mass-based indicators; we argue assessments should also include environmental and economic effects. Towards this end, these impacts can be quantified by an advanced model based on life cycle thinking, entailing the use of life cycle assessment and costing (LCA/LCC). Calculating these effects for municipal waste management is challenging due to gaps in available data for estimating generated waste. We propose a methodology to estimate more finely the amounts of waste generated in the Member States, complemented with LCA/LCC. The results highlight that important inconsistencies in municipal waste data reporting exist and that recycling rates calculated from these are lower than hitherto estimated. The impacts quantification shows great performance variation across EU27, with C-footprint ranging from -490 to 539 kg CO2-eq. t-1. Potentials for improvement are substantial and can bring up to 103 Mt CO2-eq. additional annual saving, reducing costs (calculated as Full Environmental LCC) of waste management by 8.4 billion EUR and bringing 206,100 new jobs in the sector. The approach presented highlights the rationale for improved data management on waste statistics and the potential for harmonised models. It also paves the way for more sophisticated impact analyses relevant for policymaking, by bringing a richer perspective to the environmental and economic impacts of waste management on top of tracking generated, collected and recycled waste flows.

PMID:38147702 | DOI:10.1016/j.wasman.2023.12.029

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Nevin Manimala Statistics

Stress-granules, P-bodies, and cell aging: A bioinformatics study

Biochem Biophys Res Commun. 2023 Dec 21;694:149404. doi: 10.1016/j.bbrc.2023.149404. Online ahead of print.

ABSTRACT

At the molecular level, aging is often accompanied by dysfunction of stress-induced membrane-less organelles (MLOs) and changes in their physical state (or material properties). In this work, we analyzed the proteins included in the proteome of stress granules (SGs) and P-bodies for their tendency to transform the physical state of these MLOs. Particular attention was paid to the proteins whose gene expression changes during replicative aging. It was shown that the proteome of the studied MLOs consists of intrinsically disordered proteins, 30-40% of which are potentially capable of liquid-liquid phase separation (LLPS). Proteins whose gene expression changes during the transition of human cells to a senescent state make up about 20% of the studied proteomes. There is a statistically significant increase in the number of positively charged proteins in both datasets studied compared to the complete proteomes of these organelles. An increase in the relative content of DNA-, but not RNA-binding proteins, was also found in the SG dataset with senescence-related processes. Among SGs proteins potentially involved in senescent processes, there is an increase in the abundance of potentially amyloidogenic proteins compared to the whole proteome. Proteins common to SGs and P-bodies, potentially involved in processes associated with senescence, form clusters of interacting proteins. The largest cluster is represented by RNA-binding proteins involved in RNA processing and translation regulation. These data indicate that SG proteins, but not proteins of P-bodies, are more likely to transform the physical state of MLOs. Furthermore, these MLOs can participate in processes associated with aging in a coordinated manner.

PMID:38147698 | DOI:10.1016/j.bbrc.2023.149404

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Nevin Manimala Statistics

Cytoplasmic Shotgun Proteomic Points to Key Proteins and Pathways in Temozolomide-Resistant Glioblastoma Multiforme

J Proteome Res. 2023 Dec 26. doi: 10.1021/acs.jproteome.3c00669. Online ahead of print.

ABSTRACT

Temozolomide (TMZ) is the first line of chemotherapy to treat primary brain tumors of the type glioblastoma multiforme (GBM). TMZ resistance (TMZR) is one of the main barriers to successful treatment and is a principal factor in relapse, resulting in a poor median survival of 15 months. The present paper focuses on proteomic analyses of cytosolic fractions from TMZ-resistant (TMZR) LN-18 cells. The experimental workflow includes an easy, cost-effective, and reproducible method to isolate subcellular fraction of cytosolic (CYTO) proteins, mitochondria, and plasma membrane proteins for proteomic studies. For this study, enriched cytoplasmic fractions were analyzed in replicates by nanoflow liquid chromatography tandem high-resolution mass spectrometry (nLC-MS/MS), and proteins identified were quantified using a label-free approach (LFQ). Statistical analysis of control (CTRL) and temozolomide-resistant (TMZR) proteomes revealed proteins that appear to be differentially controlled in the cytoplasm. The functions of these proteins are discussed as well as their roles in other cancers and TMZ resistance in GBM. Key proteins are also described through biological processes related to gene ontology (GO), molecular functions, and cellular components. For protein-protein interactions (PPI), network and pathway involvement analyses have been performed, highlighting the roles of key proteins in the TMZ resistance phenotypes. This study provides a detailed insight into methods of subcellular fractionation for proteomic analysis of TMZ-resistant GBM cells and the potential to apply this approach to future large-scale studies. Several key proteins, protein-protein interactions (PPI), and pathways have been identified, underlying the TMZ resistance phenotype and highlighting the proteins’ biological functions.

PMID:38147655 | DOI:10.1021/acs.jproteome.3c00669

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Nevin Manimala Statistics

Observed humidity trends in dry regions contradict climate models

Proc Natl Acad Sci U S A. 2024 Jan 2;121(1):e2302480120. doi: 10.1073/pnas.2302480120. Epub 2023 Dec 26.

ABSTRACT

Arid and semi-arid regions of the world are particularly vulnerable to greenhouse gas-driven hydroclimate change. Climate models are our primary tool for projecting the future hydroclimate that society in these regions must adapt to, but here, we present a concerning discrepancy between observed and model-based historical hydroclimate trends. Over the arid/semi-arid regions of the world, the predominant signal in all model simulations is an increase in atmospheric water vapor, on average, over the last four decades, in association with the increased water vapor-holding capacity of a warmer atmosphere. In observations, this increase in atmospheric water vapor has not happened, suggesting that the availability of moisture to satisfy the increased atmospheric demand is lower in reality than in models in arid/semi-arid regions. This discrepancy is most clear in locations that are arid/semi-arid year round, but it is also apparent in more humid regions during the most arid months of the year. It indicates a major gap in our understanding and modeling capabilities which could have severe implications for hydroclimate projections, including fire hazard, moving forward.

PMID:38147646 | DOI:10.1073/pnas.2302480120

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Nevin Manimala Statistics

Forest mosaics, not savanna corridors, dominated in Southeast Asia during the Last Glacial Maximum

Proc Natl Acad Sci U S A. 2024 Jan 2;121(1):e2311280120. doi: 10.1073/pnas.2311280120. Epub 2023 Dec 26.

ABSTRACT

The dominant paradigm is that large tracts of Southeast Asia’s lowland rainforests were replaced with a “savanna corridor” during the cooler, more seasonal climates of the Last Glacial Maximum (LGM) (23,000 to 19,000 y ago). This interpretation has implications for understanding the resilience of Asia’s tropical forests to projected climate change, implying a vulnerability to “savannization”. A savanna corridor is also an important foundation for archaeological interpretations of how humans moved through and settled insular Southeast Asia and Australia. Yet an up-to-date, multiproxy, and empirical examination of the palaeoecological evidence for this corridor is lacking. We conducted qualitative and statistical analyses of 59 palaeoecological records across Southeast Asia to test the evidence for LGM savannization and clarify the relationships between methods, biogeography, and ecological change in the region from the start of Late Glacial Period (119,000 y ago) to the present. The pollen records typically show montane forest persistence during the LGM, while δ13C biomarker proxies indicate the expansion of C4-rich grasslands. We reconcile this discrepancy by hypothesizing the expansion of montane forest in the uplands and replacement of rainforest with seasonally dry tropical forest in the lowlands. We also find that smooth forest transitions between 34,000 and 2,000 y ago point to the capacity of Southeast Asia’s ecosystems both to resist and recover from climate stressors, suggesting resilience to savannization. Finally, the timing of ecological change observed in our combined datasets indicates an ‘early’ onset of the LGM in Southeast Asia from ~30,000 y ago.

PMID:38147645 | DOI:10.1073/pnas.2311280120

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Nevin Manimala Statistics

Statistical Analysis of Radioactivity: Lamprecht Uranium Mine in Texas

Health Phys. 2024 Feb 1;126(2):65-78. doi: 10.1097/HP.0000000000001764.

ABSTRACT

The former Lamprecht uranium mine facility in Texas ceased operations well before the new millennium. However, decommissioning activities were never completed by the licensee. Consequently, a legal proceeding was authorized between state and licensee representatives. Meanwhile, state funds were used to hire an independent contractor to perform radiological surveys and assess the magnitude of residual radioactivity across the terrain at the site. The purpose of this study was to apply advanced spatial statistical methods to the survey data measured by contractors at the Lamprecht site to precisely predict remaining radioactive hotspot locations post soil remediation activities. To accomplish this, descriptive statistics such as Google maps and boxplots along with inferential spatial statistical techniques, e.g., kriging and semivariograms, were employed. R coding was also used throughout. Specifically, the descriptive statistical methods included geographical mapping of targeted areas at the site coupled with summary statistics. Inferentially, spatial analytical techniques were employed to pinpoint the locations of elevated radiation levels above regulatory limits. Our results suggest that fewer hotspots were identified after remediation activities were completed at the site. This study provides an additional analytical resource for the State of Texas regarding the release of this former in situ leach uranium mine site to landowners for unrestricted use.

PMID:38147633 | DOI:10.1097/HP.0000000000001764

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Nevin Manimala Statistics

Color Mapping using Ultrasound System-integrated Perfusion Software for Evaluation of Focal Liver Lesions: A Possible First Step for More Independent Reading

J Gastrointestin Liver Dis. 2023 Dec 22;32(4):479-487. doi: 10.15403/jgld-4997.

ABSTRACT

AIMS: To assess the value of using integrated parametric ultrasound software for contrast-enhanced ultrasonography (CEUS) of liver tumors.

METHODS: 107 patients with liver tumors were studied. CEUS were performed to detect focal lesions. Parametric images were based on continuous CINE LOOPs, from the early-arterial phase (15 s) to the portal-venous phase (1 min) generated by perfusion software. The evaluations of the parametric images and their dignity for liver lesions were performed independently by an experienced and a less-experienced investigator. Computed tomography, magnetic resonance imaging scans or histological analysis were used as references.

RESULTS: High parametric image quality were obtained in all patients. Among the patients, 44% lesions were benign, 56% were malignant. The experienced investigator correctly classified 46 of 47 (98%) as benign, and 60 of 60 (100%) as malignant tumors based on the parametric images. The less-experienced investigator correctly classified 39 of 47 (83%) as benign, and 49 of 60 (82%) malignant tumors, acheaving a high statistical accuracy of 98% with this type of diagnostic.

CONCLUSION: Parametric imaging for grading the malignant degree of tumor may be a good complement to existing ultrasound techniques and was particularly helpful for improving the assessments of the less-experienced examiner.

PMID:38147619 | DOI:10.15403/jgld-4997

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Nevin Manimala Statistics

Reduction of Fecal Calprotectin Levels Induced by a Short Course of Escherichia Coli Nissle is Associated with a Lower Likelihood of Disease Flares in Patients with Ulcerative Colitis in Clinical Remission

J Gastrointestin Liver Dis. 2023 Dec 22;32(4):438-443. doi: 10.15403/jgld-4932.

ABSTRACT

BACKGROUND AND AIMS: Fecal calprotectin (FC) is a biomarker of gut inflammation, and Escherichia coli Nissle 1917 (EcN) is a probiotic strain able to reduce gut inflammation and maintain disease remission in patients with inflammatory bowel disease (IBD). The aim is to assess the effects of EcN administration in patients with IBD in clinical remission and altered FC values.

METHODS: We prospectively included 82 patients with ulcerative colitis (UC) (n=49) and Crohn’s disease (CD) (n=33) in clinical remission and with FC values above 250 mcg/g (T0) who were treated with EcN alone for 2 months. FC values were assessed at the end of EcN treatment (T1) and clinical disease activity at 3 months (T2).

RESULTS: At T1 median FC values were significantly lower compared to T0 both in patients with CD (312 mcg/g vs 626 mcg/g, p<0.0001) and UC (100 mcg/g vs 584 mcg/g; p<0.0001). Patients with UC who experienced disease relapse at T2 had lesser reduction in median FC values at T1 (-229 mcg/g, vs -397 mcg/g, p=0.049), while in patients with CD we observed no statistically significant difference (-358 mcg/g, vs -427; p=0.568). In patients with UC, a reduction of at least 532 mcg/g in FC had an accuracy of 69.7% and a positive predictive value of 65.7% in predicting maintenance of remission.

CONCLUSIONS: A short course of EcN was associated with a reduction of FC values in patients with IBD in clinical remission and baseline altered FC values, and in patients with UC this decrease was associated with maintenance of clinical remission.

PMID:38147604 | DOI:10.15403/jgld-4932

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Nevin Manimala Statistics

The fitness consequences of genetic divergence between polymorphic gene arrangements

Genetics. 2023 Dec 26:iyad218. doi: 10.1093/genetics/iyad218. Online ahead of print.

ABSTRACT

Inversions restrict recombination when heterozygous with standard arrangements, but often have few noticeable phenotypic effects. Nevertheless, there are several examples of inversions that can be maintained polymorphic by strong selection under laboratory conditions. A long-standing model for the source of such selection is divergence between arrangements with respect to recessive or partially recessive deleterious mutations, resulting in a selective advantage to heterokaryotypic individuals over homokaryotypes. This paper uses a combination of analytical and numerical methods to investigate this model, for the simple case of an autosomal inversion with multiple independent nucleotide sites subject to mildly deleterious mutations. A complete lack of recombination in heterokaryotypes is assumed, as well as constancy of the frequency of the inversion over space and time. It is shown that a significantly higher mutational load will develop for the less frequent arrangement. A selective advantage to heterokaryotypes is only expected when the two alternative arrangements are nearly equal in frequency, so that their mutational loads are very similar in size. The effects of some Drosophila pseudoobscura polymorphic inversions on fitness traits seem to be too large to be explained by this process, although it may contribute to some of the observed effects. Several population genomic statistics can provide evidence for signatures of a reduced efficacy of selection associated with the rarer of two arrangements, but there is currently little published data that are relevant to the theoretical predictions.

PMID:38147527 | DOI:10.1093/genetics/iyad218