Category: Statistics

Oncol Rep. 2022 Jun;47(6):118. doi: 10.3892/or.2022.8329. Epub 2022 May 11.

ABSTRACT

Inflammatory signaling through prostaglandin E2 receptor subtype 2 (EP2) is associated with malignant tumor growth in both experimental models and cancer patients. Thus, the absence of EP2 receptors in host tissues appears to reduce tumor growth and systemic inflammation by inducing major alterations in gene expression levels across tumor tissue compartments. However, it is not yet well‑established how signaling pathways in tumor tissue relate to simultaneous signaling alterations in the surrounding tumor‑stroma, at conditions of reduced disease progression due to decreased host inflammation. In the present study, wild‑type tumor cells, producing high levels of prostaglandin E2 (MCG 101 cells, EP2^+/+), were inoculated into EP2 knockout (EP2^‑/‑) and EP2 wild‑type (EP2^+/+) mice. Solid tumors were dissected into tumor‑ and tumor‑stroma tissue compartments for RNA expression microarray screening, followed by metabolic pathway analyses. Immunohistochemistry was used to confirm adequate dissections of tissue compartments, and to assess cell proliferation (Ki‑67), prostaglandin enzymes (cyclooxygenase 2) and immunity biomarkers (CD4 and CD8) at the protein level. Microarray analyses revealed statistically significant alterations in gene expression in the tumor‑stroma compartment, while significantly less pathway alterations occurred in the tumor tissue compartment. The host knockout of EP2 receptors led to a significant downregulation of cell cycle regulatory factors in the tumor‑stroma compartment, while interferon γ‑related pathways, chemokine signaling pathways and anti‑tumor chemokines [chemokine (C‑X‑C motif) ligand 9 and 10] were upregulated in the tumor compartment. Thus, such gene alterations were likely related to reduced tumor growth in EP2‑deficient hosts. On the whole, pathway analyses of both tumor‑ and tumor‑stroma compartments suggested that absence of host EP2 receptor signaling reduces ‘remodeling’ of tumor microenvironments and increase local immunity, probably by decreased productions of stimulating growth factors, perhaps similar to well‑recognized physiological observations in wound healing.

PMID:35543149 | DOI:10.3892/or.2022.8329

J Laryngol Otol. 2022 May 11:1-15. doi: 10.1017/S0022215122001165. Online ahead of print.

NO ABSTRACT

PMID:35543098 | DOI:10.1017/S0022215122001165

mSystems. 2022 May 11:e0031222. doi: 10.1128/msystems.00312-22. Online ahead of print.

ABSTRACT

Microbial symbiosis drives physiological processes of higher-order systems, including the acquisition and consumption of nutrients that support symbiotic partner reproduction. Metabolic analytics provide new avenues to examine how chemical ecology, or the conversion of existing biomass to new forms, changes over a symbiotic life cycle. We applied these approaches to the nematode Steinernema carpocapsae, its mutualist bacterium, Xenorhabdus nematophila, and the insects they infect. The nematode-bacterium pair infects, kills, and reproduces in an insect until nutrients are depleted. To understand the conversion of insect biomass over time into either nematode or bacterium biomass, we integrated information from trophic, metabolomic, and gene regulation analyses. Trophic analysis established bacteria as meso-predators and primary insect consumers. Nematodes hold a trophic position of 4.6, indicative of an apex predator, consuming bacteria and likely other nematodes. Metabolic changes associated with Galleria mellonella insect bioconversion were assessed using multivariate statistical analyses of metabolomics data sets derived from sampling over an infection time course. Statistically significant, discrete phases were detected, indicating the insect chemical environment changes reproducibly during bioconversion. A novel hierarchical clustering method was designed to probe molecular abundance fluctuation patterns over time, revealing distinct metabolite clusters that exhibit similar abundance shifts across the time course. Composite data suggest bacterial tryptophan and nematode kynurenine pathways are coordinated for reciprocal exchange of tryptophan and NAD⁺ and for synthesis of intermediates that can have complex effects on bacterial phenotypes and nematode behaviors. Our analysis of pathways and metabolites reveals the chemistry underlying the recycling of organic material during carnivory. IMPORTANCE The processes by which organic life is consumed and reborn in a complex ecosystem were investigated through a multiomics approach applied to the tripartite Xenorhabdus bacterium-Steinernema nematode-Galleria insect symbiosis. Trophic analyses demonstrate the primary consumers of the insect are the bacteria, and the nematode in turn consumes the bacteria. This suggests the Steinernema-Xenorhabdus mutualism is a form of agriculture in which the nematode cultivates the bacterial food sources by inoculating them into insect hosts. Metabolomics analysis revealed a shift in biological material throughout progression of the life cycle: active infection, insect death, and conversion of cadaver tissues into bacterial biomass and nematode tissue. We show that each phase of the life cycle is metabolically distinct, with significant differences including those in the tricarboxylic acid cycle and amino acid pathways. Our findings demonstrate that symbiotic life cycles can be defined by reproducible stage-specific chemical signatures, enhancing our broad understanding of metabolic processes that underpin a three-way symbiosis.

PMID:35543104 | DOI:10.1128/msystems.00312-22

Hemoglobin. 2022 May 11:1-4. doi: 10.1080/03630269.2022.2070073. Online ahead of print.

ABSTRACT

In children with β-thalassemia (β-thal) trait, tissue damage occurs with oxidative stress due to oxygen free radicals and reactive oxygen species (ROS) production. Dynamic thiol-disulfide homeostasis (DTDH) is one of the most important indicators showing the pro-oxidant/antioxidant status in the body. In this study, we aimed to examine the status of DTDH by measuring native thiol, disulfide, and total thiol levels in children with β-thal trait. The study included 40 children with β-thal trait and 30 healthy controls (matched by age and gender). The DTDH parameters were measured by an automated method and results were compared between the groups. The levels of native thiol, total thiol, and disulfide in children with β-thal trait group were statistically significantly higher than the control group (p < 0.001). There was no significant difference in disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol levels between the groups. In addition, there was no correlation between hemoglobin (Hb) and serum ferritin levels with the markers of DTDH in children with β-thal trait. In our study, a significant increase was found in native thiol, total thiol, and disulfide levels in response to oxidative stress in children with β-thal trait compared to the healthy control group. Disulfide levels of the children with β-thal trait were higher than the control group, showing oxidative stress is high in β-thal trait. Accordingly, it increases the native thiol and total thiol capacity as compensation.

PMID:35543093 | DOI:10.1080/03630269.2022.2070073

Nutr Cancer. 2022 May 11:1-8. doi: 10.1080/01635581.2022.2074064. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this study was to investigate the effect of the body fat mass ratio on survival and prognosis in advanced non-small-cell lung cancer patients.

METHODS: The study includes 200 patients who were diagnosed with advanced non-small-cell lung cancer between 2014 and 2018 and whose body fat mass percentage and body mass index (BMI) were determined using the Tanita Body Composition Analyzer during admission.

RESULTS: All patients had advanced incurable non-small-cell lung cancer (30% had locally advanced disease, 70% were stage IV). In the univariate and multivariate analyses, age, gender, histopathological type, smoking history, comorbidities, weight loss in the last six months and body mass index had no statistically significant effect on survival (p > 0.05). However, the performance status (p = 0.008), metastatic status (p = 0.003) and body fat mass ratio (p = 0.01) were found to have a significant effect on overall survival (OS): the median OS was 16.4 mo, in patients with the BFM ratio ≤ 22% and 29.2 mo, in those with > 22% (p = 0.01).

CONCLUSION: In this study, it was found that the body fat mass ratio was an important prognostic factor in patients with advanced non-small-cell lung cancer.

PMID:35543082 | DOI:10.1080/01635581.2022.2074064

Addiction. 2022 May 11. doi: 10.1111/add.15942. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Synthetic opioids, mostly illegally manufactured fentanyl (IMF), were mentioned in 60% of U.S. drug overdose deaths in 2020, with dramatic variation across states that mirrors variation in IMF supply. However, little is known about IMF markets in the U.S. and how they are changing. Researchers have previously used data from undercover cocaine, heroin, and methamphetamine purchases and seizures to examine how their use and related harms respond to changes in price and availability. This analysis used U.S. Drug Enforcement Administration (DEA) data to address two questions: (1) To what extent does IMF supply vary over time and geography? (2) What has happened to the purity-adjusted price of IMF?

METHODS: We developed descriptive statistics and visualizations using data from 66,713 observations mentioning IMF and/or heroin from the DEA’s System to Retrieve Information from Drug Evidence (STRIDE; now STARLIMS) from 2013-2021. Price regressions were estimated with city-level fixed effects examining IMF-only powder observations with purity and price information at the low-to-medium wholesale level (>1g-≤100g; n=964).

RESULTS: From 2013 to 2021, the share of heroin and/or IMF observations mentioning IMF grew from near 0 to more than two-thirds. The share of heroin observations also containing IMF grew from less than 1% to approximately 40%. There is important geographic variation: in California, most IMF seizures involved counterfeit tablets while New York and Massachusetts largely involved powder formulation. The median price per pure gram of IMF powder sold at the >10-≤100g level fell by more than 50% from 2016 to 2021; regression analyses suggested an average annual decline of 17% (p<0.001). However, this price decline appears to have been driven by observations from the Northeast.

CONCLUSIONS: Since 2013, the illegally manufactured fentanyl problem in the United States has become more deadly and more diverse.

PMID:35543081 | DOI:10.1111/add.15942

Ecol Appl. 2022 May 11:e2654. doi: 10.1002/eap.2654. Online ahead of print.

ABSTRACT

Microplastic (MP) contamination in marine environments is of increasing concern, as plastic particles are globally ubiquitous across ecosystems. A large variety of aquatic taxa ingest MPs, but the extent to which animals accumulate and transfer MPs through food webs is largely unknown. In this study, we quantified MP uptake in bivalves, crabs, echinoderms, and fish feeding at different trophic levels at three sites on southern Vancouver Island. We paired stable isotope food web analysis with MP concentrations in digestive tracts across all trophic levels, and in the fish’s livers. We then used Bayesian generalized linear mixed models to explore whether bioaccumulation and biomagnification were occurring. Our results show that MPs (100-5000 μm along their longest dimension) are not biomagnifying in marine coastal food webs, with no correlation between the digestive tract or fish liver MP concentrations and trophic position of the various species. Ecological traits did, however, affect microplastic accumulation in digestive tracts, with suspension feeder and smaller-bodied planktivorous fish ingesting more microplastics by body weight. Trophic transfer occurred between prey and predator for rockfish, but higher concentrations in full stomachs compared with empty ones suggested rapid excretion of ingested MPs. Collectively, our findings suggest the movement of MP through marine food webs is facilitated by species-specific mechanisms, with contamination susceptibility a function of a species biology, not its trophic position. Furthermore, the statistical methods we employ, including machine learning for classifying unknown particles and a probabilistic way to account for background contamination, are universally applicable to the study of microplastics. Our findings advance understanding of how MPs enter and move through aquatic food webs, suggesting that lower trophic level animals are more at risk of ingesting >100-μm MPs, relative to higher trophic level animals. Our work also highlights the need to advance the study of <100-μm MPs, which are still poorly understood, and may need to be considered separately in ecological risk assessments.

PMID:35543035 | DOI:10.1002/eap.2654

Expert Rev Anticancer Ther. 2022 May 11. doi: 10.1080/14737140.2022.2076670. Online ahead of print.

ABSTRACT

BACKGROUND: Triple-negative-breast-cancer (TNBC) has a poor prognosis if pathologic complete response (pCR) cannot be achieved after receiving neoadjuvant chemotherapy (NAC). The group of patients that benefit most from adjuvant capecitabine remains unclear.

MATERIALS AND METHODS: We collected data from 218 consecutive patients who had previously received NAC and operated for TNBC from eight cancer centers. Data of 160 patients without PCR was included in the statistical analysis. Pathologic response to NAC was defined into two groups as having good-pathologic response (MillerPayneGrading (MPG) IV-III) or poor-pathologic response (MPG I-II). The histopathological characteristics of patients were compared in regard to adjuvant capecitabine usage.

RESULTS: Univariate-analysis revealed that age, histological subtype, clinical stage, size of tumor, number of lymph-nodes, menopausal status, pathological T and N stage, were significantly different between two groups. In multivariate-analysis, menopausal status (p=0.043) and residual tumor size (p<0.001) were found to be independent prognostic factors for pathological response. The hazard ratio for disease recurrence and death in the poor responsive group with adjuvant capecitabin was 2.94 (95% confidence interval (CI), 1.21 to 7.10; p=0.016) and 4.080 (95% CI, 1.22 to 13.64; p=0.022) respectively. DFS (p=0.58) and OS (p=0.89) improvements with adjuvant capecitabine were not demonstrated in good response groups.

CONCLUSION: This multicenter study suggested that only the poor responsive group to NAC achieved benefit from adjuvant capecitabine. Postmenopausal status and residual tumor size were related to poor prognosis.

PMID:35543015 | DOI:10.1080/14737140.2022.2076670

J Prev Alzheimers Dis. 2022;9(2):286-296. doi: 10.14283/jpad.2022.13.

ABSTRACT

BACKGROUND: There is evidence of relationships between behavioral symptoms and increased risk for Alzheimer’s Disease and/or Alzheimer’s Disease biomarkers. However, the nature of this relationship is currently unknown.

OBJECTIVES: To evaluate the relationship between anxiety and depressive symptoms and amyloid-β deposition in cognitively unimpaired older adults, and to assess mediating effects of either objective or subjective cognitive skills.

DESIGN: Cross-sectional analysis of screening data from participants enrolled in the Anti-Amyloid Treatment in Asymptomatic Alzheimer Disease (A4) Study (ClinicalTrials.gov Identifier: NCT02008357).

SETTING: Data analysis.

PARTICIPANTS: 4492 cognitively unimpaired adults, age 65-85, enrolled in the Anti-Amyloid Treatment in Asymptomatic Alzheimer Disease (A4) Study.

MEASUREMENTS: We used linear regression to estimate the associations between amyloid-β standard uptake value ratio (SUVR) and Geriatric Depression Scale (GDS) and State Trait Anxiety Inventory (STAI) scores while adjusting for potential confounding factors as well as for Cognitive Function Index (CFI) or Preclinical Alzheimer’s Cognitive Composite (PACC) scores as possible mediational variables.

RESULTS: 4399 subjects with complete covariates were included (mean age: 71.3, 59% female), GDS ranged 0-13 (mean: 1.0), and STAI ranged 6-24 (mean: 9.9). Amyloid-β SUVR was modestly associated with STAI; mean STAI score was estimated to be 0.275 points higher (95% CI: 0.038, 0.526; p-value = 0.023) for each 0.5-point increase in cortical amyloid-β SUVR. Subjective cognitive decline (CFI) attenuated the relationship between SUVR and STAI, while objective cognitive function (PACC) did not. No statistically significant relationship between SUVR and GDS was observed (p = 0.326).

CONCLUSIONS: In cognitively unimpaired adults with low levels of depression and anxiety, cortical amyloid-β deposition is associated with anxiety but not depressive symptoms. Attenuation of this relationship by subjective cognitive difficulties suggests that anxiety may be partly due to such a perception resulting from cortical amyloid-β deposition.

PMID:35543002 | DOI:10.14283/jpad.2022.13

J Prev Alzheimers Dis. 2022;9(2):323-330. doi: 10.14283/jpad.2021.71.

ABSTRACT

OBJECTIVE: To explore the association between the intake of sugar-sweetened beverages and cognitive dysfunction in middle-aged and older adults, so as to provide an evidence-based basis for the early prevention of cognitive dysfunction.

METHODS: A comprehensive search of relevant literature was conducted in PubMed, EMBase, Cochrane, ScienceDirect, and Web of Science from the inception until January 2021. Odds ratios (OR), hazard ratios (HR) and 95% confidence intervals (CI) were calculated using a random-effects, generic inverse variance method. Meta-analysis of the included studies was performed using Review Manager 5.4.

RESULTS: A total of 10 studies on the association between sugary beverages and cognitive dysfunction in middle-aged and older adults were included, of which 3 were cross-sectional studies and the rest were cohort studies. Eight of the ten studies had results suggestive of a negative association. However, Meta-analysis results showed that the association between the intake of sugar-sweetened beverages and the risk of cognitive impairment was not statistically significant (OR=1.59, 95% CI: 0.93-2.74, P=0.08); but from two studies, the hazard ratios of all-cause dementia in middle-aged and older people consuming sugar-sweetened beverages was 2.77 (95%CI: 2.24-3.43, P<0.00001); the hazard ratios of Alzheimer’s disease in middle-aged and older people consuming sugar-sweetened beverages was 2.63 (95%CI: 1.70-4.05, P<0.0001).

CONCLUSION: There is insufficient evidence to state conclusively that sugar-sweetened beverages intake causes cognitive dysfunction in middle-aged and older adults.

PMID:35543006 | DOI:10.14283/jpad.2021.71