Category: Nevin Manimala

Nat Commun. 2023 Feb 1;14(1):544. doi: 10.1038/s41467-022-35663-x.

ABSTRACT

Immune cell function can be altered by lipids in circulation, a process potentially relevant to lipid-associated inflammatory diseases including atherosclerosis and rheumatoid arthritis. To gain further insight in the molecular changes involved, we here perform a transcriptome-wide association analysis of blood triglycerides, HDL cholesterol, and LDL cholesterol in 3229 individuals, followed by a systematic bidirectional Mendelian randomization analysis to assess the direction of effects and control for pleiotropy. Triglycerides are found to induce transcriptional changes in 55 genes and HDL cholesterol in 5 genes. The function and cell-specific expression pattern of these genes implies that triglycerides downregulate both cellular lipid metabolism and, unexpectedly, allergic response. Indeed, a Mendelian randomization approach based on GWAS summary statistics indicates that several of these genes, including interleukin-4 (IL4) and IgE receptors (FCER1A, MS4A2), affect the incidence of allergic diseases. Our findings highlight the interplay between triglycerides and immune cells in allergic disease.

PMID:36725846 | DOI:10.1038/s41467-022-35663-x

Environ Sci Pollut Res Int. 2023 Feb 2. doi: 10.1007/s11356-023-25646-w. Online ahead of print.

ABSTRACT

The rapid rise of tourism in the karst regions has promoted the development of the local economy by relying on the unique landforms and landscapes. However, tourism development is often accompanied by land use changes and has an impact on the ecological environment. Exploring the coupling relationship between “tourism development-land use-landscape pattern” is very important for ecologically fragile karst areas. Taking the Yulong River Basin as an example, this research applied 3S technology, spatial analysis based on POIs, and regression analysis to the following: (1) identifying the process and effects of land use change, (2) determining the spatial pattern of tourism land and its correlation with land use change, (3) determining the characteristics and impacts of landscape pattern evolution. As the results suggested: (1) The significant expansion of construction land occupies a large amount of farmland, there is a balanced relationship between farmland and forest land for mutual conversion. (2) The aggregation of tourist land is affected by the trend of tourist behavior and the distribution of scenic spots. There is a significant moderate positive correlation between tourism land and construction land. (3) With the land use change, landscape heterogeneity has improved, but landscape fragmentation is serious and landscape connectivity is reduced. This research provides new evidences for the effect of the rapid development of tourism on land use change and ecological environment and as a reference to future orderly and moderate land development and ecological sustainability in karst regions.

PMID:36725804 | DOI:10.1007/s11356-023-25646-w

Psychometrika. 2023 Feb 1. doi: 10.1007/s11336-022-09899-x. Online ahead of print.

ABSTRACT

Reporting effect size index estimates with their confidence intervals (CIs) can be an excellent way to simultaneously communicate the strength and precision of the observed evidence. We recently proposed a robust effect size index (RESI) that is advantageous over common indices because it’s widely applicable to different types of data. Here, we use statistical theory and simulations to develop and evaluate RESI estimators and confidence/credible intervals that rely on different covariance estimators. Our results show (1) counter to intuition, the randomness of covariates reduces coverage for Chi-squared and F CIs; (2) when the variance of the estimators is estimated, the non-central Chi-squared and F CIs using the parametric and robust RESI estimators fail to cover the true effect size at the nominal level. Using the robust estimator along with the proposed nonparametric bootstrap or Bayesian (credible) intervals provides valid inference for the RESI, even when model assumptions may be violated. This work forms a unified effect size reporting procedure, such that effect sizes with confidence/credible intervals can be easily reported in an analysis of variance (ANOVA) table format.

PMID:36725775 | DOI:10.1007/s11336-022-09899-x

Biometals. 2023 Feb 1. doi: 10.1007/s10534-023-00491-z. Online ahead of print.

ABSTRACT

The COVID-19 pandemic has generated a major interest in designing inhibitors to prevent SARS-CoV-2 binding on host cells to protect against infection. One promising approach to such research utilizes molecular dynamics simulation to identify potential inhibitors that can prevent the interaction between spike (S) protein on the virus and angiotensin converting enzyme 2 (ACE2) receptor on the host cells. In these studies, many groups have chosen to exclude the ACE2-bound zinc (Zn) ion, which is critical for its enzymatic activity. While the relatively distant location of Zn ion from the S protein binding site (S1 domain), combined with the difficulties in modeling this ion has motivated the decision of exclusion, Zn can potentially contribute to the structural stability of the entire protein, and thus, may have implications on S protein-ACE2 interaction. In this study, the authors model both the ACE2-S1 and ACE2-inhibitor (mAb) system to investigate if there are variations in structure and the readouts due to the presence of Zn ion. Although distant from the S1 or inhibitor binding region, inclusion/exclusion of Zn has statistically significant effects on the structural stability and binding free energy in these systems. In particular, the binding free energy of the ACE2-S1 and ACE2-inhibitor structures is – 3.26 and – 14.8 kcal/mol stronger, respectively, in the Zn-bound structure than in the Zn-free structures. This finding suggests that including Zn may be important in screening potentially inhibitors and may be particularly important in modeling monoclonal antibodies, which may be more sensitive to changes in antigen structure.

PMID:36725769 | DOI:10.1007/s10534-023-00491-z

J Cancer Res Clin Oncol. 2023 Feb 1. doi: 10.1007/s00432-023-04597-2. Online ahead of print.

ABSTRACT

BACKGROUND: Interest in image-guidance superficial radiation therapy (IGSRT) for the treatment of early-stage non-melanoma skin cancer (NMSC) has resurfaced given its low complication rates, superior cosmesis and local control and cure rates. In addition, it has been recommended by the American Academy of Dermatology (AAD) for early-stage NMSC in patients who are considered poor surgical candidates.

METHODS: 1899 NMSC lesions were treated with energies ranging from 50 to 100 kilovoltage (kV), for a mean of 20.2 fractions, and treatment dose of 5364.4 centigray (cGy). Lesions were treated for a mean of 7.5 weeks and followed for 65.5 weeks. SAS studio was used to conduct Kaplan-Meier analysis to calculate local control rates and account for differences in follow-up intervals. A log-rank test was used to calculate statistical differences between histologies.

RESULTS: Absolute lesion control was achieved in 99.7% of the patients after an average of 7.5 weeks of treatment, with a stable control rate of 99.6% when the follow-up duration was over 12 months. 95% of lesions with toxicity scoring received a Radiation Treatment Oncology Group Toxicity (RTOG) score of 1 or 2.

CONCLUSION: IGSRT has a high safety profile, can achieve superior cosmesis and should be considered first-line for treating early-stage NMSC tumors as cure rates have been shown to be effective in all NMSC on early follow-up.

PMID:36725752 | DOI:10.1007/s00432-023-04597-2

Eur Radiol. 2023 Feb 1. doi: 10.1007/s00330-023-09391-9. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare the diagnostic efficiency of contrast-enhanced ultrasound (CEUS) with that of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for the differential diagnosis of clear and non-clear cell renal cell carcinoma, as confirmed by subsequent pathology.

METHODS: A total of 181 patients with 184 renal lesions diagnosed by both CEUS and DCE-MRI were enrolled in the study, including 136 clear cell renal cell carcinoma (ccRCC) and 48 non-clear cell renal cell carcinoma (non-ccRCC) tumors. All lesions were confirmed by histopathologic diagnosis after surgical resection. Interobserver agreement was estimated using a weighted kappa statistic. Diagnostic efficiency in evaluating ccRCC and non-ccRCC was compared between CEUS and DCE-MRI.

RESULTS: The weighted kappa value for interobserver agreement was 0.746 to 0.884 for CEUS diagnosis and 0.764 to 0.895 for DCE-MRI diagnosis. Good diagnostic performance in differential diagnosis of ccRCC and non-ccRCC was displayed by both CEUS and DCE-MRI: sensitivity was 89.7% and 91.9%, respectively; specificity was 77.1% and 68.8%, respectively; and area under the receiver operating curve was 0.834 and 0.803, respectively. No statistically significant differences were present between the two methods (p = 0.54).

CONCLUSIONS: Both CEUS and DCE-MRI imaging are effective for the differential diagnosis of ccRCC and non-ccRCC. Thus, CEUS could be an alternative to DCE-MRI as a first test for patients at risk of renal cancer, particularly where DCE-MRI cannot be carried out.

KEY POINTS: • CEUS and DCE-MRI features can help differentiate ccRCC and non-ccRCC. • The differential diagnosis of ccRCC and non-ccRCC by CEUS is comparable to that of DCE-MRI. • Interobserver agreement is generally high using CEUS and DCE-MRI.

PMID:36725722 | DOI:10.1007/s00330-023-09391-9

Eur Radiol. 2023 Feb 1. doi: 10.1007/s00330-023-09393-7. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the clinical value of contrast-enhanced ultrasound (CEUS) with time-intensity curve (TIC) in distinguishing different types of hypovascular solid pancreatic lesions.

METHODS: A total of 89 patients with 90 pancreatic lesions (all confirmed by surgery or biopsy pathology) that manifested hypoenhancement on contrast-enhanced ultrasound (CEUS) were included in this study. Six peak enhancement patterns were proposed for differentiating hypovascular pancreatic lesions. CEUS qualitative and TIC-based quantitative parameters were analyzed, and each lesion was scored based on the statistically significant qualitative parameters to evaluate the diagnostic ability of CEUS for hypovascular solid pancreatic lesions.

RESULTS: Qualitative parameters such as peak enhancement pattern II/III/IV, penetrating vessels, centripetal enhancement, and early washout were reliable indicators of malignant lesions, and lesions scored based on these qualitative parameters, with a score ≥ 2, were highly suspected to be malignant lesions. Pattern I had an accuracy of 83.33% for predicting mass-forming pancreatitis (MFP), pattern V had an accuracy of 96.67% for predicting solid pseudopapillary tumors of the pancreas (SPTP), and pattern VI had an accuracy of 81.11% for predicting neuroendocrine tumors/carcinomas (NETs/NECs). For quantitative analysis, nodule/pancreatic parenchyma echo intensity reduction ratio was significantly greater in malignant lesions.

CONCLUSIONS: CEUS qualitative and TIC-based quantitative parameters have clinical value in distinguishing malignant from benign hypovascular pancreatic lesions.

KEY POINTS: • Contrast-enhanced ultrasound helps clinicians assess patients with pancreatic lesions. • Six peak enhancement patterns are proposed for differentiating pancreatic hypovascular lesions. • Qualitative parameters such as peak enhancement pattern II/III/IV, penetrating vessels, centripetal enhancement, early washout, and quantitative parameter nodule/pancreatic parenchyma echo intensity reduction ratio were important characteristics to discriminate malignant from hypovascular benign lesions.

PMID:36725721 | DOI:10.1007/s00330-023-09393-7

J Ocul Pharmacol Ther. 2023 Feb 1. doi: 10.1089/jop.2022.0102. Online ahead of print.

ABSTRACT

Purpose: To investigate the characteristics of sustained drug release systems established by an arginine-glycine-aspartic acid (RGD) peptide hydrogel and mitomycin C (MMC) in vitro, and verify their antiscar effects in rat ocular injury model. Methods: Low, medium, and high loading doses of MMC were added to 5 mL 0.25%, 0.5%, and 1% wt RGD peptide hydrogel, respectively, to prepare 9 ratios of MMC-RGD systems. Drug release characteristics of the systems in phosphate-buffered saline solution were investigated by plotting the drug release curves and fitting them with mathematical models in OriginPro8.0 software. Appropriate ratios of MMC-RGD systems were selected as treatment in rat ocular injury model. Scar formation was observed by Masson staining and immunohistochemical staining with alpha-smooth muscle actin (α-SMA) and fibronectin (FN). Results: Nine ratios of MMC-RGD systems could release drug slowly. The maximum drug release proportions of all systems were >80%, and the time to maximum release proportions statistically prolonged with the increase of drug loading. Fitting with mathematical models indicated that the mechanisms of drug release were mainly Fick diffusion at early stage and Anomalous Transport at later stage. Systems of 1% wt RGD hydrogel were evaluated in animal experiments, which could inhibit hyperplasia of collagen and expression of α-SMA and FN. Conclusions: The RGD peptide hydrogel could be used as the carrier of MMC to establish sustained drug release system, which could inhibit scar formation after rat’s ocular injury.

PMID:36724493 | DOI:10.1089/jop.2022.0102

Am Nat. 2023 Feb;201(2):287-301. doi: 10.1086/722504. Epub 2023 Jan 4.

ABSTRACT

AbstractTerrestrial mammals span seven orders of magnitude in body size, ranging from the <2-g Etruscan pygmy shrew (Suncus etruscus) to the >3,900-kg African elephant (Loxodonta africana). Although body size profoundly affects the behavior, physiology, ecology, and evolution of species, how investment in functional immune defenses changes with body size across species is unknown. Here, we (1) developed a novel 12-point dilution curve approach to describe and compare antibacterial capacity against three bacterial species among >160 terrestrial species of mammals and (2) tested published predictions about the scaling of immune defenses. Our study focused on the safety factor hypothesis, which predicts that broad, early-acting immune defenses should scale hypermetrically with body mass. However, our three statistical approaches demonstrated that antibacterial activity in sera across mammals exhibits isometry; killing capacity did not change with body size across species. Intriguingly, this result indicates that the serum of a large mammal is less hospitable to bacteria than would be predicted by its metabolic rates. In other words, if metabolic rates underlie the rates of physiological reactions as postulated by the metabolic theory of ecology, large species should have disproportionately lower antibacterial capacity than small species, but they do not. These results have direct implications for effectively modeling the evolution of immune defenses and identifying potential reservoir hosts of pathogens.

PMID:36724463 | DOI:10.1086/722504

Facts Views Vis Obgyn. 2022 Dec;14(4):309-315. doi: 10.52054/FVVO.14.4.043.

ABSTRACT

BACKGROUND: The COVID-19 pandemic has had a significant effect on healthcare services, particularly affecting patients who suffer from chronic conditions. However, the pandemic’s effect on endometriosis surgery is not yet known.

OBJECTIVES: To determine the impact of the COVID-19 pandemic on surgery for severe endometriosis in the UK at a national, regional and centre-level.

MATERIALS AND METHODS: The British Society for Gynaecological Endoscopy (BSGE) collects data nationally on all operations for severe endometriosis which involve dissection of the pararectal space. Annual audits of this database were obtained from the BSGE. Publicly available data on COVID-19 cases and population were obtained from the UK Office for National Statistics.

MAIN OUTCOME MEASURES: Numbers of annual BSGE-registered endometriosis operations.

RESULTS: A total of 8204 operations were performed. The number of operations decreased by 49.4% between 2019 and 2020 and then increased in 2021, but remained 10.5% below average pre-pandemic levels, indicating at least 980 missed operations between 2019-2020. Median operations per centre decreased by 51.0% in 2020 (IQR 29.4% – 75.0%) and increased in 2021 but remained 33% below pre-pandemic levels. There was no change in the type of surgery performed. All 11 administrative regions of Great Britain had reduced numbers of operations in 2020 compared with the average for 2017-2019, with a median 44.2% decrease (range 13.3% – 67.5%). Regional reduction in operations was correlated with COVID-19 infection rates (r=0.54, 95% CI of r 0.022 – 1.00, p=0.043).

CONCLUSION: The number of operations performed annually in the UK for severe endometriosis fell dramatically during the COVID-19 pandemic and is yet to normalise.

WHAT’S NEW?: This study shows the dramatic effect that the COVID-19 pandemic has had on UK services for endometriosis surgery, which may continue to affect patients and clinicians for a considerable time to come.

PMID:36724422 | DOI:10.52054/FVVO.14.4.043