Category: Statistics

Sci Total Environ. 2023 Jul 18:165609. doi: 10.1016/j.scitotenv.2023.165609. Online ahead of print.

ABSTRACT

Water replenishment can be a key factor of driving lake eutrophication status. In arid and semi-arid regions China, water replenishment for a lake has been widely carried out for not only improving water environmental quality, but also maintaining ecological system function. However, it is still unclear in terms of mechanism by which water replenishment drives lake eutrophication status. In this study, fluorescence excitation-emission matrix spectroscopy (EEMs) combined with multiple statistical analysis models (including parallel factor analysis, correlation analysis, redundancy analysis, and partial least squares structural equation modeling) was utilized to reveal potential driving mechanism and causality between water replenishment, dissolved organic matter (DOM) fractions and eutrophic status of Lake Shahu in China. Based on variations of DOM fractions, fulvic-like substance could be accumulated during the replenishment period, while nutrients carried along the replenishment might conduce to increase microbial activities during the non-replenishment period. This should contributed to an alteration of prominent component from fulvic-like substances to tyrosine-like substances during the replenishment period to non-replenishment period. According to partial least squares structural equation modeling, two potential indirect paths were finally revealed, i.e., water replenishment derived the eutrophic status of Lake Shahu: water replenishment → microbial activity → algae → eutrophication, and water replenishment → microbial activity → eutrophication. This supposed that the water replenishment should indirectly drive the algae and eutrophication of the lake by promoting the transformation of DOM fractions. In addition, natural conditions could indirectly contribute to the eutrophication of the lake through impacting the algae growth. These findings should be conducive to trace the alteration of DOM fractions in lakes by water replenishment and in recognizing potential driving mechanisms of water replenishment on eutrophication of lakes by changing DOM fractions. This could provide basic theoretical support for policymakers to regulate and treat the eutrophication of lakes.

PMID:37474068 | DOI:10.1016/j.scitotenv.2023.165609

Sci Total Environ. 2023 Jul 18:165653. doi: 10.1016/j.scitotenv.2023.165653. Online ahead of print.

ABSTRACT

Soil minor and trace elements are vital regulators of ecological processes that sustain alpine ecosystem functions. In this study, the vertical pattern and driving factors of element concentrations in alpine soils of the Tibetan Plateau were investigated. Three snow mountains (Meili, Baima, and Haba) part of the Hengduan Mountain range, were selected as the study area to determine the vertical distribution of 12 typical elements (Cr, Ni, Cu, Fe, Mn, Zn, Cd, Pb, Ca, Sr, As, and Se) in topsoil with increasing and decreasing elevation, as well as the dominant driving factors of their spatial heterogeneity. Results showed that all elements, except Se, showed strong vertical heterogeneity, among which Cr, Ni, Cu, and Fe showed peak concentrations at 2700-3000 m; the highest concentrations of Mn and Zn were at 3200 m and 2700 m, with Cd and Pb at 2500 m. Ca and Sr levels gradually decreased with increasing elevation. According to the structural equation model and random forest analysis, the vertical heterogeneity of soil elements is directly regulated by the variability of climate and soil properties due to changes in elevation. A three-way PERMANOVA further quantized the contributions of climate and soil properties on vertical heterogeneity of all soil elements, which were 35.2 % and 50.5 %, respectively. This study used various statistical tools to reveal the dominant factors affecting the vertical heterogeneity of soil elements. These findings provided a scientific overview of element distribution on the Tibetan Plateau and significant references for the vertical distribution of elements in the topsoil of other snow mountains worldwide.

PMID:37474062 | DOI:10.1016/j.scitotenv.2023.165653

Sci Total Environ. 2023 Jul 18:165588. doi: 10.1016/j.scitotenv.2023.165588. Online ahead of print.

ABSTRACT

BACKGROUND: Although emerging studies have illuminated the protective association between greenness and respiratory mortality, efforts to quantify the potentially complex role of air pollution in the causal pathway are still limited. We aimed to examine the potential roles of air pollution in the causal pathway between greenness and respiratory mortality in China.

METHODS: We used data from a community-based prospective cohort of 654,115 participants in southern China (Jan 2009-Dec 2020). We evaluated the greenness exposure as a three-year moving average Normalized Difference Vegetation Index (NDVI) within the 500 m buffer around the residence. Cox proportional hazards model was applied to estimate the association between greenness and respiratory mortality. Causal mediation analysis combined with a four-way dimensional decomposition method was utilized to simultaneously quantify the interaction and mediation role of air pollution including PM_2.5, PM₁₀, or NO₂ on the greenness-respiratory mortality relationship.

FINDINGS: We observed 6954 respiratory deaths during 12 years of follow-up. Increasing NDVI level from the lowest to the highest quartile is associated with a 19 % (95%CI: 13-25 %) reduction in the respiratory mortality risk. For the total protective effect, the proportion attributable to the overall negative interaction between greenness and air pollution (PM_2.5, PM_10, or NO₂) was 2.2 % (1.7-3.2 %), 3.5 % (0.4-3.7 %), or 25.0 % (22.8-27.1 %), respectively. Simultaneously, we estimated 25.5 % (20.1-32.0 %), 49.5 % (32.5-71.9 %), or 1.0 % (0.8-1.2 %) of the total protective association was mediated through a reduction in PM_2.5, PM₁₀, or NO₂, respectively.

INTERPRETATION: Increased greenness exposure mitigated respiratory mortality through both the antagonistic interaction and mediation pathway of air pollution (PM_2.5, PM₁₀, or NO₂).

PMID:37474059 | DOI:10.1016/j.scitotenv.2023.165588

Orthop Traumatol Surg Res. 2023 Jul 18:103661. doi: 10.1016/j.otsr.2023.103661. Online ahead of print.

ABSTRACT

BACKGROUND: Trochanteric fractures are a public health issue due to the aging of the population. Treatment aims to reduce their related morbidity and mortality and to allow an early return to independence. Post-operative anemia is associated with poorer functional recovery and an increased mortality rate. The aim of this study was to assess whether minimally invasive side plate fixation (Minimal Invasive Screw System, MISS™) resulted in reduced perioperative bleeding compared with conventional fixation (Pertrochanteric Hip Screw, PHS™).

HYPOTHESIS: We hypothesized that minimally invasive side plate fixation (MISS) would result in reduced perioperative bleeding compared with conventional fixation (PHS).

PATIENTS AND METHODS: We conducted an open randomized controlled trial with blinded assessment of the primary outcome. Inclusion criteria were patients aged over 65 years with isolated reducible trochanteric fracture. The 2 surgical implants were of the same shape, the only difference between them being the locking mode of the femoral neck screw on the plate of the MISS device, allowing a percutaneous approach. Primary outcome was perioperative bleeding evaluated with Mercuriali’s formula. Secondary outcomes included operating time, scar length, length of hospital stay, radiological criteria such as quality of fracture reduction, implant positioning and bone healing, and complications and functional recovery compared between the 2 groups.

RESULTS: One hundred eight patients met the inclusion criteria and were randomized to receive either PHS (n = 54) or MISS (n = 54). Osteosynthesis with MISS significatively reduced perioperative bleeding (median 243 ml, interquartile range [152-410] vs 334 ml [247-430] with PHS (p = 0.0299)), operating time (65 min [57-73] vs 79 min [66-89] (p = 0.0002)) and scar length after 45 days (7 cm [5-8] vs 14 cm [12-15] (p < 0.0001)). There was no statistically significant difference between groups in postoperative complications, revision surgery or serious adverse events.

CONCLUSION: Compared with PHS, MISS reduced operating time, perioperative bleeding and scar length with no observed functional difference.

LEVEL OF EVIDENCE: I.

PMID:37474020 | DOI:10.1016/j.otsr.2023.103661

Exp Eye Res. 2023 Jul 18:109592. doi: 10.1016/j.exer.2023.109592. Online ahead of print.

ABSTRACT

Understanding the metabolic dysfunctions and underlying complex pathological mechanisms of neurodegeneration in glaucoma could help discover disease pathways, identify novel biomarkers, and rationalize newer therapeutics. Therefore, we aimed to investigate the local metabolomic alterations in the aqueous humor and plasma of primary glaucomatous patients. This study cohort comprised primary open-angle glaucoma (POAG), primary angle-closure glaucoma (PACG), and cataract control groups. Aqueous humor and plasma samples were collected from patients undergoing trabeculectomy or cataract surgery and subjected to high-resolution mass spectrometry (HRMS) analysis. Spectral information was processed, and the acquired data were subjected to uni-variate as well as multi-variate statistical analyses using MetaboAnalyst ver5.0. To further understand the localized metabolic abnormalities in glaucoma, metabolites affected in aqueous humor were distinguished from metabolites altered in plasma in this study. Nine and twelve metabolites were found to be significantly altered (p < 0.05, variable importance of projection >1 and log₂ fold change ≥0.58/≤ -0.58) in the aqueous humor of PACG and POAG patients, respectively. The galactose and amino acid metabolic pathways were locally affected in the PACG and POAG groups, respectively. Based on the observation of the previous findings, gene expression profiles of trace amine-associated receptor-1 (TAAR-1) were studied in rat ocular tissues. The pharmacodynamics of TAAR-1 were explored in rabbits using topical administration of its agonist, β-phenyl-ethylamine (β-PEA). TAAR-1 was expressed in the rat’s iris-ciliary body, optic nerve, lens, and cornea. β-PEA elicited a mydriatic response in rabbit eyes without altering intraocular pressure. Targeted analysis of β-PEA levels in the aqueous humor of POAG patients showed an insignificant elevation. This study provides new insights regarding alterations in both localized and systemic metabolites in primary glaucomatous patients. This study also demonstrated the propensity of β-PEA to cause an adrenergic response through the TAAR-1 pathway.

PMID:37474016 | DOI:10.1016/j.exer.2023.109592

Exp Eye Res. 2023 Jul 18:109590. doi: 10.1016/j.exer.2023.109590. Online ahead of print.

ABSTRACT

Animal models of choroidal neovascularization (CNV) are extensively used in translational studies of CNV formation and to evaluate angiostatic treatment strategies. However, the current paucity of large animal models compared with rodent models constitutes a knowledge gap regarding the clinical translation of findings. Ocular anatomical and physiological similarities to humans suggest the pig as a relevant model animal. Thus, a systematic survey of porcine CNV models was performed to identify pertinent model parameters and suggest avenues for model standardization and optimization. A systematic search was performed in PubMed and EMBASE on November 28, 2022 for porcine models of CNV. Following inclusion by two investigators, data from the articles were extracted according to a predefined protocol. A total of 14 articles, representing 19 independent porcine CNV models were included. The included models were almost equally divided between laser-induced (53%) and surgically-induced (47%) models. Different specified breeds of domestic pigs (71%) were most commonly used in the studies. All studies used normal animals. Female pigs were reported used in 43% of the studies, while 43% did not report on sex of the animals. Younger pigs were typically used. The surgical models reported consistent CNV induction following mechanical Bruch’s membrane rupture. The laser models used variants of the infrared diode laser (40%) or the frequency-doubled Nd:YAG laser (50%). Both lasers enabled successful CNV induction with reported induction rates ranging from 60 to 100%. Collateral damage to the neuroretina was reported for the infrared diode laser. CNV evaluation varied across studies with fluorescein angiography (50%) as the most used in vivo method and retinal sections (71%) as the most used ex vivo method. In interventional studies, quantification of lesions was in general performed between 7 and 14 days. The field of porcine CNV models is relatively small and heterogeneous and almost equally divided between surgically-induced and laser-induced models. Both methods have allowed successful modeling of CNV formation with induction rates comparable to those of non-human primates. However, the field would benefit from standardization of model parameters and reporting. This includes laser parameters and validation of CNV formation as well as methods of CNV evaluation and statistical analysis.

PMID:37474015 | DOI:10.1016/j.exer.2023.109590

Mod Pathol. 2023 Jul 18:100285. doi: 10.1016/j.modpat.2023.100285. Online ahead of print.

ABSTRACT

We have developed an artificial intelligence (AI)-based digital pathology model for the evaluation of histologic features related to eosinophilic esophagitis (EoE). In this study, we evaluate the performance of our AI model in a cohort of pediatric and adult patients for histologic features included in the Eosinophilic Esophagitis Histologic Scoring System (EoEHSS). We collected a total of 203 esophageal biopsies from patients with mucosal eosinophilia of any degree (91 adults, 112 pediatric patients) and 10 normal controls from a prospectively maintained database. All cases were assessed by a specialized gastrointestinal (GI) pathologist for features in the EoEHSS at the time of original diagnosis and re-scored by a central GI pathologist. We have subsequently analyzed whole-slide image digital slides using a supervised AI model operating in a cloud-based, deep-learning artificial intelligence platform (Aiforia Technologies, Helsinki, Finland) for peak eosinophil count (PEC) and several histopathologic features in the EoEHSS. The correlation and inter-observer agreement between the AI model and pathologists (r_s=0.89 and ICC=0.87 vs. original pathologist [OP]; r_s =0.91 and ICC=0.83 vs. central pathologist [CP]) was similar to the correlation and inter-observer agreement between pathologists for PEC (r_s=0.88 and ICC=0.91) and broadly similar for most other histologic features in the EoEHSS. The AI model PEC also accurately identified >15 eosinophils/HPF by the OP (AUC [area under the curve]=0.98) and CP (AUC=0.98) and had similar AUCs for the presence of EoE-related endoscopic features than pathologists’ assessment. Average eosinophils per epithelial unit area had similar performance compared to AI HPF-based analysis. Our newly developed AI model can accurately identify, quantify, and score several of the main histopathologic features in the EoE spectrum, with agreement regarding EoEHSS scoring, which was similar to that seen among GI pathologists.

PMID:37474003 | DOI:10.1016/j.modpat.2023.100285

J Thorac Cardiovasc Surg. 2023 Jul 18:S0022-5223(23)00612-8. doi: 10.1016/j.jtcvs.2023.07.008. Online ahead of print.

ABSTRACT

OBJECTIVE: We have recently reported the primary results of CALGB 140503 (Alliance), a randomized trial in patients with peripheral cT1aN0 NSCLC (AJCC 7^th) treated with either lobar (LR) or sublobar resection (SLR). Here we report differences in disease-free survival (DFS), overall survival (OS) and lung cancer specific survival (LCSS) between LR, segmental (SR) and wedge resections (WR). We also report differences between WR and SR in surgical margins, rates of locoregional recurrence (LRR) and expiratory flow rates at 6 months postoperatively.

METHODS: Between 6/2007 and 3/2017, 697 patients were randomized to LR (357) or SLR (340) stratified by clinical tumor size, histology and smoking history. Ten patients were converted from SLR to LR and 5 from LR to SLR. Survival end points were estimated by the Kaplan-Meier estimator and tested by the stratified Log rank test. Kruskal-Wallis testing was used to compare margins and FEV1 changes between groups; and a Chi-square test was used to test the association between recurrence and groups.

RESULTS: A total of 362 patients had LR, 131 had SR and 204 had WR. Basic demographic and clinical and pathological characteristics were similar between all three groups. Five-year DFS was 64.7% after LR [95% CI; 59.6-70.1%], 63.8% after SR [ 95% C; 55.6 – 73.2%] and 62.5% after WR [95% CI; 55.8 – 69.9%] (Log rank, p = 0.888). Five-year OS was 78.7% after LR, 81.9% after SR and 79.7% after WR (Log rank, p = 0.873). Five-year LCSS was 86.8% after LR, 89.2% after SR and 89.7% after WR (Log rank, p = 0.903). LRR occurred in 12% after SR and 14% after WR (p=0.295). At 6 months postoperatively, the median reduction in % FEV1 was 5% after WR and 3% after SR (p=0.930) CONCLUSIONS: In this large, randomized trial, LR, SR and WR were associated with similar survival outcomes. Although LRR was numerically higher after WR compared to SR, the difference was not clinically meaningful statistically significant. There was no significant difference in the reduction of FEV1 between the SR and WR groups.

PMID:37473998 | DOI:10.1016/j.jtcvs.2023.07.008

Neuroimage Clin. 2023 Jul 11;39:103471. doi: 10.1016/j.nicl.2023.103471. Online ahead of print.

ABSTRACT

BACKGROUND: Using multi-block methods we combined multimodal neuroimaging metrics of thalamic morphology, thalamic white matter tract diffusion metrics, and cortical thickness to examine changes in behavioural variant frontotemporal dementia. (bvFTD).

METHOD: Twenty-three patients with sporadic bvFTD and 24 healthy controls underwent structural and diffusion MRI scans. Clinical severity was assessed using the Clinical Dementia Rating scale and behavioural severity using the Frontal Behaviour Inventory by patient caregivers. Thalamic volumes were manually segmented. Anterior and posterior thalamic radiation fractional anisotropy and mean diffusivity were extracted using Tract-Based Spatial Statistics. Finally, cortical thickness was assessed using Freesurfer. We used shape analyses, diffusion measures, and cortical thickness as features in sparse multi-block partial least squares (PLS) discriminatory analyses to classify participants within bvFTD or healthy control groups. Sparsity was tuned with five-fold cross-validation repeated 10 times. Final model fit was assessed using permutation testing. Additionally, sparse multi-block PLS was used to examine associations between imaging features and measures of dementia severity.

RESULTS: Bilateral anterior-dorsal thalamic atrophy, reduction in mean diffusivity of thalamic projections, and frontotemporal cortical thinning, were the main features predicting bvFTD group membership. The model had a sensitivity of 96%, specificity of 68%, and was statistically significant using permutation testing (p = 0.012). For measures of dementia severity, we found similar involvement of regional thalamic and cortical areas as in discrimination analyses, although more extensive thalamo-cortical white matter metric changes.

CONCLUSIONS: Using multimodal neuroimaging, we demonstrate combined structural network dysfunction of anterior cortical regions, cortical-thalamic projections, and anterior thalamic regions in sporadic bvFTD.

PMID:37473493 | DOI:10.1016/j.nicl.2023.103471

Psychiatry Res. 2023 Jul 11;326:115343. doi: 10.1016/j.psychres.2023.115343. Online ahead of print.

ABSTRACT

Anxiety disorders are a group of prevalent and heritable neuropsychiatric diseases. We previously conducted a genome-wide association study (GWAS) which identified genomic loci associated with anxiety; however, the biological consequences underlying the genetic associations are largely unknown. Integrating GWAS and functional genomic data may improve our understanding of the genetic effects on intermediate molecular phenotypes such as gene expression. This can provide an opportunity for the discovery of drug targets for anxiety via drug repurposing. We used the GWAS summary statistics to determine putative causal genes for anxiety using MAGMA and colocalization analyses. A transcriptome-wide association study was conducted to identify genes with differential genetically regulated levels of gene expression in human brain tissue. The genes were integrated with a large drug-gene expression database (Connectivity Map), discovering compounds that are predicted to “normalise” anxiety-associated expression changes. The study identified 64 putative causal genes associated with anxiety (35 genes upregulated; 29 genes downregulated). Drug mechanisms adrenergic receptor agonists, sigma receptor agonists, and glutamate receptor agonists gene targets were enriched in anxiety-associated genetic signal and exhibited an opposing effect on the anxiety-associated gene expression signature. The significance of the project demonstrated genetic links for novel drug candidates to potentially advance anxiety therapeutics.

PMID:37473490 | DOI:10.1016/j.psychres.2023.115343