Category: Statistics

Sci Total Environ. 2023 Sep 22:167293. doi: 10.1016/j.scitotenv.2023.167293. Online ahead of print.

ABSTRACT

Magnesium-functionalized Magnolia grandiflora Linn leaf-derived biochar (MBC) capable of efficiently reclaiming phosphorus from urine was synthesized by slow co-pyrolysis. Four adsorption kinetic and seven adsorption isotherm models were fitted to the batch adsorption and desorption experimental data, and it was found that pseudo-first-order kinetic model and multilayer model with saturation best described the phosphate-phosphorus (PO₄^3--P) adsorption process by MBC. MBC and phosphorus-saturated MBC (P-MBC) were found to offer outstanding phosphorus adsorption and slow release properties, respectively. Based on material characterization, statistical physics, adsorption energy distribution and statistical thermodynamics, a multi-ionic, inclined orientation, entropy-driven spontaneous endothermic process of MBC on PO₄^3--P was proposed, involving physicochemical interactions (porous filling, electrostatic attraction, ligand exchange and surface precipitation). Further, seed germination and early seedling growth experiments proved that P-MBC can be used as a slow-release fertilizer. Overall, MBC offers prospective applications as an efficient phosphorus adsorbent and then as a slow-release fertilizer.

PMID:37742963 | DOI:10.1016/j.scitotenv.2023.167293

Sci Total Environ. 2023 Sep 22:167265. doi: 10.1016/j.scitotenv.2023.167265. Online ahead of print.

ABSTRACT

Africa is vulnerable to the impacts of climate change, particularly in terms of its agriculture and crop production. The majority of climate models project a negative impact of future climate change on crop production, with maize being particularly vulnerable. However, the magnitude of this change remains uncertain. Therefore, it is important to reduce the uncertainties related to the anticipated changes to guide adaptation options. This study uses a combination of local and large-scale empirical orthogonal function (EOF) predictors as a novel approach to model the impacts of future climate change on crop yields in West, East and Central Africa. Here a cross-validated Bayesian model was developed using predictors derived from the regional climate model REMO for the period 1982-2100. On average, the combined local and large-scale EOF predictors explained around 28 % of maize yield variability from 1982 to 2016 of the entire study regions. Notably, climate predictors played a significant role in West Africa, explaining up to 51 % of the maize yield variability. Large-scale climate EOF predictors contributed most to the explained variance, reflecting the role of regional climate in future maize yield variability. Under a high-emissions scenario (RCP8.5), maize yield is projected to decrease over the entire study region by 20 % by the end of the century. However, a minor increase is projected in eastern Africa. This study highlights the importance of incorporating climate predictors at various scales into crop yield modeling. Furthermore, the findings will offer valuable guidance to decision-makers in shaping adaptation options.

PMID:37742952 | DOI:10.1016/j.scitotenv.2023.167265

Hum Pathol. 2023 Sep 22:S0046-8177(23)00189-2. doi: 10.1016/j.humpath.2023.09.004. Online ahead of print.

ABSTRACT

Lymphocyte-rich hepatocellular carcinoma (LR-HCC), a newly proposed subtype of HCC, is characterized with abundant lymphocyte infiltration in the tumor. LR-HCC has a relatively good prognosis and is quite rare (< 1% of all HCC). We examined LR-HCC clinicopathological and molecular characteristics by analyzing 451 surgically resected HCC cases without any prior treatment history at our hospital between 2012 and 2021. Clinicopathological features of LR-HCC and other HCCs (non-LR-HCC) were compared. Neoplastic and nonneoplastic hepatocytes from LR-HCC (n = 4) were collected with a laser microdissection system; RNA was extracted, followed by microarray analysis to examine lymphocytic infiltration-related molecular targets. Immunohistochemical staining of identified molecular target was performed in LR-HCC and non-LR-HCC. CD3, CD20, and CD8 immunostaining was also performed in LR-HCCs. There were 28 cases of LR-HCC (6%). No statistically significant differences were found in clinicopathological features, except for gross type, between LR-HCC and non-LR-HCC cases. The LR-HCC 5-year survival rate was > 90%. Microarray analysis revealed high CCL20 expression in LR-HCC cases; immunohistochemical study showed significantly higher CCL20 expression in LR-HCC (P < 0.01) than in non-LR-HCC. CCR6, the only CCL20 receptor, was observed in infiltrating lymphocytes and HCC cells in LR-HCC. There were significantly more CD3-positive cells than CD20-positive cells (P < 0.0001) in tumor-infiltrating lymphocytes, most of which were CD8-positive T cells. In conclusion, there were no significant differences in clinicopathological characteristics between LR-HCC and non-LR-HCC, except for gross and LR microscopic features. CCL20 expression in LR-HCC may contribute to infiltration of large numbers of CD8-positive lymphocytes.

PMID:37742944 | DOI:10.1016/j.humpath.2023.09.004

Hum Pathol. 2023 Sep 22:S0046-8177(23)00187-9. doi: 10.1016/j.humpath.2023.09.002. Online ahead of print.

ABSTRACT

Molecular research on large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung cancer (SCLC) has progressed significantly. However, there are still fewer molecular markers related to prognostic/therapeutic strategies for these conditions compared to those for adenocarcinoma. We therefore investigated the molecular characteristics of neuroendocrine carcinomas (NECs). We enrolled patients surgically diagnosed with NECs between 2011 and 2019, with complete follow-up records. All were analyzed using whole exome sequencing and p53/Rb immunohistochemistry (IHC). A total of 92 cases, comprising 45 pure SCLC, 15 combined SCLC, 27 pure LCNEC, and 5 combined LCNEC, were included. TP53 (78.3%) and RB1 (34.8%) were the most common molecular alterations, followed by KMT2D, LRP1B, FAT3, NCOR2, SPTA1, and NOTCH1. The mutation frequency for EGFR was 10.9%. Sixteen patients with LCNEC who had TP53/RB1 co-alterations were SCLC-like, while the remaining were NSCLC-like. There was no statistically significant difference between the groups regarding overall survival (OS; p=0.458) and progression-free survival (PFS; p=0.157). The frequency of the loss of Rb expression by IHC in SCLC-like LCNEC was 100%. Significant pathway alterations unique to SCLC included Notch and AMPK, while HIF-1 was enriched exclusively in LCNEC. NCOR2 mutation was linked to worse OS (p=0.029) and PFS (p=0.015), while wild-type SPTA1 was associated with poor PFS (p=0.018). IHC for Rb was reliable for predicting LCNEC molecular subtypes, indicating its clinical value. NCOR2 and SPTA1 alterations were identified as prognostic factors that may provide therapeutic targets for patients with NEC.

PMID:37742943 | DOI:10.1016/j.humpath.2023.09.002

Mod Pathol. 2023 Sep 22:100336. doi: 10.1016/j.modpat.2023.100336. Online ahead of print.

ABSTRACT

Phosphaturic mesenchymal tumors (PMT) are uncommon neoplasms that cause hypophosphatemia/osteomalacia mainly by secreting fibroblast growth factor 23. We previously identified FN1::FGFR1/FGF1 fusions in nearly half of PMTs, and frequent KL (Klotho or α-Klotho) overexpression only in those with no known fusion. Here, we studied a larger cohort of PMTs for KL expression and alterations. By FN1 break-apart FISH and reappraisal of previous RNA sequencing data, 6 tumors previously considered “fusion-negative” (defined by negative results of FISH for FN1::FGFR1 fusion and FGF1 break-apart and/or of RNA sequencing) were reclassified as fusion-positive PMTs, including one containing a novel FN1::ZACN fusion. The final cohort of fusion-negative PMTs included 33 tumors from 32 patients, which occurred in bone (N=18), soft tissue (10), sinonasal tract (4) and brain. In combination with previous work, RNA sequencing, RNA in situ hybridization, and immunohistochemistry showed largely concordant results and demonstrated KL/α-Klotho overexpression in 17 of the 28 fusion-negative and none of the 10 fusion-positive PMTs studied. Prompted by a patient in this cohort harboring germline KL upstream translocation with systemic α-Klotho overexpression and multifocal PMTs, FISH was performed and revealed KL rearrangement in 16 of the 33 fusion-negative PMTs (one also with amplification), including 14 of the 17 cases with KL/α-Klotho overexpression and none of the 11 KL/α-Klotho-low fusion-negative and 11 fusion-positive cases studied. Whole genomic sequencing confirmed in 2 FISH-positive cases translocation and inversion, respectively, involving KL upstream region, warranting further investigation into the mechanism whereby these rearrangements may lead to KL upregulation. Methylated DNA immunoprecipitation and sequencing suggested no major role of promoter methylation in KL regulation in PMT. Interestingly, KL-high/-rearranged cases seemed to form a clinicopathologically homogeneous group, showing a predilection for skeletal/sinonasal locations and typically matrix-poor, cellular solitary fibrous tumor-like morphology. Importantly, FGFR1 signaling pathways were upregulated in fusion-negative PMTs regardless of the KL status compared with non-PMT mesenchymal tumors by gene set enrichment analysis, perhaps justifying FGFR1 inhibition in treating this subset of PMTs.

PMID:37742927 | DOI:10.1016/j.modpat.2023.100336

Mod Pathol. 2023 Sep 22:100335. doi: 10.1016/j.modpat.2023.100335. Online ahead of print.

ABSTRACT

Tumor cell fraction (TCF) estimation is a common clinical task with well-established large inter-observer variability. It thus provides an ideal testbed to evaluate potential impacts of employing a computer-aided diagnostic (TCFCAD) tool to support pathologists’ evaluation. During a National Slide Seminar event, pathologists (n=69) were asked to visually estimate TCF in 10 regions of interest (ROI) from hematoxylin and eosin (H&E) colorectal cancer images intentionally curated for diverse tissue compositions, cellularity, and stain intensities. Next, they re-evaluated the same ROIs while being provided a TCFCAD created overlay highlighting predicted tumor versus non-tumor cells, together with the corresponding TCF percentage. Participants also reported confidence levels in their assessments using a 5-tiers scale, indicating no confidence to high confidence, respectively. The TCF ground truth (GT) was defined by manual cell-counting by experts. When assisted, inter-observer variability significantly decreased, showing estimates converging to the GT. This improvement remained even when TCFCAD predictions deviated slightly from the GT. The standard-deviation of estimated TCF to the GT across ROIs was 9.9% vs 5.8% with TCFCAD, p < 0.0001. The intraclass correlation coefficient increased from 0.8 to 0.93 (CI95% [0.65, 0.93] vs [0.86, 0.98]) and pathologists stated feeling more confident when aided (3.67 ± 0.81 vs. 4.17 ± 0.82 with CAD). TCFCAD estimation support demonstrated improved scoring accuracy, inter-pathologist agreement and scoring confidence. Interestingly, pathologists also expressed more willingness to use such a CAD tool at the end of the survey, highlighting the importance of training/education to increase adoption of CAD systems.

PMID:37742926 | DOI:10.1016/j.modpat.2023.100335

J Pain. 2023 Sep 22:S1526-5900(23)00541-2. doi: 10.1016/j.jpain.2023.09.011. Online ahead of print.

ABSTRACT

The ATP-gated channel P2X7 is encoded by a gene enriched for common nonsynonymous variants. Many of these variants have functional cellular effects, and some been implicated in chronic pain. In this study, we first systematically characterized all 17 common nonsynonymous variants using whole-cell patch clamp electrophysiology. Then, we analyzed these variants for statistical association with chronic pain phenotypes using both individual P2RX7 variants as predictors and cumulative allele counts of same-direction cellular effect in univariate models. Association and validation analyses were conducted in the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) cohort (N=3260) and in the Complex Persistent Pain Conditions (CPPC) cohort (N= 900), respectively. Our results showed an association between allele A of rs7958311 and an increased risk of chronic pelvic pain, with convergent evidence for contribution to fibromyalgia and irritable bowel syndrome (IBS), confirmed in meta-analysis. This allelic variant produced a unique cellular phenotype: a gain-of-function (GOF) in channel opening, and loss-of-function (LOF) in pore opening. Computational study using a 12-state Markov model of ATP binding to the P2X7 receptor suggested that this cellular phenotype arises from an increased ATP binding affinity and an increased open channel conductance combined with a loss of sensitization. Cumulative allele count analysis did not provide additional insights. In conclusion, our results go beyond reproducing association for rs7958311 with chronic pain and suggest that its unique combination of GOF in channel and LOF in pore activity may explain why it is likely the only common P2RX7 variant with contribution to chronic pain. PERSPECTIVE: This study characterizes all common P2RX7 variants using cellular assays and statistical association analyses with chronic pain, with Markov state modeling of the most robustly associated variant.

PMID:37742908 | DOI:10.1016/j.jpain.2023.09.011

Crit Rev Oncol Hematol. 2023 Sep 22:104143. doi: 10.1016/j.critrevonc.2023.104143. Online ahead of print.

ABSTRACT

With increasing reliance on technology in oncology, the impact of digital clinical decision support (CDS) tools needs to be examined. A systematic review update was conducted and peer-reviewed literature from 2016 to 2022 were included if CDS tools were used for live decision making and comparatively assessed quantitative outcomes. 3,369 studies were screened and 19 were included in this updated review. Combined with a previous review of 24 studies, a total of 43 studies were analyzed. Improvements in outcomes were observed in 42 studies, and 34 of these were of statistical significance. Computerised physician order entry and clinical practice guideline systems comprise the greatest number of evaluated CDS tools (13 and 10 respectively), followed by those that utilize patient-reported outcomes (8), clinical pathway systems (8) and prescriber alerts for best-practice advisories (4). Our review indicates that CDS can improve guideline adherence, patient-centered care, and care delivery processes in oncology.

PMID:37742884 | DOI:10.1016/j.critrevonc.2023.104143

Mol Phylogenet Evol. 2023 Sep 22:107916. doi: 10.1016/j.ympev.2023.107916. Online ahead of print.

ABSTRACT

With the rapid growth of entire genome data, phylogenomics focuses on analyzing evolutionary histories and relationships of species, i.e., the tree of life. For decades it has been realized that the genome-wide phylogenetic inference can be approached based upon the dynamic pattern of gene content (the presence/absence of gene families), or extended gene content (absence, presence as a single-copy, or duplicates). Those methods, conceptually or technically, invoked the birth-and-death process to model the evolutionary process (gene duplication or gene loss. One common drawback is that the mechanism of new gene input, including de novo origin of new genes and the lateral gene transfer, has not been explicitly considered. In this paper, the author developed a new genome distance approach for genome phylogeny inference under the origin-birth-death stochastic process. The model takes gene duplication, gene loss and new gene input into account simultaneously. Computer simulations found that the two-genome approach is statistically difficult to distinguish between two proliferation parameters, i.e., the rate of gene duplication and the rate of new gene input. Nevertheless, it has also demonstrated the statistical feasibility for using the loss-genome distance to infer the genome phylogeny, which can avoid the large sampling problem. The strategy to study the universal tree of life was discussed and exemplified by an example.

PMID:37742882 | DOI:10.1016/j.ympev.2023.107916

Ann Epidemiol. 2023 Sep 22:S1047-2797(23)00180-1. doi: 10.1016/j.annepidem.2023.09.006. Online ahead of print.

ABSTRACT

PURPOSE: To assess the distribution and clustering of COVID-19 testing and incidence over space and time, U.S. Department of Veteran’s Affairs (VA) data were used to describe where and when Veterans experienced highest proportions of test positivity.

METHODS: Data for 6,342,455 Veterans who utilized VA services between January 1, 2018 and September 30, 2021 were assessed for COVID-19 testing and test positivity. Testing and positivity proportions by county were mapped and focused-cluster tests identified significant clustering aroung VA facilities. Spatial cluster analysis also identified where and when Veterans experienced highest proportions of test positivity.

RESULTS: Within the Veterans study population and our time window, 21.3% received at least one COVID-19 test, and 20.4% of those tested had at least one positive test. There was statistically significant clustering of testing around VA facilities, revealing regional variation in testing practices. Veterans experienced highest test positivity proportions between November 2020 and January 2021 in a cluster of states in the Midwest, compared to those who received testing outside of the identified cluster (RR: 3.45).

CONCLUSION: Findings reflect broad regional trends in COVID-19 positivity which can inform VA policy and resource allocation. Additional analysis is needed to understand patterns during Delta and Omicron variant periods.

PMID:37742880 | DOI:10.1016/j.annepidem.2023.09.006