Miracle-dz/UniFAR-FTUs huggingface dataset:
Abiraterone acetate and prednisone in metastatic castration-resistant prostate cancer: a real-world retrospective study in China

Background This research work was aimed at evaluating the incidence and risk factors of adverse events (AEs) occurring in patients treated with abiraterone acetate (AA) and prednisone (PDN) outside clinical trials. These associations were assessed regarding the survival outcomes. Methods The study included 191 patients aged ≥18 years of confirmed metastatic castration-resistant prostate cancer (mCRPC) between March 2017 and April 2022. AE incidences were descriptively summarized from the whole cohort. Baseline characteristics, safety (treatment-emergent AEs and severe AEs), and efficacy [progression-free survival (PFS)] were analyzed. Multi-variable Cox proportional hazards models were employed to assess the factors linked with PFS. Results Overall, the median PFS was 17.16 months (range, 0.5–57.58). Patient baseline prostate-specific antigen (PSA) ≧̸10 ng/ml (p = 0.000), multiple organ metastasis (p = 0.007), hypertension (p = 0.004), and coronary heart disease (p = 0.004) were associated with worse PFS; however, radiotherapy (p = 0.028) was linked to better PFS at univariate analysis in the overall cohort. Baseline multiple organ metastasis, hypertension, and radiotherapy remained statistically significant in multivariable models (p = 0.007, p= 0.005, and p = 0.011, respectively). Incidence of AEs showed increased bilirubin (BIL) (55/191 patients, 28.8%) followed by increased alanine aminotransferase/aspartate aminotransferase (ALT/AST) (48/191 patients, 25.09%). The most common grade 3 AEs were increased ALT (3/191, 1.57%) followed by elevated BIL, hypercholesterolemia, and hypokalemia. Anemia had shorter PFS. There were no unexpected AEs in any patient. Conclusion AA is effective and tolerated in asymptomatic or slightly symptomatic mCRPC in “real-life” setting. The survival outcomes are influenced by multiple organ metastasis, hypertension, and radiotherapy.
Investigating the effects of long-term Aroclor 1260 exposure on fatty liver disease in a diet-induced obesity mouse model

Introduction Polychlorinated biphenyls (PCBs) are persistent environmental toxicants that have been implicated in numerous health disorders including liver diseases such as non-alcoholic fatty liver disease (NAFLD). Toxicant-associated NAFLD, also known as toxicant-associated fatty liver disease (TAFLD), consists of a spectrum of disorders ranging from steatosis and steatohepatitis to fibrosis and hepatocellular carcinoma. Previously, our group demonstrated that 12-week exposure to the PCB mixture, Aroclor 1260, exacerbated steatohepatitis in high-fat diet (HFD)-fed mice; however, the longer-term effects of PCBs on TAFLD remain to be elucidated. This study aims to examine the longer-term effects of Aroclor 1260 (>30 weeks) in a diet-induced obesity model to better understand how duration of exposure can impact TAFLD. Methods Male C57BL/6 mice were exposed to Aroclor 1260 (20 mg/kg) or vehicle control by oral gavage at the beginning of the study period and fed either a low-fat diet (LFD) or HFD throughout the study period. Results Aroclor 1260 exposure (>30 weeks) led to steatohepatitis only in LFD-fed mice. Several Aroclor 1260 exposed LFD-fed mice also developed hepatocellular carcinoma (25%), which was absent in HFD-fed mice. The LFD+Aroclor1260 group also exhibited decreased hepatic Cyp7a1 expression and increased pro-fibrotic Acta2 expression. In contrast, longer term Aroclor 1260 exposure in conjunction with HFD did not exacerbate steatosis or inflammatory responses beyond those observed with HFD alone. Further, hepatic xenobiotic receptor activation by Aroclor 1260 was absent at 31 weeks post exposure, suggesting PCB redistribution to the adipose and other extra-hepatic tissues with time. Discussion Overall, the results demonstrated that longer-term PCB exposure worsened TAFLD outcomes independent of HFD feeding and suggests altered energy metabolism as a potential mechanism fueling PCB mediated toxicity without dietary insult. Additional research exploring mechanisms for these longer-term PCB mediated toxicity in TAFLD is warranted.
Advanced monitoring of soil-vegetation co-dynamics reveals the successive controls of snowmelt on soil moisture and on plant seasonal dynamics in a mountainous watershed

Evaluating the interactions between above- and below-ground processes is important to understand and quantify how ecosystems respond differently to atmospheric forcings and/or perturbations and how this depends on their intrinsic characteristics and heterogeneity. Improving such understanding is particularly needed in snow-impacted mountainous systems where the complexity in water and carbon storage and release arises from strong heterogeneity in meteorological forcing and terrain, vegetation and soil characteristics. This study investigates spatial and temporal interactions between terrain, soil moisture, and plant seasonal dynamics at the intra- and inter-annual scale along a 160 m long mountainous, non-forested hillslope-to-floodplain system in the upper East River Watershed in the upper Colorado River Basin. To this end, repeated UAV-based multi-spectral aerial imaging, ground-based soil electrical resistivity imaging, and soil moisture sensors were used to quantify the interactions between above and below-ground compartments. Results reveal significant soil-plant co-dynamics. The spatial variation and dynamics of soil water content and electrical conductivity, driven by topographic and soil intrinsic characteristics, correspond to distinct plant types, with highest plant productivity in convergent areas. Plant productivity in heavy snow years benefited from more water infiltration as well as a shallow groundwater table depth. In comparison, low snowpack years with an early first bare-ground date, which are linked to an early increase in plant greenness, imply a short period of saturated conditions that leads to lower average and maximum greenness values during the growing season. Overall, these results emphasize the strong impact of snowpack dynamics, and terrain and subsurface characteristics on the heterogeneity in plant type and seasonal dynamics.
Identification of a chemoresistance-related prognostic gene signature by comprehensive analysis and experimental validation in pancreatic cancer

Background Chemoresistance is a major hurdle to improving the prognosis of pancreatic cancer (PC). This study aimed to identify key genes regulating chemoresistance and develop a chemoresistance-related gene signature for prognosis prediction. Methods A total of 30 PC cell lines were subtyped according to gemcitabine sensitivity data from the Cancer Therapeutics Response Portal (CTRP v2). Differentially expressed genes (DEGs) between gemcitabine-resistant and gemcitabine-sensitive cells were subsequently identified. These upregulated DEGs associated with prognostic values were incorporated to build a LASSO Cox risk model for The Cancer Genome Atlas (TCGA) cohort. Four datasets (GSE28735, GSE62452, GSE85916, and GSE102238) from the Gene Expression Omnibus (GEO) were used as an external validation cohort. Then, a nomogram was developed based on independent prognostic factors. The responses to multiple anti-PC chemotherapeutics were estimated by the “oncoPredict” method. Tumor mutation burden (TMB) was calculated using the “TCGAbiolinks” package. Analysis of the tumor microenvironment (TME) was performed using the “IOBR” package, while the TIDE and “easier” algorithms were employed to estimate immunotherapy efficacy. Finally, RT-qPCR, Western blot and CCK-8 assays were conducted to validate the expression and functions of ALDH3B1 and NCEH1. Results A five-gene signature and a predictive nomogram were developed from six prognostic DEGs, including EGFR, MSLN, ERAP2, ALDH3B1, and NCEH1. Bulk and single-cell RNA sequencing analyses indicated that all five genes were highly expressed in tumor samples. This gene signature was not only an independent prognostic factor but also a biomarker forecasting chemoresistance, TMB, and immune cells. In vitro experiments suggested that ALDH3B1 and NCEH1 were involved in PC progression and gemcitabine chemoresistance. Conclusion This chemoresistance-related gene signature links prognosis with chemoresistance, TMB, and immune features. ALDH3B1 and NCEH1 are two promising targets for treating PC.
The role of peroxisome proliferator-activated receptors in the tumor microenvironment, tumor cell metabolism, and anticancer therapy

Peroxisome proliferator-activated receptors (PPARs) have been extensively studied for over 3 decades and consist of three isotypes, including PPARα, γ, and β/δ, that were originally considered key metabolic regulators controlling energy homeostasis in the body. Cancer has become a leading cause of human mortality worldwide, and the role of peroxisome proliferator-activated receptors in cancer is increasingly being investigated, especially the deep molecular mechanisms and effective cancer therapies. Peroxisome proliferator-activated receptors are an important class of lipid sensors and are involved in the regulation of multiple metabolic pathways and cell fate. They can regulate cancer progression in different tissues by activating endogenous or synthetic compounds. This review emphasizes the significance and knowledge of peroxisome proliferator-activated receptors in the tumor microenvironment, tumor cell metabolism, and anti-cancer treatment by summarizing recent research on peroxisome proliferator-activated receptors. In general, peroxisome proliferator-activated receptors either promote or suppress cancer in different types of tumor microenvironments. The emergence of this difference depends on various factors, including peroxisome proliferator-activated receptor type, cancer type, and tumor stage. Simultaneously, the effect of anti-cancer therapy based on drug-targeted PPARs differs or even opposes among the three peroxisome proliferator-activated receptor homotypes and different cancer types. Therefore, the current status and challenges of the use of peroxisome proliferator-activated receptors agonists and antagonists in cancer treatment are further explored in this review.
Single cell RNA sequencing reveals distinct clusters of Irf8-expressing pulmonary conventional dendritic cells

A single population of interferon-regulatory factor 8 (Irf8)-dependent conventional dendritic cell (cDC type1) is considered to be responsible for both immunogenic and tolerogenic responses depending on the surrounding cytokine milieu. Here, we challenge this concept of an omnipotent single Irf8-dependent cDC1 cluster through analysis of pulmonary cDCs at single cell resolution. We report existence of a pulmonary cDC1 cluster lacking Xcr1 with an immunogenic signature that clearly differs from the Xcr1 positive cDC1 cluster. The Irf8+Batf3+Xcr1- cluster expresses high levels of pro-inflammatory genes associated with antigen presentation, migration and co-stimulation such as Ccr7, Cd74, MHC-II, Ccl5, Il12b and Relb while, the Xcr1+ cDC1 cluster expresses genes corresponding to immune tolerance mechanisms like Clec9a, Pbx1, Cadm1, Btla and Clec12a. In concordance with their pro-inflammatory gene expression profile, the ratio of Xcr1- cDC1s but not Xcr1+cDC1 is increased in the lungs of allergen-treated mice compared to the control group, in which both cDC1 clusters are present in comparable ratios. The existence of two distinct Xcr1+ and Xcr1- cDC1 clusters is furthermore supported by velocity analysis showing markedly different temporal patterns of Xcr1- and Xcr1+cDC1s. In summary, we present evidence for the existence of two different cDC1 clusters with distinct immunogenic profiles in vivo. Our findings have important implications for DC-targeting immunomodulatory therapies.
Grain size and mineralogical constraints on leaching in the bottom ashes from municipal solid waste incineration: a comparison of five plants in northern Italy

Introduction: Bottom ashes (BA) from municipal solid waste incinerators (MSWIs) are currently classified by the European Waste Catalogue as industrial non-hazardous waste. To promote their reuse, identification and characterization of the heavy metal-bearing phases (both glass and minerals), as well as their weathering behavior, must be addressed for what concern the chemical composition, mineralogical phases, and in high concentrations and pollutants’ mobility. An important point to be noted is whether the results from a given plant can be generalized. Materials and methods: In this work, BA from five waste-to-energy (WtE) plants in northern Italy were sorted based on different grain sizes. The area showed similar MSW production, collected from a culturally homogeneous area, and similar collection management. For each grain size, a mineralogical, chemical, and physical characterization was carried out using XRF, XRD, TGA, and the leaching test. Results and discussion: We found that for major elements, the average chemical composition of the incinerators is similar, with some differences in minor elements. Ferrara (FE) and Forlì-Cesena (FC) BA show portlandite, higher ettringite, and less amorphous than the Torino (TO), Parma (PR), and Piacenza (PC) BA. This affects the pH, the release, and toxicity of the leachates. In FE and FC ashes, ettringite is insoluble, and we not only have low sulfate but also Ni and Ba beyond reglementary limits, suggesting that Ni and Ba are present as hydroxides with portlandite, which are soluble. In TO, PR, and PC, Cr and sulfates are beyond limits, suggesting that Cr comes from dissolution in ettringite. Cu and Cl are always beyond limits; the dissolution of chlorides accounts for only 30%–35% of the global Cl leachate. We observe that in the assessment of the potential toxicity of the ashes, mineralogy has a higher effect than the bulk chemical composition. Grain size sorting, although useful together with other techniques, is not by itself able to comply with the PTE risk level. Conclusion: The findings contribute to the development of efficient treatment strategies for BA, highlighting the need for a more thorough investigation to understand composition and properties and to find innovative ways to reuse, promoting the circular economy and sustainable waste management practices.
Factors that influence outcomes and device use for pediatric cochlear implant recipients with unilateral hearing loss

Introduction Candidacy criteria for cochlear implantation in the United States has expanded to include children with single-sided deafness (SSD) who are at least 5 years of age. Pediatric cochlear implant (CI) users with SSD experience improved speech recognition with increased daily device use. There are few studies that report the hearing hour percentage (HHP) or the incidence of non-use for pediatric CI recipients with SSD. The aim of this study was to investigate factors that impact outcomes in children with SSD who use CIs. A secondary aim was to identify factors that impact daily device use in this population. Methods A clinical database query revealed 97 pediatric CI recipients with SSD who underwent implantation between 2014 and 2022 and had records of datalogs. The clinical test battery included speech recognition assessment for CNC words with the CI-alone and BKB-SIN with the CI plus the normal-hearing ear (combined condition). The target and masker for the BKB-SIN were presented in collocated and spatially separated conditions to evaluate spatial release from masking (SRM). Linear mixed-effects models evaluated the influence of time since activation, duration of deafness, HHP, and age at activation on performance (CNC and SRM). A separate linear mixed-effects model evaluated the main effects of age at testing, time since activation, duration of deafness, and onset of deafness (stable, progressive, or sudden) on HHP. Results Longer time since activation, shorter duration of deafness, and higher HHP were significantly correlated with better CNC word scores. Younger age at device activation was not found to be a significant predictor of CNC outcomes. There was a significant relationship between HHP and SRM, with children who had higher HHP experiencing greater SRM. There was a significant negative correlation between time since activation and age at test with HHP. Children with sudden hearing loss had a higher HHP than children with progressive and congenital hearing losses. Conclusion The present data presented here do not support a cut-off age or duration of deafness for pediatric cochlear implantation in cases of SSD. Instead, they expand on our understanding of the benefits of CI use in this population by reviewing the factors that influence outcomes in this growing patient population. Higher HHP, or greater percentage of time spent each day using bilateral input, was associated with better outcomes in the CI-alone and in the combined condition. Younger children and those within the first months of use had higher HHP. Clinicians should discuss these factors and how they may influence CI outcomes with potential candidates with SSD and their families. Ongoing work is investigating the long-term outcomes in this patient population, including whether increasing HHP after a period of limited CI use results in improved outcomes.
The influence of conceptual concreteness on the reading acquisition and integration of novel words into semantic memory via thematic relations

Plenty of studies have been conducted to reveal neurocognitive underpinnings of conceptual representation. Compared with that of concrete concepts, the neurocognitive correlates of abstract concepts remain elusive. The current study aimed to investigate the influence of conceptual concreteness on the reading acquisition and integration of novel words into semantic memory. We constructed two-sentence contexts in which two-character pseudowords were embedded as novel words. Participants read the contexts to infer the meaning of novel words which were either concrete or abstract, and then performed a lexical decision task and a cued-recall memory task. In lexical decision task, primed by the learned novel words, their corresponding concepts, thematically related or unrelated words as well as unlearned pseudowords were judged whether they were words or not. In memory task, participants were presented with the novel words and asked to write down their meaning. The contextual reading and memory test can demonstrate the modulation of conceptual concreteness on novel word learning and the lexical decision task can reveal whether concrete and abstract novel words are integrated into semantic memory similarly or not. During contextual reading, abstract novel words presented for the first time elicited a larger N400 than concrete ones. In memory task, the meaning of concrete novel words was recollected better than abstract novel words. These results indicate that abstract novel words are more difficult to acquire during contextual reading, and to retain afterwards. For lexical decision task behavioral and ERPs were graded, with the longest reaction time, the lowest accuracy and the largest N400s for the unrelated words, then the thematically related words and finally the corresponding concepts of the novel words, regardless of conceptual concreteness. The results suggest that both concrete and abstract novel words can be integrated into semantic memory via thematic relations. These findings are discussed in terms of differential representational framework which posits that concrete words connect with each other via semantic similarities, and abstract ones via thematic relations.
A New Bias Corrected Version of Heteroscedasticity Consistent Covariance Estimator

In the presence of heteroscedasticity, different available flavours of the heteroscedasticity consistent covariance estimator (HCCME) are used. However, the available literature shows that these estimators can be considerably biased in small samples. Cribari–Neto et al. (2000) introduce a bias adjustment mechanism and give the modified White estimator that becomes almost bias-free even in small samples. Extending these results, Cribari-Neto and Galvao (2003) present a similar bias adjustment mechanism that can be applied to a wide class of HCCMEs’. In the present article, we follow the same mechanism as proposed by Cribari-Neto and Galvao to give bias-correction version of HCCME but we use adaptive HCCME rather than the conventional HCCME. The Monte Carlo study is used to evaluate the performance of our proposed estimators.
Characterization, comparative analyses, and phylogenetic implications of mitochondrial genomes among bark and ambrosia beetles (Coleoptera: Curculionidae, Scolytinae)

Bark and ambrosia beetles of Scolytinae are well-known forest pests which can cause significant economic losses to trees and timber. Comparative analyses of structural characteristics of mitochondrial genomes (mitogenomes) and phylogenetic analyses could significantly improve our understanding of mitogenomic evolution and evolutionary history of this important group. Here, we have assembled new mitogenome data of four taxa (Euwallacea interjectus, E. fornicatus, E. similis, and Xylosandrus sp.) and presented a comparative analysis with available mitogenomes of Scolytinae. Phylogenetic analyses of Scolytinae were also conducted with different methods and datasets. The four mitogenomes are 15,419–16,265 bp in length and contain 13 protein-coding genes (PCGs), 22 transfer RNA genes, two ribosomal RNA genes, and a control region, except for E. similis wherein the trnI is not detected. All PCGs initiate with either standard start codon of ATN or nonstandard GTG/TTG. TAA codon is used for termination more than TAG and incomplete T. The analysis of nonsynonymous/synonymous mutation ratio (Ka/Ks) of PCGs suggests the highest and lowest evolutionary rates are within nad4 and cox1, respectively. The heterogeneity analyses of different mitogenomic datasets show excluding the third-codon positions from the datasets largely reduce their heterogeneity. Our phylogenetic analyses derived from mitogenome data provide new evidence toward the revision of the distinguishing characteristics of related genera in this subfamily and highly supported most of nodes at deeper and shallow level. The present study highlights the utility of mitogenome data for resolving the phylogenetic framework of bark and ambrosia beetles, although more taxa sampling is needed to elucidate the complicated relationships of Scolytinae.