Miracle-dz/UniFAR-FTUs huggingface dataset:
Reactive oxygen species as a double‐edged sword: The role of oxidative enzymes in antitumor therapy

A number of approaches have been developed over the years to manage cancer, such as chemotherapy using low‐molecular‐mass molecules and radiotherapy. Here, enzymes can also find useful applications. Among them, oxidases have attracted attention because of their ability to produce reactive oxygen species (ROS, especially hydrogen peroxide) in tumors and potentially modulate the production of this cytotoxic compound when enzymes active on substrates present in low amounts are used, such as the d‐amino acid oxidase and d‐amino acid couple system. These treatments have been also developed for additional cancer treatment approaches, such as phototherapy, nutrient starvation, and metal‐induced hydroxyl radical production. In addition, to improve tumor specificity and decrease undesired side effects, oxidases have been targeted by means of nanotechnologies and protein engineering (i.e., by designing chimeric proteins able to accumulate in the tumor). The most recent advances obtained by using six different oxidases (i.e., the FAD‐containing enzymes glucose oxidase, d‐ and l‐amino acid oxidases, cholesterol oxidase and xanthine oxidase, and the copper‐containing amine oxidase) have been reported. Anticancer therapy based on oxidase‐based ROS production has now reached maturity and can be applied in the clinic.
Spray dried nanospheres for inclusion complexes of cefpodoxime proxetil with β-cyclodextrin, 2-hydroxypropyl-β-cyclodextrin and methyl-β-cyclodextrin: improved dissolution and enhanced antibacterial activity

Abstract Objective The aim of the current research was the development hard cellulose capsules containing cefpodoxime proxetil (CEF) (BCS-Class II) encapsulated nanospheres of inclusion complexes with β-CD, HP-β-CD and M-β-CD for efficient antibacterial therapy. Significance The reason for this phenomenon is to bring an innovative approach to effective oral antimicrobial therapy with hard cellulose capsules containing spray dried nanospheres of CEF with β-CD, HP-β-CD and M-β-CD by means of increased solubility, dissolution rate and improved antibacterial efficiency with lower oral dose. Methods Phase solubility analyses was performed to evaluate the drug/CD interaction, involving the stoichiometry and apparent stability constant. Following the preparation of inclusion complexes by spray-drying method, complexes were characterized for physical, solid-state and microbiological analyses. In vitro dissolution from hard cellulose capsules containing CEF and CEF/β-CD, CEF/HP-β-CD and CEF/M-β-CD complexes were performed. Results According to AL type phase solubility curves, complexes were formulated as 1:1 molar ratio. The solubility of pure CEF was determined as 0.241 ± 0.002 mg mL−1, the solubility of inclusion complexes increased solubility from 3 to 5 times. The strong host–guest interaction was confirmed for CEF/HP-β-CD and CEF/M-β-CD complexes with SEM, DSC, FT-IR and 1H-NMR analyses. Inclusion complexes were more efficient on bacterial cells (2–4 fold) than pure CEF both Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae. Hard-cellulose capsules filled with inclusion complexes exhibited significantly faster release than unprocessed CEF. Conclusion Hard-cellulose capsules containing CEF/HP-β-CD and CEF/M-β-CD complexes appear to be superior alternative to commercially available CEF tablets for effective antibacterial therapy.
Taking apart what brings us together: The role of action prediction, perspective-taking, and theory of mind in joint action

The ability to act together with others to achieve common goals is crucial in life, yet there is no full consensus on the underlying cognitive skills. While influential theoretical accounts suggest that interaction requires sophisticated insights into others’ minds, alternative views propose that high-level social skills might not be necessary because interactions are grounded on sensorimotor predictive mechanisms. At present, empirical evidence is insufficient to decide between the two. This study addressed this issue and explored the association between performance at joint action tasks and cognitive abilities in three domains—action prediction, perspective-taking, and theory of mind—in healthy adults (N = 58). We found that, while perspective-taking played a role in reading the behaviour of others independently of the social context, action prediction abilities specifically influenced the agents’ performance in an interactive task but not in a control (social but non-interactive) task. In our study, performance at a theory of mind test did not play any role, as confirmed by Bayesian analyses. The results suggest that, in adults, sensorimotor predictive mechanisms might play a significant and specific role in supporting interpersonal coordination during motor interactions. We discuss the implications of our findings for the contrasting theoretical views described earlier and propose a way they might be partly reconciled.
Revealing Lipid Body Formation and its Subcellular Reorganization in Oleaginous Microalgae Using Correlative Optical Microscopy and Infrared Nanospectroscopy

The purpose of this work is to develop an integrated imaging approach to characterize without labeling at the sub-cellular level the formation of lipid body droplets (LBs) in microalgae undergoing nitrogen starvation. First conventional optical microscopy approaches, gas chromatography, and turbidimetry measurements allowed to monitor the biomass and the total lipid content in the oleaginous microalgae Parachlorella kesslerii during the starvation process. Then a local analysis of the LBs was proposed using an innovative infrared nanospectroscopy technique called atomic force microscopy-based infrared spectroscopy (AFM-IR). This label-free technique assessed the formation of LBs and allowed to look into the LB composition thanks to the acquisition of local infrared spectra. Last correlative measurements using fluorescence microscopy and AFM-IR were performed to investigate the subcellular reorganization of LB and the chloroplasts.
Jackknife model averaging for high‐dimensional quantile regression

In this paper, we propose a frequentist model averaging method for quantile regression with high‐dimensional covariates. Although research on these subjects has proliferated as separate approaches, no study has considered them in conjunction. Our method entails reducing the covariate dimensions through ranking the covariates based on marginal quantile utilities. The second step of our method implements model averaging on the models containing the covariates that survive the screening of the first step. We use a delete‐one cross‐validation method to select the model weights, and prove that the resultant estimator possesses an optimal asymptotic property uniformly over any compact (0,1) subset of the quantile indices. Our proof, which relies on empirical process theory, is arguably more challenging than proofs of similar results in other contexts owing to the high‐dimensional nature of the problem and our relaxation of the conventional assumption of the weights summing to one. Our investigation of finite‐sample performance demonstrates that the proposed method exhibits very favorable properties compared to the least absolute shrinkage and selection operator (LASSO) and smoothly clipped absolute deviation (SCAD) penalized regression methods. The method is applied to a microarray gene expression data set.
Effects of progesterone nanoparticles on the sperm capacitation and acrosome reaction in asthenozoospermia men

Low motility is one of the causes of male infertility. In this study, the effects of progesterone solid lipid nanoparticles (SLNs) on sperm capacitation, acrosome reaction, oxidative stress and expression of SPACA1 and MAPK way genes were investigated. Progesterone SLNs were synthesized using the solvent emulsification evaporation method. Twenty asthenozoospermia samples were selected, and sperm and acrosome membrane integrity, acrosome reaction, sperm motility, viability, total antioxidant capacity (TAC), total oxidative status tests and PKA, PTK, P38MAPK and SPACA1 gene expressions were assessed. The synthesized nanoparticles were prepared with the size (187.6 nm), PDI (0.184), EE (85.82%), LP (3.43%) and ZP (−23.5mV). Progesterone SLNs increased sperm and acrosome membrane integrity and TAC (p < .05). Also, the expression of P38MAPK, PKA, PTK, and SPACA1 genes in this group showed a significant increase (p < .001). Progesterone SLNs increased acrosome reaction, sperm capacitation and TAC. Also, it increased the expression of PTK PKA, SPACA1 and P38MAPK genes.
BRCA1/Trp53 heterozygosity and replication stress drive esophageal cancer development in a mouse model

Significance Although germline heterozygous BRCA1 mutations predispose human carriers to cancer, heterozygous mouse BRCA1 mutations do not. We find that exposure to a source of upper gastrointestinal replication stress (RS) elicited a marked cancer incidence in Brca1+/−;Trp53+/− heterozygous mice but not in wild-type mice (Brca1+/+;Trp53+/−). Oral delivery of 4 nitroquinoline-1-oxide induced esophageal epithelial RS, an increased esophageal mutation rate, loss of esophageal Brca1 heterozygosity (LOH), and accelerated esophageal tumorigenesis. These data underscore the necessity of combining otherwise nontumorigenic BRCA1 heterozygosity with simultaneous induction of RS for the generation of not only BRCA1 mutant esophageal cancer, but also a dramatically accelerated form thereof. These results strongly imply that RS is both a major contributor to BRCA1 cancer development and a marked accelerant thereof. BRCA1 germline mutations are associated with an increased risk of breast and ovarian cancer. Recent findings of others suggest that BRCA1 mutation carriers also bear an increased risk of esophageal and gastric cancer. Here, we employ a Brca1/Trp53 mouse model to show that unresolved replication stress (RS) in BRCA1 heterozygous cells drives esophageal tumorigenesis in a model of the human equivalent. This model employs 4-nitroquinoline-1-oxide (4NQO) as an RS-inducing agent. Upon drinking 4NQO-containing water, Brca1 heterozygous mice formed squamous cell carcinomas of the distal esophagus and forestomach at a much higher frequency and speed (∼90 to 120 d) than did wild-type (WT) mice, which remained largely tumor free. Their esophageal tissue, but not that of WT control mice, revealed evidence of overt RS as reflected by intracellular CHK1 phosphorylation and 53BP1 staining. These Brca1 mutant tumors also revealed higher genome mutation rates than those of control animals; the mutational signature SBS4, which is associated with tobacco-induced tumorigenesis; and a loss of Brca1 heterozygosity (LOH). This uniquely accelerated Brca1 tumor model is also relevant to human esophageal squamous cell carcinoma, an often lethal tumor.
Effect of the compound bacterial agent on microbial community of the aerobic compost of food waste

In our study, we used 16SrRNA and ITS to investigate the microbial community composition and the effect of compound bacterial agent on the microbial community composition in the aerobic composting process of food waste (FW). At the bacterial level, the main phyla of Group A (compost naturally) were Proteobacteria and Firmicutes, and the main species were Pseudomonas_sp. _GR7, Bacillus licheniformis and Pediococcus acidilactici. The main phyla of Group B (compost with compound bacterial agent) were Proteobacteria, Firmicutes and Streptophyta, and the main species were Klebsiella pneumoniae, Cronobacter sakazakii, Macrococcus caseolyticus, Enterococcus faecalis, Citrobacter freundii and Bacillus velezensis. It is worth noting that M. caseolyticus may be able to improve the effect of odour which is an important sensory index during aerobic composting. At the fungal level, the main phylum of both Groups A and B was Ascomycota, and the main species of Group A were Paecilomyces variotii, Byssochlamys spectabilis and Aspergillus fumigatus. The main species of Group B were Ogataea polymorpha and Millerozyma farinosa. Finally, the degradation rate of Group B was 81% that was about 15% higher than that of Group A, indicating that the compound bacterial agent could effectively improve the degradation rate and the composting process, while the low abundance of the compound bacterial agent in the composting process might be due to the small initial addition or the inhibition of other bacteria or fungi in the composting process.
The Effects of Home Health Value-Based Purchasing on Home Health Care Quality in For-Profit and Nonprofit Agencies: A Comparative Interrupted Time-Series Analysis, 2012–2018

Beginning in 2016, the Home Health Value-Based Purchasing (HHVBP) model incentivized U.S. Medicare-certified home health agencies (HHAs) in nine states to improve quality of patient care and patient experience. Here, we quantified HHVBP effects upon quality over time (2012–2018) by HHA ownership (i.e., for-profit vs. nonprofit) using a comparative interrupted time-series design. Our outcome measures were Care Quality and Patient Experience indices composed of 10 quality of patient care measures and five patient experience measures, respectively. Overall, 17.7% of HHAs participated in the HHVBP model of which 81.4% were for-profit ownership. Each year after implementation, HHVBP was associated with a 1.59 (p < .001) percentage point increase in the Care Quality index among for-profit HHAs and a 0.71 (p = .024) percentage point increase in the Patient Experience index among nonprofits. The differences of quality improvement under the HHVBP model by ownership indicate variations in HHA leadership responses to HHVBP.
Neural Reflectance Capture in the View-Illumination Domain

We propose a novel framework to efficiently capture the unknown reflectance on a non-planar 3D object, by learning to probe the 4D view-lighting domain with a high-performance illumination multiplexing setup. The core of our framework is a deep neural network, specifically tailored to exploit the multi-view coherence for efficiency. It takes as input the photometric measurements of a surface point under learned lighting patterns at different views, automatically aggregates the information and reconstructs the anisotropic reflectance. We also evaluate the impact of different sampling parameters over our network. The effectiveness of our framework is demonstrated on high-quality reconstructions of a variety of physical objects, with an acquisition efficiency outperforming state-of-the-art techniques.
Are Serum Ferritin Levels a Reliable Cancer Biomarker? A Systematic Review and Meta-Analysis

Abstract Although serum ferritin (SF) has been shown in several studies to be a potential cancer biomarker, the results are inconsistent. Herein, a systematic review was performed to investigate the clinical SF levels in different types of tumors in order to verify the role of SF levels as a biomarker for cancer diagnosis. The search was performed using the PubMed/Medline, Cochrane Library, and Scopus databases. Observational studies comparing SF levels between healthy adults and patients with cancer were included. The meta-analysis was carried out according to the inverse variance and random effects model. The standardized mean differences (SMDs) were assessed at 95% confidence intervals (CIs). We found that SF was higher in patients with cancer (SMD 3.07; CI 1.96,4.17), especially for head and neck cancer (SMD 3.88; CI 0.42,7.34), lung cancer (SMD 1.72; CI 0.67,2.78), pancreatic cancer (SMD 6.79; CI 5.66,7.91), and renal cell carcinoma (SMD 1.77; CI 0.48,3.05). Moreover, in the advanced stages (Stages III and IV), ferritin levels were higher than in healthy adults (SMD 4.89; CI 2.72,7.06, and SMD 8.40; CI 6.99,9.82, respectively). SF acts as a biomarker for pancreatic cancer, renal cell carcinoma, lung cancer, and head and neck cancer and is a sensitive biomarker for the detection of advanced stages of tumors.
RUNX2 and LAMC2: promising pancreatic cancer biomarkers identified by an integrative data mining of pancreatic adenocarcinoma tissues

Pancreatic carcinoma (PC) is a severe disease associated with high mortality. Although strategies for cancer therapy have made great progress, outcomes of pancreatic carcinoma patients remain extremely poor. Therefore, it is urgent to find novel biomarkers and therapeutic targets. To identify biomarkers for early diagnosis and therapy, three mRNA microarray datasets and two miRNA datasets were selected, and combinative analysis was performed by GEO2R. Functional and pathway enrichment analysis were performed using DAVID database. MiRTarBase, miRWalk and Diana Tools were used to get key genes. TCGA, HPA and western blotting were used to verify diagnostic and prognostic value of key genes. By integrating mRNA and miRNA expression profiles, we identified 114 differentially expressed genes and 114 differentially expressed miRNAs, respectively. Then, three overlapping key genes, RUNX2, LAMC2 and FBXO32, were found. Their protein levels in pancreatic tissue from PC patients and normal people were analyzed by immunohistochemical staining and western blotting. RUNX2 showed a potential property to identify PC. Aberrant over-expression of LAMC2 was associated with poor prognosis of PC patients, tumor status and subtypes. In summary, our current study identified that RUNX2 and LAMC2 may be promising targets for early diagnosis and therapy of PC patients.
Adult mental health service engagement with patients who are parents: Evidence from 15 English mental health trusts.

OBJECTIVES Ascertaining whether mental health service users have children is a clinical requirement in UK health services, and acknowledgement of a patient's parenting role is necessary to enable engagement with their parenting experience and to facilitate support, both of which are associated with improved outcomes for the parent-child dyad. The current study sought to investigate the practice of mental health practitioners working in UK adult mental health services with regard to the following: Ascertaining whether patients have children; engagement with the parenting role of patients; engagement with the construct of 'think patient as parent'. METHODS Self-report online/paper survey of 1105 multi-disciplinary adult mental health practitioners working in 15 mental health trusts in England. RESULTS A quarter of adult mental health practitioners did not routinely ascertain whether patients had dependent children. Less than half of practitioners engaged with the parenting experience or the potential impact of parental mental health on children. CONCLUSIONS The parenting role of patients is not routinely captured by large numbers of practitioners working in adult mental health settings. This is despite it being a mandatory requirement and an integral component of the systematic care of the adult, and preventative care for the offspring. Failure to engage with patients who are parents is a missed opportunity with profound downstream public health implications. The practice deficits identified in this study should be viewed in terms of broader structural failures to address the intergenerational transmission of poor mental health. PRACTITIONER POINTS Some parents who have mental health difficulties may struggle to provide appropriate and effective care to their children. The parenting role can also exacerbate mental health difficulties. Identification of dependent children is a mandatory component of adult mental health clinical practice and is necessary to understand a parent's support needs. A quarter of adult mental health practitioners are failing to do so. A missed opportunity to engage with the support needs of the parent-child dyad.
Assessing deep learning methods in cis-regulatory motif finding based on genomic sequencing data

Abstract Identifying cis-regulatory motifs from genomic sequencing data (e.g. ChIP-seq and CLIP-seq) is crucial in identifying transcription factor (TF) binding sites and inferring gene regulatory mechanisms for any organism. Since 2015, deep learning (DL) methods have been widely applied to identify TF binding sites and predict motif patterns, with the strengths of offering a scalable, flexible and unified computational approach for highly accurate predictions. As far as we know, 20 DL methods have been developed. However, without a clear and systematic assessment, users will struggle to choose the most appropriate tool for their specific studies. In this manuscript, we evaluated 20 DL methods for cis-regulatory motif prediction using 690 ENCODE ChIP-seq, 126 cancer ChIP-seq and 55 RNA CLIP-seq data. Four metrics were investigated, including the accuracy of motif finding, the performance of DNA/RNA sequence classification, algorithm scalability and tool usability. The assessment results demonstrated the high complementarity of the existing DL methods. It was determined that the most suitable model should primarily depend on the data size and type and the method’s outputs.
Sources of variation in search and foraging: A theoretical perspective

Search—the problem of exploring a space of alternatives to identify target goals—is a fundamental behaviour for many species. Although its foundation lies in foraging, most studies of human search behaviour have been directed towards understanding the attentional mechanisms that underlie the efficient visual exploration of two-dimensional (2D) scenes. With this review, we aim to characterise how search behaviour can be explained across a wide range of contexts, environments, spatial scales, and populations, both typical and atypical. We first consider the generality of search processes across psychological domains. We then review studies of interspecies differences in search. Finally, we explore in detail the individual and contextual variables that affect visual search and related behaviours in established experimental psychology paradigms. Despite the heterogeneity of the findings discussed, we identify that variations in control processes, along with the ability to regulate behaviour as a function of the structure of search space and the sampling processes adopted, to be central to explanations of variations in search behaviour. We propose a tentative theoretical model aimed at integrating these notions and close by exploring questions that remain unaddressed.
Verbascoside inhibits paraquate-induced pulmonary toxicity via modulating oxidative stress, inflammation, apoptosis and DNA damage in A549 cell

Abstract Paraquat (PQ), one of the most frequently used herbicides, can cause serious health problems in an exposed individual. In the present study, we investigated the protective effect of verbascoside (VB), a phenylpropanoid glycoside from lemon verbena, against PQ-induced A549 cell injury with a particular focus on the possible molecular pathways involved. A549 cells were exposed to PQ (300 µM) and different concentrations of VB (12.5, 25, and 50 µM). Cell viability, ROS content, the level of antioxidant enzymes (SOD, CAT and GPx) and inflammatory markers (IL-6 and TNF-α), as well as 8-OHdG, were detected using MTT assay and an ELISA kit. Western blotting and qRT-PCR were performed to measure the levels of caspase3 and NF-κB mRNA and protein expression. Exposure of cells to PQ caused viability loss and ROS increase. PQ also increased the levels of IL-6, TNF-α and 8-OHdG and decreased the antioxidant enzymes content. PQ treatment resulted in cell death by increasing the gene and protein expression level of caspase 3 and NF-κB. Treatment with VB notably increased cell survival, antioxidant enzymes activity, which concomitantly attenuated ROS, NF-κB and inflammatory mediator production. VB also inhibited apoptosis expression markers. These results indicated that VB could protect A549 cells against PQ induced cell injury by attenuation of ROS and inflammatory marker production and modulation of antioxidant enzymes. VB efficiently suppressed increased NF-κB and caspase-3 activity and formation of 8-OHdG and ultimately improved cell viability. Therefore, VB may be useful in the development of a new therapy for PQ-induced pulmonary toxicity. Graphical Abstract