Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic Value of Chromatin Structure Typing in Early-Stage Non-Small Cell Lung Cancer

Simple Summary In this work, we evaluated the prognostic value of the chromatin structure in patients with early-stage lung cancer. We assessed the associations of DNA ploidy, nucleotyping, and tumor–stroma ratio (TSR) with 5-year disease-free survival rates. Clarifying whether patients with homogeneous and heterogeneous chromatin can benefit from adjuvant chemotherapy can guide the decision-making regarding chemotherapy after lung cancer resection, improve the survival rate of patients, and reduce the incidence and cost of adverse events related to lung treatment. Abstract (1) Background: Chromatin structure typing has been used for prognostic risk stratification among cancer survivors. This study aimed to ascertain the prognostic values of ploidy, nucleotyping, and tumor–stroma ratio (TSR) in predicting disease progression for patients with early-stage non-small cell lung cancer (NSCLC), and to explore whether patients with different nucleotyping profiles can benefit from adjuvant chemotherapy. (2) Methods: DNA ploidy, nucleotyping, and TSR were measured by chromatin structure typing analysis (Matrix Analyser, Room4, Kent, UK). Cox proportional hazard regression models were used to assess the relationships of DNA ploidy, nucleotyping, and TSR with a 5-year disease-free survival (DFS). (3) Results: among 154 early-stage NSCLC patients, 102 were non-diploid, 40 had chromatin heterogeneity, and 126 had a low stroma fraction, respectively. Univariable analysis suggested that non-diploidy was associated with a significantly lower 5-year DFS rate. After combining DNA ploidy and nucleotyping for risk stratification and adjusting for potential confounders, the DNA ploidy and nucleotyping (PN) high-risk group and PN medium-risk group had a 4- (95% CI: 1.497–8.754) and 3-fold (95% CI: 1.196–6.380) increase in the risk of disease progression or mortality within 5 years of follow-up, respectively, compared to the PN low-risk group. In PN high-risk patients, adjuvant therapy was associated with a significantly improved 5-year DFS (HR = 0.214, 95% CI: 0.048–0.957, p = 0.027). (4) Conclusions: the non-diploid DNA status and the combination of ploidy and nucleotyping can be useful prognostic indicators to predict long-term outcomes in early-stage NSCLC patients. Additionally, NSCLC patients with non-diploidy and chromatin homogenous status may benefit from adjuvant therapy.
“My Cross-Border PhD Journey”: A Qualitative Study on the Educational and Life Challenges of Mainland Chinese PhD Students in Hong Kong

PhD students’ poor mental health has been increasingly concerning. However, challenges among PhD students studying aboard are understudied. The Educational and Life Transitions (ELT) model postulates that international PhD students are subject to both academic and acculturative stressors; however, relevant research is limited in the Chinese context. We examined mainland Chinese PhD students’ study and living experiences in Hong Kong using a qualitative approach. Through purposive sampling, 37 mainland Chinese PhD students in different disciplines from public-funded universities in Hong Kong were recruited to participate in online focus group interviews (December 2020–February 2021). The interviews were analyzed using the framework analysis method. Ten themes of academic/acculturative stressors were identified. The academic stressors included: (1) high expectations from the supervisors; (2) emphasis on self-discipline as PhD students; (3) peer comparison in academia; (4) difficulties shifting research directions/academic disciplines; (5) uncertainties about future career. The acculturative stressors included: (1) differences in the political environment; (2) language barriers; (3) difficulties living in Hong Kong; (4) limited social interaction with others; (5) local people’s discriminatory behaviors. This study sheds light on the stressors experienced by mainland Chinese PhD students in Hong Kong. To better address those students’ academic and acculturative stressors, cross-cultural training and additional support from supervisors/the university could be provided.
Camera-Based Respiration Monitoring of Unconstrained Rodents

Simple Summary Monitoring vitals sign such as the respiratory rate, heart rate, or temperature is of high importance to medical and biological research. Using camera-based methods, we monitored the respiratory rate of unconstrained laboratory rats by analyzing the visible breathing movement in the thorax. We hope this is a further step to enabling the non-invasive monitoring of rodent in an experimental environment without using implanted sensors, reducing the stress and pain within an otherwise unneeded operation. Abstract Animal research has always been crucial for various medical and scientific breakthroughs, providing information on disease mechanisms, genetic predisposition to diseases, and pharmacological treatment. However, the use of animals in medical research is a source of great controversy and ongoing debate in modern science. To ensure a high level of bioethics, new guidelines have been adopted by the EU, implementing the 3R principles to replace animal testing wherever possible, reduce the number of animals per experiment, and refine procedures to minimize stress and pain. Supporting these guidelines, this article proposes an improved approach for unobtrusive, continuous, and automated monitoring of the respiratory rate of laboratory rats. It uses the cyclical expansion and contraction of the rats’ thorax/abdominal region to determine this physiological parameter. In contrast to previous work, the focus is on unconstrained animals, which requires the algorithms to be especially robust to motion artifacts. To test the feasibility of the proposed approach, video material of multiple rats was recorded and evaluated. High agreement was obtained between RGB imaging and the reference method (respiratory rate derived from electrocardiography), which was reflected in a relative error of 5.46%. The current work shows that camera-based technologies are promising and relevant alternatives for monitoring the respiratory rate of unconstrained rats, contributing to the development of new alternatives for a continuous and objective assessment of animal welfare, and hereby guiding the way to modern and bioethical research.
An Observational Study on Play and Physical Activity Associated with a Recreational Facility-Led Park-Based “Loose Parts” Play Intervention during the COVID-19 Pandemic

Play is a human right, yet opportunities for unstructured play are declining. The COVID-19 pandemic further reduced children’s play opportunities. We conducted an observational study of a novel community-based intervention (play hubs) that facilitated unstructured play by offering loose parts in parks (Calgary, Canada) during the pandemic. Our descriptive study included systematic observation using the System for Observing Children’s Activity and Relationships During Play (SOCARP) and Tool for Observing Play Outdoors (TOPO) to capture physical activity, play, and social and environment interactions among children participating in the play hubs for 10-weeks in 2021 (n = 160) and 2022 (n = 147). Play hub attendance was low. Most children observed were aged 5 to 12 years (2021: 93% and 2022 98%), with boys and girls represented (2021: 58% male/42% female and 2022: 52% male/48% female). Standing, sitting, and moderate activity were common activities. Physical, exploratory, and expressive play were common, while digital, bio, and rule-based play were less common. Children typically played alone or in small groups and engaged with loose parts or played in the open spaces. The play hubs encouraged unstructured play and promoted positive social interactions among children, despite the challenges of implementing a community-based intervention under pandemic public health restrictions.
Endoscopic Resection of Early Gastric Cancer and Pre-Malignant Gastric Lesions

Simple Summary Although its incidence and the mortality with which it is related seem to be decreasing, gastric cancer remains the fifth most common cause of new cancer cases and the fourth most lethal cancer worldwide. Late diagnosis occurs in a substantial portion of patients, but the increased identification of risk factors and precancerous conditions has allowed for the stratification of risk, leading to tailored patient surveillance and the early recognition of pre-malignant and malignant lesions. Since the 1990s, innovative endoscopic resection techniques have revolutionized the treatment of early gastric cancer, which would otherwise be subject to surgical resection. Abstract Early gastric cancer comprises gastric malignancies that are confined to the mucosa or submucosa, irrespective of lymph node metastasis. Endoscopic resection is currently pivotal for the management of such early lesions, and it is the recommended treatment for tumors presenting a very low risk of lymph node metastasis. In general, these lesions consist of two groups of differentiated mucosal adenocarcinomas: non-ulcerated lesions (regardless of their size) and small ulcerated lesions. Endoscopic submucosal dissection is the technique of choice in most cases. This procedure has high rates of complete histological resection while maintaining gastric anatomy and its functions, resulting in fewer adverse events than surgery and having a lesser impact on patient-reported quality of life. Nonetheless, approximately 20% of resected lesions do not fulfill curative criteria and demand further treatment, highlighting the importance of patient selection. Additionally, the preservation of the stomach results in a moderate risk of metachronous lesions, which underlines the need for surveillance. We review the current evidence regarding the endoscopic treatment of early gastric cancer, including the short-and long-term results and management after resection.
Ectopic Expression of BcCUC2 Involved in Sculpting the Leaf Margin Serration in Arabidopsis thaliana

Leaf margin serration is a morphological characteristic in plants. The CUC2 (CUP-SHAPED COTYLEDON 2) gene plays an important role in the outgrowth of leaf teeth and enhances leaf serration via suppression of growth in the sinus. In this study, we isolated the BcCUC2 gene from Pak-choi (Brassica rapa ssp. chinensis), which contains a 1104 bp coding sequence, encoding 367 amino acid residues. Multiple sequence alignment exhibited that the BcCUC2 gene has a typical conserved NAC domain, and phylogenetic relationship analysis showed that the BcCUC2 protein has high identity with Cruciferae plants (Brassica oleracea, Arabidopsis thaliana, and Cardamine hirsuta). The tissue-specific expression analysis displayed that the BcCUC2 gene has relatively high transcript abundance in floral organs. Meanwhile, the expression profile of BcCUC2 was relatively higher in the ‘082’ lines with serrate leaf margins than the ‘001’ lines with smooth leaf margins in young leaves, roots, and hypocotyls. In addition, the transcript level of BcCUC2 was up-regulated by IAA and GA3 treatment, especially at 1–3 h. The subcellular localization assay demonstrated that BcCUC2 was a nuclear-target protein. Furthermore, leaf serration occurred, and the number of the inflorescence stem was increased in the transgenic Arabidopsis thaliana plants’ overexpressed BcCUC2 gene. These data illustrated that BcCUC2 is involved in the development of leaf margin serration, lateral branches, and floral organs, contributing to further uncovering and perfecting the regulation mechanism of leaf serration in Pak-choi.
Role of CIV NS1 Protein in Innate Immunity and Viral Replication

The innate immune pathway serves as the first line of defense against viral infections and plays a crucial role in the host’s immune response in clearing viruses. Prior research has indicated that the influenza A virus has developed various strategies to avoid host immune responses. Nevertheless, the role of the NS1 protein of the canine influenza virus (CIV) in the innate immune pathway remains unclear. In this study, eukaryotic plasmids of NS1, NP, PA, PB1, and PB2 were constructed, and it was found that these proteins interact with melanoma differentiation-associated gene 5 (MDA5) and antagonize the activation of IFN-β promoters by MDA5. We selected the NS1 protein for further study and found that NS1 does not affect the interaction between the viral ribonucleoprotein (RNP) subunit and MDA5, but that it downregulates the expression of the laboratory of genetics and physiology 2 (LGP2) and retinoic acid-inducible gene-I (RIG-I) receptors in the RIG-I pathway. Additionally, NS1 was found to inhibit the expression of several antiviral proteins and cytokines, including MX dynamin like GTPase 1 (MX1), 2′-5′oligoadenylate synthetase (OAS), Signal Transducers and Activators of Transcription (STAT1), tripartite motif 25 (TRIM25), interleukin-2 (IL-2), IFN, IL-8, and IL-1β. To further investigate the role of NS1, a recombinant H3N2 virus strain (rH3N2) and an NS1-null virus (rH3N2ΔNS1) were rescued using reverse-genetic technology. The rH3N2ΔNS1 virus exhibited lower viral titers compared to rH3N2, but had a stronger activation effect on the receptors LGP2 and RIG-I. Furthermore, when compared to rH3N2, rH3N2ΔNS1 exhibited a more pronounced activation of antiviral proteins such as MX1, OAS, STAT1, and TRIM25, as well as antiviral cytokines such as IL-6, IFN-β, and IL-1β. These findings suggest a new mechanism by which NS1, a nonstructural protein of CIV, facilitates innate immune signaling and provides new avenues for the development of antiviral strategies.
Prediction Equations for In Vitro Ileal Disappearance of Dry Matter and Crude Protein Based on Chemical Composition in Dog Diets

Simple Summary Protein digestibility is important because protein consists of amino acids that are essential to dogs. As various feed ingredients, including plant or animal ingredients, are used in dog diets, protein digestibility values are variable among diets due to different diet formulations and nutrient compositions in the ingredients. In addition, protein digestibility may also be affected by feed processing procedures. However, animal experiments using dogs are expensive and time-consuming, and it has become a great concern for animal welfare and ethical issues. In this study, the nutrient digestibility of 18 commercial dog diets was measured using in vitro assays and prediction equations were developed for estimating in vitro nutrient disappearance of dog diets. The nutrient digestibility of dog diets was negatively correlated with fiber contents. Equations for estimating ileal protein digestibility of dog diets were developed: digestibility of crude protein (%) = 0.33 × crude protein (% as-is) − 0.49 × neutral detergent fiber (% as-is) + 81.25. Overall, in vitro ileal nutrient disappearance in a commercial dog diet can be estimated using the equations with protein and fiber. Abstract The aims of this study were to determine in vitro ileal disappearance (IVID) of dry matter (DM) and crude protein (CP) in commercial dog diets and to develop equations for predicting the IVID of DM and CP in dog diets based on chemical composition. Eighteen commercial dog diets were analyzed for IVID of DM and CP using a two-step in vitro procedure for dogs. The diet samples in flasks with digestive enzymes were incubated for 2 h and 4 h to simulate digestion in the stomach and the small intestine, respectively. The contents of CP, ether extract, neutral detergent fiber (NDF), and ash in the diets ranged from 14.4 to 42.5%, 3.5 to 23.5%, 6.4 to 34.6%, and 4.9 to 10.0%, respectively, on an as-is basis. The NDF contents were negatively correlated with the IVID of DM and CP (r = −0.73 and r = −0.62, respectively; p < 0.05). The most suitable prediction equations for the IVID of DM and CP in the dog diets were: IVID of DM (%) = 81.33 + 0.46 × CP − 0.77 × NDF, R2 = 0.78; IVID of CP (%) = 81.25 + 0.33 × CP − 0.49 × NDF, R2 = 0.64, where all nutrients were in % on an as-is basis. In conclusion, dry matter and protein utilization of dog diets based on in vitro digestibility assays can be estimated fairly well using protein and fiber concentrations as independent variables.
Understanding the Experiences of Clinicians Accessing Electronic Databases to Search for Evidence on Pain Management Using a Mixed Methods Approach

The act of searching and retrieving evidence falls under the second step of the EBP process—tracking down the best evidence. The purpose of this study is to understand the competencies of clinicians accessing electronic databases to search for evidence on pain management using a mixed methods approach. Thirty-seven healthcare professionals (14 occupational therapists, 13 physical therapists, 8 nurses, and 2 psychologists) who are actively involved in pain management were included. This study involved two parts (a qualitative and a quantitative part) that ran in parallel. Participants were interviewed using a semi-structured interview guide (qualitative data); data were transcribed verbatim. During the interview, participants were evaluated in comparison to a set of pre-determined practice competencies using a chart-stimulated recall (CSR) technique (quantitative data). CSR was scored on a 7-point Likert scale. Coding was completed by two raters; themes across each of the competencies were integrated by three raters. Seven themes evolved out of the qualitative responses to these competencies: formulating a research question, sources of evidence accessed, search strategy, refining the yield, barriers and facilitators, clinical decision making, and knowledge and awareness about appraising the quality of evidence. The qualitative results informed an understanding of the strengths and weaknesses in the competencies evaluated. In conclusion, using a mixed methods approach, we found that clinicians were performing well with their basic literature review skills, but when it came to advanced skills like using Boolean operators, critical appraisal and finding levels of evidence they seem to require more training.
What does the future look like for kelp when facing multiple stressors?

Abstract As primary producers and ecosystem engineers, kelp (generally Order Laminariales) are ecologically important, and their decline could have far‐reaching consequences. Kelp are valuable in forming habitats for fish and invertebrates and are crucial for adaptation to climate change by creating coastal defenses and in providing key functions, such as carbon sequestration and food provision. Kelp are threatened by multiple stressors, such as climate change, over‐harvesting of predators, and pollution. In this opinion paper, we discuss how these stressors may interact to affect kelp, and how this varies under different contexts. We argue that more research that bridges kelp conservation and multiple stressor theory is needed and outline key questions that should be addressed as a priority. For instance, it is important to understand how previous exposure (either to earlier generations or life stages) determines responses to emerging stressors, and how responses in kelp scale up to alter food webs and ecosystem functioning. By increasing the temporal and biological complexity of kelp research in this way, we will improve our understanding allowing better predictions. This research is essential for the effective conservation and potential restoration of kelp in our rapidly changing world.
Biofilm Formation and Genetic Diversity of Microbial Communities in Anaerobic Batch Reactor with Polylactide (PLA) Addition

In this paper, an anaerobic digestion (AD) study was conducted on confectionery waste with granular polylactide (PLA) as a cell carrier. Digested sewage sludge (SS) served as the inoculum and buffering agent of systems. This article shows the results of the analyses of the key experimental properties of PLA, i.e., morphological characteristics of the microstructure, chemical composition and thermal stability of the biopolymer. The evaluation of quantitative and qualitative changes in the genetic diversity of bacterial communities, performed using the state-of-the-art next generation sequencing (NGS) technique, revealed that the material significantly enhanced bacterial proliferation; however, it does not change microbiome biodiversity, as also confirmed via statistical analysis. More intense microbial proliferation (compared to the control sample, without PLA and not digested, CW–control, CW–confectionery waste) may be indicative of the dual role of the biopolymer—support and medium. Actinobacteria (34.87%) were the most abundant cluster in the CW–control, while the most dominant cluster in digested samples was firmicutes: in the sample without the addition of the carrier (CW–dig.) it was 68.27%, and in the sample with the addition of the carrier (CW + PLA) it was only 26.45%, comparable to the control sample (CW–control)—19.45%. Interestingly, the number of proteobacteria decreased in the CW–dig. sample (17.47%), but increased in the CW + PLA sample (39.82%) compared to the CW–control sample (32.70%). The analysis of biofilm formation dynamics using the BioFlux microfluidic system shows a significantly faster growth of the biofilm surface area for the CW + PLA sample. This information was complemented by observations of the morphological characteristics of the microorganisms using fluorescence microscopy. The images of the CW + PLA sample showed carrier sections covered with microbial consortia.
Metabolism of Acetaminophen by Enteric Epithelial Cells Mitigates Hepatocellular Toxicity In Vitro

The gut–liver axis is defined by dietary and environmental communication between the gut, microbiome and the liver with its redox and immune systems, the overactivation of which can lead to hepatic injury. We used media preconditioning to mimic some aspects of the enterohepatic circulation by treating the human Caco-2 intestinal epithelial cell line with 5, 10 and 20 mM paracetamol (N-acetyl-para-aminophenol; APAP) for 24 h, after which cell culture supernatants were transferred to differentiated human hepatic HepaRG cells for a further 24 h. Cell viability was assessed by mitochondrial function and ATP production, while membrane integrity was monitored by cellular-based impedance. Metabolism by Caco-2 cells was determined by liquid chromatography with tandem mass spectrometry. Caco-2 cell viability was not affected by APAP, while cell membrane integrity and tight junctions were maintained and became tighter with increasing APAP concentrations, suggesting a reduction in the permeability of the intestinal epithelium. During 24 h incubation, Caco-2 cells metabolised 64–68% of APAP, leaving 32–36% of intact starting compound to be transferred to HepaRG cells. When cultured with Caco-2-preconditioned medium, HepaRG cells also showed no loss of cell viability or membrane integrity, completely in contrast to direct treatment with APAP, which resulted in a rapid loss of cell viability and membrane integrity and, ultimately, cell death. Thus, the pre-metabolism of APAP could mitigate previously observed hepatotoxicity to hepatic tight junctions caused by direct exposure to APAP. These observations could have important implications for the direct exposure of hepatic parenchyma to APAP, administered via the intravenous route.