Miracle-dz/UniFAR-FTUs huggingface dataset:
Integrated analysis of canine soft tissue sarcomas identifies recurrent mutations in TP53, KMT genes and PDGFB fusions

Soft tissue sarcomas (STS) are a heterogenous group of mesenchymal tumors representing over 50 distinct types with overlapping histological features and non-specific anatomical locations. Currently, localized sarcomas are treated with surgery + / − radiation in both humans and dogs with few molecularly targeted therapeutic options. However, to improve precision-based cancer therapy through trials in pet dogs with naturally occurring STS tumors, knowledge of genomic profiling and molecular drivers in both species is essential. To this purpose, we sought to characterize the transcriptomic and genomic mutation profiles of canine STS subtypes (fibrosarcoma, undifferentiated pleomorphic sarcoma, and peripheral nerve sheath tumors), by leveraging RNAseq, whole exome sequencing, immunohistochemistry, and drug assays. The most common driver mutations were in cell cycle/DNA repair (31%, TP53 -21%) and chromatin organization/binding (41%, KMT2D -21%) genes. Similar to a subset of human sarcomas, we identified fusion transcripts of platelet derived growth factor B and collagen genes that predict sensitivity to PDGFR inhibitors. Transcriptomic profiling grouped these canine STS tumors into 4 clusters, one PNST group (H1), and 3 FSA groups selectively enriched for extracellular matrix interactions and PDFGB fusions (H2), homeobox transcription factors (H3), and elevated T-cell infiltration (H4). This multi-omics approach provides insights into canine STS sub-types at a molecular level for comparison to their human counterparts, to improve diagnosis, and may provide additional targets for chemo- and immuno-therapy.
Anaerobe isolation from denitrifying benzene-degrading enrichment culture and their capacity to mineralize benzene

Only a few benzene-mineralizing anaerobes have been isolated to date. In an attempt using classical isolation techniques to isolate benzene-mineralizing pure cultures from a benzene-mineralizing nitrate-reducing microbial community, two putative isolates were gained under nitrate-reducing conditions spiked separately with acetate and benzene as sole sources of carbon and energy with media containing ammonium or without ammonium. Both putative isolates; Bz4 (with ammonium) and Bz7 (without ammonium) - mineralized 13C-labelled acetate under anoxic conditions at 3.3 and 2.7 μM day-1, respectively, revealed by analysis of evolved 13CO2. However, only Bz4 mineralized [13C6]-labelled benzene (0.298 μM benzene mineralized day-1) generated up to 960.2 ± 0.3 ‰ δ13C-CO2 during 184 days while producing only slight amounts of nitrite (4.60 ± 0.004 μM); no benzene was mineralized by Bz7 during 184 d, and no nitrite was detected. The 16S rRNA gene amplicon sequencing of the acetate-grown bacteria revealed consortia enriched in Nocardioides (8.9%), Pseudomonas (18.2%), Rhizobiaceae (21.0%), Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium (51.4%) for Bz4 and Simplicispira (96.7%) for Bz7. The gained Bz4 consortium that mineralized benzene under anoxic condition can be further purified and explored for their metabolic potentials.
CAT PETR: A Graphical User Interface for Diﬀerential Analysis of ProteinPhosphorylation Data

Analysis of signal transduction pathways relies on monitoring global changes in cellular response to perturbation or genetic manipulation. Antibody microarray data provides an increasingly viable tool for the monitoring and analyzing high throughput expression and protein phosphorylation data. However, computational tools designed speciﬁcally for the analysis of antibody microarray data are few and far between; forcing researchers to use applications primarily designed for other data types. Here we present CAT PETR (Convenient Analysis Tool for Phosphorylation and Expression Testing), a user friendly web application that provides interactive and publication ready plots for the diﬀerential analysis of expression and phosphorylation data collected via antibody microarrays. Our tool is made available as a web application at https://av-gay-ubc.shinyapps. io/CAT-PETR/. The code is publicly available on GitHub (https://github.com/Raif-ﬂ/CAT-PETR) with documentation containing tutorials and datasets.
VHL Mutation Drives Human Clear Cell Renal Cell Carcinoma Progression Through PI3K/AKT-Dependent Cholesteryl Ester Accumulation

Background Cholesteryl ester (CE) accumulation in intracellular lipid droplets (LDs) is an essential signature of clear cell renal cell carcinoma (ccRCC), but its molecular mechanism and pathological significance remain elusive. Methods Enabled by the label-free Raman spectromicroscopy, which integrated stimulated Raman scattering microscopy with confocal Raman spectroscopy on the same platform, we quantitatively analyzed LD distribution and composition at the single cell level in intact ccRCC cell and tissue specimens in situ without any processing or exogenous labeling. Since we found that commonly used ccRCC cell lines actually did not show the CE-rich signature, primary cancer cells were isolated from human tissues to retain the lipid signature of ccRCC with CE level as high as the original tissue, which offers a preferable cell model for the study of cholesterol metabolism in ccRCC. Moreover, we established a patient-derived xenograft (PDX) mouse model that retained the CE-rich phenotype of human ccRCC. Findings Surprisingly, our results revealed that CE accumulation was induced by tumor suppressor VHL mutation, the most common mutation of ccRCC. Moreover, VHL mutation was found to promote CE accumulation by upregulating HIFα and subsequent PI3K/AKT/mTOR/SREBPs pathway. Inspiringly, inhibition of cholesterol esterification remarkably suppressed ccRCC aggressiveness in vitro and in vivo with negligible toxicity, through the reduced membrane cholesterol-mediated downregulations of integrin and MAPK signaling pathways. Interpretation Collectively, our study improves current understanding of the role of CE accumulation in ccRCC and opens up new opportunities for treatment. Funding This work was supported by National Natural Science Foundation of China (No. U23B2046 and No. 62027824), National Key R&D Program of China (No. 2023YFC2415500), Fundamental Research Funds for the Central Universities (No. YWF-22-L-547), PKU-Baidu Fund (No. 2020BD033), Peking University First Hospital Scientific and Technological Achievement Transformation Incubation Guidance Fund (No.2022CX02), and Beijing Municipal Health Commission (No. 2020-2Z-40713).
Sustainability assessment of Cerrado and Caatinga biomes in Brazil: A proposal for collaborative index construction in the context of the 2030 Agenda and the Water-Energy-Food Nexus

The 2030 Agenda framework represents an opportunity for the co-development of local indicators and shares the same principles of cross-sectoral integration and universality as the water–energy–food nexus. This research aimed to develop a quantitative-collaborative methodology for constructing indicators and indexes for the sustainability of the Cerrado and Caatinga Brazilian biomes, considering the connection and synergies between the Nexus perspective and the 2030 Agenda’s SDG–target framework. The study was applied in 2,512 municipalities that make up the total of the mentioned biomes. The methodology consists of four major blocks: i) identification and construction of indicators based on the association of them with one or more 2030 Agenda’s targets, in a collaborative way from expert groups; ii) generation of weights by an indicator considering leverage, according to the number of target assignments, and importance, attributed by experts for each indicator to the target; iii) generation of sustainable development goal indexes, considering the performance of the SDGs; Nexus performance, considering different weights between the SDGs; Nexus synergistic, the standard deviation between the SDGs; and Nexus overall, a combination of the last two; and iv) sensitivity analysis for performance indexes considering the assignment of zero values to the governance indicators. In general, the regions of MATOPIBA, northern and western of Cerrado and the Caatinga, are, on average, the areas of greatest vulnerability. The targets that respond to this inequality are related to eradicating hunger, sustainable and climate-resilient production systems, universal access to water, water quality, efficiency of multiple water uses, access to energy, and the participation of renewable energies. We found that in areas of better average nexus performance, there is also greater inequality between nexus dimensions; therefore, the Nexus overall index is penalized. The federal units and areas with the worst Nexus dimension performances and with insufficient governance measures are north and northwest of Bahia and municipalities bordering the State of Tocantins—food; Maranhão and Piauí, northeast of Mato Grosso, northwest of Goiás, Rio Grande do Norte and Paraíba—water; and Maranhão, extreme southeast of Pará, and more sparsely in Paraíba—energy.
Non-deacetylated poly-N-acetylglucosamine-hyperproducing Staphylococcus aureus undergoes immediate autoaggregation upon vortexing

Biofilms are microbial communities of cells embedded in a matrix of extracellular polymeric substances generated and adhering to each other or to a surface. Cell aggregates formed in the absence of a surface and floating pellicles that form biofilms at the air-liquid interface are also considered to be a type of biofilm. Staphylococcus aureus is a well-known cause of biofilm infections and high-molecular-weight polysaccharides, poly-N-acetylglucosamine (PNAG) is a main constituent of the biofilm. An icaADBC operon comprises major machinery to synthesize and extracellularly secrete PNAG. Extracellular PNAG is partially deacetylated by IcaB deacetylase, and the positively charged PNAG hence interacts with negatively charged cell surface to form the major component of biofilm. We previously reported a new regulator of biofilm (Rob) and demonstrated that Rob binds to a unique 5-bp motif, TATTT, present in intergenic region between icaADBC operon and its repressor gene icaR in Yu et al. The deletion of the 5-bp motif induces excessive adherent biofilm formation. The real function of the 5-bp motif is still unknown. In an attempt to isolate the 5-bp motif deletion mutant, we isolated several non-adherent mutants. They grew normally in turbid broth shaking culture but immediately auto-aggregated upon weak vortexing and sedimented as a lump resulting in a clear supernatant. Whole genome sequencing of the mutants identified they all carried mutations in icaB in addition to deletion of the 5-bp motif. Purification and molecular characterization of auto-aggregating factor in the culture supernatant of the mutant identified that the factor was a massively produced non-deacetylated PNAG. Therefore, we created a double deficient strain of biofilm inhibitory factors (5-bp motif, icaR, rob) and icaB to confirm the aggregation phenomenon. This peculiar phenomenon was only observed in Δ5bpΔicaB double mutant but not in ΔicaR ΔicaB or ΔrobΔicaB mutant. This study explains large amount of extracellularly produced non-deacetylated PNAG by Δ5bpΔicaB double mutation induced rapid auto-aggregation of S. aureus cells by vortexing. This phenomenon indicated that Staphylococcus aureus may form biofilms that do not adhere to solid surfaces and we propose this as a new mechanism of non-adherent biofilm formation of S. aureus.
Linking perceived social support to self-esteem and social integration among adolescents with visual impairment: A cross-lagged study

This study examines the relationship between perceived social support and self-esteem and between perceived social support and social integration among adolescents with visual impairments. Adolescents with visual impairments (Ntime1 = 311, Ntime2 = 170) from four special education schools in eastern China participated in this study within a 1-year interval. The Child and Adolescent Social Support Scale, Rosenberg Self-esteem Questionnaire, and Interpersonal Adaptation Scale were used to collect data. The results from cross-lagged panel modeling showed reciprocal positive relationships between parental support and self-esteem. Self-esteem at T1 positively predicted three other sources of perceived social support at T2: teacher support, classmate support, and close-friend support. Social integration at T1 positively predicted close-friend support at T2. This study extends understanding of the relationships among perceived social support, self-esteem, and social integration, and provides practical implications for parents, schools, and communities to improve psychosocial outcomes in adolescents with visual impairment.
Monitoring the impact of the COVID-19 lockdown on air quality in Lanzhou: Implications for future control strategies

China implemented a one-month lockdown after the 2020 Spring Festival to prevent the spread of COVID-19. The closure measures provide a rare opportunity to understand the resulting changes in air pollution levels and to test the effectiveness of previous environmental protection measures. We used the time series decomposition method to quantify the air pollution in Lanzhou during the closure period. The results showed that during the epidemic lockdown period, although the concentration of SO2 in Lanzhou decreased substantially, there was a significant increase in the concentration of O3 (by 19.14%), followed by a gradual return to the normal level. Most of the changes during the COVID-19 lockdown were within the range of fluctuations over the past five years. The trend of decreasing SO2 and CO in 2020 was less than that during 2015–2019, and the continuous decline of the PM10 concentration exceeded expectations. NO2, PM2.5 and O3 maintained the trend of the previous five years. Our results show that temporary social closure measures have a limited effect on improving air quality in Lanzhou, and they emphasize the importance of reducing the O3 concentration in the future.
Bacterial composition of a competitive exclusion product and its correlation with product efficacy at reducing Salmonella in poultry

The mature intestinal microbiome is a formidable barrier to pathogen colonization. Day-old chicks seeded with cecal contents of adult hens are resistant to colonization with Salmonella, the basis of competitive exclusion. Competitive exclusion products can include individual microbes but are commonly undefined intestinal communities taken from adult animals and in commercial production is amplified in fermentator and sold commercially in freeze dried lots. While superior to single and multiple species probiotics, reducing Salmonella colonization by multiple logs, undefined products have limited acceptance because of their uncharacterized status. In this study, the bacterial composition of the master stock, preproduction seed stocks and commercial lots of a poultry competitive exclusion product, was defined by 16S rRNA sequence analysis, targeting the 16S rRNA variable region (V1-V3). The samples contained a diversity of genera (22–52 distinct genera) however, the commercial lots displayed less diversity compared to the seeds and the master stock. Community composition varied between seeds and the master stock and was not a good predictor of potency, in terms of log10 reduction in Salmonella abundance. While there was significant correlation in composition between seeds and their commercial lots, this too was a not a good predictor of potency. There was linear correlation between unclassified Actinobacteria, Peptococcus, and unclassified Erysipelotrichaceae, and Salmonella abundance (r 2 > .75) for commercial seeds. However, upon review of the literature, these three genera were not consistently observed across studies or between trials that examined the correlation between intestinal community composition and Salmonella prevalence or abundance.
Solid Fuel Use and the Progression of Multimorbidity in Middle-Aged Chinese Participants: A Prospective Cohort Study

Objectives: This study aimed to examine the association of solid fuel use for cooking and heating with the progression of multimorbidity. Methods: A total of 5,437 participants from the China Health and Retirement Longitudinal Study were included. Multivariate logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for the associations of the independent and joint effects of solid fuel use for cooking and heating with the progression of multimorbidity. Results: The proportion of participants reporting solid fuel use for both cooking and heating was 59.0% at baseline. Solid fuel use for both cooking and heating was associated with the progression of multimorbidity (adjusted OR: 1.42, 95% CI: 1.19–1.70), compared with clean fuel use for both. Conclusion: Solid fuel use for cooking and heating play an important role in the progression of multimorbidity. Therefore, solid fuel reduction should be considered in developing multimorbidity control and prevention programmes.
Artificial intelligence (AI) acceptance in primary care during the coronavirus pandemic: What is the role of patients' gender, age and health awareness? A two-phase pilot study

Background Artificial intelligence (AI) is steadily entering and transforming the health care and Primary Care (PC) domains. AI-based applications assist physicians in disease detection, medical advice, triage, clinical decision-making, diagnostics and digital public health. Recent literature has explored physicians' perspectives on the potential impact of digital public health on key tasks in PC. However, limited attention has been given to patients' perspectives of AI acceptance in PC, specifically during the coronavirus pandemic. Addressing this research gap, we administered a pilot study to investigate criteria for patients' readiness to use AI-based PC applications by analyzing key factors affecting the adoption of digital public health technology. Methods The pilot study utilized a two-phase mixed methods approach. First, we conducted a qualitative study with 18 semi-structured interviews. Second, based on the Technology Readiness and Acceptance Model (TRAM), we conducted an online survey (n = 447). Results The results indicate that respondents who scored high on innovativeness had a higher level of readiness to use AI-based technology in PC during the coronavirus pandemic. Surprisingly, patients' health awareness and sociodemographic factors, such as age, gender and education, were not significant predictors of AI-based technology acceptance in PC. Conclusions This paper makes two major contributions. First, we highlight key social and behavioral determinants of acceptance of AI-enabled health care and PC applications. Second, we propose that to increase the usability of digital public health tools and accelerate patients' AI adoption, in complex digital public health care ecosystems, we call for implementing adaptive, population-specific promotions of AI technologies and applications.
Sociodemographic, economic, physical, and mental health status of previously hospitalised patients with COVID-19 symptoms in Bangladesh: Protocol for a mixed-method study

Introduction Not much is known about the long-term consequences of COVID-19, popularly known as long COVID. This is particularly so in terms of patterns and clusters of symptoms over time, sociodemographic and economic characteristics of patients, and related clinical history. This is crucial for resource-constrained health systems such as Bangladesh to address long COVID as a forthcoming challenge. This protocol aims to investigate the consequences of COVID-19 over time for physical and mental health and how these are associated with demographic and socio-economic factors. Methods and analysis This mixed-method study collected information on all patients with symptoms of COVID-19 admitted to and discharged after recovery from a COVID-19-dedicated hospital in Bangladesh (N = 942), from April to December 2020. The sources of data were admission records and discharge certificates from the hospital for clinical history, cross-sectional survey on physical and mental health (assessed by DASS21 scale)-related symptoms and socioeconomic changes after recovery, and qualitative in-depth interviews on experiences of COVID-19. Interviews were conducted over the phone. Quantitative analysis was done to estimate the prevalence of physical and mental health consequences of COVID-19 after recovery and the association with socio-economic and demographic information. The qualitative analysis was performed using a thematic analysis approach. Discussion It is imperative to understand the post-COVID consequences and related health and non-health aspects to inform evidence-based policymaking, especially for resource-poor contexts such as Bangladesh. Given the dearth of evidence in this regard, the proposed study will contribute to bridging this knowledge gap. It is important to note that this study is one of the few which presents information on post-COVID-19 consequences in the context of low- and middle-income countries and the first in Bangladesh.
Improved targeting of the 16S rDNA nanopore sequencing method enables rapid pathogen identification in bacterial pneumonia in children

Objectives To develop a rapid and low-cost method for 16S rDNA nanopore sequencing. Methods This was a prospective study on a 16S rDNA nanopore sequencing method. We developed this nanopore barcoding 16S sequencing method by adding barcodes to the 16S primer to reduce the reagent cost and simplify the experimental procedure. Twenty-one common pulmonary bacteria (7 reference strains, 14 clinical isolates) and 94 samples of bronchoalveolar lavage fluid from children with severe pneumonia were tested. Results indicating low-abundance pathogenic bacteria were verified with the polymerase chain reaction (PCR). Further, the results were compared with those of culture or PCR. Results The turnaround time was shortened to 6~8 hours and the reagent cost of DNA preparation was reduced by employing a single reaction adding barcodes to the 16S primer in advance. The accuracy rate for the 21 common pulmonary pathogens with an abundance ≥ 99% was 100%. Applying the culture or PCR results as the gold standard, 71 (75.5%) of the 94 patients were positive, including 25 positive cultures (26.6%) and 52 positive quantitative PCRs (55.3%). The median abundance in the positive culture and qPCR samples were 29.9% and 6.7%, respectively. With an abundance threshold increase of 1%, 5%, 10%, 15% and 20%, the test sensitivity decreased gradually to 98.6%, 84.9%, 72.6%, 67.1% and 64.4%, respectively, and the test specificity increased gradually to 33.3%, 71.4%, 81.0%, 90.5% and 100.0%, respectively. Conclusions The nanopore barcoding 16S sequencing method can rapidly identify the pathogens causing bacterial pneumonia in children.