Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic and Expression Analyses Define MUC17 and PCNX1 as Predictors of Chemotherapy Response in Breast Cancer

Poor-prognosis breast cancers are treated with cytotoxic chemotherapy, but often without any guidance from therapy predictive markers because universally accepted markers are not currently available. Treatment failure, in the form of recurrences, is relatively common. We aimed to identify chemotherapy predictive markers and resistance pathways in breast cancer. Our hypothesis was that tumor cells remaining after neoadjuvant chemotherapy (NAC) contain somatic variants causing therapy resistance, while variants present pre-NAC but lost post-NAC cause sensitivity. Whole-exome sequencing was performed on matched pre- and post-NAC cancer cells, which were isolated by laser microdissection, from 6 cancer cases, and somatic variants selected for or against by NAC were identified. Somatic variant diversity was significantly reduced after therapy (P < 0.05). MUC17 variants were identified in 3 tumors and were selected against by NAC in each case, while PCNX1 variants were identified in 2 tumors and were selected for in both cases, implicating the function of these genes in defining chemoresponse. In vitro knockdown of MUC17 or PCNX1 was associated with significantly increased or decreased chemotherapy sensitivity, respectively (P < 0.05), further supporting their roles in chemotherapy response. Expression was tested for predictive value in two independent cohorts of chemotherapy-treated breast cancers (n = 53, n = 303). Kaplan–Meier analyses revealed that low MUC17 expression was significantly associated with longer survival after chemotherapy, whereas low PCNX1 was significantly associated with reduced survival. We concluded that therapy-driven selection of somatic variants allows identification of chemotherapy response genes. With respect to MUC17 and PCNX1, therapy-driven selection acting on somatic variants, in vitro knockdown data concerning drug sensitivity, and survival analysis of expression levels in patient cohorts all define the genes as mediators of and predictive markers for chemotherapy response in breast cancer.
Plant–herbivorous insect networks: who is eating what revealed by long barcodes using high‐throughput sequencing and Trinity assembly

Interactions between plants and insects are among the most important life functions for all organism at a particular natural community. Usually a large number of samples are required to identify insect diets in food web studies. Previously, Sanger sequencing and next generation sequencing (NGS) with short DNA barcodes were used, resulting in low species‐level identification; meanwhile the costs of Sanger sequencing are expensive for metabarcoding together with more samples. Here, we present a fast and effective sequencing strategy to identify larvae of Lepidoptera and their diets at the same time without increasing the cost on Illumina platform in a single HiSeq run, with long‐multiplex‐metabarcoding (COI for insects, rbcL, matK, ITS and trnL for plants) obtained by Trinity assembly (SHMMT). Meanwhile, Sanger sequencing (for single individuals) and NGS (for polyphagous) were used to verify the reliability of the SHMMT approach. Furthermore, we show that SHMMT approach is fast and reliable, with most high‐quality sequences of five DNA barcodes of 63 larvae individuals (54 species) recovered (full length of 100% of the COI gene and 98.3% of plant DNA barcodes) using Trinity assembly (up‐sized to 1015 bp). For larvae diets identification, 95% are reliable; the other 5% failed because their guts were empty. The diets identified by SHMMT approach are 100% consistent with the host plants that the larvae were feeding on during our collection. Our study demonstrates that SHMMT approach is reliable and cost‐effective for insect‐plants network studies. This will facilitate insect‐host plant studies that generally contain a huge number of samples.
Environmental Toxicology and Chemistry

Regulatory jurisdictions worldwide are increasingly incorporating bioavailability‐based toxicity models into development of protective values (PVALs) for freshwater and saltwater aquatic life (e.g., water quality criteria, standards, and/or guidelines) for metals. Use of such models for regulatory purposes should be contingent on their ability to meet performance criteria as specified through a model‐validation process. Model validation generally involves an assessment of a model's appropriateness, relevance, and accuracy. We review existing guidance for validation of bioavailability‐based toxicity models, recommend questions that should be addressed in model‐validation studies, discuss model study type and design considerations, present several new ways to evaluate model performance in validation studies, and suggest a framework for use of model validation in PVAL development. We conclude that model validation should be rigorous but flexible enough to fit the user's purpose. Although a model can never be fully validated to a level of zero uncertainty, it can be sufficiently validated to fit a specific purpose. Therefore, support (or lack of support) for a model should be presented in such a way that users can choose their own level of acceptability. We recommend that models be validated using experimental designs and endpoints consistent with the data sets that were used to parameterize and calibrate the model and validated across a broad range of geographically and ecologically relevant water types. Environ Toxicol Chem 2020;39:101–117. © 2019 SETAC
Projected 20- and 30-Year Outcomes for Pediatric Liver Transplant Recipients in the United States.

BACKGROUND Observed long-term outcomes no longer reflect the survival trajectory facing pediatric liver transplant (LT) recipients today. We aimed to use national registry data and parametric models to project 20- and 30-year post-transplant outcomes for recently transplanted pediatric LT recipients. METHODS We conducted a retrospective cohort study of 13,442 first-time pediatric (age < 18) LT recipients using 1987-2018 SRTR data. We validated the proposed method (i.e. to project long-term patient and graft survival using parametric survival models and short-term data) in two historic cohorts (1987-1996 and 1997-2006) and estimated long-term projections among patients transplanted between 2007-2018. Projections were stratified by graft type, recipient age, and indication for transplant. RESULTS Parsimonious parametric models with Weibull distribution can be applied to post-transplant data and used to project long-term outcomes for pediatric LT recipients beyond observed data. Projected 20-year patient survival for pediatric LT recipients transplanted in 2007-2018 was 84.0% (95% CI 81.5-85.8), compared to observed 20-year survival of 72.8% and 63.6% among those transplanted in 1997-2006 and 1987-1996, respectively. Projected 30-year survival for pediatric LT recipients in 2007-2018 was 80.1% (75.2-82.7), compared to projected 30-year survival of 68.6% (66.1-70.9) in the 1997-2006 cohort and observed 30-year survival of 57.5% in the 1987-1996 cohort. Twenty- and 30-year patient and graft survival varied slightly by recipient age, graft type, and indication for transplant. CONCLUSIONS Projected long-term outcomes for recently transplanted pediatric LT recipients are excellent, reflective of substantial improvements in medical care, and informative for physician-patient education and decision making in the current era.
Inoculum Source Determines Acetate and Lactate Production during Anaerobic Digestion of Sewage Sludge and Food Waste

Acetate production from food waste or sewage sludge was evaluated in four semi-continuous anaerobic digestion processes. To examine the importance of inoculum and substrate for acid production, two different inoculum sources (a wastewater treatment plant (WWTP) and a co-digestion plant treating food and industry waste) and two common substrates (sewage sludge and food waste) were used in process operations. The processes were evaluated with regard to the efficiency of hydrolysis, acidogenesis, acetogenesis, and methanogenesis and the microbial community structure was determined. Feeding sewage sludge led to mixed acid fermentation and low total acid yield, whereas feeding food waste resulted in the production of high acetate and lactate yields. Inoculum from WWTP with sewage sludge substrate resulted in maintained methane production, despite a low hydraulic retention time. For food waste, the process using inoculum from WWTP produced high levels of lactate (30 g/L) and acetate (10 g/L), while the process initiated with inoculum from the co-digestion plant had higher acetate (25 g/L) and lower lactate (15 g/L) levels. The microbial communities developed during acid production consisted of the major genera Lactobacillus (92–100%) with food waste substrate, and Roseburia (44–45%) and Fastidiosipila (16–36%) with sewage sludge substrate. Use of the outgoing material (hydrolysates) in a biogas production system resulted in a non-significant increase in bio-methane production (+5–20%) compared with direct biogas production from food waste and sewage sludge.
Multilayer network analysis unravels haulage vehicles as a hidden threat to the British swine industry.

When assessing the role of live animal trade networks in the spread of infectious diseases in livestock, attention has focused mainly on direct movements of animals between premises, whereas the role of haulage vehicles used during transport, an indirect route for disease transmission, has largely been ignored. Here, we have assessed the impact of sharing haulage vehicles from livestock transport service providers on the connectivity between farms as well as on the spread of swine infectious diseases in Great Britain (GB). Using all pig movement records between April 2012 and March 2014 in GB, we built a series of directed and weighted static multiplex networks consisting of two layers of identical nodes, where nodes (farms) are linked either by (1) the direct movement of pigs and (2) the shared use of haulage vehicles. The haulage contact definition integrates the date of the move and the duration Δs that lorries are left contaminated by pathogens, hence accounting for the temporal aspect of contact events. For increasing Δs, descriptive network analyses were performed to assess the role of haulage on network connectivity. We then explored how viruses may spread throughout the GB pig sector by computing the reproduction number R. Our results showed that sharing haulage vehicles increases the number of contacts between farms by > 50% and represents an important driver of disease transmission. In particular, sharing haulage vehicles, even if < Δs1 day, will limit the benefit of the standstill regulation, increase the number of premises that could be infected in an outbreak, and more easily raise R above 1. This work confirms that sharing haulage vehicles has significant potential for spreading infectious diseases within the pig sector. The cleansing and disinfection process of haulage vehicles is therefore a critical control point for disease transmission risk mitigation.
Treatment of chronic thromboembolic pulmonary hypertension in a multidisciplinary team

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) may be treated with pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA) and medical therapy (MT). Assessment in a multidisciplinary team of experts (CTEPH team) is currently recommended for treatment decision making. The aim of the present study was to report the effects of such an interdisciplinary concept. Methods and results: A total of 160 patients were consulted by the CTEPH team between December 2015 and September 2018. Patient baseline characteristics, CTEPH team decisions and implementation rates of diagnostic and therapeutic procedures were analysed. Change in World Health Organization (WHO) functional class and survival rates were evaluated by treatment strategy. A total of 51 (32%) patients were assessed as operable and 109 (68%) were deemed inoperable. Thirty-one (61% of operable patients) underwent PEA. Patients treated with PEA, BPA(+MT) and MT alone were 50.9 ± 14.7, 62.9 ± 15.1 and 68.9 ± 12.7 years old, respectively. At the follow-up, PEA patients had the highest WHO functional class improvement. Patients treated with BPA(+MT) had significantly better survival than PEA (p = 0.04) and MT patients (p = 0.04; 2-year survival of 92%, 79% and 79%, respectively). Conclusions: The CTEPH team ensures that necessary diagnostic procedures are performed. A relatively low proportion of patients was assessed by the CTEPH team as operable and underwent surgery, which in survivors resulted in the best functional improvement. Although patients undergoing BPA(+MT) were older than patients treated with PEA, their survival was better than patients subjected to PEA or MT alone. The reviews of this paper are available via the supplemental material section.
Specificity Assessment of CRISPR Genome Editing of Oncogenic EGFR Point Mutation with Single-Base Differences

In CRISPR genome editing, CRISPR proteins form ribonucleoprotein complexes with guide RNAs to bind and cleave the target DNAs with complete sequence complementarity. CRISPR genome editing has a high potential for use in precision gene therapy for various diseases, including cancer and genetic disorders, which are caused by DNA mutations within the genome. However, several studies have shown that targeting the DNA via sequence complementarity is imperfect and subject to unintended genome editing of other genomic loci with similar sequences. These off-target problems pose critical safety issues in the therapeutic applications of CRISPR technology, with particular concerns in terms of the genome editing of pathogenic point mutations, where non-mutant alleles can become an off-target with only a one-base difference. In this study, we sought to assess a novel CRISPR genome editing technique that has been proposed to achieve a high specificity by positioning the mismatches within the protospacer adjacent motif (PAM) sequence. To this end, we compared the genome editing specificities of the PAM-based and conventional methods on an oncogenic single-base mutation in the endothelial growth factor receptor (EGFR). The results indicated that the PAM-based method provided a significantly increased genome editing specificity for pathogenic mutant alleles with single-base precision.
Exercise-Based Interventions in Hemodialysis Patients: A Systematic Review with a Meta-Analysis of Randomized Controlled Trials

There is a lack of agreement on the efficacy of different exercise interventions in hemodialysis patients. We analyzed which exercise type is the most beneficial in terms of functional fitness and inflammation. A literature search of seven databases yielded 33 studies that met the inclusion criteria. Compared with an inactive control, the intervention group showed moderate effects (ES = 0.74; 95% CI 0.35 to 1.14; p < 0.001; and ES = 0.70; 95% CI 0.39 to 1.01; p < 0.001; respectively) on functional capacity (six-minute walk test) and oxygen consumption. Small nonsignificant effects were observed for aerobic (ES = −0.36; 95% CI −0.85 to 0.13; p = 0.154) and resistance (ES = −0.44; 95% CI −1.07 to 0.19; p = 0.169) training types, whereas moderate effects were found for combined (ES = −0.69; 95% CI −1.47 to 0.10; p = 0.088) training type based on a 10-repetition sit-to-stand test. Further, large and small effects were observed for aerobic (ES = −1.21; 95% CI −1.94 to −0.49; p = 0.001) and resistance training (ES = −0.54; 95% CI −0.90 to −0.17; p = 0.004) types on C-reactive protein. Overall, the results showed the numerically largest effect sizes for combined types compared to solely aerobic or resistance training types, with the differences between training types not reaching statistical significance. There was a significant modifying impact of age, training frequency, and session duration on performance and inflammatory outcomes.
Evidence of Leptospiral Presence in the Cumberland Gap Region

Background Leptospirosis is a widespread zoonotic disease that causes reproductive losses and/or hepatorenal failure in a number of animal species. Wild reservoirs of the disease, such as rodents, harbor the causative bacterium, Leptospira spp. , in their kidneys and contaminate the environment by excreting infected urine. In this study, we tested small wild mammals, environmental water, and livestock in the Cumberland Gap region of southeastern Appalachia for the presence of pathogenic Leptospira or leptospiral antibodies. Methods/Results Small wild mammals (n = 101) and environmental water samples (n = 89) were screened by a real time quantitative PCR that targets the pathogenic Leptospira-specific lipl32 gene. Kidneys from 63 small wild mammals (62.37%) and two water sources (2.25%) tested positive for leptospiral DNA. To identify the infecting leptospiral species in qPCR-positive water and kidney samples, a fragment of leptospiral rpoB gene was PCR amplified and sequenced. L. kirschneri and L. interrogans were the leptospiral species carried by small wild mammals. Furthermore, sera from livestock (n = 52; cattle and horses) were screened for leptospiral antibodies using microscopic agglutination test (MAT). Twenty sera (38.46%) from livestock had antibodies to one or more serovars of pathogenic Leptospira spp. Conclusions In conclusion, results from our study show exposure to leptospiral infection in farm animals and the presence of this zoonotic pathogen in the environmental water and kidneys of a significant number of small wild mammals. The public health implications of these findings remain to be assessed.
Depth-Sensing Indentation Creep Behavior of Nanostructured Thermal Barrier Coatings from As-Synthesized t’-8YSZ Feedstocks

Nano-indentation is a popular method to characterize the micromechanical properties of nanostructured 8YSZ coatings. However, little research has focused on the creep behavior of nano-indentation and only the elastic modulus and nanohardness have been analyzed. Herein, for the first time, the nano-indentation creep behavior of plasma-sprayed nanostructured 8YSZ coatings using as-prepared nanostructured non-transformable tetragonal (t’) feedstocks was investigated. The indentation creep behavior can be well characterized by the power-law equation and the strain rate sensitivity has been calculated in light of the equation. The strain rate sensitivity was sensitive to the load and the reasons were analyzed in detail. The current results can further guide and design thermal barrier coatings from the point of indentation creep property.
High Fibre Gluten-Free Fresh Pasta with Tiger Nut, Chickpea and Fenugreek: Technofunctional, Sensory and Nutritional Properties

Gluten-free pasta production with a low glycaemic index and improved nutritional profile is still a challenge for the food industry. In this study, pasta was produced from fenugreek (FF), chickpea (CPF) and tiger nut (TNF) flours. CPF and FF are interesting for a balanced contribution of soluble and insoluble fibre by combining the health benefits of each type of fibre that promotes health. TNF, also rich in insoluble fibre, can provide additional healthy properties. The partial substitution of TNF for FF (0, 2.5, 5, 7.5 and 10% w/w solids) was assessed, and the relation linking chemical composition, structure, cooking and rheological properties and predictive in-vitro starch digestion (eGI, expected glycaemic index) was analysed. The results revealed that FF, rich in galactomannans, not only improves the nutritional profile and lowers the eGI but also helps to naturally enhance the structure of the pasta product and, thus, cooking behaviour (higher swelling index and fewer cooking losses).
Gene Profiling in the Adipose Fin of Salmonid Fishes Supports Its Function as a Flow Sensor

In stock enhancement and sea-ranching procedures, the adipose fin of hundreds of millions of salmonids is removed for marking purposes annually. However, recent studies proved the significance of the adipose fin as a flow sensor and attraction feature. In the present study, we profiled the specific expression of 20 neuron- and glial cell-marker genes in the adipose fin and seven other tissues (including dorsal and pectoral fin, brain, skin, muscle, head kidney, and liver) of the salmonid species rainbow trout Oncorhynchus mykiss and maraena whitefish Coregonus maraena. Moreover, we measured the transcript abundance of genes coding for 15 mechanoreceptive channel proteins from a variety of mechanoreceptors known in vertebrates. The overall expression patterns indicate the presence of the entire repertoire of neurons, glial cells and receptor proteins on the RNA level. This quantification suggests that the adipose fin contains considerable amounts of small nerve fibers with unmyelinated or slightly myelinated axons and most likely mechanoreceptive potential. The findings are consistent for both rainbow trout and maraena whitefish and support a previous hypothesis about the innervation and potential flow sensory function of the adipose fin. Moreover, our data suggest that the resection of the adipose fin has a stronger impact on the welfare of salmonid fish than previously assumed.
Synthesis and Physicochemical Characterization of Undecylenic Acid Grafted to Hyaluronan for Encapsulation of Antioxidants and Chemical Crosslinking

In this work, a new amphiphilic derivative made of 10-undecylenic acid grafted to hyaluronan was prepared by mixed anhydrides. The reaction conditions were optimized, and the effect of the molecular weight (Mw), reaction time, and the molar ratio of reagents was explored. Using this methodology, a degree of substitution up to 50% can be obtained. The viscosity of the conjugate can be controlled by varying the substitution degree. The physicochemical characterization of the modified hyaluronan was performed by infrared spectroscopy, Nuclear Magnetic Resonance, Size-Exclusion Chromatography combined with Multiangle Laser Light Scattering (SEC-MALLS), and rheology. The low proton motility and self-aggregation of the amphiphilic conjugate produced overestimation of the degree of substitution. Thus, a novel method using proton NMR was developed. Encapsulation of model hydrophobic guest molecules, coenzyme Q10, curcumin, and α-tocopherol into the micellar core was also investigated by solvent evaporation. HA-UDA amphiphiles were also shown to self-assemble into spherical nanostructures (about 300 nm) in water as established by dynamic light scattering. Furthermore, HA-UDA was crosslinked via radical polymerization mediated by ammonium persulphate (APS/TEMED). The cross-linking was also tested by photo-polymerization catalyzed by Irgacure 2959. The presence of the hydrophobic moiety decreases the swelling degree of the prepared hydrogels compared to methacrylated-HA. Here, we report a novel hybrid hyaluronan (HA) hydrogel system of physically encapsulated active compounds and chemical crosslinking for potential applications in drug delivery.