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1,4-Dioxane concentration in most contaminated water is much less than 1 mg/L, which cannot sustain the growth of most reported 1,4-dioxane-metabolizing pure cultures. These pure cultures were isolated following enrichment of mixed cultures at high concentrations (20 to 1,000 mg/L). This study is based on a different strategy: 1,4-dioxane-metabolizing mixed cultures were enriched by periodically spiking 1,4-dioxane at low concentrations (≤1 mg/L). Five 1,4-dioxane-metabolizing pure strains LCD6B, LCD6D, WC10G, WCD6H, and WD4H were isolated and characterized. The partial 16S rRNA gene sequencing showed that the five bacterial strains were related to Dokdonella sp. (98.3%), Acinetobacter sp. (99.0%), Afipia sp. (99.2%), Nitrobacter sp. (97.9%), and Pseudonocardia sp. (99.4%), respectively. Nitrobacter sp. WCD6H is the first reported 1,4-dioxane-metabolizing bacterium in the genus of Nitrobacter. The net specific growth rates of these five cultures are consistently higher than those reported in the literature at 1,4-dioxane concentrations

Electrochemical CO2 reduction reaction (CO2RR) has been recognized as an appealing route to remarkably accelerate the carbon‐neutral cycle and reduce carbon emissions. Notwithstanding great catalytic activity that has been acquired in neutral and alkaline conditions, the carbonates generated from the inevitable reaction of the input CO2 with the hydroxide severely lower carbon utilization and energy efficiency. By contrast, CO2RR in an acidic condition can effectively circumvent the carbonate issues; however, the activity and selectivity of CO2RR in acidic electrolytes will be decreased significantly due to the competing hydrogen evolution reaction (HER). Enriching the CO2 and the key intermediates around the catalyst surface can promote the reaction rate and enhance the product selectivity, providing a promising way to boost the performance of CO2RR. In this review, the catalytic mechanism and key technique challenges of CO2RR are first introduced. Then, the critical progress of enrichment strategies for promoting the CO2RR in the acidic electrolyte is summarized with three aspects: catalyst design, electrolyte regulation, and electrolyzer optimization. Finally, some insights and perspectives for further development of enrichment strategies in acidic CO2RR are expounded. [ABSTRACT FROM AUTHOR]

Purpose: Success of clinical trials increasingly relies on effective selection of the target patient populations. We hypothesize that computational analysis of pre-accrual imaging data can be used for patient enrichment to better identify patients who can potentially benefit from investigational agents. Methods: This was tested retrospectively in soft-tissue sarcoma (STS) patients accrued into a randomized clinical trial (SARC021) that evaluated the efficacy of evofosfamide (Evo), a hypoxia activated prodrug, in combination with doxorubicin (Dox). Notably, SARC021 failed to meet its overall survival (OS) objective. We tested whether a radiomic biomarker-driven inclusion/exclusion criterion could have been used to improve the difference between the two arms (Evo + Dox vs. Dox) of the study. 164 radiomics features were extracted from 296 SARC021 patients with lung metastases, divided into training and test sets. Results: A single radiomics feature, Short Run Emphasis (SRE), was representative of a group of correlated features that were the most informative. The SRE feature value was combined into a model along with histological classification and smoking history. This model as able to identify an enriched subset (52%) of patients who had a significantly longer OS in Evo + Dox vs. Dox groups [p = 0.036, Hazard Ratio (HR) = 0.64 (0.42–0.97)]. Applying the same model and threshold value in an independent test set confirmed the significant survival difference [p = 0.016, HR = 0.42 (0.20–0.85)]. Notably, this model was best at identifying exclusion criteria for patients most likely to benefit from doxorubicin alone. Conclusions: The study presents a first of its kind clinical-radiomic approach for patient enrichment in clinical trials. We show that, had an appropriate model been used for selective patient inclusion, SARC021 trial could have met its primary survival objective for patients with metastatic STS.

Background: Sepsis is a heterogeneous syndrome, and enrollment of more homogeneous patients is essential to improve the efficiency of clinical trials. Artificial intelligence (AI) has facilitated the identification of homogeneous subgroups, but how to estimate the uncertainty of the model outputs when applying AI to clinical decision-making remains unknown., Objective: We aimed to design an AI-based model for purposeful patient enrollment, ensuring that a patient with sepsis recruited into a trial would still be persistently ill by the time the proposed therapy could impact patient outcome. We also expected that the model could provide interpretable factors and estimate the uncertainty of the model outputs at a customized confidence level., Methods: In this retrospective study, 9135 patients with sepsis requiring vasopressor treatment within 24 hours after sepsis onset were enrolled from Beth Israel Deaconess Medical Center. This cohort was used for model development, and 10-fold cross-validation with 50 repeats was used for internal validation. In total, 3743 patients with sepsis from the eICU Collaborative Research Database were used as the external validation cohort. All included patients with sepsis were stratified based on disease progression trajectories: rapid death, recovery, and persistent ill. A total of 148 variables were selected for predicting the 3 trajectories. Four machine learning algorithms with 3 different setups were used. We estimated the uncertainty of the model outputs using conformal prediction (CP). The Shapley Additive Explanations method was used to explain the model., Results: The multiclass gradient boosting machine was identified as the best-performing model with good discrimination and calibration performance in both validation cohorts. The mean area under the receiver operating characteristic curve with SD was 0.906 (0.018) for rapid death, 0.843 (0.008) for recovery, and 0.807 (0.010) for persistent ill in the internal validation cohort. In the external validation cohort, the mean area under the receiver operating characteristic curve (SD) was 0.878 (0.003) for rapid death, 0.764 (0.008) for recovery, and 0.696 (0.007) for persistent ill. The maximum norepinephrine equivalence, total urine output, Acute Physiology Score III, mean systolic blood pressure, and the coefficient of variation of oxygen saturation contributed the most. Compared to the model without CP, using the model with CP at a mixed confidence approach reduced overall prediction errors by 27.6% (n=62) and 30.7% (n=412) in the internal and external validation cohorts, respectively, as well as enabled the identification of more potentially persistent ill patients., Conclusions: The implementation of our model has the potential to reduce heterogeneity and enroll more homogeneous patients in sepsis clinical trials. The use of CP for estimating the uncertainty of the model outputs allows for a more comprehensive understanding of the model's reliability and assists in making informed decisions based on the predicted outcomes., (©Meicheng Yang, Jinqiang Zhuang, Wenhan Hu, Jianqing Li, Yu Wang, Zhongheng Zhang, Chengyu Liu, Hui Chen. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 04.09.2024.)

Purpose: Success of clinical trials increasingly relies on effective selection of the target patient populations. We hypothesize that computational analysis of pre-accrual imaging data can be used for patient enrichment to better identify patients who can potentially benefit from investigational agents. Methods: This was tested retrospectively in soft-tissue sarcoma (STS) patients accrued into a randomized clinical trial (SARC021) that evaluated the efficacy of evofosfamide (Evo), a hypoxia activated prodrug, in combination with doxorubicin (Dox). Notably, SARC021 failed to meet its overall survival (OS) objective. We tested whether a radiomic biomarker-driven inclusion/exclusion criterion could have been used to improve the difference between the two arms (Evo + Dox vs. Dox) of the study. 164 radiomics features were extracted from 296 SARC021 patients with lung metastases, divided into training and test sets. Results: A single radiomics feature, Short Run Emphasis (SRE), was representative of a group of correlated features that were the most informative. The SRE feature value was combined into a model along with histological classification and smoking history. This model as able to identify an enriched subset (52%) of patients who had a significantly longer OS in Evo + Dox vs. Dox groups [p = 0.036, Hazard Ratio (HR) = 0.64 (0.42–0.97)]. Applying the same model and threshold value in an independent test set confirmed the significant survival difference [p = 0.016, HR = 0.42 (0.20–0.85)]. Notably, this model was best at identifying exclusion criteria for patients most likely to benefit from doxorubicin alone. Conclusions: The study presents a first of its kind clinical-radiomic approach for patient enrichment in clinical trials. We show that, had an appropriate model been used for selective patient inclusion, SARC021 trial could have met its primary survival objective for patients with metastatic STS. [ABSTRACT FROM AUTHOR]

Cysteine S- nitrosation mediates NO signaling and protein function under pathophysiological conditions. Herein, we provide a detailed protocol regarding the organic mercury chemoselective enrichment of S- nitrosated proteins and peptides. We discuss key aspects of the enrichment strategy and provide technical tips for the best performance of the experimental protocol. • Detailed protocol for synthesis of organic mercury resin. • Detailed protocol for selective enrichment for S-nitrosocysteine proteins and peptides by organic mercury resin. • Discussion and technical tips for the best performance of the enrichement strategy. [ABSTRACT FROM AUTHOR]

Fish welfare is becoming a priority for the fish farming industry. The search for practical, easy-to-implement methods to promote farmed fish welfare is therefore essential. Environmental enrichment aims to improve the psychological and physiological needs of a captive animal by increasing the complexity of its environment. During previous studies, we observed that fish seemed to be positively affected by short diffusions of air bubbles. In this study, we evaluated the effects of an innovative enrichment strategy consisting of introducing into the tank at the earliest stages of life, a pipe generating a curtain of air bubbles. Using rainbow trout (Oncorhynchus mykiss) as a captive fish model, we compared the short- (∼7 weeks) and long-term (∼21 weeks) effects of this bubble curtain diffused for one hour four times a day (Bubble condition) to a standard condition without bubbles (Control) on fish growth, aggressive and abnormal behaviors, as well as on fish motivation to access a bubble curtain, their emotional responses and their learning abilities. We found that bubble diffusion decreased aggressive and abnormal behaviors during diffusions in both the short-term and the long-term experiments. In the long-term experiment, this decrease was also observed during feedings and neutral periods when no bubble was diffused. Bubbles were found to be attractive for young Control fish (bubble-naive fish) subjected to a motivation test in the short-term experiment. When subjected to the emotional reactivity test, Bubble fish seemed less fearful, exhibiting a lower maximum velocity than Control fish in the long-term experiment only. However, the other behavioral parameters measured during this test, appetite and plasma cortisol levels were similar between treatments, irrespective of the experimental period. The latency to consume the reward observed in the spatial learning test in the long-term experiment was decreased in Bubble fish compared with Control fish, showing enhanced learning abilities in fish that experienced bubbles for 21 weeks. Growth parameters and fin erosion index did not differ between treatments. We conclude that repeated bubble diffusions act as an environmental enrichment for fish, combining physical, occupational, and sensory enrichment via the tactile stimulations provided by the air bubbles. This type of enrichment had a positive impact on the behavior of farmed rainbow trout in the long term, and would make it possible to integrate the notion of "positive welfare" into fish farms, while guaranteeing easy technical maintenance. • A bubble curtain acts as a physical, occupational and sensory enrichment for trout. • Aggressive and abnormal behaviors decrease in fish reared with bubble diffusions. • Repeated bubble diffusions reduce fish fearfulness and improves learning abilities. • 7-week bubble-naive fish are motivated to be in physical contact with bubbles. • A bubble curtain is a practical enrichment with positive effects on fish welfare. [ABSTRACT FROM AUTHOR]

Clinical trials in the era of precision cancer medicine aim to identify and validate biomarker signatures which can guide the assignment of individually optimal treatments to patients. In this article, we propose a group sequential randomized phase II design, which updates the biomarker signature as the trial goes on, utilizes enrichment strategies for patient selection, and uses Bayesian response-adaptive randomization for treatment assignment. To evaluate the performance of the new design, in addition to the commonly considered criteria of Type I error and power, we propose four new criteria measuring the benefits and losses for individuals both inside and outside of the clinical trial. Compared with designs with equal randomization, the proposed design gives trial participants a better chance to receive their personalized optimal treatments and thus results in a higher response rate on the trial. This design increases the chance to discover a successful new drug by an adaptive enrichment strategy, i.e. identification and selective enrollment of a subset of patients who are sensitive to the experimental therapies. Simulation studies demonstrate these advantages of the proposed design. It is illustrated by an example based on an actual clinical trial in non-small-cell lung cancer. [ABSTRACT FROM AUTHOR]

1,4-Dioxane concentration in most contaminated water is much less than 1 mg/L, which cannot sustain the growth of most reported 1,4-dioxane-metabolizing pure cultures. These pure cultures were isolated following enrichment of mixed cultures at high concentrations (20 to 1,000 mg/L). This study is based on a different strategy: 1,4-dioxane-metabolizing mixed cultures were enriched by periodically spiking 1,4-dioxane at low concentrations (≤1 mg/L). Five 1,4-dioxane-metabolizing pure strains LCD6B, LCD6D, WC10G, WCD6H, and WD4H were isolated and characterized. The partial 16S rRNA gene sequencing showed that the five bacterial strains were related to Dokdonella sp. (98.3%), Acinetobacter sp. (99.0%), Afipia sp. (99.2%), Nitrobacter sp. (97.9%), and Pseudonocardia sp. (99.4%), respectively. Nitrobacter sp. WCD6H is the first reported 1,4-dioxane-metabolizing bacterium in the genus of Nitrobacter . The net specific growth rates of these five cultures are consistently higher than those reported in the literature at 1,4-dioxane concentrations <0.5 mg/L. Compared to the literature, our newly discovered strains have lower half-maximum-rate concentrations (1.8 to 8.2 mg-dioxane/L), lower maximum specific 1,4-dioxane utilization rates (0.24 to 0.47 mg-dioxane/(mg-protein ⋅ d)), higher biomass yields (0.29 to 0.38 mg-protein/mg-dioxane), and lower decay coefficients (0.01 to 0.02 d -1 ). These are characteristics of microorganisms living in oligotrophic environments., Competing Interests: The authors declare there is no conflict., (© 2024 The Authors This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC BY-NC-ND 4.0), which permits copying and redistribution for non-commercial purposes with no derivatives, provided the original work is properly cited (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

HBV-specific CD8+ T cells are only present at the low frequency during chronic infection. Thus, they are often undetectable by conventional ex vivo staining methods using peptide-loaded HLA class I tetramers. Detection sensitivity can be increased by magnetic bead-based enrichment strategies following staining with peptide-loaded HLA class I tetramers. Additionally, some downstream applications like e.g., single cell RNA sequencing of virus-specific CD8+ T cells may also require a pre-enrichment step to increase the frequency of the cells of interest. For this, peptide-loaded HLA class I tetramers-associated magnetic bead-based enrichment is also a suitable method., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Clinical trials in the era of precision medicine require assessment of biomarkers to identify appropriate subgroups of patients for targeted therapy. In a biomarker-stratified design (BSD), biomarkers are measured on all patients and used as stratification variables. However, such a trial can be both inefficient and costly, especially when the prevalence of the subgroup of primary interest is low and the cost of assessing the biomarkers is high. Efficiency can be improved and costs reduced by using enriched biomarker-stratified designs, in which patients of primary interest, typically the biomarker-positive patients, are oversampled. We consider a special type of enrichment design, an auxiliary variable-enriched design (AEBSD), in which enrichment is based on some inexpensive auxiliary variable that is positively correlated with the true biomarker. The proposed AEBSD reduces the total cost of the trial compared with a standard BSD when the prevalence rate of true biomarker positivity is small and the positive predictive value (PPV) of the auxiliary biomarker is larger than the prevalence rate. In addition, for an AEBSD, we can immediately randomize the patients selected in the screening process without waiting for the result of the true biomarker test, reducing the treatment waiting time. We propose an adaptive Bayesian method to adjust the assumed PPV while the trial is ongoing. Numerical studies and an example illustrate the approach. An R package is available. [ABSTRACT FROM AUTHOR]

Sustainable biofuels, biomaterials, and fine chemicals production is a critical matter that research teams around the globe are focusing on nowadays. Polyhydroxyalkanoates represent one of the biomaterials of the future due to their physicochemical properties, biodegradability, and biocompatibility. Designing efficient and economic bioprocesses, combined with the respective social and environmental benefits, has brought together scientists from different backgrounds highlighting the multidisciplinary character of such a venture. In the current review, challenges and opportunities regarding polyhydroxyalkanoate production are presented and discussed, covering key steps of their overall production process by applying pure and mixed culture biotechnology, from raw bioprocess development to downstream processing.

[Display omitted] • A generic imprinted fiber array strategy was proposed. • Adsorption throughput was significantly enhanced by the imprinted fiber array extraction. • Trace multiple neonicotinoids in food samples could be efficiently quantified. • More fiber arrays could be enlightened by this proposed strategy. Herein, a new generic fiber array based on molecular imprinting solid-phase microextraction (MIP-SPME) technology, was described to enrich trace multiple neonicotinoids with high flux from the food matrix. To begin with adsorption experiments coupled with theoretical calculations provided universal means for selecting the preferred template molecule clothianidin (CLT). Results demonstrated that the CLT-MIP fiber array exhibited significantly superior enrichment ability of 1189–2356-folds for six neonicotinoids compared with two kinds of commercial fiber arrays. Furthermore, the practicability of the CLT-MIP fiber array was verified by simultaneously determining multiple neonicotinoids in tea and honey samples. The CLT-MIP fiber array showed a limit of detection (LOD) of 0.03–0.58 μg/L for six neonicotinoids. The method also exhibited satisfactory recoveries ranging from 85.4% to 116.8% with RSD (n = 3) less than 8.8%. The imprinted fiber array has the advantages of high-throughput, predominant reproducibility, and accurate quantitation multi-component, and it may open up a new mean to efficiently enrich high-throughput and simultaneously detect multiple compounds from food samples. [ABSTRACT FROM AUTHOR]

Background: Growing interest in treating Alzheimer's disease (AD) patients in the earliest stages requires new clinical endpoints. Currently, there is no established clinical endpoint or treatment duration for mild cognitive impairment (MCI) trials. Objective: This analysis attempts to answer 'how long the MCI clinical trial would be necessary' using the Clinical Dementia Rating Sum of Boxes (CDR-SB) as a clinical endpoint, where CDR-SB is an example of a suitable tool to assess both cognition and function as a single primary efficacy outcome. Methods: A longitudinal model was developed to predict the CDR-SB time-profile. The CDR-SB is considered ideal to assess both cognition and function as a single primary endpoint in MCI trials. The median time for clinically 'worsening', defined using several thresholds for change from baseline, was calculated using individual CDR-SB predictions. Covariates predictive of worsening were also evaluated. Results: The median time to a 1-point change in CDR-SB was approximately 2 years in MCI patients. Higher baseline severity in disease, lower hippocampal volume, and ApoE4 carrier status were significant covariates predicting shorter times to worsening (faster progress). The results indicate that at least a 2-year trial would be necessary with 30% (or more) disease modifying drug with a sample size of n = 350 to detect the significant difference from placebo (80% power) and to achieve the target mean effect size of 0.5 point change in CDR-SB. Conclusion: Predictions of CDR-SB changes from a longitudinal model are able to inform study design and possible enrichment strategies, based on covariate analyses, for prospective planning of clinical trials in MCI patients. [ABSTRACT FROM AUTHOR]

This paper studies level set topology optimization of structures predicting the structural response by the eXtended Finite Element Method (XFEM). In contrast to Ersatz material approaches, the XFEM represents the geometry in the mechanical model by crisp boundaries. The traditional XFEM approach augments the approximation of the state variable fields with a fixed set of enrichment functions. For complex material layouts with small geometric features, this strategy may result in interpolation errors and non-physical coupling between disconnected material domains. These defects can lead to numerical instabilities in the optimized material layout, similar to checker-board patterns found in density methods. In this paper, a generalized Heaviside enrichment strategy is presented that adapts the set of enrichment functions to the material layout and consistently interpolates the state variable fields, bypassing the limitations of the traditional approach. This XFEM formulation is embedded into a level set topology optimization framework and studied with 'material-void' and 'material-material' design problems, optimizing the compliance via a mathematical programming method. The numerical results suggest that the generalized formulation of the XFEM resolves numerical instabilities, but regularization techniques are still required to control the optimized geometry. It is observed that constraining the perimeter effectively eliminates the emergence of small geometric features. In contrast, smoothing the level set field does not provide a reliable geometry control but mainly improves the convergence rate of the optimization process. [ABSTRACT FROM AUTHOR]

Abstract: Strain isolation using conventional roll tube/plating technique is time consuming and is able to culture in vitro only a small fraction of existing microbes in a natural microflora. This paper proposed a simple and rapid method to select the as-simple-as-possible biological consortium by serially diluting the original mixed culture. The diluted which remains, while the one diluted in serial loses the target function, is defined as the functional consortium of the original mixed culture. Since the microbial structure and the reaction pathway incorporated with the functional consortium is much simpler than its original mother liquor, detailed analysis on the strain interaction is possible without the risk of losing key functional strains as often caused from conventional isolation method. The rumen liquor that can degrade cellulose and produce hydrogen is used as a demonstration example. A “rumen cellulose-degrading bacterial consortium” (RCBC) was identified using the proposed enrichment strategy. [ABSTRACT FROM AUTHOR]

Abstract: We sought to develop an enrichment crossover study design that would allow us to efficiently evaluate and compare promising candidate neuropathic pain drugs. We evaluated the efficacy of gabapentin or tramadol vs. active placebo (diphenhydramine) in subjects with biopsy-proven painful idiopathic small fiber neuropathy (SFN) who were self-reported gabapentin responders. Eligible subjects entered two single blind run-in phases. In the first phase (Period A), subjects were treated with single blinded gabapentin at their prestudy dose followed by a second run-in phase (Period B) in which they were treated with diphenhydramine active placebo. Subjects with ⩾3 pain and a ⩾30% increase in pain intensity in Period B compared to Period A were then randomized to a double-blind three period cross over trial of gabapentin at pre study dosage, tramadol 50mg QID and diphenhydramine 50mgqhs. Of the 59 subjects enrolled, 41 subjects were excluded: Twenty-three had an insufficient rise in pain intensity in Period B; eight had skin biopsies that did not confirm SFN. Eighteen subjects were randomized into the double-blind, crossover phase. There was a significant treatment effect of gabapentin vs. diphenhydramine (p =0.001) and tramadol vs. diphenhydramine (p =0.018) by the before-bed daily pain score averaged over the final 7 days of each treatment period. We conclude that gabapentin and tramadol were effective in the treatment of painful SFN and that this experimental enrichment paradigm is attractive to screen potential neuropathic pain compounds for efficacy in proof-of-concept studies. [Copyright &y& Elsevier]

What is already known about this subject • In major depressive disorder an appreciable percentage (40%) of patients in antidepressant trials will have a placebo response. • In these trials, early changes (i.e. within the first 4 weeks) of the clinical score scale (e.g. HAMD-17) are associated with response at end-point. • Unpredictable placebo response is one of the major reasons for clinical trial failure in the evaluation of antidepressant drugs. What this study adds • Provides a model to describe the time course of individual and population placebo response. • Provides a methodology to forecast the individual probability to be placebo responder based on early HAMD-17 measurements with an assessment of the prognostic power. • Provides a methodological framework to implement a population enrichment strategy in the design of clinical trials for the assessment of novel antidepressant drugs. Aims To develop a probabilistic and longitudinal model describing the time course of Hamilton's Rating Scale for Depression (HAMD-17) total score in patients with major depressive disorders treated with placebo and to develop predictive models to estimate the response at end-point given HAMD-17 measurements at weeks 2 and 4. Methods Patients ( n = 691) from seven clinical trials were analysed in WinBUGS using a Bayesian approach. The whole dataset was randomly split in a learning (359 patients for model definition) and a test dataset (332 patients for assessment of model predictive performance). The analysis of the learning dataset assumed uninformative priors, whereas the analysis of the test dataset used the posterior parameter estimates of the learning dataset as priors. ROC curve analysis estimated the optimal sensitivity/specificity cut-off between false-negative and false-positive rates and determined the prognostic allocation rule for patients to responder and nonresponder groups. Results A Weibull/linear model accurately described the population and individual HAMD-17 time course. The total area under the ROC curve, ranging from 0.76 (logistic model with data at week 2) to 0.86 (longitudinal model with data at week 4), provided a measure of the prognostic discriminatory power of early HAMD-17 measures using the two models. The best placebo-responder classification score (86.32% true and 13.68% false positive) was associated with the longitudinal model with HAMD-17 measures at week 4. Conclusion Results showed the relevance of the Bayesian approach to predict HAMD-17 score at study end and to classify a patient as a placebo responder given the uncertainty in parameters derived from historical data and early HAMD-17 measurements. [ABSTRACT FROM AUTHOR]

Purpose: Success of clinical trials increasingly relies on effective selection of the target patient populations. We hypothesize that computational analysis of pre-accrual imaging data can be used for patient enrichment to better identify patients who can potentially benefit from investigational agents. Methods: This was tested retrospectively in soft-tissue sarcoma (STS) patients accrued into a randomized clinical trial (SARC021) that evaluated the efficacy of evofosfamide (Evo), a hypoxia activated prodrug, in combination with doxorubicin (Dox). Notably, SARC021 failed to meet its overall survival (OS) objective. We tested whether a radiomic biomarker-driven inclusion/exclusion criterion could have been used to improve the difference between the two arms (Evo + Dox vs. Dox) of the study. 164 radiomics features were extracted from 296 SARC021 patients with lung metastases, divided into training and test sets. Results: A single radiomics feature, Short Run Emphasis (SRE), was representative of a group of correlated features that were the most informative. The SRE feature value was combined into a model along with histological classification and smoking history. This model as able to identify an enriched subset (52%) of patients who had a significantly longer OS in Evo + Dox vs. Dox groups [ p = 0.036, Hazard Ratio (HR) = 0.64 (0.42-0.97)]. Applying the same model and threshold value in an independent test set confirmed the significant survival difference [ p = 0.016, HR = 0.42 (0.20-0.85)]. Notably, this model was best at identifying exclusion criteria for patients most likely to benefit from doxorubicin alone. Conclusions: The study presents a first of its kind clinical-radiomic approach for patient enrichment in clinical trials. We show that, had an appropriate model been used for selective patient inclusion, SARC021 trial could have met its primary survival objective for patients with metastatic STS.

• Reverse crude glycerol gradient strategy made glycerol mainly flow to PHA production. • Reverse crude glycerol gradient strategy improved q PHA to 0.65 g COD/gX−1·h−1. • Maximum PHA content of culture enriched from reverse strategy was more stable. • Candidatus Saccharibacteria was first found to be dominant PHA-producers. • Reverse strategy and mixed substrate of glycerol and VFAs promote PHA content. Crude glycerol is by-product produced from biodiesel industry and can be converted directly by mixed microbial culture (MMC) into polyhydroxyalkanoates (PHAs). This study investigated the effects of the reverse (SBR_A) and positive (SBR_B) glycerol gradient substrate strategy on PHA-accumulating culture enrichment and the maximum PHA accumulating stability under substrates with different glycerol and volatile fatty acid (VFA) proportion. The results showed that crude glycerol was mainly used for PHA production rather than biomass growth in SBR_A. The maximum q PHA was 0.65 g COD/g X−1·h−1 under sole crude glycerol condition in SBR_A, which was 2.41 times higher than that of SBR_B. Moreover, the PHA accumulating ability of the biomass from SBR_A was more stable than SBR_B. Saccharibacteria_genera_incertae_sedis was for the first time found to be the dominant genus using crude glycerol for PHA production. This research provides an insight into enrichment strategy to effectively enrich PHA-accumulating culture from crude glycerol. [ABSTRACT FROM AUTHOR]

Recalcitrant relationships are characterized by very short internodes that can be found among shallow and deep phylogenetic scales all over the tree of life. Adding large amounts of presumably informative sequences, while decreasing systematic error, has been suggested as a possible approach to increase phylogenetic resolution. The development of enrichment strategies, coupled with next generation sequencing, resulted in a cost-effective way to facilitate the reconstruction of recalcitrant relationships. By applying the anchored hybrid enrichment (AHE) genome partitioning strategy to Aristolochia using an universal angiosperm probe set, we obtained 231-233 out of 517 single or low copy nuclear loci originally contained in the enrichment kit, resulting in a total alignment length of 154,756bp to 160,150bp. Since Aristolochia (Piperales; magnoliids) is distantly related to any angiosperm species whose genome has been used for the plant AHE probe design (Amborella trichopoda being the closest), it serves as a proof of universality for this probe set. Aristolochia comprises approximately 500 species grouped in several clades (OTUs), whose relationships to each other are partially unknown. Previous phylogenetic studies have shown that these lineages branched deep in time and in quick succession, seen as short-deep internodes. Short-shallow internodes are also characteristic of some Aristolochia lineages such as Aristolochia subsection Pentandrae, a clade of presumably recent diversification. This subsection is here included to test the performance of AHE at species level. Filtering and subsampling loci using the phylogenetic informativeness method resolves several recalcitrant phylogenetic relationships within Aristolochia. By assuming different ploidy levels during bioinformatics processing of raw data, first hints are obtained that polyploidization contributed to the evolution of Aristolochia. Phylogenetic results are discussed in the light of current systematics and morphology., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Sustainable biofuels, biomaterials, and fine chemicals production is a critical matter that research teams around the globe are focusing on nowadays. Polyhydroxyalkanoates represent one of the biomaterials of the future due to their physicochemical properties, biodegradability, and biocompatibility. Designing efficient and economic bioprocesses, combined with the respective social and environmental benefits, has brought together scientists from different backgrounds highlighting the multidisciplinary character of such a venture. In the current review, challenges and opportunities regarding polyhydroxyalkanoate production are presented and discussed, covering key steps of their overall production process by applying pure and mixed culture biotechnology, from raw bioprocess development to downstream processing., Competing Interests: The authors declare no conflict of interest.