Miracle-dz/UniFAR-FTUs huggingface dataset:
Coupling an Electroactive Pseudomonas putida KT2440 with Bioelectrochemical Rhamnolipid Production

Sufficient supply of oxygen is a major bottleneck in industrial biotechnological synthesis. One example is the heterologous production of rhamnolipids using Pseudomonas putida KT2440. Typically, the synthesis is accompanied by strong foam formation in the reactor vessel hampering the process. It is caused by the extensive bubbling needed to sustain the high respirative oxygen demand in the presence of the produced surfactants. One way to reduce the oxygen requirement is to enable the cells to use the anode of a bioelectrochemical system (BES) as an alternative sink for their metabolically derived electrons. We here used a P. putida KT2440 strain that interacts with the anode using mediated extracellular electron transfer via intrinsically produced phenazines, to perform heterologous rhamnolipid production under oxygen limitation. The strain P. putida RL-PCA successfully produced 30.4 ± 4.7 mg/L mono-rhamnolipids together with 11.2 ± 0.8 mg/L of phenazine-1-carboxylic acid (PCA) in 500-mL benchtop BES reactors and 30.5 ± 0.5 mg/L rhamnolipids accompanied by 25.7 ± 8.0 mg/L PCA in electrode containing standard 1-L bioreactors. Hence, this study marks a first proof of concept to produce glycolipid surfactants in oxygen-limited BES with an industrially relevant strain.
Temperature‐mediated plasticity in incubation schedules is unlikely to evolve to buffer embryos from climatic challenges in a seasonal songbird

Phenotypic plasticity is hypothesized to facilitate adaptive responses to challenging conditions, such as those resulting from climate change. However, tests of the key predictions of this ‘rescue hypothesis’, that variation in plasticity exists and can evolve to buffer unfavourable conditions, remain rare. Here, we investigate among‐female variation in temperature‐mediated plasticity of incubation schedules and consequences for egg temperatures using the chestnut‐crowned babbler (Pomatostomus ruficeps) from temperate regions of inland south‐eastern Australia. Given recent phenological advances in this seasonal breeder and thermal requirements of developing embryos (>~25°C, optimally ~38°C), support for evolutionary rescue—perhaps paradoxically—requires that plasticity serves to buffer embryos more from sub‐optimally low temperatures. We found significant variation in the duration of incubation bouts (mean ± SD = 27 ± 22 min) and foraging bouts (mean ± SD = 17 ± 11 min) in this maternal‐only incubator. However, variation in each arose because of variation in the extent to which mothers increased on‐ and off‐bout durations when temperatures (0–36°C) were more favourable rather than unfavourable as required under rescue. In addition, there was a strong positive intercept‐slope correlation in on‐bout durations, indicating that those with stronger plastic responses incubated more at average temperatures (~19°C). Combined, these effects reduced the functional significance of plastic responses: an individual's plasticity was neither associated with daily contributions to incubation (i.e. attentiveness) nor average egg temperatures. Our results highlight that despite significant among‐individual variation in environmental‐sensitivity, plasticity in parental care traits need not evolve to facilitate buffering against unfavourable conditions.
Identification of an immune-related six-long noncoding RNA signature as a novel prognosis biomarker for adenocarcinoma of lung

Abstract Background: Lung adenocarcinoma (LUAD) is a heterogeneous disease with high mortality. Close attention has been paid to immunotherapy in LUAD treatment. However, immunotherapy has produced different therapeutic effects because of immune heterogeneity. Long noncoding RNAs (lncRNAs) are survival prognostic indicators with functions in the immune process. The present study was designed to examine the predictive power of immune-related lncRNAs in LUAD prognosis and investigated potential molecular mechanisms. Methods: Transcriptome profiling and LUAD sample clinical information were retrieved from online database. The immune-related lncRNAs signature was identified by Cox regression. Survival analysis was used to verify the validity of the prognosis model. Then, possible biological functions were predicted and the abundance of infiltrating immune cells in LUAD samples were further analyzed. Results: An immune-associated lncRNAs signature was established by combining six lncRNAs. Patients with LUAD were stratified into high- and low-risk groups using the six lncRNAs signature. Patients in different risk levels had significantly different prognoses (P<0.001), and the immune-associated lncRNAs signature was identified as an independent prognostic factor for LUAD. The functions of the lncRNA signature were confirmed as ubiquitin mediated proteolysis and signal sequence binding. The lncRNA signature negatively correlates with B-cell immune infiltration. Conclusion: A reliable immune-related lncRNAs prognosis model for LUAD was identified. lncRNAs played a vital role in the tumor immune process and were associated with the LUAD prognosis. Research of lncRNAs in B-cell immune infiltration could provide new insight into the immunotherapy of LUAD.
Review and Mechanism of the Thickness Effect of Solid Dielectrics

The thickness effect of solid dielectrics means the relation between the electric breakdown strength (EBD) and the dielectric thickness (d). By reviewing different types of expressions of EBD on d, it is found that the minus power relation (EBD = E1d −a) is supported by plenty of experimental results. The physical mechanism responsible for the minus power relation of the thickness effect is reviewed and improved. In addition, it is found that the physical meaning of the power exponent a is approximately the relative standard error of the EBD distributions in perspective of the Weibull distribution. In the end, the factors influencing the power exponent a are discussed.
Dysregulated Interferon Response Underlying Severe COVID-19

Innate immune interferons (IFNs), including type I and III IFNs, constitute critical antiviral mechanisms. Recent studies reveal that IFN dysregulation is key to determine COVID-19 pathogenesis. Effective IFN stimulation or prophylactic administration of IFNs at the early stage prior to severe COVID-19 may elicit an autonomous antiviral state, restrict the virus infection, and prevent COVID-19 progression. Inborn genetic flaws and autoreactive antibodies that block IFN response have been significantly associated with about 14% of patients with life-threatening COVID-19 pneumonia. In most severe COVID-19 patients without genetic errors in IFN-relevant gene loci, IFN dysregulation is progressively worsened and associated with the situation of pro-inflammation and immunopathy, which is prone to autoimmunity. In addition, the high correlation of severe COVID-19 with seniority, males, and individuals with pre-existing comorbidities will be plausibly explained by the coincidence of IFN aberrance in these situations. Collectively, current studies call for a better understanding of the IFN response regarding the spatiotemporal determination and subtype-specificity against SARS-CoV-2 infections, which are warranted to devise IFN-related prophylactics and therapies.
Trends and Characteristics of Emergency Medical Services in Italy: A 5-Years Population-Based Registry Analysis

Background: Emergency Medical Services (EMS) plays a fundamental role in providing good quality healthcare services to citizens, as they are the first responders in distressing situations. Few studies have used available EMS data to investigate EMS call characteristics and subsequent responses. Methods: Data were extracted from the emergency registry for the period 2013–2017. This included call and rescue vehicle dispatch information. All relationships in analyses and differences in events proportion between 2013 and 2017 were tested against the Pearson’s Chi-Square with a 99% level of confidence. Results: Among the 2,120,838 emergency calls, operators dispatched at least one rescue vehicle for 1,494,855. There was an estimated overall incidence of 96 emergency calls and 75 rescue vehicles dispatched per 1000 inhabitants per year. Most calls were made by private citizens, during the daytime, and were made from home (63.8%); 31% of rescue vehicle dispatches were advanced emergency medical vehicles. The highest number of rescue vehicle dispatches ended at the emergency department (74.7%). Conclusions: Our data showed that, with some exception due to environmental differences, the highest proportion of incoming emergency calls is not acute or urgent and could be more effectively managed in other settings than in an Emergency Departments (ED). Better management of dispatch can reduce crowding and save hospital emergency departments time, personnel, and health system costs.
A Comprehensive Evaluation of Risk Factors for Pneumocystis jirovecii Pneumonia in Adult Solid Organ Transplant Recipients: A Systematic Review and Meta-analysis

Supplemental Digital Content is available in the text. Background. There is no consensus guidance on when to reinitiate Pneumocystis jirovecii pneumonia (PJP) prophylaxis in solid organ transplant (SOT) recipients at increased risk. The 2019 American Society of Transplantation Infectious Diseases Community of Practice (AST IDCOP) guidelines suggested to continue or reinstitute PJP prophylaxis in those receiving intensified immunosuppression for graft rejection, cytomegalovirus (CMV) infection, higher dose of corticosteroids, or prolonged neutropenia. Methods. A literature search was conducted evaluating all literature from existence through April 22, 2020, using MEDLINE and EMBASE. (The International Prospective Register of Systematic Reviews registration number: CRD42019134204). Results. A total of 30 studies with 413 276 SOT recipients were included. The following factors were associated with PJP development: acute rejection (pooled odds ratio [pOR], 2.35; 95% confidence interval [CI], 1.69-3.26); study heterogeneity index [I2] = 23.4%), CMV-related illnesses (pOR, 3.14; 95% CI, 2.30-4.29; I2 = 48%), absolute lymphocyte count <500 cells/mm3 (pOR, 6.29; 95% CI, 3.56-11.13; I2 = 0%), BK polyomavirus-related diseases (pOR, 2.59; 95% CI, 1.22-5.49; I2 = 0%), HLA mismatch ≥3 (pOR, 1.83; 95% CI, 1.06-3.17; I2 = 0%), rituximab use (pOR, 3.03; 95% CI, 1.82-5.04; I2 = 0%), and polyclonal antibodies use for rejection (pOR, 3.92; 95% CI, 1.87-8.19; I2 = 0%). On the other hand, sex, CMV mismatch, interleukin-2 inhibitors, corticosteroids for rejection, and plasmapheresis were not associated with developing PJP. Conclusions. PJP prophylaxis should be considered in SOT recipients with lymphopenia, BK polyomavirus-related infections, and rituximab exposure in addition to the previously mentioned risk factors in the American Society of Transplantation Infectious Diseases Community of Practice guidelines.
On the possibility of exsolution of apatite from feldspars in granite “à dents de cheval” from Santa Teresa, Rocha, Uruguay

I n the granite " a dents de cheval" from Santa Teresa, Uruguay, two oligoclase generations are found. One of them is poikilitic and occurs in the porphyroblastic microcline. I t has an albite rim. The Ρ content of this oligoclase has a definite relation with the An content, increasing with decreasing An content, down to about the upper limit of the peristerite gap. For lower An contents Ρ unmixes as apat i te and the plagioclase contains practically no P. I t is concluded t h a t Ρ subst i tutes for Si in the ΑΙ-Si framework of these plagioclases.
Dynamic evolution of the major transcription factor DNA binding domain, and protein-protein interaction families during the evolution of the avian lineage

Transcription factors are characterized by their domain architecture, including DNA binding and protein-protein interaction domain combinations, which regulate their binding specificity, as well as their ability to effect a change on gene expression of their downstream targets. Transcription factors are central to organismal development, thus they potentially are instrumental in producing phenotypic diversity. Transcription factor abundance was estimated via 49 major DNA binding domain families, as well as 34 protein-protein interaction domain families, in 48 bird genomes, which were then compared with 6 available reptile genomes, in an effort to assess the degree to which these domains are potentially connected to increased phenotypic diversity in the avian lineage. We hypothesized that there would be increased abundance in multiple transcription factor domain families, as well as domains associated with protein-protein interactions, that would correlate with the increased phenotypic diversity found in birds; instead, this data shows a general loss/contraction of major domain families, with the largest losses in domain families associated with multiple developmental (feather, body-plan, immune) and metabolic processes. Ultimately, the results of this analyses represent a general characterization of domain family composition in birds, thus the specific domain composition of TF families should be probed further, especially those with the largest reductions seen in this study.
Kinetic gait analysis in healthy dogs and dogs with osteoarthritis: An evaluation of precision and overlap performance of a pressure-sensitive walkway and the use of symmetry indices

In veterinary practice, a thorough gait examination is essential in the clinical workup of any orthopedic patient, including the large population of dogs with chronic pain as a result of osteoarthritis. The traditional visual gait examination is, however, a subjective discipline, and systems for kinetic gait analysis may potentially offer an objective alternative for gait assessment by the measurement of ground reaction forces. In order to avoid unnecessary testing of patients, a thorough, stepwise evaluation of the diagnostic performance of each system is recommended before clinical use for diagnostic purposes. The aim of the study was to evaluate the Tekscan pressure-sensitive walkway system by assessing precision (agreement between repetitive measurements in individual dogs) and overlap performance (the ability to distinguish dogs with lameness due to osteoarthritis from clinically healthy dogs). Direction of travel over the walkway was investigated as a possible bias. Symmetry indices are commonly used to assess lameness by comparing ground reaction forces across different combinations of limbs in each dog. However, SIs can be calculated in several different ways and specific recommendations for optimal use of individual indices are currently lacking. Therefore the present study also compared indices in order to recommend a specific index preferable for future studies of canine osteoarthritis. Forty-one clinically healthy dogs and 21 dogs with osteoarthritis were included in the study. High precision was demonstrated. The direction of travel over the walkway was excluded as a possible bias. A significant overlap was observed when comparing ground reaction forces measured in dogs with osteoarthritis compared to clinically healthy dogs. In some affected dogs, symmetry indices comparing contralateral limbs differed from clinically healthy dogs, but in general, the overlap performance was insufficient and, consequently, general use of this method for diagnostic purposes in dogs with osteoarthritis cannot be recommended.
Towards Deep Neural Network Models for the Prediction of the Blood–Brain Barrier Permeability for Diverse Organic Compounds

Permeation through the blood–brain barrier (BBB) is among the most important processes controlling the pharmacokinetic properties of drugs and other bioactive compounds. Using the fragmental (substructural) descriptors representing the occurrence number of various substructures, as well as the artificial neural network approach and the double cross-validation procedure, we have developed a predictive in silico LogBB model based on an extensive and verified dataset (529 compounds), which is applicable to diverse drugs and drug-like compounds. The model has good predictivity parameters (Q2=0.815, RMSEcv=0.318) that are similar to or better than those of the most reliable models available in the literature. Larger datasets, and perhaps more sophisticated network architectures, are required to realize the full potential of deep neural networks. The analysis of fragment contributions reveals patterns of influence consistent with the known concepts of structural characteristics that affect the BBB permeability of organic compounds. The external validation of the model confirms good agreement between the predicted and experimental LogBB values for most of the compounds. The model enables the evaluation and optimization of the BBB permeability of potential neuroactive agents and other drug compounds.
The γH2AX Peak in the S Phase After UV Irradiation Corresponds to the sites of DNA Replication and not DNA Damage

Ultraviolet (UV) radiation is a major environmental mutagen. Exposure to UV leads to a sharp peak of γH2AX—the phosphorylated form of a histone variant H2AX—in the S phase cells within a population. γH2AX has been considered as a definitive marker of DNA damage inside a cell. In this report we show that the γH2AX peak in the S phase after UV irradiation does not report on the extent of DNA damage. Instead it corresponds to the accumulation of γH2AX at the sites of active replication at the time of UV irradiation. We further show that these colocalization sites do not correspond to stalled replication forks—DNA synthesis is still carried on there, albeit at slower speeds. In fact, most of the S phase cells at the time of UV irradiation complete the replication of their DNA and later arrest in the G2 phase of the cell cycle. The study poses new questions as to the roles of γH2AX in the maintenance of genome stability at the replication forks by challenging the conventional idea of γH2AX as simply a mediator and hence a marker of DNA damage and subsequent repair.
Accuracy of bone segmentation and surface generation strategies analyzed by using synthetic CT volumes

Different kinds of bone measurements are commonly derived from computed‐tomography (CT) volumes to answer a multitude of questions in biology and related fields. The underlying steps of bone segmentation and, optionally, polygon surface generation are crucial to keep the measurement error small. In this study, the performance of different, easily accessible segmentation techniques (global thresholding, automatic local thresholding, weighted random walk, neural network, and watershed) and surface generation approaches (different algorithms combined with varying degrees of simplification) was analyzed and recommendations for minimizing inaccuracies were derived. The different approaches were applied to synthetic CT volumes for which the correct segmentation and surface geometry were known. The most accurate segmentations of the synthetic volumes were achieved by setting a case‐specific window to the gray value histogram and subsequently applying automatic local thresholding with appropriately chosen thresholding method and radius. Surfaces generated by the Amira® module Generate Lego Surface in combination with careful surface simplification were the most accurate. Surfaces with sub‐voxel accuracy were obtained even for synthetic CT volumes with low contrast‐to‐noise ratios. Segmentation trials with real CT volumes supported the findings. Very accurate segmentations and surfaces can be derived from CT volumes by using readily accessible software packages. The presented results and derived recommendations will help to reduce the measurement error in future studies. Furthermore, the demonstrated strategies for assessing segmentation and surface qualities can be adopted to quantify the performance of new segmentation approaches in future studies.
Treatment-Resistant Depression in a Real-World Setting: First Interim Analysis of Characteristics, Healthcare Resource Use, and Utility Values of the FondaMental Cohort

Background: Major depressive disorder (MDD) is among the most common psychiatric disorders. One-third of patients are usually unresponsive to several lines of treatment. This study aimed to describe the FondaMental French cohort of patients with treatment-resistant depression (TRD) and to estimate utility and healthcare resource use outcomes. Methods: Patients with TRD were evaluated prospectively over four years (baseline, 6, 12, 18, 24, 36 and 48 months) in a real-world clinical setting. Interim analyses focused on the first two consecutive years. Four MDD-related states (major depressive episode (MDE), response, remission, recovery) were defined based on the MADRS (Montgomery–Åsberg depression rating scale) and other clinical events. Health status was assessed with the EuroQol 5 Dimensions 5 Level (EQ-5D-5L) questionnaire. Utility values were estimated as preference measures that the patients assigned to their overall health status. Results: This study was based on 252 patients with TRD. The mean utility value by health state was 0.41, 0.63, 0.80, and 0.90, for MDE, response, remission, and recovery, respectively. At baseline, 59% of patients had an MADRS score of at least 28. Their baseline average utility value was lower compared to the other patients (0.43 versus 0.58, p < 0.001). This significant difference persisted at the following visits. The rate of patients in MDEs having at least one hospitalisation for depression or other reasons than depression was generally higher than that in the other health states. Conclusion: This study documented patterns in healthcare resource consumption, quality of life, and other characteristics in patients with TRD, both globally and by health state and depression severity.
Fungal Dysbiosis Correlates with the Development of Tumor-Induced Cachexia in Mice

Cachexia (CC) is a devastating metabolic syndrome associated with a series of underlying diseases that greatly affects life quality and expectancy among cancer patients. Studies involving mouse models, in which CC was induced through inoculation with tumor cells, originally suggested the existence of a direct correlation between the development of this syndrome and changes in the relative proportions of several bacterial groups present in the digestive tract. However, these analyses have focus solely on the characterization of bacterial dysbiosis, ignoring the possible existence of changes in the relative populations of fungi, during the development of CC. Thus, the present study sought to expand such analyses, by characterizing changes that occur in the gut fungal population (mycobiota) of mice, during the development of cancer-induced cachexia. Our results confirm that cachectic animals, submitted to Lewis lung carcinoma (LLC) transplantation, display significant differences in their gut mycobiota, when compared to healthy controls. Moreover, identification of dysbiotic fungi showed remarkable consistency across successive levels of taxonomic hierarchy. Many of these fungi have also been associated with dysbioses observed in a series of gut inflammatory diseases, such as obesity, colorectal cancer (CRC), myalgic encephalomyelitis (ME) and inflammatory bowel disease (IBD). Nonetheless, the dysbiosis verified in the LLC model of cancer cachexia seems to be unique, presenting features observed in both obesity (reduced proportion of Mucoromycota) and CRC/ME/IBD (increased proportions of Sordariomycetes, Saccharomycetaceae and Malassezia). One species of Mucoromycota (Rhyzopus oryzae) stands out as a promising probiotic candidate in adjuvant therapies, aimed at treating and/or preventing the development of CC.