Miracle-dz/UniFAR-FTUs huggingface dataset:
The Pepper RING-Type E3 Ligase CaAIRF1 Regulates ABA and Drought Signaling via CaADIP1 Protein Phosphatase Degradation1

RING-type E3 ligase controls clade A protein phosphatase 2C, a core ABA component indirectly or directly at the transcriptional and posttranslational levels in ABA and drought signaling. Ubiquitin-mediated protein modification occurs at multiple steps of abscisic acid (ABA) signaling. Here, we sought proteins responsible for degradation of the pepper (Capsicum annuum) type 2C protein phosphatase CaADIP1 via the 26S proteasome system. We showed that the RING-type E3 ligase CaAIRF1 (Capsicum annuum ADIP1 Interacting RING Finger Protein 1) interacts with and ubiquitinates CaADIP1. CaADIP1 degradation was slower in crude proteins from CaAIRF1-silenced peppers than in those from control plants. CaAIRF1-silenced pepper plants displayed reduced ABA sensitivity and decreased drought tolerance characterized by delayed stomatal closure and suppressed induction of ABA- and drought-responsive marker genes. In contrast, CaAIRF1-overexpressing Arabidopsis (Arabidopsis thaliana) plants exhibited ABA-hypersensitive and drought-tolerant phenotypes. Moreover, in these plants, CaADIP1-induced ABA hyposensitivity was strongly suppressed by CaAIRF1 overexpression. Our findings highlight a potential new route for fine-tune regulation of ABA signaling in pepper via CaAIRF1 and CaADIP1.
Cancer Survivorship Care: Person Centered Care in a Multidisciplinary Shared Care Model

Survivors of childhood and adult-onset cancer are at lifelong risk for the development of late effects of treatment that can lead to serious morbidity and premature mortality. Regular long-term follow-up aiming for prevention, early detection and intervention of late effects can preserve or improve health. The heterogeneous and often serious character of late effects emphasizes the need for specialized cancer survivorship care clinics. Multidisciplinary cancer survivorship care requires a coordinated and well integrated health care environment for risk based screening and intervention. In addition survivors engagement and adherence to the recommendations are also important elements. We developed an innovative model for integrated care for cancer survivors, the “Personalized Cancer Survivorship Care Model”, that is being used in our clinic. This model comprises 1. Personalized follow-up care according to the principles of Person Centered Care, aiming to empower survivors and to support self management, and 2. Organization according to a multidisciplinary and risk based approach. The concept of person centered care is based on three components: initiating, integrating and safeguarding the partnership with the patient. This model has been developed as a universal model of care that will work for all cancer survivors in different health care systems. It could be used for studies to improve self efficacy and the cost-effectiveness of cancer survivorship care.
Sentinel-1A SAR data for global urban mapping: Preliminary results

In this paper, Sentinel-1A SAR data were evaluated for urban extent extraction using the KTH-Pavia Urban Extractor. The methodology is based on texture measures and spatial statistics as well as decision level fusion. Sentinel-1A data in Stripmap mode (SM) or Interferometric Wide Swath mode (IW) were acquired in five cities around the world. For two European cities Milan, Italy and Stockholm, Sweden, accuracy assessments were performed by comparing the extracted urban areas with the Urban Atlas in 2010. The preliminary results show that the Sentinel-1A Stripmap mode is very suitable for urban extraction, reaching an agreement of more than 83%. The Interferometric Wideswath mode shows potential as well reaching an agreement of 77%, but urban extraction over Stockholm had high omission errors in low density built up areas.
Assessing the Value of the Zebrafish Conditioned Place Preference Model for Predicting Human Abuse Potential

Regulatory agencies recommend that centrally active drugs are tested for abuse potential before approval. Standard preclinical assessments are conducted in rats or non-human primates (NHPs). This study evaluated the ability of the zebrafish conditioned place preference (CPP) model to predict human abuse outcomes. Twenty-seven compounds from a variety of pharmacological classes were tested in zebrafish CPP, categorized as positive or negative, and analyzed using standard diagnostic tests of binary classification to determine the likelihood that zebrafish correctly predict robust positive signals in human subjective effects studies (+HSE) and/or Drug Enforcement Administration drug scheduling. Results were then compared with those generated for rat self-administration and CPP, as well as NHP self-administration, using this same set of compounds. The findings reveal that zebrafish concordance and sensitivity values were not significantly different from chance for both +HSE and scheduling. Although significant improvements in specificity and negative predictive values were observed for zebrafish relative to +HSE, specificity without sensitivity provides limited predictive value. Moreover, assessments in zebrafish provided no added value for predicting scheduling. By contrast, rat and NHP models generally possessed significantly improved concordance, sensitivity, and positive predictive values for both clinical measures. Although there may be predictive value with compounds from specific pharmacological classes (e.g., µ-opioid receptor agonists, psychostimulants) for zebrafish CPP, altogether these data highlight that using the current methodology, the zebrafish CPP model does not add value to the preclinical assessment of abuse potential.
Mortality Trends among Cocaine Users Treated between 1989 and 2013 in Northern Italy: Results of a Longitudinal Study

ABSTRACT A total of 852 participants attending 11 centers for addiction treatment in north Italy following problems due to cocaine abuse between 1989 and 2013 were recruited. Two typologies were created: cocaine users (never heroin) (CU) and heroin and cocaine users (HCU). During the 38-year follow-up period, 4.8% of the whole cohort died. Over the whole period, tumors were the main causes of death; starting in 2010, suicide deaths became the first cause of death. Among CUs, most deaths were due to road accidents and suicide; among HCUs, most of the deaths were from opiate overdose and from cardio-circulatory system diseases. The excess mortality observed for all causes in either sex was 6.24; higher in females (15.03) as compared in males (6.23), higher in HCUs (9.06) as compared in CUs (5.21). The directly age-sex standardized mortality rates were 5.31 per 100, higher for females, declining after 2009 for all patients and after 2004 for HCUs. Multivariate analysis confirms the decreasing trend in the risk of death and shows a higher mortality risk for participants in the under-25 age group. Among cocaine users, special attention should be paid to the prevention of suicide deaths.
Chlorogenic Acid Ameliorates Experimental Colitis by Promoting Growth of Akkermansia in Mice

Chlorogenic acid (ChA)—one of the most abundant polyphenol compounds in the human diet—exerts anti-inflammatory activities. The aim of this study was to investigate the effect of ChA on gut microbiota in ulcerative colitis (UC). Colitis was induced by 2.5% dextran sulfate sodium (DSS) in C57BL/6 mice, which were on a control diet or diet with ChA (1 mM). The histopathological changes and inflammation were evaluated. Fecal samples were analyzed by 16S rRNA gene sequencing. ChA attenuated several effects of DSS-induced colitis, including weight loss, increased disease activity index, and improved mucosal damage. Moreover, ChA could significantly suppress the secretion of IFNγ, TNFα, and IL-6 and the colonic infiltration of F4/80+ macrophages, CD3+ T cells, and CD177+ neutrophils via inhibition of the active NF-κB signaling pathway. In addition, ChA decreased the proportion of Firmicutes and Bacteroidetes. ChA also enhanced a reduction in fecal microbiota diversity in DSS treated mice. Interestingly, ChA treatment markedly increased the proportion of the mucin-degrading bacterium Akkermansia in colitis mice. ChA acted as the intestine-modifying gut microbial community structure, resulting in a lower intestinal and systemic inflammation and also improving the course of the DSS-induced colitis, which is associated with a proportional increase in Akkermansia.
Statistical Package for Growth Rates Made Easy

Growth rates are an important tool in microbiology because they provide high throughput fitness measurements. The release of GrowthRates, a program that uses the output of plate reader files to automatically calculate growth rates, has facilitated experimental procedures in many areas. However, many sources of variation within replicate growth rate data exist and can decrease data reliability. We have developed a new statistical package, CompareGrowthRates (CGR), to enhance the program GrowthRates and accurately measure variation in growth rate data sets. We define a metric, Variability-score (V-score), that can help determine if variation within a data set might result in false interpretations. CGR also uses the bootstrap method to determine the fraction of bootstrap replicates in which a strain will grow the fastest. We illustrate the usage of CGR with growth rate data sets similar to those in Mira, Meza, et al. (Adaptive landscapes of resistance genes change as antibiotic concentrations change. Mol Biol Evol. 32(10): 2707-2715). These statistical methods are compatible with the analytic methods described in Growth Rates Made Easy and can be used with any set of growth rate output from GrowthRates.
Martensitic transformation induced by cold deformation of lean duplex stainless steel UNS S32304

Lean duplex UNS S32304 is an austenitic ferritic stainless steel with pitting resistance equivalent number around 24-25. Its corrosion resistance is similar to AISI 316L steel, but with the advantage of a yield limit two times superior to conventional austenitic grades. Deformation induced martensitic transformations (γ→e and γ→ α') have been extensively studied in austenitic steels, but few works were published about these reactions in austenitic ferritic grades. In the present work, deformation induced martensitic transformation in lean duplex UNS S32304 was investigated by means of magnetic measurements and X-ray diffraction. The curves of α' martensite volume fraction against true deformation by cold rolling were constructed and compared to duplex and austenitic grades. It was found that lean duplex UNS S32304 is much more susceptible to martensitic transformation than duplex UNS S31803, which can be explained by its lower Mo and Ni contents.
Risk Assessment Integrated QbD Approach for Development of Optimized Bicontinuous Mucoadhesive Limicubes for Oral Delivery of Rosuvastatin

Statins are widely prescribed for hyperlipidemia, cancer, and Alzheimer’s disease but are facing some inherent challenges such as low solubility and drug loading, higher hepatic metabolism, as well as instability at gastric pH. So, relatively higher circulating dose, required for exerting the therapeutic benefits, leads to dose-mediated severe toxicity. Furthermore, due to low biocompatibility, high toxicity, and other regulatory caveats such as product conformity, reproducibility, and stability of conventional formulations as well as preferentially higher bioabsorption of lipids in their favorable cuboidal geometry, enhancement in in vivo biopharmaceutical performance of Rosuvastatin could be well manifested in Quality by Design (QbD) integrated cuboidal-shaped mucoadhesive microcrystalline delivery systems (Limicubes). Here, quality-target-product-profile (QTPPs), critical quality attributes (CQAs), Ishikawa fishbone diagram, and integration of risk management through risk assessment matrix for failure mode and effects analysis (FMEA) followed by processing of Plackett-Burman design matrix using different statistical test for the first time established an approach to substantiate the claims that controlling levels of only these three screened out independent process variables, i.e., Monoolein (B = 800–1100 μL), Poloxamer (C = 150–200 mg), and stirring speed (F = 700–1000 rpm) were statistically significant to modulate and improve the biopharmaceutical performance affecting key attributes, viz., average particle size (Y1 = 1.40–2.70 μ), entrapment efficiency (Y2 = 62.60–88.80%), and drug loading (Y3 = 0.817–1.15%), in QbD-enabled process. The optimal performance of developed Limicubes exhibited an average particle size of 1.8 ± 0.2 μ, entrapment efficiency 80.32 ± 2.88%, and drug loading 0.93 ± 0.08% at the level of 1100 μL (+ 1), 200 mg (+ 1), and 700 rpm (− 1) for Monoolein, Poloxamer, and stirring speed, respectively.
TS-fuzzy modeling based on ε-insensitive smooth support vector regression

This paper establishes a connection between Takagi-Sugeno TS fuzzy systems and e-insensitive smooth support vector regression e-SSVR, a smooth strategy for solving e-SVR. In previous e-SVR-based fuzzy models, the form of membership functions is restricted by the Mercer condition. The e-SSVR formulation puts no restrictions on the kernel. Therefore, the proposed e-SSVR-based TS-fuzzy modeling method relaxes the restriction on membership functions. By applying the reduced kernel technique, the number of fuzzy rules is reduced without scarifying the generalization ability. The computational complexity is also reduced by the reduced kernel technique. The performance of our method is illustrated by extensive experiments and comparisons.
How intensive care nurses perceive good death

ABSTRACT This study was to determine the attitude of nurses regarding the concept of a good death and terminal phase was conducted to determine the effect on patient care. This is a descriptive and analytical study. The study was conducted with 102 nurses who worked at an intensive care unit and were willing to participate to the study. The mean Good Death Scale total score was 56.75 ± 8.90 and the Frommelt Scale score was 95.10 ± 8.53. In conclusion, our study results suggest that the attitudes of the nurses during care to moribund patients are moderate and, when appropriate care is given, they perceive the death as a positive experience.
Concise Review: Organ Engineering: Design, Technology, and Integration

Engineering complex tissues and whole organs has the potential to dramatically impact translational medicine in several avenues. Organ engineering is a discipline that integrates biological knowledge of embryological development, anatomy, physiology, and cellular interactions with enabling technologies including biocompatible biomaterials and biofabrication platforms such as three‐dimensional bioprinting. When engineering complex tissues and organs, core design principles must be taken into account, such as the structure‐function relationship, biochemical signaling, mechanics, gradients, and spatial constraints. Technological advances in biomaterials, biofabrication, and biomedical imaging allow for in vitro control of these factors to recreate in vivo phenomena. Finally, organ engineering emerges as an integration of biological design and technical rigor. An overall workflow for organ engineering and guiding technology to advance biology as well as a perspective on necessary future iterations in the field is discussed. Stem Cells 2017;35:51–60
A novel interpolation algorithm for nonlinear omni-catadioptric images

This paper proposes a novel omni-image Interpolation technique and a new method to evaluation its performance. Omni-images are taken by non-linear catadioptric camera and offer important scientific and engineering benefits but often at the expense of the reduced visual accuracy. Interpolation algorithms aiming at improving the resolution of omni-images are deemed as an effective approach to deal with such a lack of visual content. Main contribution of this paper is that we propose an interpolation algorithm which could not only enhance the visual quality but also maintain camera parameters. Camera properties of the interpolated images are preserved by utilizing the epipolar geometry constraint of non-linear images. In our experiment, good performance was found on four sets of omni-images using the proposed method compared with the standard bilinear algorithm and bicubic algorithm.
A Rho-GTPase based model explains spontaneous collective migration of neural crest cell clusters

We propose a model to explain the spontaneous collective migration of neural crest cells in the absence of an external gradient of chemoattractants. The model is based on the dynamical interaction between Rac1 and RhoA that is known to regulate the polarization, contact inhibition and co-attraction of neural crest cells. Coupling the reaction-diffusion equations for active and inactive Rac1 and RhoA on the cell membrane with a mechanical model for the overdamped motion of membrane vertices, we show that co-attraction and contact inhibition cooperate to produce persistence of polarity in a cluster of neural crest cells by suppressing the random onset of Rac1 hotspots that may mature into new protrusion fronts. This produces persistent directional migration of cell clusters in corridors. Our model confirms a prior hypothesis that co-attraction and contact inhibition are key to spontaneous collective migration, and provides an explanation of their cooperative working mechanism in terms of Rho GTPase signaling. The model shows that the spontaneous migration is more robust for larger clusters, and is most efficient in a corridor of optimal confinement.
Service failures and challenges in responding to people bereaved through drugs and alcohol: An interprofessional analysis

ABSTRACT This article reports findings from the first two stages of a three-stage qualitative study which considered the role of services, including public, private and charitable organisations, in responding to the needs of adults bereaved following the drug and/or alcohol-related death of someone close. The study, the first of its kind to explore the landscape and role of services in substance use deaths, was conducted over two sites: south west England and Scotland. In stage 1 of the research, adopting both convenience and purposive sampling, data were collected via semi-structured interviews on experiences and support needs of bereaved individuals (n = 106). In stage 2, six focus groups were conducted with a purposive sample of practitioners (n = 40), including those working for the police, coroner’s service, procurator fiscal depute (Scotland), health service, funeral service, press, clergy, Public Health England, Drugs Policy Unit, bereavement counselling/support and alcohol and drug treatment services, to investigate how services may better respond to this bereavement. Thematic analysis from both data-sets identified two overarching themes. The first, focusing on practitioner responses, captures how these bereaved people may meet with inadequate, unkind, and discriminatory responses from services. Having to navigate unfamiliar, fragmented, and time-consuming procedures compounds the bereaved’s distress at an already difficult time, illustrated by a ‘mapping’ of relevant services. The second relates to challenges and opportunities for those responding. Service failures reflect practitioners’ poor understanding of both substance use bereavement and the range of other practitioners and services involved. Those bereaved are a poorly understood, neglected and stigmatised group of service users. There is a need for services to respond without judgement or insensitive language, and provide information about, communicate and work closely with, other services despite differences in working practices and cultures. These recommendations could positively affect bereaved peoples’ experiences, alleviating stress and overwhelm at a particularly vulnerable time.
The Effect of Cryopreserved Human Placental Tissues on Biofilm Formation of Wound-Associated Pathogens

Biofilm, a community of bacteria, is tolerant to antimicrobial agents and ubiquitous in chronic wounds. In a chronic DFU (Diabetic Foot Ulcers) clinical trial, the use of a human cryopreserved viable amniotic membrane (CVAM) resulted in a high rate of wound closure and reduction of wound-related infections. Our previous study demonstrated that CVAM possesses intrinsic antimicrobial activity against a spectrum of wound-associated bacteria under planktonic culture conditions. In this study, we evaluated the effect of CVAM and cryopreserved viable umbilical tissue (CVUT) on biofilm formation of S. aureus and P. aeruginosa, the two most prominent pathogens associated with chronic wounds. Firstly, we showed that, like CVAM, CVUT released antibacterial activity against multiple bacterial pathogens and the devitalization of CVUT reduced its antibacterial activity. The biofilm formation was then measured using a high throughput method and an ex vivo porcine dermal tissue model. We demonstrate that the formation of biofilm was significantly reduced in the presence of CVAM- or CVUT-derived conditioned media compared to control assay medium. The formation of P. aeruginosa biofilm on CVAM-conditioned medium saturated porcine dermal tissues was reduced 97% compared with the biofilm formation on the control medium saturated dermal tissues. The formation of S. auerus biofilm on CVUT-conditioned medium saturated dermal tissues was reduced 72% compared with the biofilm formation on the control tissues. This study is the first to show that human cryopreserved viable placental tissues release factors that inhibit biofilm formation. Our results provide an explanation for the in vivo observation of their ability to support wound healing.
Evaluating Health Span in Preclinical Models of Aging and Disease: Guidelines, Challenges, and Opportunities for Geroscience

Life extension is no longer considered sufficient evidence of delayed aging in research animals. It must also be demonstrated that a broad swathe of health indicators have been extended. During a retreat of the Geroscience Network, a consortium of basic and clinical aging researchers, potential measures of mouse health were considered for their potential as easily standardized, highly informative metrics. Major health domains considered were neuromuscular, cognitive, cardiovascular, metabolic, and inflammatory functions as well as body composition and energetics and a multitude of assays interrogating these domains. A particularly sensitive metric of health is the ability to respond to, and recover, from stress. Therefore, the Network also considered stresses of human relevance that could be implemented in mouse models to assess frailty and resilience. Mouse models already exist for responses to forced immobility, cancer chemotherapy, infectious diseases, dietary challenges, and surgical stress, and it was felt that these could be employed to determine whether putative senescence-retarding interventions increased and extended organismal robustness. The Network discussed challenges in modeling age-related human chronic diseases and concluded that more attention needs to be paid to developing disease models with later age of onset, models of co- and multimorbidity, diversifying the strains and sexes commonly used in aging research, and considering additional species.