The silicon trypanosome

African trypanosomes have emerged as promising unicellular model organisms for the next generation of systems biology. They offer unique advantages, due to their relative simplicity, the availability of all standard genomics techniques and a long history of quantitative research. Reproducible cultivation methods exist for morphologically and physiologically distinct life-cycle stages. The genome has been sequenced, and microarrays, RNA-interference and high-accuracy metabolomics are available. Furthermore, the availability of extensive kinetic data on all glycolytic enzymes has led to the early development of a complete, experiment-based dynamic model of an important biochemical pathway. Here we describe the achievements of trypanosome systems biology so far and outline the necessary steps towards the ambitious aim of creating a , a comprehensive, experiment-based, multi-scale mathematical model of trypanosome physiology. We expect that, in the long run, the quantitative modelling enabled by the Silicon Trypanosome will play a key role in selecting the most suitable targets for developing new anti-parasite drugs

Skin Lesion Analyser: An Efficient Seven-Way Multi-Class Skin Cancer Classification Using MobileNet

Skin cancer, a major form of cancer, is a critical public health problem with 123,000 newly diagnosed melanoma cases and between 2 and 3 million non-melanoma cases worldwide each year. The leading cause of skin cancer is high exposure of skin cells to UV radiation, which can damage the DNA inside skin cells leading to uncontrolled growth of skin cells. Skin cancer is primarily diagnosed visually employing clinical screening, a biopsy, dermoscopic analysis, and histopathological examination. It has been demonstrated that the dermoscopic analysis in the hands of inexperienced dermatologists may cause a reduction in diagnostic accuracy. Early detection and screening of skin cancer have the potential to reduce mortality and morbidity. Previous studies have shown Deep Learning ability to perform better than human experts in several visual recognition tasks. In this paper, we propose an efficient seven-way automated multi-class skin cancer classification system having performance comparable with expert dermatologists. We used a pretrained MobileNet model to train over HAM10000 dataset using transfer learning. The model classifies skin lesion image with a categorical accuracy of 83.1 percent, top2 accuracy of 91.36 percent and top3 accuracy of 95.34 percent. The weighted average of precision, recall, and f1-score were found to be 0.89, 0.83, and 0.83 respectively. The model has been deployed as a web application for public use at (https://saketchaturvedi.github.io). This fast, expansible method holds the potential for substantial clinical impact, including broadening the scope of primary care practice and augmenting clinical decision-making for dermatology specialists.Comment: This is a pre-copyedited version of a contribution published in Advances in Intelligent Systems and Computing, Hassanien A., Bhatnagar R., Darwish A. (eds) published by Chaturvedi S.S., Gupta K., Prasad P.S. The definitive authentication version is available online via https://doi.org/10.1007/978-981-15-3383-9_1

Patients with Inflammatory Bowel Disease Have Heterogeneous Treatment Preferences That Are Largely Determined by the Avoidance of Abdominal Pain and Side Effects [P-POWER IBD Study].

peer reviewedBACKGROUND AND AIMS: Patient-centric management of inflammatory bowel disease [IBD] is important, with consensus considering patient-reported outcomes alongside clinical and endoscopic assessment by healthcare providers. However, evidence about patients' treatment priorities is still limited. This study aimed to elicit benefit-risk trade-offs that patients with IBD are willing to make, to help inform discussions about patient-centric treatment targets. METHODS: This was a cross-sectional online survey of adults with self-confirmed Crohn's disease [CD] or ulcerative colitis [UC] receiving IBD treatment. The impact of efficacy, administration, and safety on treatment preferences was elicited using a discrete choice experiment. Relative attribute importance [RAI] and maximum acceptable risk of mild-to-moderate side effects [SEs] were estimated from a mixed logit model. RESULTS: 400 patients [CD: 54%; UC: 46%; female: 38.0%; age range: 18-78] were recruited. Efficacy, administration, and safety affected treatment preferences to varying degrees, with abdominal pain being most important [RAI 33%] followed by risks of mild-to-moderate SEs [RAI 27%], and serious infections [RAI 16%]. To reduce abdominal pain from severe to moderate/mild, patients accepted an additional 18.8% or 30.6% risk of mild-to-moderate SEs, respectively. While average preferences between patients with CD and UC were similar, patients with CD placed greater importance on abdominal pain [p < 0.05], and patients with UC on bowel urgency [p < 0.05]. However, preferences varied notably. CONCLUSIONS: While avoiding abdominal pain, SEs, and serious infections had on average the highest treatment priority, preferences varied between patients. Treatment strategies should consider the trade-offs individuals are willing to make

Recommendations From the International Consortium on Professional Nursing Practice in Long-Term Care Homes

AbstractIn response to the International Association of Gerontology and Geriatrics' global agenda for clinical research and quality of care in long-term care homes (LTCHs), the International Consortium on Professional Nursing Practice in Long Term Care Homes (the Consortium) was formed to develop nursing leadership capacity and address the concerns regarding the current state of professional nursing practice in LTCHs. At its invitational, 2-day inaugural meeting, the Consortium brought together international nurse experts to explore the potential of registered nurses (RNs) who work as supervisors or charge nurses within the LTCHs and the value of their contribution in nursing homes, consider what RN competencies might be needed, discuss effective educational (curriculum and practice) experiences, health care policy, and human resources planning requirements, and to identify what sustainable nurse leadership strategies and models might enhance the effectiveness of RNs in improving resident, family, and staff outcomes. The Consortium made recommendations about the following priority issues for action: (1) define the competencies of RNs required to care for older adults in LTCHs; (2) create an LTCH environment in which the RN role is differentiated from other team members and RNs can practice to their full scope; and (3) prepare RN leaders to operate effectively in person-centered care LTCH environments. In addition to clear recommendations for practice, the Consortium identified several areas in which further research is needed. The Consortium advocated for a research agenda that emphasizes an international coordination of research efforts to explore similar issues, the pursuit of examining the impact of nursing and organizational models, and the showcasing of excellence in nursing practice in care homes, so that others might learn from what works. Several studies already under way are also described

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

SnoN expression is differently regulated in microsatellite unstable compared with microsatellite stable colorectal cancers

BACKGROUND: SnoN is an important regulator of the transforming growth factor beta (TGFβ) signalling pathway and has been shown to exhibit both tumour promotion and suppression activity. METHODS: To further explore the role of this complex molecule in colorectal tumorigenesis, we examined 52 paired normal and tumour colorectal specimens stratified by level of microsatellite instability; 18 with high-level microsatellite instability (MSI-H) and 34 microsatellite stable (MSS). SnoN transcript expression was quantitated by real-time PCR and analysed with respect to clinical indicators of prognosis. RESULTS: Within the MSI-H subgroup, SnoN was commonly either up-regulated (6/18, 33%) or down-regulated (7/18, 39%). A significantly different distribution of SnoN expression was observed in MSS cancers compared with MSI-H (P ≤ 0.001). Whilst 17/34 (50%) of MSS tumours demonstrated up-regulation, none showed down-regulated expression. Within the MSI-H subgroup, up-regulation was significantly correlated with lack of repeat tract mutation in the TGFβRII gene (P ≤ 0.025), suggesting that SnoN is more frequently up-regulated in the presence of functional TGFβ signalling. CONCLUSION: Together these data support the notion that SnoN has both oncogenic and tumour suppressive properties depending on other genetic changes within the tumour, and that the MSI-H pathway of colorectal tumorigenesis presents an excellent model for the study of these opposing functions

Complement Factor H-Related Proteins CFHR2 and CFHR5 Represent Novel Ligands for the Infection-Associated CRASP Proteins of Borrelia burgdorferi

Background: One virulence property of Borrelia burgdorferi is its resistance to innate immunity, in particular to complement-mediated killing. Serum-resistant B. burgdorferi express up to five distinct complement regulator-acquiring surface proteins (CRASP) which interact with complement regulator factor H (CFH) and factor H-like protein 1 (FHL1) or factor H-related protein 1 (CFHR1). In the present study we elucidate the role of the infection-associated CRASP-3 and CRASP-5 protein to serve as ligands for additional complement regulatory proteins as well as for complement resistance of B. burgdorferi. Methodology/Principal Findings: To elucidate whether CRASP-5 and CRASP-3 interact with various human proteins, both borrelial proteins were immobilized on magnetic beads. Following incubation with human serum, bound proteins were eluted and separated by Glycine-SDS-PAGE. In addition to CFH and CFHR1, complement regulators CFHR2 and CFHR5 were identified as novel ligands for both borrelial proteins by employing MALDI-TOF. To further assess the contributions of CRASP-3 and CRASP-5 to complement resistance, a serum-sensitive B. garinii strain G1 which lacks all CFH-binding proteins was used as a valuable model for functional analyses. Both CRASPs expressed on the B. garinii outer surface bound CFH as well as CFHR1 and CFHR2 in ELISA. In contrast, live B. garinii bound CFHR1, CFHR2, and CFHR5 and only miniscute amounts of CFH as demonstrated by serum adsorption assays and FACS analyses. Further functional analysis revealed that upon NHS incubation, CRASP-3 or CRASP-5 expressing borreliae were killed by complement. Conclusions/Significance: In the absence of CFH and the presence of CFHR1, CFHR2 and CFHR5, assembly and integration of the membrane attack complex was not efficiently inhibited indicating that CFH in co-operation with CFHR1, CFHR2 and CFHR5 supports complement evasion of B. burgdorferi