Alternative splicing analysis benchmark with DICAST

Alternative splicing is a major contributor to transcriptome and proteome diversity in health and disease. A plethora of tools have been developed for studying alternative splicing in RNA-seq data. Previous benchmarks focused on isoform quantification and mapping. They neglected event detection tools, which arguably provide the most detailed insights into the alternative splicing process. DICAST offers a modular and extensible framework for the analysis of alternative splicing integrating 11 splice-aware mapping and eight event detection tools. We benchmark all tools extensively on simulated as well as whole blood RNA-seq data. STAR and HISAT2 demonstrated the best balance between performance and run time. The performance of event detection tools varies widely with no tool outperforming all others. DICAST allows researchers to employ a consensus approach to consider the most successful tools jointly for robust event detection. Furthermore, we propose the first reporting standard to unify existing formats and to guide future tool development.

Tailoring Pullulanase PulAR from Anoxybacillus sp. AR-29 for Enhanced Catalytic Performance by A Structure-Guided Consensus Approach

Pullulanase is a well-known debranching enzyme that can specially hydrolyze α-1,6-glycosidic linkages in starch and oligosaccharides, however, it suffers from low stability and catalytic efficiency under industrial conditions. In the present study, four sites (A365, V401, H499, and T504) lining the catalytic pocket of Anoxybacillus sp. AR-29 pullulanase PulAR were selected for site-directed mutagenesis (SDM) by using a structure-guided consensus approach. Four beneficial mutants (PulAR-A365V, PulAR-V401C, PulAR-A365/V401C, PulAR-A365V/V401C/T504V, and PulAR-A365V/V401C/T504V/H499A) were created, which showed enhanced thermostability, pH stability, and catalytic efficiency. Among them, the quadruple mutant PulAR-A365V/V401C/T504V/H499A displayed 6.6- and 9.6-fold higher catalytic efficiency toward pullulan at 60 ℃, pH 5.0 and 6.0, respectively. In addition, its thermostabilities at 60 ℃ and 65 ℃ were improved by 2.6- and 3.1-fold, respectively, compared to those of the wild-type (WT). Meanwhile, its pH stabilities at pH 4.5 and 5.0 were 1.6- and 1.8-fold higher than those of WT, respectively. In summary, the catalytic performance of PulAR was significantly enhanced via rational engineering by a structure-guided consensus approach. The resultant quadruple mutant PulAR-A365V/V401C/T504V/H499A demonstrated potential applications in the starch industry.

Cancer as a Chronic Illness in Colombia: A Normative Consensus Approach to Improving Healthcare Services for those Living with and beyond Cancer and Its Treatment

Cancer survivorship care in Colombia is of increasing importance. International survivorship initiatives and studies show that continuing symptoms, psychological distress, and late effects impact the quality of life for survivors. Priorities for quality survivorship according to Colombian patients and clinicians are unknown. We undertook a nominal consensus approach with 24 participants using virtual meeting technology to identify the priorities for cancer survivorship. We applied an iterative approach conducted over eight weeks with five workshops and one patient focus group followed by a priority setting survey. The consensus group established six main themes, which were subsequently evaluated by experts: (i) symptoms and secondary effects of cancer; (ii) care coordination to increase patient access and integration of cancer care; (iii) psychosocial support after cancer treatment; (iv) mapping information resources and available support services for long-term cancer care; (v) identifying socioeconomic and regional inequalities in cancer survival to improve care and outcomes; and (vi) health promotion and encouraging lifestyle change. The order of priorities differed between clinicians and patients: patients mentioned psychosocial support as the number one priority, and clinicians prioritized symptoms and surveillance for cancer recurrence. Developing survivorship care needs consideration of both views, including barriers such as access to services and socioeconomic disparities.

Reinforcing SLA Consensus on Blockchain

Cloud Infrastructure as a Service (IaaS) Service Level Agreements (SLAs) assessment constitutes the de facto area of interest and applications in the public cloud infrastructure. However, the domination of colossal corporations tends to monopolize the way metrics and Key Performance Indicators (KPIs) are measured and determined, leading to governed environments where the clientele is unable to obtain accurate and unbiased assessment of SLAs. Leaning toward SLA self-assessment, this paper provides a fair SLA consensus approach with innate transparency and privacy by leveraging permissioned blockchains that are equipped with Trusted Execution Environments (TEEs). The SLA assessment intelligence is performed inside enclaved smart contracts isolated from the on-chain entities views. The result constitutes a permissioned blockchain ecosystem where the IaaS and their clientele commonly agree on all the respective SLA monitoring and computation rules beforehand, as defined in any SLA assessment process, while the SLA consensus scheme constantly audits the SLA metrics based on these pre-approved regulations.

Recommendations for the management of diabetic macular oedema with intravitreal dexamethasone implant: A national Delphi consensus study

Purpose The intravitreal dexamethasone implant (DEX-I) is an alternative to anti-VEGF for the first-line treatment of diabetic macular oedema (DME). However, several questions remain regarding its routine use and its place in certain situations not always specified in current recommendations. A national consensus approach was, therefore, initiated by French retinal experts. Methods An iterative Delphi consensus approach was used. A steering committee (SC) of seven experts analysed data from the literature to formulate statements divided into five key areas of treatment. These statements were submitted to the independent and anonymous electronic vote of 87 French retina experts among whom 39 expressed their opinion and therefore constituted the voting panel. Results After two rounds of voting, 22 and 7 of 38 statements received a strong consensus and a good consensus, respectively. The consensus level was higher for statements regarding first-line indications and safety of DEX-I compared to those regarding efficacy assessment, reprocessing time or pathophysiological biomarkers. The panellists recommended the preferential use of DEX-I for patients with limited availability for multiple injections, those who needed to undergo cataract surgery or who had a recent cardiovascular history, and as a therapeutic alternative to anti-VEGF in patients with a history of vitrectomy, retinal serous detachment, hyper-reflective points or dry exudates in optical coherence tomography (OCT). However, some statements proposed by SC experts were not validated. Conclusion This study provides some key recommendations to clinicians treating diabetic macular oedema, which may be useful when using intravitreal dexamethasone implants in daily practice.

P.117 Pediatric acute ischemic stroke protocols

Background: Approximately 1,000 children present with AIS annually in North America. Most suffer from long-term disability. Childhood AIS is diagnosed after a median of 23 hours post-symptom onset, limiting thrombolytic treatment options that may improve outcomes. Pediatric stroke protocols decrease time to diagnosis. AIS treatment is not uniform across Canada, nor are pediatric stroke protocols standardized. Methods: We contacted neurologists at all 16 Canadian pediatric hospitals regarding their AIS management. Results: Response rate was 100%. Seven centers have an AIS protocol and two have a protocol under development. Seven centers do not have a protocol – two redirect patients to adult neurology, and five use a case-by-case approach for management. Analysis of the seven AIS protocols reveals differences: 1) IV-tPA dosage: age-dependent 0.75-0.9 mg/kg (n=1) versus age-independent 0.9 mg/kg (n=6), with maximum doses 75 mg (n=1) or 90 mg (n=6); 2) IV-tPA lower age cut-off: 2 years (n=4) versus 3, 4 or 10 years (n=1); 3) IV-tPA exclusion criteria: PedNIHSS score <4 (n=3), <5 (n=1), or <6 (n=3); 4) Pre-treatment neuroimaging: CT (n=3) versus MRI (n=4); 5) Intra-arterial tPA use (n=3). Conclusions: The seven Canadian pediatric AIS protocols show prominent differences. We plan a teleconference discussing a Canadian pediatric AIS consensus approach.

Clinical Reasoning Needs to Be Explicitly Addressed in Health Professions Curricula: Recommendations from a European Consortium

Clinical reasoning entails the application of knowledge and skills to collect and integrate information, typically with the goal of arriving at a diagnosis and management plan based on the patient’s unique circumstances and preferences. Evidence-informed, structured, and explicit teaching and assessment of clinical reasoning in educational programs of medical and other health professions remain unmet needs. We herein summarize recommendations for clinical reasoning learning objectives (LOs), as derived from a consensus approach among European and US researchers and health professions educators. A four-step consensus approach was followed: (1) identification of a convenience sample of the most relevant and applied national LO catalogues for health professions educational programs (N = 9) from European and US countries, (2) extraction of LOs related to clinical reasoning and translation into English, (3) mapping of LOs into predefined categories developed within the Erasmus+ Developing, implementing, and disseminating an adaptive clinical reasoning curriculum for healthcare students and educators (DID-ACT) consortium, and (4) synthesis of analysis findings into recommendations for how LOs related to clinical reasoning could be presented and incorporated in LO catalogues, upon consensus. Three distinct recommendations were formulated: (1) make clinical reasoning explicit, (2) emphasize interprofessional and collaboration aspects of clinical reasoning, and (3) include aspects of teaching and assessment of clinical reasoning. In addition, the consortium understood that implementation of bilingual catalogues with English as a common language might contribute to lower heterogeneity regarding amount, structure, and level of granularity of clinical reasoning LOs across countries. These recommendations will hopefully motivate and guide initiatives towards the implementation of LOs related to clinical reasoning in existing and future LO catalogues.