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On behalf of the Canadian Association of Medical Oncologists, we are pleased to present the Abstracts of the 2021 Annual Meeting. The National CAMO Residents Research Day was held virtually on 1 April 2021 and the CAMO Virtual Annual Scientific Meeting (ASM) & Annual General Meeting (AGM) took place on 22 April 2021. Twenty (20) abstracts were selected for presentation as oral presentations and rapid-fire presentations. Awards for the top three (3) abstracts were presented during the ASM and AGM. All of them were marked as “Award Recipient”. We congratulate all the presenters on their research work and contribution.

Abstract Electric power grid infrastructure has revolutionized our world and changed the way of living. So has blockchain technology. The hierarchical electric power grid has been shifting from a centralized structure to a decentralized structure to achieve higher flexibility and stability, and blockchain technology has been widely adopted in the energy sector to deal with grid management, billing, metering, and so on, because of its nature of decentralization. Here, the aim is to provide a multi‐dimensional review on the technological advances of the blockchain in smart grids. Its corresponding applications based on these advances, including company projects and use cases, are summarized. Furthermore, the security threat issues in smart grids, Ethereum Virtual Machine (i.e. the operating environment of consensus mechanisms), and smart contracts are analysed, with a brief conclusion to manifest the prior tasks in building secure blockchain‐based infrastructures in smart grids. As such, the challenges and features of different protocols and their applicability in each use case are identified to provide an insightful guide for future research studies.

In addition to microgravity, spaceflight simultaneously exposes biology to a suite of other stimuli. For example, in space, organisms experience ionizing radiation environments that significantly differ in both quality and quantity from those normally experienced on Earth. However, data on radiation exposure during space missions is often complex to access and to understand, limiting progress towards defining how radiation affects organisms against the unique background of spaceflight. To help address this challenge, we have developed the Rad-Bio-App. This web-accessible database imports radiation metadata from experiments archived in NASA’s GeneLab data repository, and then allows the user to explore these experiments both in the context of their radiation exposure and through their other metadata and results. Rad-Bio-App provides an easy-to-use, graphically-driven environment to enable both radiation biologists and non-specialist researchers to visualize, and understand the impact of ionizing radiation on various biological systems in the context of spaceflight.

Abstract Background Alterations in levels of circulating micro-RNAs might reflect within organ signaling or subclinical tissue injury that is linked to risk of diabetes and cardiovascular risk. We previously found that serum levels of miR-483-5p is correlated with cardiometabolic risk factors and incidence of cardiometabolic disease in a case–control sample from the populations-based Malmö Diet and Cancer Study Cardiovascular Cohort (MDC-CC). We here aimed at replicating these findings and to test for association with carotid atherosclerosis. Methods We measured miR-483-5p in fasting serum of 1223 healthy subjects from the baseline examination of the population-based, prospective cohort study Malmö Offspring Study (MOS) and correlated miR-483-5p to cardiometabolic risk factors and to incidence of diabetes mellitus and coronary artery disease (CAD) during 3.7 (± 1.3) years of follow-up using logistic regression. In both MOS and MDC-CC we related mir-483-5p to carotid atherosclerosis measured with ultrasound. Results In cross-sectional analysis miR-483-5p was correlated with BMI, waist circumference, HDL, and sex. After adjustment for age and sex, the association remained significant for all risk factors except for HDL. Logistic regression analysis showed significant associations between miR-483-5p and new-onset diabetes (OR = 1.94, 95% CI 1.06–3.56, p = 0.032) and cardiovascular disease (OR = 1.99, 95% CI 1.06–3.75, p = 0.033) during 3.7 (± 1.3) years of follow-up. Furthermore, miR-483-5p was significantly related with maximum intima-media thickness of the carotid bulb in MDC-CC (p = 0.001), but not in MOS, whereas it was associated with increasing number of plaques in MOS (p = 0.007). Conclusion miR-483-5p is related to an unfavorable cardiometabolic risk factor profile and predicts diabetes and CAD, possibly through an effect on atherosclerosis. Our results encourage further studies of possible underlying mechanisms and means of modifying miR-483-5p as a possible interventional target in prevention of cardiometabolic disease.

BackgroundTranscranial direct current stimulation (tDCS) has been shown to modulate cortical motor excitability and improve bradykinesia symptoms in Parkinson's disease. It is unclear how targeting different cortical motor areas with tDCS may differentially influence upper limb function for individuals diagnosed with PD.ObjectiveThis study investigated whether anodal tDCS applied separately to the primary motor cortex and the supplementary motor area would improve upper limb function for individuals with Parkinson's disease. In addition, a startling acoustic stimulus was used to differentiate between the effect of stimulation on motor preparatory and initiation processes associated with upper limb movements.MethodsEleven participants with idiopathic Parkinson's disease performed two upper limb simple reaction time tasks, involving elbow extension or a button press before and after either anodal tDCS or sham tDCS was applied over the primary motor cortex or supplementary motor area. A loud, startling stimulus was presented on a selection of trials to involuntarily trigger the prepared action.ResultsAnodal tDCS led to improved premotor reaction time in both tasks, but this was moderated by reaction time in pre-tDCS testing, such that individuals with slower pre-tDCS reaction time showed the greatest reaction time improvements. Startle-trial reaction time was not modified following tDCS, suggesting that the stimulation primarily modulated response initiation processes.ConclusionAnodal tDCS improved response initiation speed, but only in slower reacting individuals with PD. However, no differences attributable to tDCS were observed in clinical measures of bradykinesia or kinematic variables, suggesting that reaction time may represent a more sensitive measure of some components of bradykinesia.

Summary: Background: In moderate-to-severe COVID-19 pneumonia, dexamethasone (DEX) and tocilizumab (TCZ) reduce the occurrence of death and ventilatory support. We investigated the efficacy and safety of DEX+TCZ in an open randomized clinical trial. Methods: From July 24, 2020, through May 18, 2021, patients with moderate-to-severe COVID-19 pneumonia requiring oxygen (>3 L/min) were randomly assigned to receive DEX (10 mg/d 5 days tapering up to 10 days) alone or combined with TCZ (8 mg/kg IV) at day 1, possibly repeated with a fixed dose of 400 mg i.v. at day 3. The primary outcome was time from randomization to mechanical ventilation support or death up to day 14, analysed on an intent-to-treat basis using a Bayesian approach. ClinicalTrials.gov number, NCT04476979. Findings: A total of 453 patients were randomized, 3 withdrew consent, 450 were analysed, of whom 226 and 224 patients were assigned to receive DEX or TCZ+DEX, respectively. At day 14, mechanical ventilation or death occurred in 32/226 (14%) and 27/224 (12%) in the DEX and TCZ+DEX arms, respectively (hazard ratio [HR] 0·85, 90% credible interval [CrI] 0·55 to 1·31). At day 14, the World health Organization (WHO) clinical progression scale (CPS) was significantly improved in the TCZ+DEX arm (OR 0·69, 95% CrI, 0·49 to 0.97). At day 28, the cumulative incidence of oxygen supply independency was 82% in the TCZ+DEX arms and 72% in the DEX arm (HR 1·36, 95% CI 1·11 to 1·67). On day 90, 24 deaths (11%) were observed in the DEX arm and 18 (8%) in the TCZ+DEX arm (HR 0·77, 95% CI 0·42–1·41). Serious adverse events were observed in 25% and 21% in DEX and TCZ+DEX arms, respectively. Interpretation: Mechanical ventilation need and mortality were not improved with TCZ+DEX compared with DEX alone. The safety of both treatments was similar. However, given the wide confidence intervals for the estimate of effect, definitive interpretation cannot be drawn. Funding: Programme Hospitalier de Recherche Clinique [PHRC COVID-19–20–0151, PHRC COVID-19–20–0029], Fondation de l'Assistance Publique – Hôpitaux de Paris (Alliance Tous Unis Contre le Virus) and from Fédération pour la Recherche Médicale” (FRM). Tocilizumab was provided by Roche.

Demam Berdarah Dengue (DBD) masih menjadi masalah utama di Indonesia sampai sekarang. Pemanfaatan ikan kepala timah (Aplocheilus panchax / A. panchax) sebagai pengendali vektor secara biologis bertujuan untuk memutus rantai penularan. Tujuan: Menentukan kemampuan predasi dan keefektifan ikan A. panchax jantan dan betina terhadap larva nyamuk Aedes aegypti. Metode: Penelitian ini menggunakan metode post-test only design. Pengamatan dilakukan dengan menghitung jumlah larva yang dipredasi setiap lima menit hingga 20 larva habis termakan kemudian dianalisis dengan independent sample t-test untuk mengetahui rerata kemampuan predasi kedua kelompok ikan. Hasil: (1) ikan betina memakan rerata 9.20 larva per lima menit sedangkan ikan jantan 7.40 larva per lima menit. (2) ikan betina paling cepat menghabiskan 20 larva nyamuk dalam waktu 6 menit 44 detik sedangkan ikan jantan 9 menit 8 detik. Simpulan: Ikan A. panchax betina lebih efektif dari yang jantan sehingga berpotensi untuk dimanfaatkan sebagai pengendalian vektor DBD. Kata kunci: aplocheilus panchax, aedes aegypti, DBD, pengendalian vektor

Fifth Generation (5G) cellular networks aim to overcome the pressing demands posed by dynamic Quality of Service (QoS) constraints, which have primarily remained unaddressed using conventional network infrastructure. Cellular networks of the future necessitate the formulation of efficient resource allocation schemes that readily meet throughput requirements. The idea of combining Device-to-Device (D2D), Mobile Edge Computing (MEC), and Network slicing (NS) can improve spectrum utilization with better performance and scalability. This work presents a spectrum efficiency optimization problem in D2D based 5G-Heterogeneous Cellular Network (5G-HCN) with NS. Owing to the shortage of resources, we propose an underlay model where macro-cell users (MUs), small-cell users (SUs), and D2D users (DUs) reuse the resources while considering the effects of interference. The goal is to maximize the average network spectrum efficiency (SE) and throughput without degrading the system performance. The problem at hand is naturally a non-convex mixed-integer non-linear programming (MINLP) problem that is intractable. Therefore, we have suggested a distributed resource allocation strategy with an edge computing (DRA-EC) approach to find the sub-optimal solution. In distributed augmented Lagrange method, each edge router located at BS will solve its problem locally, and the consensus algorithm will find the global solution using these local estimates. The central slice controller will cut the customized network slices according to the bandwidth requirements of each user type with optimized spectrum information. The simulation outcomes prove that our proposed method is near the central optimization scheme with low computational complexity. It is much better because it reduces the computational time and system overhead.

MDM2 and BET inhibitors have shown efficacy in AML treatment. Here, the authors show that the two compounds can synergize through both p53 protein stabilization and inhibition of BRD4-mediated repression of p53 target genes.

The X-linked SMC1A gene encodes a core subunit of the cohesin complex that plays a pivotal role in genome organization and gene regulation. Pathogenic variants in SMC1A are often dominant-negative and cause Cornelia de Lange syndrome (CdLS) with growth retardation and typical facial features; however, rare SMC1A variants cause a developmental and epileptic encephalopathy (DEE) with intractable early-onset epilepsy that is absent in CdLS. Unlike the male-to-female ratio of 1:2 in those with CdLS associated with dominant-negative SMC1A variants, SMC1A-DEE loss-of-function (LOF) variants are found exclusively in females due to presumed lethality in males. It is unclear how different SMC1A variants cause CdLS or DEE. Here, we report on phenotypes and genotypes of three females with DEE and de novo SMC1A variants, including a novel splice-site variant. We also summarize 41 known SMC1A-DEE variants to characterize common and patient-specific features. Interestingly, compared to 33 LOFs detected throughout the gene, 7/8 non-LOFs are specifically located in the N/C-terminal ATPase head or the central hinge domain, both of which are predicted to affect cohesin assembly, thus mimicking LOFs. Along with the characterization of X-chromosome inactivation (XCI) and SMC1A transcription, these variants strongly suggest that a differential SMC1A dosage effect of SMC1A-DEE variants is closely associated with the manifestation of DEE phenotypes.

Background: This systematic review and meta-analysis (SRMA) aimed to synthesize the current literature on the impacts of adolescent and young adult (AYA, ages 15–39 years) cancer on reproductive health outcomes. Methods: EMBASE and Medline were searched from 1 January 2000 to 26 January 2022 for observational studies that included individuals with AYA cancer and controls which evaluated reproductive health outcomes. We used random effects models and 95% confidence intervals to obtain pooled measures of associations between AYA cancer, cancer treatment, and reproductive health outcomes. Results: The search identified 8625 articles; 21 were included. 62 reproductive outcomes were assessed and classified according to a sex-based framework as fetal/neonatal (n = 26), maternal (n = 11), fetal/neonatal-maternal (n = 23), and maternal-paternal (n = 2). Meta-analyses of crude estimates showed significant associations between AYA cancer and outcomes including preterm birth (pooled odds ratio [pOR] 1.31; 95% CI: 1.22, 1.42), gestational diabetes (pOR 1.43; 95% CI: 1.03, 1.99), and fertility treatment (pOR 2.66; 95% CI 1.71, 4.11). We also found higher odds of preterm birth (pOR 1.65; 95% CI: 1.21, 2.26) and low APGAR score at birth (pOR 2.03; 95% CI: 1.32, 3.13) among AYA cancer patients who received radiation compared to controls. Conclusions: Our SRMA quantified impacts of AYA cancers and treatments on several reproductive health outcomes.

We explore the properties of galaxies in the proximity (within a ∼2 Mpc radius sphere) of Type I quasars at 0.1 < z

Circular RNAs contribute to the regulation of β-cell specific functions. Here the authors show that a circular RNA derived from one of the introns of the insulin gene is necessary for optimal insulin secretion from pancreatic islets and that its level is reduced in the islets of diabetic subjects.

Abstract Background High-throughput sequencing can establish the functional capacity of a microbial community by cataloging the protein-coding sequences (CDS) present in the metagenome of the community. The relative performance of different computational methods for identifying CDS from whole-genome shotgun sequencing is not fully established. Results Here we present an automated benchmarking workflow, using synthetic shotgun sequencing reads for which we know the true CDS content of the underlying communities, to determine the relative performance (sensitivity, positive predictive value or PPV, and computational efficiency) of different metagenome analysis tools for extracting the CDS content of a microbial community. Assembly-based methods are limited by coverage depth, with poor sensitivity for CDS at

Background The efficacy of immunotherapies in metastatic melanoma depends on a robust T cell infiltration. Oncogenic alterations of tumor cells have been associated to T cell exclusion. Identifying novel cancer cell-intrinsic non-genetic mechanisms of immune escape, the targeting of which would reinstate T cell recruitment, would allow to restore the response to anti-programmed cell death protein 1 (PD-1) antibody therapy. The epithelial-to-mesenchymal transition (EMT)-inducing transcription factor ZEB1 is a major regulator of melanoma cell plasticity, driving resistance to mitogen-activated protein kinase (MAPK) targeted therapies. We thus wondered whether ZEB1 signaling in melanoma cells may promote immune evasion and resistance to immunotherapy.Methods We evaluated the putative correlation between ZEB1 expression in melanoma cells and the composition of the immune infiltrate in a cohort of 60 human melanoma samples by combining transcriptomic (RNA-sequencing) and seven-color spatial multi-immunofluorescence analyses. Algorithm-based spatial reconstitution of tumors allowed the quantification of CD8+, CD4+ T cells number and their activation state (PD-1, Ki67). ZEB1 gain-of-function or loss-of-function approaches were then implemented in syngeneic melanoma mouse models, followed by monitoring of tumor growth, quantification of immune cell populations frequency and function by flow cytometry, cytokines secretion by multiplex analyses. Chromatin-immunoprecipitation was used to demonstrate the direct binding of this transcription factor on the promoters of cytokine-encoding genes. Finally, the sensitivity to anti-PD-1 antibody therapy upon ZEB1 gain-of-function or loss-of-function was evaluated.Results Combined spatial and transcriptomic analyses of the immune infiltrates in human melanoma samples demonstrated that ZEB1 expression in melanoma cells is associated with decreased CD8+ T cell infiltration, independently of β-catenin pathway activation. ZEB1 ectopic expression in melanoma cells impairs CD8+ T cell recruitment in syngeneic mouse models, resulting in tumor immune evasion and resistance to immune checkpoint blockade. Mechanistically, we demonstrate that ZEB1 directly represses the secretion of T cell-attracting chemokines, including CXCL10. Finally, Zeb1 knock-out, by promoting CD8+ T cell infiltration, synergizes with anti-PD-1 antibody therapy in promoting tumor regression.Conclusions We identify the ZEB1 transcription factor as a key determinant of melanoma immune escape, highlighting a previously unknown therapeutic target to increase efficacy of immunotherapy in melanoma.Trial registration number NCT02828202.

ABSTRACT In an ongoing microbial tracking investigation of the International Space Station (ISS), several Sphingomonas strains were isolated. Based on the 16S rRNA gene sequence, phylogenetic analysis identified the ISS strains as Sphingomonas sanguinis (n = 2) and one strain isolated from the Kennedy Space Center cleanroom (used to assemble various Mars mission spacecraft components) as Sphingomonas paucimobilis. Metagenomic sequence analyses of different ISS locations identified 23 Sphingomonas species. An abundance of shotgun metagenomic reads were detected for S. sanguinis in the location from where the ISS strains were isolated. A complete metagenome-assembled genome was generated from the shotgun reads metagenome, and its comparison with the whole-genome sequences (WGS) of the ISS S. sanguinis isolates revealed that they were highly similar. In addition to the phylogeny, the WGS of these Sphingomonas strains were compared with the WGS of the type strains to elucidate genes that can potentially aid in plant growth promotion. Furthermore, the WGS comparison of these strains with the well-characterized Sphingomonas sp. LK11, an arid desert strain, identified several genes responsible for the production of phytohormones and for stress tolerance. Production of one of the phytohormones, indole-3-acetic acid, was further confirmed in the ISS strains using liquid chromatography-mass spectrometry. Pathways associated with phosphate uptake, metabolism, and solubilization in soil were conserved across all the S. sanguinis and S. paucimobilis strains tested. Furthermore, genes thought to promote plant resistance to abiotic stress, including heat/cold shock response, heavy metal resistance, and oxidative and osmotic stress resistance, appear to be present in these space-related S. sanguinis and S. paucimobilis strains. Characterizing these biotechnologically important microorganisms found on the ISS and harnessing their key features will aid in the development of self-sustainable long-term space missions in the future. IMPORTANCE Sphingomonas is ubiquitous in nature, including the anthropogenically contaminated extreme environments. Members of the Sphingomonas genus have been identified as potential candidates for space biomining beyond earth. This study describes the isolation and identification of Sphingomonas members from the ISS, which are capable of producing the phytohormone indole-3-acetic acid. Microbial production of phytohormones will help future in situ studies, grow plants beyond low earth orbit, and establish self-sustainable life support systems. Beyond phytohormone production, stable genomic elements of abiotic stress resistance, heavy metal resistance, and oxidative and osmotic stress resistance were identified, rendering the ISS Sphingomonas isolate a strong candidate for biotechnology-related applications.

BackgroundDistrust, and more broadly, public perception of government's handling of a crisis, has been a widely studied topic within health crisis research and suggests that these perceptions are significantly associated with the behavior of its citizens.PurposeTo understand which aspects of the public's perception of government handling of the COVID-19 pandemic predicted engagement of protective behaviors among older adults, who are the most vulnerable to COVID-19.MethodsParticipants were recruited from an ongoing biopsychosocial study on aging amongst community-dwelling older adults. There were two rounds of data collection, during the national lockdown and post-lockdown. The average length of follow-up was 5.88 months. N = 421 completed the first round of data collection and N = 318 subsequently completed the second round of questionnaires.ResultsDuring the lockdown, perceptions that pandemic-related measures in place were sufficient, effective, timely, provided a sense of safety, important information was easily accessible, and government handling of the pandemic could be trusted, were found to significantly predict engagement in protective behaviors. During post-lockdown, only perceptions that measures in place were sufficient, provided a sense of safety, and important information was easily accessible, remained significant predictors. The perception that COVID-19 measures were clear and easy to understand now became a significant predictor.ConclusionsPublic perceptions of government handling of the pandemic predicted engagement in protective behaviors but were less important during post-lockdown. To effectively engage older adults in protective behavior, our findings suggest for pandemic-related information to be accessible, introducing timely safety measures, and having easy-to-understand instructions for nuanced measures.

Evidence for beneficial effects of corticotropin releasing hormone (CRH) antagonists in abdominal and pelvic organs is emerging in preclinical studies. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement a compilation of preclinical studies using CRH receptor antagonists as a treatment for abdominal and pelvic disease was carried out. The Animal Research: Reporting of In Vivo Experiments (ARRIVE) essential 10 guidelines were used to determine quality of the included studies. A total of 40 studies from the last 15 years studying irritable bowel syndrome, inflammatory bowel disease, endometriosis, enteritis, stress impact on gastrointestinal processes and exogenous CRH administration effects were included. Blockage of the CRH receptor 1 was mainly associated with beneficial effects while that of CRH receptor 2 worsened studied effects. However, time of administration, route of administration and the animal model used, all had an impact on the beneficial outcomes. Frequency of drugs administered indicated that astressin-2B, astressin and antalarmin were among the most utilized antagonists. Of concern, studies included were predominantly carried out in male models only, representing a gender discrepancy in preclinical studies compared to the clinical scenario. The ARRIVE score average was 13 with ~60% of the studies failing to randomize or blind the experimental units. Despite the failure to date of the CRH antagonists in moving across the clinical trials pipeline, there is evidence for their beneficial effects beyond mood disorders. Future pre-clinical studies should be tailored towards effectively predicting the clinical scenario, including reduction of bias and randomization.

Ferredoxin:NAD+ oxidoreductase (NADH-FNOR) catalyzes the transfer of electrons from reduced ferredoxin to NAD+. This enzyme has been hypothesized to be the main enzyme responsible for ferredoxin oxidization in the NADH-based ethanol pathway in Thermoanaerobacterium saccharolyticum; however, the corresponding gene has not yet been identified. Here, we identified the Tsac_1705 protein as a candidate FNOR based on the homology of its functional domains. We then confirmed its activity in vitro with a ferredoxin-based FNOR assay. To determine its role in metabolism, the tsac_1705 gene was deleted in different strains of T. saccharolyticum. In wild-type T. saccharolyticum, deletion of tsac_1705 resulted in a 75% loss of NADH-FNOR activity, which indicated that Tsac_1705 is the main NADH-FNOR in T. saccharolyticum. When both NADH- and NADPH-linked FNOR genes were deleted, the ethanol titer decreased and the ratio of ethanol to acetate approached unity, indicative of the absence of FNOR activity. Finally, we tested the effect of heterologous expression of Tsac_1705 in Clostridium thermocellum and found improvements in both the titer and the yield of ethanol. [ABSTRACT FROM AUTHOR]

Edge computing is a promising infrastructure evolution to reduce traffic loads and support low-latency communications. Furthermore, content-centric networks provide a natural solution to cache contents at edge nodes. However, it is a challenge for edge nodes to handle massive and highly dynamic content requests by users, and if without an efficient content caching strategy, the edge nodes will encounter high traffic load and latency due to increasing retrieval from content providers. This paper formulates a proactive edge caching problem to minimize the content retrieval cost at edge nodes. We exploit the inherent content caching and request aggregation mechanism in the content-centric networks to jointly minimize traffic load and content retrieval delay cost generated by the massive and dynamic content requests. We develop a Q-learning algorithm, which is an online optimal caching strategy, as it is adaptable to dynamic content popularity and content request intensity, and derive the long-term minimization of the content retrieval cost. Simulation results illustrate that the proposed algorithm can achieve a lower content retrieval cost compared with several baseline caching schemes.

A novel Radio Frequency Identification (RFID) based sensor supporting touch detection and localization features is proposed in this work. The formulated sensor leverages chipless variant of RFID technology for the design of a passive fully-printable frequency domain-based sensor-incorporated tag. The sensor is composed of square resonators arranged in a peculiar fashion laid down across a $3\times2$ grid. The proposed sensor incorporated-tag readily keeps track of human-digit position, allowing for tracking of finger-swipes which, in turn, can potentially be used for recognition of unlock patterns and security codes. Performance of the sensor is analyzed using its Radar Cross Section (RCS) response observable in the spectral domain. Each constituent resonant-element making up the sensor resonates at a single frequency represented by a distinct dip in the RCS response. The spectral dip drifts well outside of its allocated band upon occurrence of a touch event. A functional prototype of the sensor tag is fabricated on a 0.508 mm thick Rogers RT/Duroid® 5880 laminate is scrutinized of its electromagnetic performance. The sensor possesses a compact physical footprint equal to 45 mm $\times55$ mm. The obtained results solidify the suitability of the proposed sensor for deployment in secure access control settings prevalent in smart cities and connected home applications.

Ecocriticism is very wide in its scope and this paper will focus on the branch of ecocriticism that analyses imaginative texts and argues that such texts can provide a regenerative and revitalising message for the world. Ecocriticism did not take off as a coherent movement until the 1990s but critics found valuable messages in Sketches of Etruscan Places from the early years following its publication in 1932. This paper will examine the developing reception of the book from the outset with particular reference to its ecological value, not what Lawrence saw as its value purely as another of his travel books.

Abstract: Travel is often thought to be an adventure, an exploration, a way of knowing self and world, a break from the stresses of everyday life, a vacation. But there can be a dark side to travel, as in voyages that are part of invasion, conflict and enforced transport. Here, I wish to concentrate on conflict, domination, murder and genocide and do so, at various moments, by referring to the Norse sagas, including the encounter with the Skrælings in the New World and, more briefly, Columbus’ and the Spaniards’ violent treatment of the Natives in the New World and the German transport, torture and murder of Jews in the Shoah, or Holocaust.

An adaptive response renewable energy plant (AREP) that provides grid balancing services and XeV station fuelling services (where “X” is any type) using renewable energy located in urban centres is described. The AREP has its own primary renewable energy sources and adapts operation in the short term to changing levels of excess or deficient energy on LV and MV electricity grids. The AREP adaptively responds by (1) storing excess energy in batteries for the short term and in hydrogen tanks after energy conversion by electrolysers for the long term; (2) returning power to the grid from either the AREP's own primary (electron-based) energy sources or batteries and/or from hydrogen via conversion in fuel cells; (3) providing electricity for fast charging BeVs and PHeVs and hydrogen for FCeVs; and (4) exporting excess stored energy as hydrogen to domestic markets. The AREP also adapts over the long term by predictive planning of charging capacity such that the type and capacity of renewable energy equipment is optimised for future operations. A key advantage of this AREP configuration is a flexible, “plug and play” capability with modular extension of energy assets. If the AREP footprint is constrained, interaction with neighbouring AREPs as a mini-VPP-AREP network can assist in balancing short-term operating requirements.The benefits of this grid balancing and XeV renewable energy filling station, or AREP, are environmental, social and economic through efficient functionality of appropriately sized components. AREPs provide a net zero emissions electricity solution to an existing network with short and long-term storage options as well as a net zero emissions fuel alternative to the transport sector, while leveraging existing infrastructure with minimal upfront CAPEX. AREPs can give the flexibility a grid needs to enable high levels of renewable installations while developing green hydrogen production.

Introduction Exercise and physical activity (PA) are fundamental to the treatment of type 2 diabetes. Current exercise and PA strategies for newly diagnosed individuals with type 2 diabetes are either clinically effective but unsuitable in routine practice (supervised exercise) or suitable in routine practice but clinically ineffective (PA advice). Mobile health (mHealth) technologies, offering biometric data to patients and healthcare professionals, may bridge the gap between supervised exercise and PA advice, enabling patients to engage in regular long-term physically active lifestyles. This feasibility randomised controlled trial (RCT) will evaluate the use of mHealth technology when incorporated into a structured home-based exercise and PA intervention, in those recently diagnosed with type 2 diabetes.Methods and analysis This feasibility multicentre, parallel group RCT will recruit 120 individuals with type 2 diabetes (diagnosis within 5–24 months, aged 40–75 years) in the UK (n=60) and Canada (n=60). Participants will undertake a 6-month structured exercise and PA intervention and be supported by an exercise specialist (active control). The intervention group will receive additional support from a smartwatch and phone app, providing real-time feedback and enabling improved communication between the exercise specialist and participant. Primary outcomes are recruitment rate, adherence to exercise and loss to follow-up. Secondary outcomes include a qualitative process evaluation and piloting of potential clinical outcome measures for a future RCT.Ethics and dissemination The trial was approved in the UK by the South East Scotland Research Ethics Committee 01 (20/SS/0101) and in Canada by the Clinical Research Ethics Board of the University of British Columbia (H20-01936), and is being conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. Results will be published in peer-reviewed journals and presented at national and international scientific meetings.Trial registration numbers ISRCTN14335124; ClinicalTrials.gov: NCT04653532.

Abstract The present study aimed to evaluate the frequency of immediate care seeking after traumatic dental injury (TDI) in primary dentition and its association with the children’s characteristics, socioeconomic status, and TDI characteristics. This was a cross-sectional study with dental records of children aged 9 months to 6 years who attended a reference center in TDI in primary dentition between 2007 and 2018. Immediate care seeking after TDI, child’s characteristics, sociodemographic conditions and TDI characteristics were collected. Descriptive statistics and Poisson regression analysis with robust variance were performed (p < 0.05; 95%CI). Among the 493 dental records, 61.1% (n = 301) were of males and 50.5% (n = 249) were from children aged 2 years or less. More than one third of the sample (36.9%; n = 182) sought immediate care after TDI. Among the types of TDI, the prevalence of soft tissue injuries was 59.0% (n = 291), while 51.7% (n = 255) were hard tissue injuries and 54.0% (n = 266) were supporting tissue injuries. Immediate care seeking after TDI was higher in children who needed suture (PR: 1.39; 95%CI: 1.01–1.92. p = 0.039), had luxation (lateral, intrusion, or extrusion) (PR: 2.36; 95%CI: 1.36–4.08. p = 0.002) or avulsion (PR: 2.18; 95%CI: 1.28–3.70. p = 0.004). The need for suture, luxation (lateral, intrusion and extrusion), and avulsion were determinant factors for the immediate care seeking after TDI, regardless of the child’s characteristics and socioeconomic status.

Background: ICIs have dramatically improved patient outcomes in different malignancies. However, the impact of liver metastases (LM) and number of metastatic sites (MS) remains unclear in patients treated with single-agent anti-PD(L)1. Methods: We aimed to assess the prognostic impact of LM and MS number on progression-free survival (PFS) and overall survival (OS) in a large single-arm retrospective multicentric cohort (IMMUCARE) of patients treated with anti-PD(L)-1 for different solid tumors. Results: A total of 759 patients were enrolled from January 2012 to October 2018. The primary tumor types were non-small cell lung cancer (71%), melanoma (19%), or urologic cancer (10%). At the time of ICI initiation, 167 patients (22%) had LM and 370 patients (49%) had more than MS. LM was associated with a shorter median PFS of 1.9 months (95% CI: 1.8–2.5) vs. 4.0 months (95% CI: 3.6–5.4) in patients without LM (p < 0.001). The median OS of patients with LM was of 5.2 months (95% CI: 4.0–7.7) compared with 12.8 months (95% CI: 11.2–15.1) (p < 0.001). Interestingly, LM were not associated with shorter PFS, or OS compared to other MS types (brain, bone, or lung) in patients with only one MS. Patients with multiple MS also had poor clinical outcomes compared to patients with only one MS. The presence of LM and MS number were independent prognostic factors on overall survival. Conclusion: The presence of LM or multiple MS were associated with poorer survival outcomes in patients treated with anti-PD(L)-1.

Extracellular vesicles (EVs) from stem cells have shown significant therapeutic potential to repair injured cardiac tissues and regulate pathological fibrosis. However, scalable generation of stem cells and derived EVs for clinical utility remains a huge technical challenge. Here, we report a rapid size-based extrusion strategy to generate EV-like membranous nanovesicles (NVs) from easily sourced human iPSCs in large quantities (yield 900× natural EVs). NVs isolated using density-gradient separation (buoyant density 1.13 g/mL) are spherical in shape and morphologically intact and readily internalised by human cardiomyocytes, primary cardiac fibroblasts, and endothelial cells. NVs captured the dynamic proteome of parental cells and include pluripotency markers (LIN28A, OCT4) and regulators of cardiac repair processes, including tissue repair (GJA1, HSP20/27/70, HMGB1), wound healing (FLNA, MYH9, ACTC1, ILK), stress response/translation initiation (eIF2S1/S2/S3/B4), hypoxia response (HMOX2, HSP90, GNB1), and extracellular matrix organization (ITGA6, MFGE8, ITGB1). Functionally, NVs significantly promoted tubule formation of endothelial cells (angiogenesis) (p < 0.05) and survival of cardiomyocytes exposed to low oxygen conditions (hypoxia) (p < 0.0001), as well as attenuated TGF-β mediated activation of cardiac fibroblasts (p < 0.0001). Quantitative proteome profiling of target cell proteome following NV treatments revealed upregulation of angiogenic proteins (MFGE8, MYH10, VDAC2) in endothelial cells and pro-survival proteins (CNN2, THBS1, IGF2R) in cardiomyocytes. In contrast, NVs attenuated TGF-β-driven extracellular matrix remodelling capacity in cardiac fibroblasts (ACTN1, COL1A1/2/4A2/12A1, ITGA1/11, THBS1). This study presents a scalable approach to generating functional NVs for cardiac repair.

Extracellular vesicles (EVs) hold great promise as therapeutic modalities due to their endogenous characteristics, however, further bioengineering refinement is required to address clinical and commercial limitations. Clinical applications of EV-based therapeutics are being trialed in immunomodulation, tissue regeneration and recovery, and as delivery vectors for combination therapies. Native/biological EVs possess diverse endogenous properties that offer stability and facilitate crossing of biological barriers for delivery of molecular cargo to cells, acting as a form of intercellular communication to regulate function and phenotype. Moreover, EVs are important components of paracrine signaling in stem/progenitor cell-based therapies, are employed as standalone therapies, and can be used as a drug delivery system. Despite remarkable utility of native/biological EVs, they can be improved using bio/engineering approaches to further therapeutic potential. EVs can be engineered to harbor specific pharmaceutical content, enhance their stability, and modify surface epitopes for improved tropism and targeting to cells and tissues in vivo. Limitations currently challenging the full realization of their therapeutic utility include scalability and standardization of generation, molecular characterization for design and regulation, therapeutic potency assessment, and targeted delivery. The fields’ utilization of advanced technologies (imaging, quantitative analyses, multi-omics, labeling/live-cell reporters), and utility of biocompatible natural sources for producing EVs (plants, bacteria, milk) will play an important role in overcoming these limitations. Advancements in EV engineering methodologies and design will facilitate the development of EV-based therapeutics, revolutionizing the current pharmaceutical landscape.

Patients with end-stage renal disease treated with dialysis are often prescribed complex medication regimens, placing them at risk for drug-drug interactions and other medication-related problems. Particularly in the context of a broader interest in more patient-centered value-based care, improving medication management is an increasingly important focus area. However, current medication management metrics, designed for the broader patient population, may not be well suited to the specific needs of patients with kidney disease, especially given the complexity of medication regimens used by dialysis patients. We propose a kidney pharmacy-focused quality pyramid that is intended to provide a framework to guide dialysis organizations, health care providers, and/or clinicians with respect to an optimal medication management approach for dialysis patients. Incorporation of core programs in medication management, including medication reconciliation, safety programs, and medication therapy management for patients at high risk for medication-related problems, may result in improved outcomes. Although a growing body of evidence supports the concept that active medication management can improve medication adherence and reduce medication-related problems, these strategies are viewed as costly and are not widely deployed. However, if done effectively, pharmacy-led medication management has the potential to be one of the more cost-effective disease management strategies and may greatly improve outcomes for these complex patients. Index Words: end-stage renal disease, medication management, pharmacy

La vitamina D es una hormona cumple una función en la regulación de numerosos genes que participan en la proliferación y maduración celular. El objetivo de este trabajo fue determinar la prevalencia de valores inadecuados de esta vitamina en jóvenes sanos de Asunción e identificar los posibles factores de riesgo asociados. Estudio observacional descriptivo basado en datos clínico-epidemiológicos y en la determinación de la 25-hidroxivitamina D (25-OH vitamina D) por el método de quimioluminiscencia (CMIA). Se consideró valor adecuado ≥30 ng/dl, inadecuado por debajo de este rango y deficiente ≤20 ng/dl. El análisis estadístico se realizó con el programa R–proyect. Para establecer factores de riesgo para tener deficiencia de vitamina D se utilizó regresión logística bi y multivariante. Se incluyeron 817 jóvenes universitarios de edad promedio 21 años. La concentración de vitamina D tuvo una media de 25 ± 8 ng/dl, oscilando entre 64,3 y 2,4 ng/dl. El 75,5% de los participantes tenían valores inadecuados de vitamina D. La deficiencia de vitamina D fue significativamente (p = 0,006) más frecuente en mujeres, personas con sobrepeso (p = 0,03), con falta de exposición al sol (p = 0,001) y con sedentarismo (p = 0,0001). Este estudio confirma la elevada prevalencia de valores inadecuados de vitamina D en nuestro país y permite definir un perfil de muy alto riesgo para las jóvenes sedentarias y con sobrepeso, lo que justifica una atención especial de parte de los médicos y las instituciones responsables de la salud pública en nuestro país.

This article offers a conceptual study of a scientific practice. Phylogenetic analysis is one of the main methods of evolutionary biology as it allows us to deduce the evolutionary relationships between different species or organisms. In current practice, these analyses are often performed with the help of molecular data, resulting in what are called molecular phylogenies. A major question is what is the best way to characterize this practice? We begin with a presentation of this method articulated in four stages: (1) identification; (2) alignment of homologous sequences (stemming from a common ancestor); (3) construction (4) interpretation of phylogenetic trees. We show that phylogenetic analyses are not experiments, and therefore do not belong to the “laboratory style”, as defined by Hacking. This practice does not correspond to a typical practice from the historical sciences, as described by Cleland. Although there is only a partial correspondence between phylogenetic analysis and these conceptualizations, we argue that each confrontation sheds light on distinct aspects of this practice. We also question the idea of a strong methodological separation between experimental sciences and historical sciences.

El lupus eritematoso sistémico (LES) es una enfermedad autoinmune, de etiología desconocida que presenta manifestaciones clínicas de gravedad y curso impredecible. Se ha observado en varias cohortes que esta enfermedad tiene un comportamiento más agresivo en la población no caucásica debido a diferencias socioeconómicas, demográficas y genéticas. El objetivo del estudio es describir las características clínico-epidemiológicas de los pacientes con LES incluidos en la cohorte LUPUS-PY y la situación actual de las muestras custodiadas en el BIOBANCO IMID-PY. Estudio basado en la revisión de historias clínicas y en los cuestionarios clínico-epidemiológicos del día de la inclusión al registro LUPUS-PY. Se calcularon las frecuencias para las variables categóricas y las medias con su desvío estándar para las continuas. Se incluyeron de forma consecutiva, 83 pacientes con diagnóstico de LES (edad media: 34,4±10,0 años), el 86,7% era del sexo femenino, el 55% provenía de Asunción, el 49,1% tenía nivel educativo básico, el 45% percibía un ingreso mensual de un sueldo mínimo (aproximadamente 350 dólares americanos) o menos. El 46,8% no realizaba ningún tipo de actividad física. La media del tiempo trascurrido desde el inicio de los síntomas y el diagnóstico del LES fue de 9,3±13,7 años y el tiempo de evolución de la enfermedad hasta el ingreso al registro fue de 5,9±6,3. El 16% refirió antecedentes familiares de enfermedades autoinmunes. La primera manifestación de la enfermedad más descripta fue la articular (45%). Los pacientes con LES de nuestro centro tienen características tanto clínicas como epidemiológicas similares a las reportadas por otras cohortes.

Natural gas reservoirs in the oceanic subsurface sustain complex communities of anaerobic microbes. Here, Seitz et al. describe a previously unknown archaeal phylum, Helarchaeota, belonging to the Asgard superphylum and with the potential for oxidation of hydrothermally generated short-chain hydrocarbons.

In this paper, we analyze the impact of buffer-aided full-duplex successive relay selection schemes with energy harvesting capability of relay nodes in amplifying and forward (AF) and decode and forward (DF) relaying environments for the Internet of Things networks. We propose to select a relay pair based on the energy harvested and signal strength at relay and destination to receive and transmit in the same time slot, respectively. Contrary to the previous relay pair selection schemes which are based on the signal strength only and cause the relay overuse problem, the proposed scheme ensures the balanced use of energy of relay nodes. The proposed relay selection scheme is implemented with the time switching (TS) and power splitting (PS)-based energy harvesting models in AF and DF relaying environments separately. Furthermore, we derive the closed-form expression of the outage probability and average throughput for both the TS and PS approaches in the DF and AF relaying modes. We compare the proposed relay selection scheme with the S-MMRS scheme and prove that the proposed scheme significantly reduces the outage probability and improves the average throughput. Furthermore, the analytical findings are reinforced with the extensive Monte Carlo simulations.

In this paper, a compact and fully passive bit encoding circuit, capable of operating as a chipless radio frequency identification (RFID) tag is presented. The structure consists of novel concentric trefoil-shaped slot resonators realized using Rogers RT/duroid® 5880 laminate, occupying a physical footprint of 13.55 $\times $ 13.55 mm2. Each resonating element is associated with a particular data bit, having a 1:1 resonator-to-bit correspondence. Bit sequences are configured through introducing modifications in the geometric structure either by addition or exclusion of each nested slot resonator. Such changes manifest directly in the electromagnetic signature of the tag as presence or absence of corresponding resonant peaks. The proposed 10-bit tag offers minimized inter-resonator mutual coupling and insensitivity to changes in polarization and incident angles thereby demonstrating orientation independent functionality. Moreover, error-free encoding is achieved through stabilizing the shift in resonant frequencies for a variety of different geometric configurations and orientation of the structure. The tag operates within the license-free ultra-wideband ranging from 5.4 to 10.4 GHz, providing spectral bit capacity and bit density of 2 bits/GHz and 5.44 bits/cm2 respectively.