Showing papers by "Nova Southeastern University published in 2020"

MEMOTE for standardized genome-scale metabolic model testing

Abstract: We acknowledge D. Dannaher and A. Lopez for their supporting work on the Angular parts of MEMOTE; resources and support from the DTU Computing Center; J. Cardoso, S. Gudmundsson, K. Jensen and D. Lappa for their feedback on conceptual details; and P. D. Karp and I. Thiele for critically reviewing the manuscript. We thank J. Daniel, T. Kristjansdottir, J. Saez-Saez, S. Sulheim, and P. Tubergen for being early adopters of MEMOTE and for providing written testimonials. J.O.V. received the Research Council of Norway grants 244164 (GenoSysFat), 248792 (DigiSal) and 248810 (Digital Life Norway); M.Z. received the Research Council of Norway grant 244164 (GenoSysFat); C.L. received funding from the Innovation Fund Denmark (project “Environmentally Friendly Protein Production (EFPro2)”); C.L., A.K., N. S., M.B., M.A., D.M., P.M, B.J.S., P.V., K.R.P. and M.H. received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement 686070 (DD-DeCaF); B.G.O., F.T.B. and A.D. acknowledge funding from the US National Institutes of Health (NIH, grant number 2R01GM070923-13); A.D. was supported by infrastructural funding from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), Cluster of Excellence EXC 2124 Controlling Microbes to Fight Infections; N.E.L. received funding from NIGMS R35 GM119850, Novo Nordisk Foundation NNF10CC1016517 and the Keck Foundation; A.R. received a Lilly Innovation Fellowship Award; B.G.-J. and J. Nogales received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no 686585 for the project LIAR, and the Spanish Ministry of Economy and Competitivity through the RobDcode grant (BIO2014-59528-JIN); L.M.B. has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement 633962 for project P4SB; R.F. received funding from the US Department of Energy, Offices of Advanced Scientific Computing Research and the Biological and Environmental Research as part of the Scientific Discovery Through Advanced Computing program, grant DE-SC0010429; A.M., C.Z., S.L. and J. Nielsen received funding from The Knut and Alice Wallenberg Foundation, Advanced Computing program, grant #DE-SC0010429; S.K.’s work was in part supported by the German Federal Ministry of Education and Research (de.NBI partner project “ModSim” (FKZ: 031L104B)); E.K. and J.A.H.W. were supported by the German Federal Ministry of Education and Research (project “SysToxChip”, FKZ 031A303A); M.K. is supported by the Federal Ministry of Education and Research (BMBF, Germany) within the research network Systems Medicine of the Liver (LiSyM, grant number 031L0054); J.A.P. and G.L.M. acknowledge funding from US National Institutes of Health (T32-LM012416, R01-AT010253, R01-GM108501) and the Wagner Foundation; G.L.M. acknowledges funding from a Grand Challenges Exploration Phase I grant (OPP1211869) from the Bill & Melinda Gates Foundation; H.H. and R.S.M.S. received funding from the Biotechnology and Biological Sciences Research Council MultiMod (BB/N019482/1); H.U.K. and S.Y.L. received funding from the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries (grants NRF-2012M1A2A2026556 and NRF-2012M1A2A2026557) from the Ministry of Science and ICT through the National Research Foundation (NRF) of Korea; H.U.K. received funding from the Bio & Medical Technology Development Program of the NRF, the Ministry of Science and ICT (NRF-2018M3A9H3020459); P.B., B.J.S., Z.K., B.O.P., C.L., M.B., N.S., M.H. and A.F. received funding through Novo Nordisk Foundation through the Center for Biosustainability at the Technical University of Denmark (NNF10CC1016517); D.-Y.L. received funding from the Next-Generation BioGreen 21 Program (SSAC, PJ01334605), Rural Development Administration, Republic of Korea; G.F. was supported by the RobustYeast within ERA net project via SystemsX.ch; V.H. received funding from the ETH Domain and Swiss National Science Foundation; M.P. acknowledges Oxford Brookes University; J.C.X. received support via European Research Council (666053) to W.F. Martin; B.E.E. acknowledges funding through the CSIRO-UQ Synthetic Biology Alliance; C.D. is supported by a Washington Research Foundation Distinguished Investigator Award. I.N. received funding from National Institutes of Health (NIH)/National Institute of General Medical Sciences (NIGMS) (grant P20GM125503).

Next-generation Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines for allergic rhinitis based on Grading of Recommendations Assessment, Development and Evaluation (GRADE) and real-world evidence

Abstract: The selection of pharmacotherapy for patients with allergic rhinitis aims to control the disease and depends on many factors. Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines have considerably improved the treatment of allergic rhinitis. However, there is an increasing trend toward use of real-world evidence to inform clinical practice, especially because randomized controlled trials are often limited with regard to the applicability of results. The Contre les Maladies Chroniques pour un Vieillissement Actif (MACVIA) algorithm has proposed an allergic rhinitis treatment by a consensus group. This simple algorithm can be used to step up or step down allergic rhinitis treatment. Next-generation guidelines for the pharmacologic treatment of allergic rhinitis were developed by using existing GRADE-based guidelines for the disease, real-world evidence provided by mobile technology, and additive studies (allergen chamber studies) to refine the MACVIA algorithm.

The contribution of frailty, cognition, activity of daily life and comorbidities on outcome in acutely admitted patients over 80 years in European ICUs: the VIP2 study

Abstract: Premorbid conditions affect prognosis of acutely-ill aged patients. Several lines of evidence suggest geriatric syndromes need to be assessed but little is known on their relative effect on the 30-day survival after ICU admission. The primary aim of this study was to describe the prevalence of frailty, cognition decline and activity of daily life in addition to the presence of comorbidity and polypharmacy and to assess their influence on 30-day survival. Prospective cohort study with 242 ICUs from 22 countries. Patients 80 years or above acutely admitted over a six months period to an ICU between May 2018 and May 2019 were included. In addition to common patients’ characteristics and disease severity, we collected information on specific geriatric syndromes as potential predictive factors for 30-day survival, frailty (Clinical Frailty scale) with a CFS > 4 defining frail patients, cognitive impairment (informant questionnaire on cognitive decline in the elderly (IQCODE) with IQCODE ≥ 3.5 defining cognitive decline, and disability (measured the activity of daily life with the Katz index) with ADL ≤ 4 defining disability. A Principal Component Analysis to identify co-linearity between geriatric syndromes was performed and from this a multivariable model was built with all geriatric information or only one: CFS, IQCODE or ADL. Akaike’s information criterion across imputations was used to evaluate the goodness of fit of our models. We included 3920 patients with a median age of 84 years (IQR: 81–87), 53.3% males). 80% received at least one organ support. The median ICU length of stay was 3.88 days (IQR: 1.83–8). The ICU and 30-day survival were 72.5% and 61.2% respectively. The geriatric conditions were median (IQR): CFS: 4 (3–6); IQCODE: 3.19 (3–3.69); ADL: 6 (4–6); Comorbidity and Polypharmacy score (CPS): 10 (7–14). CFS, ADL and IQCODE were closely correlated. The multivariable analysis identified predictors of 1-month mortality (HR; 95% CI): Age (per 1 year increase): 1.02 (1.–1.03, p = 0.01), ICU admission diagnosis, sequential organ failure assessment score (SOFA) (per point): 1.15 (1.14–1.17, p < 0.0001) and CFS (per point): 1.1 (1.05–1.15, p < 0.001). CFS remained an independent factor after inclusion of life-sustaining treatment limitation in the model. We confirm that frailty assessment using the CFS is able to predict short-term mortality in elderly patients admitted to ICU. Other geriatric syndromes do not add improvement to the prediction model. Since CFS is easy to measure, it should be routinely collected for all elderly ICU patients in particular in connection to advance care plans, and should be used in decision making.

The athletic gut microbiota.

Abstract: The microorganisms in the gastrointestinal tract play a significant role in nutrient uptake, vitamin synthesis, energy harvest, inflammatory modulation, and host immune response, collectively contributing to human health. Important factors such as age, birth method, antibiotic use, and diet have been established as formative factors that shape the gut microbiota. Yet, less described is the role that exercise plays, particularly how associated factors and stressors, such as sport/exercise-specific diet, environment, and their interactions, may influence the gut microbiota. In particular, high-level athletes offer remarkable physiology and metabolism (including muscular strength/power, aerobic capacity, energy expenditure, and heat production) compared to sedentary individuals, and provide unique insight in gut microbiota research. In addition, the gut microbiota with its ability to harvest energy, modulate the immune system, and influence gastrointestinal health, likely plays an important role in athlete health, wellbeing, and sports performance. Therefore, understanding the mechanisms in which the gut microbiota could play in the role of influencing athletic performance is of considerable interest to athletes who work to improve their results in competition as well as reduce recovery time during training. Ultimately this research is expected to extend beyond athletics as understanding optimal fitness has applications for overall health and wellness in larger communities. Therefore, the purpose of this narrative review is to summarize current knowledge of the athletic gut microbiota and the factors that shape it. Exercise, associated dietary factors, and the athletic classification promote a more "health-associated" gut microbiota. Such features include a higher abundance of health-promoting bacterial species, increased microbial diversity, functional metabolic capacity, and microbial-associated metabolites, stimulation of bacterial abundance that can modulate mucosal immunity, and improved gastrointestinal barrier function.

CD73 immune checkpoint defines regulatory NK cells within the tumor microenvironment

Abstract: High levels of ecto-5'-nucleotidase (CD73) have been implicated in immune suppression and tumor progression, and have also been observed in cancer patients who progress on anti-PD-1 immunotherapy. Although regulatory T cells can express CD73 and inhibit T cell responses via the production of adenosine, less is known about CD73 expression in other immune cell populations. We found that tumor-infiltrating NK cells upregulate CD73 expression and the frequency of these CD73-positive NK cells correlated with larger tumor size in breast cancer patients. In addition, the expression of multiple alternative immune checkpoint receptors including LAG-3, VISTA, PD-1, and PD-L1 was significantly higher in CD73-positive NK cells than in CD73-negative NK cells. Mechanistically, NK cells transport CD73 in intracellular vesicles to the cell surface and the extracellular space via actin polymerization-dependent exocytosis upon engagement of 4-1BBL on tumor cells. These CD73-positive NK cells undergo transcriptional reprogramming and upregulate IL-10 production via STAT3 transcriptional activity, suppressing CD4-positive T cell proliferation and IFN-γ production. Taken together, our results support the notion that tumors can hijack NK cells as a means to escape immunity and that CD73 expression defines an inducible population of NK cells with immunoregulatory properties within the tumor microenvironment.

Genomic history and ecology of the geographic spread of rice

Abstract: Rice (Oryza sativa) is one of the world's most important food crops, and is comprised largely of japonica and indica subspecies. Here, we reconstruct the history of rice dispersal in Asia using whole-genome sequences of more than 1,400 landraces, coupled with geographic, environmental, archaeobotanical and paleoclimate data. Originating around 9,000 yr ago in the Yangtze Valley, rice diversified into temperate and tropical japonica rice during a global cooling event about 4,200 yr ago. Soon after, tropical japonica rice reached Southeast Asia, where it rapidly diversified, starting about 2,500 yr BP. The history of indica rice dispersal appears more complicated, moving into China around 2,000 yr BP. We also identify extrinsic factors that influence genome diversity, with temperature being a leading abiotic factor. Reconstructing the dispersal history of rice and its climatic correlates may help identify genetic adaptations associated with the spread of a key domesticated species.

Goods and Services of Marine Bivalves

Abstract: The aim of this book is to review and analyse the goods and services of bivalve shellfish. How they are defined, what determines the ecological functions that are the basis for the goods and services, what controversies in the use of goods and services exist, and what is needed for sustainable exploitation of bivalves from the perspective of the various stakeholders. The book is focused on the goods and services, and not on impacts of shellfish aquaculture on the benthic environment, or on threats like biotoxins; neither is it a shellfish culture handbook although it can be used in evaluating shellfish culture. The reviews and analysis are based on case studies that exemplify the concept, and show the strengths and weaknesses of the current applications. The multi-authored reviews cover ecological, economic and social aspects of bivalve goods and services. The book provides new insights for scientists, students, shellfish producers, policy advisors, nature conservationists and decision makers. This book is open access under the CC BY license.

Global injury morbidity and mortality from 1990 to 2017: results from the Global Burden of Disease Study 2017

Abstract: Background Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries. Methods We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs). Findings In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, agestandardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505). Interpretation Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in highburden populations, improving data collection and ensuring access to medical care.

Crowdsourcing hypothesis tests: Making transparent how design choices shape research results

Abstract: To what extent are research results influenced by subjective decisions that scientists make as they design studies? Fifteen research teams independently designed studies to answer five original research questions related to moral judgments, negotiations, and implicit cognition. Participants from two separate large samples (total N > 15,000) were then randomly assigned to complete one version of each study. Effect sizes varied dramatically across different sets of materials designed to test the same hypothesis: materials from different teams rendered statistically significant effects in opposite directions for four out of five hypotheses, with the narrowest range in estimates being d = -0.37 to +0.26. Meta-analysis and a Bayesian perspective on the results revealed overall support for two hypotheses, and a lack of support for three hypotheses. Overall, practically none of the variability in effect sizes was attributable to the skill of the research team in designing materials, while considerable variability was attributable to the hypothesis being tested. In a forecasting survey, predictions of other scientists were significantly correlated with study results, both across and within hypotheses. Crowdsourced testing of research hypotheses helps reveal the true consistency of empirical support for a scientific claim.

Opinion: Midwater ecosystems must be considered when evaluating environmental risks of deep-sea mining

Abstract: Despite rapidly growing interest in deep-sea mineral exploitation, environmental research and management have focused on impacts to seafloor environments, paying little attention to pelagic ecosystems. Nonetheless, research indicates that seafloor mining will generate sediment plumes and noise at the seabed and in the water column that may have extensive ecological effects in deep midwaters (1), which can extend from an approximate depth of 200 meters to 5 kilometers. Deep midwater ecosystems represent more than 90% of the biosphere (2), contain fish biomass 100 times greater than the global annual fish catch (3), connect shallow and deep-sea ecosystems, and play key roles in carbon export (4), nutrient regeneration, and provisioning of harvestable fish stocks (5). These ecosystem services, as well as biodiversity, could be negatively affected by mining. Here we argue that deep-sea mining poses significant risks to midwater ecosystems and suggest how these risks could be evaluated more comprehensively to enable environmental resource managers and society at large to decide whether and how deep-sea mining should proceed. Midwater animal biodiversity: Squid, fish, shrimp, copepods, medusa, filter-feeding jellies, and marine worms are among the midwater creatures that could be affected by deep sea mining. Photos by E. Goetze, K. Peijnenburg, D. Perrine, Hawaii Seafood Council (B. Takenaka, J. Kaneko), S. Haddock, J. Drazen, B. Robison, DEEPEND (Dante Fenolio), and MBARI. Interest in deep-sea mining for sulfide deposits near hydrothermal vents, polymetallic nodules on the abyssal seafloor, and cobalt-rich crusts on seamounts (6) has grown substantially in the last decade. Equipment and system development are already occurring. The International Seabed Authority (ISA), the international organization created under the United Nations Convention on the Law of the Sea (UNCLOS) to manage deep-sea mining beyond national jurisdiction, is developing mineral exploitation regulations, the Mining Code. Currently, 30 ISA exploration contracts cover over 1.5 million … [↵][1]1To whom correspondence should be addressed. Email: jdrazen{at}hawaii.edu. [1]: #xref-corresp-1-1

New WHO guidelines for treatment of gambiense human African trypanosomiasis including fexinidazole: substantial changes for clinical practice.

Abstract: Human African trypanosomiasis caused by Trypanosoma brucei gambiense is a parasitic infection that usually progresses to coma and death unless treated. WHO has updated its guidelines for the treatment of this infection on the basis of independent literature reviews and using the Grading of Recommendations Assessment, Development and Evaluation methodology. The first-line treatment options, pentamidine and nifurtimox-eflornithine combination therapy, have been expanded to include fexinidazole, an oral monotherapy given a positive opinion from the European Medicines Agency. Fexinidazole is recommended for individuals who are aged 6 years and older with a bodyweight of 20 kg or more, who have first-stage or second-stage gambiense human African trypanosomiasis and a cerebrospinal fluid leucocyte count less than 100 per μL. Nifurtimox-eflornithine combination therapy remains recommended for patients with 100 leucocytes per μL or more. Without clinical suspicion of severe second-stage disease, lumbar puncture can be avoided and fexinidazole can be given. Fexinidazole should only be administered under supervision of trained health staff. Because these recommendations are expected to change clinical practice considerably, health professionals should consult the detailed WHO guidelines. These guidelines will be updated as evidence accrues.

Effects of a combined transcranial magnetic stimulation (TMS) and cognitive training intervention in patients with Alzheimer's disease

Abstract: Introduction This clinical trial evaluates the efficacy and safety of a 6-week course of daily neuroAD™ therapy. Methods 131 subjects between 60 and 90 years old, unmedicated for Alzheimer's disease (AD), or on stable doses of an acetylcholinesterase inhibitor and/or memantine, with Mini–Mental State Examination scores between 18 and 26, clinical dementia rating scale scores of 1 or 2, enrolled for a prospective, randomized, double-blind, sham-controlled, multicenter clinical trial. Structural brain MRIs were obtained for transcranial magnetic stimulation targeting. Baseline Alzheimer's disease assessment scale—cognitive (ADAS-Cog) and Clinical Global Impression of Change were assessed. 129 participants were randomized to active treatment plus standard of care (SOC) or sham treatments plus SOC. Results Subjects with baseline ADAS-Cog ≤ 30 (~85% of study population) showed a statistically significant benefit favoring active over sham. Responder analysis showed 31.7% participants in the active group with ≤ −4 point improvement on ADAS-Cog versus 15.4% in the sham group. Discussion neuroAD™ Therapy System provides a low-risk therapeutic benefit for patients with milder AD (baseline ADAS-Cog ≤30) beyond pharmacologic SOC.

Long-term safety and efficacy of erenumab in patients with chronic migraine: Results from a 52-week, open-label extension study.

Abstract: BackgroundThis study reports the long-term safety and efficacy of erenumab in chronic migraine patients.MethodsThis was a 52-week open-label extension study of a 12-week double-blind treatment phas...

European energy poverty metrics: Scales, prospects and limits

Abstract: Energy poverty, a condition whereby people cannot secure adequate home energy services, is gaining prominence in public discourse and on political and policy agendas. As its measurement is operationalised, metrical developments are being socially shaped. A European Union mandate for biennial reporting on energy poverty presents an opportunity to institutionalise new metrics and thus privilege certain measurements as standards. While combining indicators at multiple scales is desirable to measure multi-dimensional aspects, it entails challenges such as database availability, coverage and limited disaggregated resolution. This article converges scholarship on metrics – which problematises the act of measurement – and on energy poverty – which apprehends socio-political and techno-economic particulars. Scholarship on metrics suggests that any basket of indicators risks silencing significant but hard to measure aspects, or unwarrantedly privileging others. State-of-the-art energy poverty scholarship calls for indicators that represent contextualised energy use issues, including energy access and quality, expenditure in relation to income, built environment related aspects and thermal comfort levels, while retaining simplicity and comparability for policy traction. We frame energy poverty metrology as the socially shaped measurement of a varied, multi-dimensional phenomenon within historically bureaucratic and publicly distant energy sectors, and assess the risks and opportunities that must be negotiated. To generate actionable knowledge, we propose an analytical framework with five dimensions of energy poverty metrology, and illustrate it using multi-scalar cases from three European countries. Dimensions include historical trajectories, data flattening, contextualised identification, new representation and policy uptake. We argue that the measurement of energy poverty must be informed by the politics of data and scale in order to institutionalise emerging metrics, while safeguarding against their co-optation for purposes other than the deep and rapid alleviation of energy poverty. This ‘dimensioned’ understanding of metrology can provide leverage to push for decisive action to address the structural underpinnings of domestic energy deprivation.

Vascular safety of erenumab for migraine prevention

Abstract: Objective To examine the cardiovascular, cerebrovascular, and peripheral vascular safety of erenumab across migraine prevention studies. Methods Vascular adverse events (AEs) and blood pressure data were integrated across 4 double-blind, placebo-controlled studies of erenumab and their open-label extensions in patients with chronic or episodic migraine. Subgroup analyses were conducted by acute migraine-specific medication use and number of vascular risk factors at baseline. Standardized search terms were used to identify vascular AEs (cardiovascular, cerebrovascular, or peripheral). An independent committee adjudicated whether targeted events were vascular in origin. Results In placebo-controlled studies, 2,443 patients received placebo (n = 1,043), erenumab 70 mg (n = 893), or erenumab 140 mg (n = 507) subcutaneously once monthly. Regardless of acute migraine-specific medication use or vascular risk factors at baseline, AE incidence was similar across the placebo and erenumab treatment groups. Hypertension AEs were reported for 0.9% (placebo), 0.8% (erenumab 70 mg), and 0.2% (erenumab 140 mg) of patients. Vascular AEs, which were similar across double-blind and open-label treatment, generally were confounded, with plausible alternative etiologies. In 18 patients with events reviewed by the independent committee, 4 events were positively adjudicated as cardiovascular in origin: 2 deaths and 2 vascular events. All 4 positively adjudicated cardiovascular events occurred during open-label erenumab treatment. Conclusion Selective blockade of the canonical calcitonin gene-related peptide receptor with erenumab for migraine prevention had a vascular safety profile comparable to that of placebo over 12 weeks, with no increased emergence of events over time. Further study of long-term safety of erenumab in patients with migraine is needed. Clinicaltrials.gov identifiers NCT02066415, NCT02456740, NCT01952574, NCT02483585, NCT02174861, and NCT01723514. Classification of evidence This analysis provides Class II evidence that for patients with migraine, erenumab does not increase the risk of vascular AEs.

Medical Electronic Prescription for Home Respiratory Care Services (PEM-CRD) at a Portuguese University Tertiary Care Centre (2014–2018): A Case Study

Abstract: Home respiratory care (HRC) is the provision of healthcare services at the place of residence of patients or their families, with the aim of meeting needs mainly resulting from chronic respiratory conditions, permanent disability, or terminal illness. In 2016, an innovative electronic prescription system, PEM-CRD, was fully implemented for HRC services in Portugal. To date, no study has addressed the impact of the execution of this digital innovation. For this purpose, we carried out an analysis of the prevalence and number of prescriptions for people with chronic respiratory diseases receiving HRC in the Lisbon metropolitan area, during 2014–2018, using the information obtained from the PEM-CRD database. The data analysis shows that while the number of patients receiving HRC treatment with a prescription has remained stable over the last four years, the number of prescriptions has significantly dropped since 2016 (2016–2018), with consequent paper and processes efficiency. The implementation of the digital Medical Electronic Prescription for Home Respiratory Care tool (PEM-CRD) and consequent dematerialization of these processes has increased the efficiency of prescribing in HRC. Additionally, the possibility of obtaining data through the PEM-CRD allows the monitoring of the evolving prevalence of therapies, improving the health services optimization and allowing reporting on data other than medicines.

Racial and Ethnic Disparities in COVID-19 Outcomes: Social Determination of Health.

Abstract: As of 18 October 2020, over 39.5 million cases of coronavirus disease 2019 (COVID-19) and 1.1 million associated deaths have been reported worldwide. It is crucial to understand the effect of social determination of health on novel COVID-19 outcomes in order to establish health justice. There is an imperative need, for policy makers at all levels, to consider socioeconomic and racial and ethnic disparities in pandemic planning. Cross-sectional analysis from COVID Boston University's Center for Antiracist Research COVID Racial Data Tracker was performed to evaluate the racial and ethnic distribution of COVID-19 outcomes relative to representation in the United States. Representation quotients (RQs) were calculated to assess for disparity using state-level data from the American Community Survey (ACS). We found that on a national level, Hispanic/Latinx, American Indian/Alaskan Native, Native Hawaiian/Pacific Islanders, and Black people had RQs > 1, indicating that these groups are over-represented in COVID-19 incidence. Dramatic racial and ethnic variances in state-level incidence and mortality RQs were also observed. This study investigates pandemic disparities and examines some factors which inform the social determination of health. These findings are key for developing effective public policy and allocating resources to effectively decrease health disparities. Protective standards, stay-at-home orders, and essential worker guidelines must be tailored to address the social determination of health in order to mitigate health injustices, as identified by COVID-19 incidence and mortality RQs.

Cannabinoid Receptors: An Update on Cell Signaling, Pathophysiological Roles and Therapeutic Opportunities in Neurological, Cardiovascular, and Inflammatory Diseases.

Abstract: The identification of the human cannabinoid receptors and their roles in health and disease, has been one of the most significant biochemical and pharmacological advancements to have occurred in the past few decades. In spite of the major strides made in furthering endocannabinoid research, therapeutic exploitation of the endocannabinoid system has often been a challenging task. An impaired endocannabinoid tone often manifests as changes in expression and/or functions of type 1 and/or type 2 cannabinoid receptors. It becomes important to understand how alterations in cannabinoid receptor cellular signaling can lead to disruptions in major physiological and biological functions, as they are often associated with the pathogenesis of several neurological, cardiovascular, metabolic, and inflammatory diseases. This review focusses mostly on the pathophysiological roles of type 1 and type 2 cannabinoid receptors, and it attempts to integrate both cellular and physiological functions of the cannabinoid receptors. Apart from an updated review of pre-clinical and clinical studies, the adequacy/inadequacy of cannabinoid-based therapeutics in various pathological conditions is also highlighted. Finally, alternative strategies to modulate endocannabinoid tone, and future directions are also emphasized.

Long-Acting Injectable Cabotegravir + Rilpivirine for HIV Maintenance Therapy: Week 48 Pooled Analysis of Phase 3 ATLAS and FLAIR Trials.

Abstract: HIV remains a major global health concern, with the Joint United Nations Programme on HIV/AIDS and the World Health Organization (WHO) estimating the number of people living with HIV (PLWH) to be ∼37.9 million in 2018.1,2 Improvements in HIV treatment efficacy are reflected in the increases in longevity of PLWH.3 Despite this progress, the effectiveness of current antiretroviral therapy (ART) is challenged by the need to maintain high levels of adherence to sustain virologic suppression.4 Factors related to regimen complexity, such as dosing frequency and pill burden, food considerations, stigma, and drug–drug interactions between oral antiretrovirals and commonly prescribed non-ART medications, are reported to contribute to this challenge.4–6 Furthermore, the emotional burden of living with HIV may be compounded by daily oral pill taking and additional complexities.7 Therefore, there is considerable interest in developing long-acting (LA) treatments that can address many of these issues while simplifying ART for PLWH.8 The recommended ART regimen for PLWH generally consists of daily doses of either an oral 2-drug or 3-drug combination.9,10 This combination typically involves an integrase strand transfer inhibitor (INSTI) (dolutegravir as the sole INSTI preferred for use in adults in the WHO guidelines9 and either dolutegravir, bictegravir, or raltegravir preferred in the US Department of Health and Human Services guidelines10), in combination with 2 nucleoside reverse transcriptase inhibitors (NRTIs); although, a single NRTI (lamivudine) in combination with dolutegravir has recently been recommended as a 2-drug regimen in HIV treatment guidelines.10 Cabotegravir (CAB) (GSK1265744) is an investigational INSTI and structural analog of dolutegravir.11 Rilpivirine (RPV) is a next-generation non-NRTI (NNRTI) currently approved as a once-daily oral tablet to be used in combination with other antiretrovirals for the treatment of HIV infection.12,13 Both compounds are formulated as LA agents to be administered intramuscularly (IM), with oral formulations of RPV and a new formulation of CAB in development.13 These oral formulations have been used during an oral lead-in phase in the ATLAS14 and FLAIR15 studies to assess safety and tolerability before study participants transitioning to LA therapy with CAB and RPV. This 2-drug oral combination therapy of CAB and RPV was assessed in the LATTE ({"type":"clinical-trial","attrs":{"text":"NCT01641809","term_id":"NCT01641809"}}NCT01641809) study and shown to provide similar antiviral activity compared with efavirenz plus dual NRTIs.16 A single IM injection of CAB LA 800 mg or RPV LA 1200 mg demonstrated sustained mean or geometric mean plasma concentrations above their respective in vitro protein-adjusted 90% inhibitory concentrations (PA-IC90) at 32 weeks postdose for CAB LA17 (PA-IC90 0.166 μg/mL), and 24 weeks postdose for RPV LA18 (PA-IC90 12 ng/mL), providing rationale to investigate the 2 drugs as an LA combination regimen. In the LATTE-2 ({"type":"clinical-trial","attrs":{"text":"NCT02120352","term_id":"NCT02120352"}}NCT02120352) randomized, open-label phase 2b clinical trial, the injectable LA combination of CAB and RPV (CAB + RPV LA) as a 2-drug HIV-1 maintenance therapy, administered every 4 or 8 weeks, was similar to daily 3-drug oral therapy of CAB plus abacavir/lamivudine in maintaining viral suppression (plasma HIV-1 RNA <50 copies per/mL; FDA Snapshot algorithm) through 96 weeks.19 Together, these results supported phase 3 investigation of CAB + RPV LA. ATLAS ({"type":"clinical-trial","attrs":{"text":"NCT02951052","term_id":"NCT02951052"}}NCT02951052)14 and FLAIR ({"type":"clinical-trial","attrs":{"text":"NCT02938520","term_id":"NCT02938520"}}NCT02938520)15 are ongoing randomized, open-label, multinational phase 3 studies. These studies demonstrated that monthly injections of CAB + RPV LA were noninferior based on the primary endpoint (participants with plasma HIV-1 RNA ≥50 copies/mL at week 48) compared with a control group who continued their oral current antiretroviral regimen (CAR). The individual results of these studies are published elsewhere.14,15 Here, we present the preplanned pooled analyses of the efficacy (noninferiority), viral resistance, pharmacokinetic analysis, safety and tolerability, and preference findings observed in participants enrolled in the ATLAS and FLAIR studies.

Marine Environmental Plastic Pollution: Mitigation by Microorganism Degradation and Recycling Valorization

Abstract: Plastic is a very useful material and presents numerous advantages in the daily life of individuals and society. However, plastics are accumulating in the environment and due to their low biodegradability rate, this problem will persist for centuries. Until recently, oceans were treated as places to dispose of litter, thus the persistent substances are causing serious pollution issues. Plastic and microplastic waste has a negative environmental, social and economic impact, e.g. causing injury/death to marine organisms and entering the food chain, which leads to health problems. The development of solutions and methods to mitigate marine (micro)plastic pollution is in high demand. There is a knowledge gap in this field, reason why research on this thematic is increasing. Recent studies reported the biodegradation of some types of polymers using different bacteria, biofilm forming bacteria, bacterial consortia, and fungi. Biodegradation is influenced by several factors, from the type of microorganism to the type of polymers, their physicochemical properties and the environment conditions (e.g. temperature, pH, UV radiation). Currently, green environmentally friendly alternatives to plastic made from renewable feedstocks are starting to enter the market. This review covers the period from 1964 to April 2020 and comprehensively gathers investigation on marine plastic and microplastic pollution, negative consequences of plastic use, bioplastic production and lists the most useful methods for plastic degradation and recycling valorization, including degradation mediated by microorganisms (biodegradation) and the methods used to detect and analyze the biodegradation.

The evolutionary history of extinct and living lions

Abstract: Lions are one of the world’s most iconic megafauna, yet little is known about their temporal and spatial demographic history and population differentiation. We analyzed a genomic dataset of 20 specimens: two ca. 30,000-y-old cave lions (Panthera leo spelaea), 12 historic lions (Panthera leo leo/Panthera leo melanochaita) that lived between the 15th and 20th centuries outside the current geographic distribution of lions, and 6 present-day lions from Africa and India. We found that cave and modern lions shared an ancestor ca. 500,000 y ago and that the 2 lineages likely did not hybridize following their divergence. Within modern lions, we found 2 main lineages that diverged ca. 70,000 y ago, with clear evidence of subsequent gene flow. Our data also reveal a nearly complete absence of genetic diversity within Indian lions, probably due to well-documented extremely low effective population sizes in the recent past. Our results contribute toward the understanding of the evolutionary history of lions and complement conservation efforts to protect the diversity of this vulnerable species.

Ensuring a Post-COVID Economic Agenda Tackles Global Biodiversity Loss

Abstract: The COVID-19 pandemic has caused dramatic and unprecedented impacts on both global health and economies. Many governments are now proposing recovery packages to get back to normal, but the 2019 Intergovernmental Science-Policy Platform for Biodiversity and Ecosystem Services Global Assessment indicated that business as usual has created widespread ecosystem degradation. Therefore, a post-COVID world needs to tackle the economic drivers that create ecological disruptions. In this perspective, we discuss a number of tools across a range of actors for both short-term stimulus measures and longer-term revamping of global, national, and local economies that take biodiversity into account. These include measures to shift away from activities that damage biodiversity and toward those supporting ecosystem resilience, including through incentives, regulations, fiscal policy, and employment programs. By treating the crisis as an opportunity to reset the global economy, we have a chance to reverse decades of biodiversity and ecosystem losses.