Researching COVID to Enhance Recovery (RECOVER) Adult Study Protocol: Rationale, Objectives, and Design

IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. METHODS: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. DISCUSSION: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options

Breast Radiotherapy after Oncoplastic Surgery—A Multidisciplinary Approach

Oncoplastic breast surgery encompasses a range of techniques used to provide equitable oncological outcomes compared with standard breast surgery while, simultaneously, prioritizing aesthetic outcomes. While the outcomes of oncoplastic breast surgery are promising, it can add an extra complexity to the treatment paradigm of breast cancer and impact on decision-making surrounding adjuvant therapies, like chemotherapy and radiotherapy. As such, early discussions at the multidisciplinary team meeting with surgeons, medical oncologists, and radiation oncologists present, should be encouraged to facilitate best patient care

Metabolomic Analysis of Prenatal Maternal Stress Effects on Offspring as a Result of the 2011 Queensland Flood

INTRODUCTION: It is widely acknowledged that the health outcomes of offspring are directly linked to the health of their mother during pregnancy. The impacts of pre-natal maternal stress (PNMS) can cascade as development of the offspring continues, and are linked to negative health outcomes. OBJECTIVE: Our goal was to determine the metabolomic differences in offspring who were exposed in utero to the 2011 Queensland Flood in relation to the mother’s level of subjective distress and objective hardship. METHODS: Ninety urine samples were obtained from 51 male and 39 female 4-year-old offspring. Metabolomic profiles were acquired using a 700 MHz Bruker Avance III HD NMR spectrometer and subsequently binned. Partial Least Squares-Discriminant Analysis (PLS-DA) was used to identify differences in high vs. low composite subjective distress and high vs. low objective hardship in metabolic profiles, in both male and female groups. Metabolites leading to significant group separation were identified using both Variable Importance Analysis based on random Variable Combination (VIAVC) and a Mann-Whitney U test. Metabolanalyst software was used for metabolite sets enrichment analysis of altered metabolites, and to identify potential biochemical pathways and disease pathologies in the offspring. RESULTS: Group separation was observed between high and low levels of both objective hardship and composite subjective distress groups, in both males and females. Several metabolites were detected as being either up- or down-regulated, thus contributing to the observed separation, including creatinine and formate. CONCLUSIONS: The metabolites identified as significantly altered have been associated with several negative health outcomes. Creatinine down- regulation has been associated with dysfunction in Krebs cycle thus potentially disturbing energy metabolism and contributing to psychiatric illness. Formate up-regulation has been linked to oxidative stress and correlated to metabolic dysfunction in genes relating to neurodegenerative diseases. Understanding the biological pathways affected by exposure to PNMS allows for an improved approach to patient treatment. *Indicates presente

Molecular networks implicated in speech-related disorders: FOXP2 regulates the SRPX2/uPAR complex

It is a challenge to identify the molecular networks contributing to the neural basis of human speech. Mutations in transcription factor FOXP2 cause difficulties mastering fluent speech (developmental verbal dyspraxia, DVD), whereas mutations of sushi-repeat protein SRPX2 lead to epilepsy of the rolandic (sylvian) speech areas, with DVD or with bilateral perisylvian polymicrogyria. Pathophysiological mechanisms driven by SRPX2 involve modified interaction with the plasminogen activator receptor (uPAR). Independent chromatin-immunoprecipitation microarray screening has identified the uPAR gene promoter as a potential target site bound by FOXP2. Here, we directly tested for the existence of a transcriptional regulatory network between human FOXP2 and the SRPX2/uPAR complex. In silico searches followed by gel retardation assays identified specific efficient FOXP2-binding sites in each of the promoter regions of SRPX2 and uPAR. In FOXP2-transfected cells, significant decreases were observed in the amounts of both SRPX2 (43.6%) and uPAR (38.6%) native transcripts. Luciferase reporter assays demonstrated that FOXP2 expression yielded a marked inhibition of SRPX2 (80.2%) and uPAR (77.5%) promoter activity. A mutant FOXP2 that causes DVD (p.R553H) failed to bind to SRPX2 and uPAR target sites and showed impaired down-regulation of SRPX2 and uPAR promoter activity. In a patient with polymicrogyria of the left rolandic operculum, a novel FOXP2 mutation (p.M406T) was found in the leucine-zipper (dimerization) domain. p.M406T partially impaired the FOXP2 regulation of SRPX2 promoter activity, whereas that of the uPAR promoter remained unchanged. Together with recently described FOXP2-CNTNAP2 and SRPX2/uPAR links, the FOXP2-SRPX2/uPAR network provides exciting insights into molecular pathways underlying speech-related disorders

Trade of Woody Biomass for Electricity Generation under Climate Mitigation Policy

Bio-energy has the potential to be a key mitigation option if combined with carbon capture and sequestration (BECCS) because it generates electricity and absorbs emissions at the same time. However, biomass is not distributed evenly across the globe, and regions with a potentially high demand might be constrained by limited domestic supply. Therefore, climate mitigation policies might create the incentive to trade biomass internationally. This paper uses scenarios generated by the integrated assessment model WITCH to study trade of woody biomass from multiple perspectives: the volume of biomass traded, its value, the impact on other power generation technologies and on marginal abatement costs. The policy scenarios consist of three representative carbon tax policies (4.8 W/m2, 3.8 W/m2 and 3.2 W/m2 radiative forcing in 2100) and a cap-and-trade scheme (3.8 W/m2 in 2100). Results show that the incentive to trade biomass is high: at least 50% of biomass consumed globally is from the international market. Regions trade 13-69 EJ/yr of woody biomass in 2050 and 55-81 EJ/yr in 2100. In 2100 the value of biomass traded is equal to US$ 0.7-7.2 Trillion. Trade of woody biomass sensibly reduces marginal abatement costs. In the tax scenarios, abatement increases by 120-323 Gt CO2 over the century. In the cap-and-trade scenario biomass trade reduces the price of emission allowances by 34% in 2100 and cumulative discounted policy costs by 14%