How does climate change impact social bees and bee sociality?

Climatic factors are known to shape the expression of social behaviours. Likewise, variation in social behaviour can dictate climate responses. Understanding interactions between climate and sociality is crucial for forecasting vulnerability and resilience to climate change across animal taxa. These interactions are particularly relevant for taxa like bees that exhibit a broad diversity of social states. An emerging body of literature aims to quantify bee responses to environmental change with respect to variation in key functional traits, including sociality. Additionally, decades of research on environmental drivers of social evolution may prove fruitful for predicting shifts in the costs and benefits of social strategies under climate change. In this review, we explore these findings to ask two interconnected questions: (a) how does sociality mediate vulnerability to climate change, and (b) how might climate change impact social organisation in bees? We highlight traits that intersect with bee sociality that may confer resilience to climate change (e.g. extended activity periods, diet breadth, behavioural thermoregulation) and we generate predictions about the impacts of climate change on the expression and distribution of social phenotypes in bees. The social evolutionary consequences of climate change will be complex and heterogeneous, depending on such factors as local climate and plasticity of social traits. Many contexts will see an increase in the frequency of eusocial nesting as warming temperatures accelerate development and expand the temporal window for rearing a worker brood. More broadly, climate-mediated shifts in the abiotic and biotic selective environments will alter the costs and benefits of social living in different contexts, with cascading impacts at the population, community and ecosystem levels.

Unraveling the Impact of miR-146a in Pulmonary Arterial Hypertension Pathophysiology and Right Ventricular Function.

Pulmonary arterial hypertension (PAH) is a chronic disorder characterized by excessive pulmonary vascular remodeling, leading to elevated pulmonary vascular resistance and right ventricle (RV) overload and failure. MicroRNA-146a (miR-146a) promotes vascular smooth muscle cell proliferation and vascular neointimal hyperplasia, both hallmarks of PAH. This study aimed to investigate the effects of miR-146a through pharmacological or genetic inhibition on experimental PAH and RV pressure overload animal models. Additionally, we examined the overexpression of miR-146a on human pulmonary artery smooth muscle cells (hPASMCs). Here, we showed that miR-146a genic expression was increased in the lungs of patients with PAH and the plasma of monocrotaline (MCT) rats. Interestingly, genetic ablation of miR-146a improved RV hypertrophy and systolic pressures in Sugen 5415/hypoxia (SuHx) and pulmonary arterial banding (PAB) mice. Pharmacological inhibition of miR-146a improved RV remodeling in PAB-wild type mice and MCT rats, and enhanced exercise capacity in MCT rats. However, overexpression of miR-146a did not affect proliferation, migration, and apoptosis in control-hPASMCs. Our findings show that miR-146a may play a significant role in RV function and remodeling, representing a promising therapeutic target for RV hypertrophy and, consequently, PAH.

Local climate change velocities and evolutionary history explain multidirectional range shifts in a North American butterfly assemblage.

Species are often expected to shift their distributions either poleward or upslope to evade warming climates and colonise new suitable climatic niches. However, from 18-years of fixed transect monitoring data on 88 species of butterfly in the midwestern United States, we show that butterflies are shifting their centroids in all directions, except towards regions that are warming the fastest (southeast). Butterflies shifted their centroids at a mean rate of 4.87 km year-1. The rate of centroid shift was significantly associated with local climate change velocity (temperature by precipitation interaction), but not with mean climate change velocity throughout the species' ranges. Species tended to shift their centroids at a faster rate towards regions that are warming at slower velocities but increasing in precipitation velocity. Surprisingly, species' thermal niche breadth (range of climates butterflies experience throughout their distribution) and wingspan (often used as metric for dispersal capability) were not correlated with the rate at which species shifted their ranges. We observed high phylogenetic signal in the direction species shifted their centroids. However, we found no phylogenetic signal in the rate species shifted their centroids, suggesting less conserved processes determine the rate of range shift than the direction species shift their ranges. This research shows important signatures of multidirectional range shifts (latitudinal and longitudinal) and uniquely shows that local climate change velocities are more important in driving range shifts than the mean climate change velocity throughout a species' entire range.

Corticotropin-releasing hormone and obesity: From fetal life to adulthood.

Obesity is among the most common chronic disorders, worldwide. It is a complex disease that reflects the interactions between environmental influences, multiple genetic allelic variants, and behavioral factors. Recent developments have also shown that biological conditions in utero play an important role in the programming of energy homeostasis systems and might have an impact on obesity and metabolic disease risk. The corticotropin-releasing hormone (CRH) family of neuropeptides, as a central element of energy homeostasis, has been evaluated for its role in the pathophysiology of obesity. This review aims to summarize the relevance and effects of the CRH family of peptides in the pathophysiology of obesity spanning from fetal life to adulthood.

Long-term therapy with itolizumab is safe and effective for patients with moderate to severe psoriasis: Results from an expanded-access program.

Itolizumab is a humanized monoclonal antibody that selectively targets the CD6-ALCAM pathway. This article reports on the safety and efficacy of itolizumab in the treatment of moderate-to-severe plaque psoriasis in a clinical study conducted in Cuba in the setting of an expanded-access program (EAP). The study included 84 patients who had previously received conventional anti-psoriatic systemic therapies but were either intolerant, had an inadequate response, or had contraindications to these therapies. It consisted of multiple phases, including a 12-week induction phase, a 40-week maintenance phase, and a 24-week off-treatment follow-up phase, using either a 0.4 or 1.6 mg/Kg dose. The results showed that itolizumab monotherapy was safe and effective during 52 weeks of continuous treatment and the subsequent 24 follow-up weeks. Itolizumab treatment resulted in a significant improvement (PASI 75) in 80 % of patients at the end of the induction phase, and this effect was sustained till week 52 during the maintenance phase. Moreover, 24 weeks after treatment stopped nearly two-thirds of patients still showed a PASI ≥ 75. The observed effects were dose-dependent, with 1.6 mg/kg being the most convenient dose. This study further supports the strategy of targeting the CD6-ALCAM signaling pathway for the treatment of psoriasis and the use of itolizumab as a valuable asset in the armamentarium of anti-psoriasis drugs.

Real-world effectiveness of the heterologous SOBERANA-02 and SOBERANA-Plus vaccine scheme in 2-11 years-old children during the SARS-CoV-2 Omicron wave in Cuba: a longitudinal case-population study.

Background: Increased pediatric COVID-19 occurrence due to the SARS-CoV-2 Omicron variant has raised concerns about the effectiveness of existing vaccines. The protection provided by the SOBERANA-02-Plus vaccination scheme against this variant has not yet been studied. We aimed to evaluate the scheme's effectiveness against symptomatic Omicron infection and severe disease in children. Methods: In September 2021, Cuba implemented a mass pediatric immunization with the heterologous SOBERANA-02-Plus scheme: 2 doses of conjugated SOBERANA-02 followed by a heterologous SOBERANA-Plus dose. By December, before the Omicron outbreak, 95.4% of 2-18 years-old had been fully immunized. During the entire Omicron wave, we conducted a nationwide longitudinal post-vaccination case-population study to evaluate the real-world effectiveness of the SOBERANA-02-Plus scheme against symptomatic infection and severe disease in children without previous SARS-CoV-2 infection. The identification of COVID-19 cases relied on surveillance through first line services, which refer clinical suspects to pediatric hospitals where they are diagnosed based on a positive RT-PCR test. We defined the Incidence Rate ratio (IRR) as IRvaccinated age group/IRunvaccinated 1-year-old and calculated vaccine effectiveness as VE = (1-IRR)∗100%. 24 months of age being the 'eligible for vaccination' cut-off, we used a regression discontinuity approach to estimate effectiveness by contrasting incidence in all unvaccinated 1-year-old versus vaccinated 2-years-old. Estimates in the vaccinated 3-11 years-old are reported from a descriptive perspective. Findings: We included 1,098,817 fully vaccinated 2-11 years-old and 98,342 not vaccinated 1-year-old children. During the 24-week Omicron wave, there were 7003/26,241,176 person-weeks symptomatic COVID-19 infections in the vaccinated group (38.2 per 105 person-weeks in 2-years-old and 25.5 per 105 person-weeks in 3-11 years-old) against 3577/2,312,273 (154.7 per 105 person-weeks) in the unvaccinated group. The observed overall vaccine effectiveness against symptomatic infection was 75.3% (95% CI, 73.5-77.0%) in 2-years-old children, and 83.5% (95% CI, 82.8-84.2%) in 3-11 years-old. It was somewhat lower during Omicron BA.1 then during Omicron BA.2 variant circulation, which took place 1-3 and 4-6 months after the end of the vaccination campaign. The effectiveness against severe symptomatic disease was 100.0% (95% CI not estimated) and 94.6% (95% CI, 82.0-98.6%) in the respective age groups. No child death from COVID-19 was observed. Interpretation: Immunization of 2-11 years-old with the SOBERANA-02-Plus scheme provided strong protection against symptomatic and severe disease caused by the Omicron variant, which was sustained during the six months post-vaccination follow-up. Our results contrast with the observations in previous real-world vaccine effectiveness studies in children, which might be explained by the type of immunity a conjugated protein-based vaccine induces and the vaccination strategy used. Funding: National Fund for Science and Technology (FONCI-CITMA-Cuba).

Combination therapy of Epidermal Growth Factor and Growth Hormone-Releasing Hexapeptide in acute ischemic stroke: a phase I/II non-blinded, randomized clinical trial.

Objective: This study tested the hypothesis that a neuroprotective combined therapy based on epidermal growth factor (EGF) and growth hormone-releasing hexapeptide (GHRP6) could be safe for acute ischemic stroke patients, admitting up to 30% of serious adverse events (SAE) with proven causality. Methods: A multi-centric, randomized, open-label, controlled, phase I-II clinical trial with parallel groups was conducted (July 2017 to January 2018). Patients aged 18-80 years with a computed tomography-confirmed ischemic stroke and less than 12 h from the onset of symptoms were randomly assigned to the study groups I (75 µg rEGF + 3.5 mg GHRP6 i.v., n=10), II (75 µg rEGF + 5 mg GHRP6 i.v., n=10), or III (standard care control, n=16). Combined therapy was given BID for 7 days. The primary endpoint was safety over 6 months. Secondary endpoints included neurological (NIHSS) and functional [Barthel index and modified Rankin scale (mRS)] outcomes. Results: The study population had a mean age of 66 ± 11 years, with 21 men (58.3%), a baseline median NIHSS score of 9 (95% CI: 8-11), and a mean time to treatment of 7.3 ± 2.8 h. Analyses were conducted on an intention-to-treat basis. SAEs were reported in 9 of 16 (56.2%) patients in the control group, 3 of 10 (30%) patients in Group I (odds ratio (OR): 0.33; 95% CI: 0.06-1.78), and 2 of 10 (20%) patients in Group II (OR: 0.19; 95% CI: 0.03-1.22); only two events in one patient in Group I were attributed to the intervention treatment. Compliance with the study hypothesis was greater than 0.90 in each group. Patients treated with EGF + GHRP6 had a favorable neurological and functional evolution at both 90 and 180 days, as evidenced by the inferential analysis of NIHSS, Barthel, and mRS and by their moderate to strong effect size. At 6 months, proportion analysis evidenced a higher survival rate for patients treated with the combined therapy. Ancillary analysis including merged treated groups and utility-weighted mRS also showed a benefit of this combined therapy. Conclusion: EGF + GHRP6 therapy was safe. The functional benefits of treatment in this study supported a Phase III study. Clinical Trial Registration: RPCEC00000214 of the Cuban Public Registry of Clinical Trials, Unique identifier: IG/CIGB-845I/IC/1601.

The Ketone Bridge Between the Heart and the Bladder: How Fast Should We Go?

Metabolic syndrome (MS) is associated with both cardiovascular and bladder dysfunction. Insulin resistance (IR) and central obesity, in particular, are the main risk factors. In these patients, vicious pathological cycles exacerbate abnormal carbohydrate metabolism and sustain an inflammatory state, with serious implications for both the heart and bladder. Ketone bodies serve as an alternative energy source in this context. They are considered a "super-fuel" because they generate adenosine triphosphate with less oxygen consumption per molecule, thus enhancing metabolic efficiency. Ketone bodies have a positive impact on all components of MS. They aid in weight loss and glycemic control, lower blood pressure, improve lipid profiles, and enhance endothelial function. Additionally, they possess direct anti-inflammatory, antioxidant, and vasodilatory properties. A shared key player in dysfunction of both the heart and bladder dysfunction is the formation of the NLRP3 inflammasome, which ketone bodies inhibit. Interventions that elevate ketone body levels-such as fasting, a ketogenic diet, ketone supplements, and sodium-glucose cotransporter 2 inhibitors-have been shown to directly affect cardiovascular outcomes and improve lower urinary tract symptoms derived from MS. This review explores the pathophysiological basis of the benefits of ketone bodies in cardiac and bladder dysfunction.

Biosensors for natriuretic peptides in cardiovascular diseases. A review.

Heart failure (HF) is a complex clinical syndrome associated with high rates of morbidity and mortality. Over the years, it has been crucial to find accurate biomarkers capable of doing a precise monitor of HF and provide an early diagnosis. Of these, it has been established an important role of natriuretic peptides in HF assessment. Moreover, the development of biosensors has been garnering interest as new diagnostic medical tools. In this review we first provide a general overview of HF, its pathogenesis, and diagnostic features. We then discuss the role of natriuretic peptides in heart failure by characterizing them and point out their potential as biomarkers. Finally, we adress the evolution of biosensors development and the available natriuretic peptides biosensors for disease monitoring.

Immunogenicity and safety of heterologous boost immunization with PastoCovac Plus against COVID-19 in ChAdOx1-S or BBIBP-CorV primed individuals.

BACKGROUND: This study aimed at evaluation and comparison of PastoCovac Plus protein-subunit vaccine in parallel with ChAdOx1-S (AstraZeneca) and BBIBP-CorV (Sinopharm) in primarily vaccinated volunteers with two doses of ChAdOx1-S or BBIBP-CorV. MATERIALS AND METHODS: 194 volunteers enrolled the study who were previously primed with 2 doses of ChAdOx1-S or BBIBP-CorV vaccines. They were divided into two heterologous regimens receiving a third dose of PastoCovac Plus, and two parallel homologous groups receiving the third dose of BBIBP-CorV or ChAdOx1-S. Serum samples were obtained just before and 4 weeks after booster dose. Anti-spike IgG and neutralizing antibodies were quantified and the conventional live-virus neutralization titer, (cVNT50) assay was done against Omicron BA.5 variant. Moreover, the adverse events data were recorded after receiving booster doses. RESULTS: ChAdOx1-S/PastoCovac Plus group reached 73.0 units increase in anti-Spike IgG rise compared to the ChAdOx1-S/ ChAdOx1-S (P: 0.016). No significant difference was observed between the two groups regarding neutralizing antibody rise (P: 0.256), indicating equivalency of both booster types. Adjusting for baseline titers, the BBIBP-CorV/PastoCovac Plus group showed 135.2 units increase (P<0.0001) in anti-Spike IgG, and 3.1 (P: 0.008) unit increase in mean rise of neutralizing antibodies compared to the homologous group. Adjustment for COVID-19 history, age, underlying diseases, and baseline antibody titers increased the odds of anti-Spike IgG fourfold rise both in the ChAdOx1-S (OR: 1.9; P: 0.199) and BBIBP CorV (OR: 37.3; P< 0.0001) heterologous groups compared to their corresponding homologous arms. The odds of neutralizing antibody fourfold rise, after adjustment for the same variables, was 2.4 (P: 0.610) for the ChAdOx1-S heterologous group and 5.4 (P: 0.286) for the BBIBP CorV heterologous groups compared to their corresponding homologous groups. All the booster types had the potency to neutralize BA.5 variant with no significant difference. The highest rate of adverse event incidence was recorded for ChAdOx1-S homologous group. CONCLUSIONS: PastoCovac Plus booster application in primed individuals with BBIBP-CorV or ChAdOx1-S successfully increased specific antibodies' levels without any serious adverse events. This vaccine could be administrated in the heterologous regimen to effectively boost humoral immune responses.

Therapeutic Approaches in Pulmonary Arterial Hypertension with Beneficial Effects on Right Ventricular Function-Preclinical Studies.

Pulmonary hypertension (PH) is a progressive condition that affects the pulmonary vessels, but its main prognostic factor is the right ventricle (RV) function. Many mice/rat models are used for research in PAH, but results fail to translate to clinical trials. This study reviews studies that test interventions on pulmonary artery banding (PAB), a model of isolated RV disfunction, and PH models. Multiple tested drugs both improved pulmonary vascular hemodynamics in PH models and improved RV structure and function in PAB animals. PH models and PAB animals frequently exhibited similar results (73.1% concordance). Macitentan, sildenafil, and tadalafil improved most tested pathophysiological parameters in PH models, but almost none in PAB animals. Results are frequently not consistent with other studies, possibly due to the methodology, which greatly varied. Some research groups start treating the animals immediately, and others wait up to 4 weeks from model induction. Treatment duration and choice of anaesthetic are other important differences. This review shows that many drugs currently under research for PAH have a cardioprotective effect on animals that may translate to humans. However, a uniformization of methods may increase comparability between studies and, thus, improve translation to clinical trials.

NKG2D-CAR memory T cells target pediatric T-cell acute lymphoblastic leukemia in vitro and in vivo but fail to eliminate leukemia initiating cells.

Introduction: Refractory/relapsed pediatric acute leukemia are still clinically challenging and new therapeutic strategies are needed. Interactions between Natural Killer Group 2D (NKG2D) receptor, expressed in cytotoxic immune cells, and its ligands (NKG2DL), which are upregulated in leukemic blasts, are important for anti-leukemia immunosurveillance. Nevertheless, leukemia cells may develop immunoescape strategies as NKG2DL shedding and/or downregulation. Methods: In this report, we analyzed the anti-leukemia activity of NKG2D chimeric antigen receptor (CAR) redirected memory (CD45RA-) T cells in vitro and in a murine model of T-cell acute lymphoblastic leukemia (T-ALL). We also explored in vitro how soluble NKG2DL (sNKG2DL) affected NKG2D-CAR T cells' cytotoxicity and the impact of NKG2D-CAR T cells on Jurkat cells gene expression and in vivo functionality. Results: In vitro, we found NKG2D-CAR T cells targeted leukemia cells and showed resistance to the immunosuppressive effects exerted by sNKG2DL. In vivo, NKG2D-CAR T cells controlled T cell leukemia burden and increased survival of the treated mice but failed to cure the animals. After CAR T cell treatment, Jurkat cells upregulated genes related to proliferation, survival and stemness, and in vivo, they exhibited functional properties of leukemia initiating cells. Discussion: The data here presented suggest, that, in combination with other therapeutic approaches, NKG2D-CAR T cells could be a novel treatment for pediatric T-ALL.

Cardiovascular effects of relaxin-2: therapeutic potential and future perspectives.

The hormone relaxin-2 has emerged as a promising player in regulating the physiology of the cardiovascular system. Through binding to the relaxin family peptide receptor 1 (RXFP1), this hormone elicits multiple physiological responses including vasodilation induction, reduction of inflammation and oxidative stress, and angiogenesis stimulation. The role of relaxin-2, or its recombinant human form known as serelaxin, has been investigated in preclinical and clinical studies as a potential therapy for cardiovascular diseases, especially heart failure, whose current therapy is still unoptimized. However, evidence from past clinical trials has been inconsistent and further research is needed to fully understand the potential applications of relaxin-2. This review provides an overview of serelaxin use in clinical trials and discusses future directions in the development of relaxin-2 mimetics, which may offer new therapeutic options for patients with heart failure.

Life cycle complexity and body mass drive erratic changes in climate vulnerability across ontogeny in a seasonally migrating butterfly.

Physiological traits are often used for vulnerability assessments of organismal responses to climate change. Trait values can change dramatically over the life cycle of organisms but are typically assessed at a single developmental stage. Reconciling ontogenetic changes in physiological traits with vulnerability assessments often reveals early life-stage vulnerabilities. The degree to which ontogenetic changes in physiological traits are due to changes in body mass over development versus stage-specific responses determines the degree to which mass can be used as a proxy for vulnerability. Here, we use the painted lady butterfly, Vanessa cardui, to test ontogenetic changes in two physiological traits, the acute thermal sensitivity of routine metabolic rate (RMR Q10) and the critical thermal maximum (CTmax). RMR Q10 generally followed ontogenetic changes in body mass, with stages characterized by smaller body mass exhibiting lower acute thermal sensitivity. However, CTmax was largely decoupled from ontogenetic changes in body mass. In contrast with trends from other studies showing increasing vulnerability among progressively earlier developmental stages, our study revealed highly erratic patterns of vulnerability across ontogeny. Specifically, we found the lowest joint-trait vulnerability (both RMR Q10 and CTmax) in the earliest developmental stage we tested (3rd instar larvae), the highest vulnerabilities in the next two developmental stages (4th and 5th instar larvae), and reduced vulnerability into the pupal and adult stages. Our study supports growing evidence of mechanistic decoupling of physiology across developmental stages and suggests that body mass is not a universal proxy for all physiological trait indicators of climate vulnerability.

PPM1D modulates hematopoietic cell fitness and response to DNA damage and is a therapeutic target in myeloid malignancy.

PPM1D encodes a phosphatase that is recurrently activated across cancer, most notably in therapy-related myeloid neoplasms. However, the function of PPM1D in hematopoiesis and its contribution to tumor cell growth remain incompletely understood. Using conditional mouse models, we uncover a central role for Ppm1d in hematopoiesis and validate its potential as a therapeutic target. We find that Ppm1d regulates the competitive fitness and self-renewal of hematopoietic stem cells (HSCs) with and without exogenous genotoxic stresses. We also show that although Ppm1d activation confers cellular resistance to cytotoxic therapy, it does so to a lesser degree than p53 loss, informing the clonal competition phenotypes often observed in human studies. Notably, loss of Ppm1d sensitizes leukemias to cytotoxic therapies in vitro and in vivo, even in the absence of a Ppm1d mutation. Vulnerability to PPM1D inhibition is observed across many cancer types and dependent on p53 activity. Importantly, organism-wide loss of Ppm1d in adult mice is well tolerated, supporting the tolerability of pharmacologically targeting PPM1D. Our data link PPM1D gain-of-function mutations to the clonal expansion of HSCs, inform human genetic observations, and support the therapeutic targeting of PPM1D in cancer.

Physiological and pathophysiological roles of the KCNK3 potassium channel in the pulmonary circulation and the heart.

Potassium channel subfamily K member 3 (KCNK3), encoded by the KCNK3 gene, is part of the two-pore domain potassium channel family, constitutively active at resting membrane potentials in excitable cells, including smooth muscle and cardiac cells. Several physiological and pharmacological mediators, such as intracellular signalling pathways, extracellular pH, hypoxia and anaesthetics, regulate KCNK3 channel function. Recent studies show that modulation of KCNK3 channel expression and function strongly influences pulmonary vascular cell and cardiomyocyte function. The altered activity of KCNK3 in pathological situations such as atrial fibrillation, pulmonary arterial hypertension and right ventricular dysfunction demonstrates the crucial role of KCNK3 in cardiovascular homeostasis. Furthermore, loss of function variants of KCNK3 have been identified in patients suffering from pulmonary arterial hypertension and atrial fibrillation. This review focuses on current knowledge of the role of the KCNK3 channel in pulmonary circulation and the heart, in healthy and pathological conditions.

The final frontier: ecological and evolutionary dynamics of a global parasite invasion.

Studying rapid biological changes accompanying the introduction of alien organisms into native ecosystems can provide insights into fundamental ecological and evolutionary theory. While powerful, this quasi-experimental approach is difficult to implement because the timing of invasions and their consequences are hard to predict, meaning that baseline pre-invasion data are often missing. Exceptionally, the eventual arrival of Varroa destructor (hereafter Varroa) in Australia has been predicted for decades. Varroa is a major driver of honeybee declines worldwide, particularly as vectors of diverse RNA viruses. The detection of Varroa in 2022 at over a hundred sites poses a risk of further spread across the continent. At the same time, careful study of Varroa's spread, if it does become established, can provide a wealth of information that can fill knowledge gaps about its effects worldwide. This includes how Varroa affects honeybee populations and pollination. Even more generally, Varroa invasion can serve as a model for evolution, virology and ecological interactions between the parasite, the host and other organisms.

Efficacy and Safety of a Protein-Based SARS-CoV-2 Vaccine: A Randomized Clinical Trial.

Importance: The protein-based SARS-CoV-2 vaccines FINLAY-FR-2 (Soberana 02) and FINLAY-FR-1A (Soberana Plus) showed good safety and immunogenicity in phase 1 and 2 trials, but the clinical efficacy of the vaccine remains unknown. Objective: To evaluate the efficacy and safety of a 2-dose regimen of FINLAY-FR-2 (cohort 1) and a 3-dose regimen of FINLAY-FR-2 with FINLAY-FR-1A (cohort 2) in Iranian adults. Design, Setting, and Participants: A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial was conducted at 6 cities in cohort 1 and 2 cities in cohort 2. Participants included individuals aged 18 to 80 years without uncontrolled comorbidities, coagulation disorders, pregnancy or breastfeeding, recent immunoglobulin or immunosuppressive therapy, and clinical presentation or laboratory-confirmed COVID-19 on enrollment. The study was conducted from April 26 to September 25, 2021. Interventions: In cohort 1, 2 doses of FINLAY-FR-2 (n = 13 857) or placebo (n = 3462) were administered 28 days apart. In cohort 2, 2 doses of FINLAY-FR-2 plus 1 dose of FINLAY-FR-1A (n = 4340) or 3 placebo doses (n = 1081) were administered 28 days apart. Vaccinations were administered via intramuscular injection. Main Outcomes and Measures: The primary outcome was polymerase chain reaction-confirmed symptomatic COVID-19 infection at least 14 days after vaccination completion. Other outcomes were adverse events and severe COVID-19. Intention-to-treat analysis was performed. Results: In cohort 1 a total 17 319 individuals received 2 doses and in cohort 2 5521 received 3 doses of the vaccine or placebo. Cohort 1 comprised 60.1% men in the vaccine group and 59.1% men in the placebo group; cohort 2 included 59.8% men in the vaccine group and 59.9% in the placebo group. The mean (SD) age was 39.3 (11.9) years in cohort 1 and 39.7 (12.0) years in cohort 2, with no significant difference between the vaccine and placebo groups. The median follow-up time in cohort 1 was 100 (IQR, 96-106) days and, in cohort 2, 142 (137-148) days. In cohort 1, 461 (3.2%) cases of COVID-19 occurred in the vaccine group and 221 (6.1%) in the placebo group (vaccine efficacy: 49.7%; 95% CI, 40.8%-57.3%) vs 75 (1.6%) and 51 (4.3%) in cohort 2 (vaccine efficacy: 64.9%; 95% CI, 49.7%-59.5%). The incidence of serious adverse events was lower than 0.1%, with no vaccine-related deaths. Conclusions and Relevance: In this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial of the efficacy and safety of FINLAY-FR-2 and FINLAY-FR-1A, 2 doses of FINLAY-FR-2 plus the third dose of FINLAY-FR-1A showed acceptable vaccine efficacy against symptomatic COVID-19 as well as COVID-19-related severe infections. Vaccination was generally safe and well tolerated. Therefore, Soberana may have utility as an option for mass vaccination of the population, especially in resource-limited settings, because of its storage condition and affordable price. Trial Registration: isrctn.org Identifier: IRCT20210303050558N1.

Can suitability indices predict plant growth in the invaded range? The case of Acacias species.

Introduction: Forestry in many parts of the world depends on exotic species, making this industry a source of invasions in some countries. Among others, plantations of the genus Pinus, Eucalyptus, Acacia, Populus, and Pseudotsuga underpin the forestry industry and are a vital component of many countries economies. Among woody plants, the cosmopolitan genus Acacia includes some of the most commonly planted trees worldwide. In order to prevent, manage and control invasive plant species, one of the most used tools is species distribution models. The output of these models can also be used to obtain information about population characteristics, such as spatial abundance patterns or species performance. Although ecological theory suggests a direct link between fitness and suitability, this link is often absent. The reasons behind the lack of this relationship are multiple. Chile is one of the countries where Acacia species, in particular, A. dealbata and A. melanoxylon, have become invaders. Methods: Here, we used climatic and edaphic variables to predict thepotentially suitable habitats for A. dealbata and A. melanoxylon in continental Chile and evaluate if the suitability indices obtained from these models are associated with the observed performance of the trees along the country. Results: Our models show that variable importance showed significant similarities between the variables that characterize each species' niche. However, despite the high accuracy of our models, we did not observe an association between suitability and tree growth. Discussion: This disconnection between suitability and performance can result from multiple causes, from structural limitations, like the lack of biotic interactions in the models, to methodological issues, like the usefulness of the performance metric used. Whatever the scenario, our results suggest that plans to control invasive species should be cautious in assuming this relationship in their design and consider other indicators such as species establishment success.