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Johann Kuhn,1 Valérie Olié,2 Clémence Grave,2 Yann Le Strat,1 Christophe Bonaldi,1 Pierre Joly3 1Department of Support, Data Processing and Analysis, French National Public Health Agency, Saint-Maurice, France; 2Department of Chronic Diseases and Injuries, French National Public Health Agency, Saint-Maurice, France; 3Centre Inserm U1219 – Bordeaux Population Health, Université de Bordeaux - ISPED, Bordeaux, FranceCorrespondence: Johann Kuhn, Department of Support, Data Processing and Analysis, French National Public Health Agency, 12 rue du Val d’Osne, Saint-Maurice, 94410, France, Tel/Fax +33 1 71 80 15 44, Email johann.kuhn@santepubliquefrance.frPurpose: In France, myocardial infarction (MI) was the second leading cause of years of life lost in 2019. Estimating the burden of MI in future years could help policymakers and other actors anticipate care and prevention needs and guide them in public health decision-making.Materials and Methods: Using data from the French hospital discharge database from 2007 to 2015 (n = 519,400), demographic data, and an illness-death model, we projected incidence, prevalence, number of prevalent cases and mean age of incident MI cases in France. The methodology took into account the age-cohort effect on MI incidence, mortality of healthy and diseased subjects, and the time since disease onset.Results: Projections highlighted an increase in MI prevalence in men between 2015 and 2035 from 2.52% (95% uncertainty interval (UI): [2.48– 2.56]) in 2015 to 4.02% ([3.92– 4.12]) in 2035, and from 0.85% ([0.83– 0.87]) to 1.44% ([1.38– 1.50]) in women. This corresponds to an increase of 365,000 cases between 2015 and 2035 (+81.1%) for men and 146,000 cases for women (+88.0%). The difference in the mean age of incident cases between men and women decreased from 9.52 in 2015 to 5.49 years in 2035.Conclusion: Our projections forecast an increase in MI prevalence between 2015 and 2035 in men and women, especially in relatively younger women. Using statistical models such as ours can help assess the impact of prevention campaigns for the main cardiovascular disease risk factors on the future MI prevalence.Keywords: myocardial infarction, projection, burden, prevalence, incidence, age-period-cohort model

Abstract Background Elevated body mass index (BMI) represents a risk factor for cancer-related fatigue (CRF). Weight loss interventions are feasible and safe in cancer survivors, leading to improved cardio-metabolic and quality of life (QOL) outcomes and modulating inflammatory biomarkers. Randomized data are lacking showing that a lifestyle intervention aimed at weight loss, combining improved diet, exercise, and motivational counseling, reduces CRF. Motivating to Exercise and Diet, and Educating to healthy behaviors After breast cancer (MEDEA) is a multi-center, randomized controlled trial evaluating the impact of weight loss on CRF in overweight or obese survivors of breast cancer. Herein, we described the MEDEA methodology. Methods Patients (N = 220) with stage I–III breast cancer and BMI ≥ 25 kg/m2, within 12 months of primary treatment, and able to walk ≥ 400 m are eligible to enroll. Participants are randomized 1:1 to health education alone vs. a personalized telephone-based weight loss intervention plus health education. Both arms receive a health education program focusing on healthy living. Patients in the intervention arm are paired with an individual lifestyle coach, who delivers the intervention through 24 semi-structured telephone calls over 1 year. Intervention goals include weight loss ≥ 10% of baseline, caloric restriction of 500–1000 Kcal/day, and increased physical activity (PA) to 150 (initial phase) and 225–300 min/week (maintenance phase). The intervention is based on the social cognitive theory and is adapted from the Breast Cancer Weight Loss trial (BWEL, A011401). The primary endpoint is the difference in self-reported CRF (EORTC QLQ-C30) between arms. Secondary endpoints include the following: QOL (EORTC QLQ-C30, -BR45, -FA12), anxiety, and depression (HADS); weight and BMI, dietary habits and quality, PA, and sleep; health care costs (hospital-admissions, all-drug consumption, sick leaves) and cost-effectiveness (cost per quality-adjusted life-year); and patient motivation and satisfaction. The primary analysis of MEDEA will compare self-reported CRF at 12 months post-randomization between arms, with 80.0% power (two-sided α = 0.05) to detect a standardized effect size of 0.40. Discussion MEDEA will test the impact of a weight loss intervention on CRF among overweight or obese BC survivors, potentially providing additional management strategies and contributing to establish weight loss support as a new standard of clinical care. Trial registration ClinicalTrials.gov NCT04304924

Abstract Complaints of sleep disturbance are prevalent among breast cancer (BC) patients and are predictors of quality of life. Still, electrophysiological measures of sleep are missing in patients, which prevents from understanding the pathophysiological consequences of cancer and its past treatments. Using polysomnography, sleep can be investigated in terms of macro- (e.g. awakenings, sleep stages) and micro- (i.e. cortical activity) structure. We aimed to characterize sleep complaints, and macro- and microstructure in 33 BC survivors untreated by chemotherapy and that had finished radiotherapy since at least 6 months (i.e. out of the acute effects of radiotherapy) compared to 21 healthy controls (HC). Compared to HC, BC patients had a larger number of awakenings (p = 0.008); and lower Delta power (p

Abstract Background In the field of autoimmune demyelinating diseases, visual impairments have extensively been studied using the experimental autoimmune encephalomyelitis (EAE) mouse model, which is classically induced by immunization with myelin oligodendrocyte glycoprotein peptide (MOG35–55). However, this model does not involve B cells like its human analogs. New antigens have thus been developed to induce a B cell-dependent form of EAE that better mimics human diseases. Methods The present study aimed to characterize the visual symptoms of EAE induced with such an antigen called bMOG. After the induction of EAE with bMOG in C57BL/6J mice, visual function changes were studied by electroretinography and optomotor acuity tests. Motor deficits were assessed in parallel with a standard clinical scoring method. Histological examinations and Western blot analyses allowed to follow retinal neuron survival, gliosis, microglia activation, opsin photopigment expression in photoreceptors and optic nerve demyelination. Disease effects on retinal gene expression were established by RNA sequencing. Results We observed that bMOG EAE mice exhibited persistent loss of visual acuity, despite partial recovery of electroretinogram and motor functions. This loss was likely due to retinal inflammation, gliosis and synaptic impairments, as evidenced by histological and transcriptomic data. Further analysis suggests that the M-cone photoreceptor pathway was also affected. Conclusion Therefore, by documenting visual changes induced by bMOG and showing similarities to those seen in diseases such as multiple sclerosis and neuromyelitis optica, this study offers a new approach to test protective or restorative ophthalmic treatments.

Abstract Background Chronic heart failure (CHF) is one of the most common causes of mortality in industrialized countries despite regular therapeutic advances. Numerous factors influence mortality in CHF patients, including nutritional status. It is known that malnutrition is a risk factor for mortality, whereas obesity may play a protective role, a phenomenon dubbed the “obesity paradox”. However, the effect of the obesity-malnutrition association on mortality has not been previously studied for CHF. Our aim was to study the effect of nutritional status on overall mortality in CHF patients. Methods This retrospective, multicenter study was based on a French nationwide database (PMSI). We included all CHF patients aged ≥18 years admitted to all public and private hospitals between 2012 and 2016 and performed a survival analysis over 1 to 4 years of follow-up. Results Malnutrition led to a significant decrease in life expectancy in CHF patients when compared with normal nutritional status (aHR=1.16 [1.14-1.18] at one year and aHR=1.04 [1.004-1.08] at four years), obese, and obese-malnutrition groups. In contrast, obesity led to a significant increase in life expectancy compared with normal nutritional status (aHR=0.75 [0.73-0.78] at one year and aHR=0.85 [0.81-0.90] at four years), malnutrition, and obese-malnutrition groups. The mortality rate was similar in patients presenting both malnutrition and obesity and patients with normal nutritional status. Conclusions Our results indicate that the protective effect on mortality observed in obese CHF patients seems to be linked to fat massincrease. Furthermore, malnourished obese and normal nutritional status patients had similar mortality rates. Further studies should be conducted to confirm our results and to explore the physiopathological mechanisms behind these effects.

Abstract Background Fusobacterium nucleatum is an anaerobic bacterium mainly responsible for acute or chronic infection of the ear, nose, and throat, potentially bacteremic with a risk of extraoral metastatic infection. Bacteremia occurs mainly in the elderly or in immunodeficient individuals, with high mortality. F. nucleatum is not the first cause of tonsillar infection in emergency departments, which are more often the consequence of a viral or streptococcal infection, but it is a risk factor for severe bacterial infection, especially in a viral pandemic context. Case presentation A 25-year-old European woman with no history presented to the emergency department with fever (38.9 °C), pharyngeal symptoms, intermittent headaches, and alteration of general condition. On examination, she presented odynophagia associated with moderate tonsillar hypertrophy, her neck was painful but flexible. A rapid diagnostic test for beta-hemolytic group streptococcus was negative. First biological analyses revealed an inflammatory syndrome with C-reactive protein of 76 mg/L. Procalcitonin was measured secondarily, and was 2.16 µg/L. Faced with discordant clinical and biological findings, a lumbar puncture was performed, which came back negative. At hour eight, hypotension was observed but corrected after filling with physiological serum. The patient was hospitalized for monitoring, based on a hypothesis of severe viral presentation. At hour 24, pyrexia confirmed this hypothesis. A spontaneous but transient improvement and no new hemodynamic event led to early discharge. At day three, she was rehospitalized for increased and continuous headaches, without hemodynamic severity. A broad-spectrum probabilistic antibiotic therapy of ceftriaxone and metronidazole was started due to first blood cultures positive for anaerobic Gram-negative bacilli, while waiting for identification of the pathogen. Three days later, F. nucleatum was identified. According to the microbiological results, antibiotic therapy was adapted with amoxicillin and clavulanic acid, and no further complications were observed during clinical or complementary examinations. The final diagnosis was a F. nucleatum oropharyngeal infection complicated by bacteremia, without metastatic spread. Conclusion The etiologies of tonsillar infection are not limited to benign viruses or bacteria. These should not be overlooked in emergency medicine, especially when the clinical presentation is discrepant. A combination of early bacterial investigations as blood culture and close clinical monitoring is the only safe way to detect bacteremia, especially in immunocompetent patients.

Abstract Background Considering the growing body of evidence suggesting a potential implication of herpesviruses in the development of dementia, several authors have questioned a protective effect of antiherpetic drugs (AHDs) which may represent a new means of prevention, well tolerated and easily accessible. Subsequently, several epidemiological studies have shown a reduction in the risk of dementia in subjects treated with AHDs, but the biological plausibility of this association and the impact of potential methodological biases need to be discussed in more depth. Methods Using a French medico-administrative database, we assessed the association between the intake of systemic AHDs and the incidence of (i) dementia, (ii) Alzheimer’s disease (AD), and (iii) vascular dementia in 68,291 subjects over 65 who were followed between 2009 and 2017. Regarding potential methodological biases, Cox models were adjusted for numerous potential confounding factors (including proxies of sociodemographic status, comorbidities, and use of healthcare) and sensitivity analyses were performed in an attempt to limit the risk of indication and reverse causality biases. Results 9.7% of subjects (n=6642) had at least one intake of systemic AHD, and 8883 incident cases of dementia were identified. Intake of at least one systemic AHD during follow-up was significantly associated with a decreased risk of AD (aHR 0.85 95% confidence interval [0.75–0.96], p=0.009) and, to a lesser extent with respect to p values, to both dementia from any cause and vascular dementia. The association with AD remained significant in sensitivity analyses. The number of subjects with a regular intake was low and prevented us from studying its association with dementia. Conclusions Taking at least one systemic AHD during follow-up was significantly associated with a 15% reduced risk of developing AD, even after taking into account several potential methodological biases. Nevertheless, the low frequency of subjects with a regular intake questions the biological plausibility of this association and highlights the limits of epidemiological data to evaluate a potential protective effect of a regular treatment by systemic AHDs on the incidence of dementia

We present here the results obtained during an intensive field campaign conducted in the framework of the French “BIO-MAÏDO” (Bio-physico-chemistry of tropical clouds at Maïdo (Réunion Island): processes and impacts on secondary organic aerosols' formation) project. This study integrates an exhaustive chemical and microphysical characterization of cloud water obtained in March–April 2019 in Réunion (Indian Ocean). Fourteen cloud samples have been collected along the slope of this mountainous island. Comprehensive chemical characterization of these samples is performed, including inorganic ions, metals, oxidants, and organic matter (organic acids, sugars, amino acids, carbonyls, and low-solubility volatile organic compounds, VOCs). Cloud water presents high molecular complexity with elevated water-soluble organic matter content partly modulated by microphysical cloud properties. As expected, our findings show the presence of compounds of marine origin in cloud water samples (e.g. chloride, sodium) demonstrating ocean–cloud exchanges. Indeed, Na+ and Cl− dominate the inorganic composition contributing to 30 % and 27 %, respectively, to the average total ion content. The strong correlations between these species (r2 = 0.87, p value: < 0.0001) suggest similar air mass origins. However, the average molar Cl-/Na+ ratio (0.85) is lower than the sea-salt one, reflecting a chloride depletion possibly associated with strong acids such as HNO3 and H2SO4. Additionally, the non-sea-salt fraction of sulfate varies between 38 % and 91 %, indicating the presence of other sources. Also, the presence of amino acids and for the first time in cloud waters of sugars clearly indicates that biological activities contribute to the cloud water chemical composition. A significant variability between events is observed in the dissolved organic content (25.5 ± 18.4 mg C L−1), with levels reaching up to 62 mg C L−1. This variability was not similar for all the measured compounds, suggesting the presence of dissimilar emission sources or production mechanisms. For that, a statistical analysis is performed based on back-trajectory calculations using the CAT (Computing Atmospheric Trajectory Tool) model associated with the land cover registry. These investigations reveal that air mass origins and microphysical variables do not fully explain the variability observed in cloud chemical composition, highlighting the complexity of emission sources, multiphasic transfer, and chemical processing in clouds. Even though a minor contribution of VOCs (oxygenated and low-solubility VOCs) to the total dissolved organic carbon (DOC) (0.62 % and 0.06 %, respectively) has been observed, significant levels of biogenic VOC (20 to 180 nmol L−1) were detected in the aqueous phase, indicating the cloud-terrestrial vegetation exchange. Cloud scavenging of VOCs is assessed by measurements obtained in both the gas and aqueous phases and deduced experimental gas-/aqueous-phase partitioning was compared with Henry's law equilibrium to evaluate potential supersaturation or unsaturation conditions. The evaluation reveals the supersaturation of low-solubility VOCs from both natural and anthropogenic sources. Our results depict even higher supersaturation of terpenoids, evidencing a deviation from thermodynamically expected partitioning in the aqueous-phase chemistry in this highly impacted tropical area.

One of the challenges of all synchrotron facilities is to offer the highest performance detectors for all their specific experiments, in particular for X-ray diffraction imaging and its high throughput data collection. In that context, the DiffAbs beamline, the Detectors and the Design and Engineering groups at Synchrotron SOLEIL, in collaboration with ImXPAD and Cegitek companies, have developed an original and unique detector with a circular shape. This detector is based on the hybrid pixel photon-counting technology and consists of the specific assembly of 20 hybrid pixel array detector (XPAD) modules. This article aims to demonstrate the main characteristics of the CirPAD (for Circular Pixel Array Detector) and its performance – i.e. excellent pixel quality, flat-field correction, high-count-rate performance, etc. Additionally, the powder X-ray diffraction pattern of an LaB6 reference sample is presented and refined. The obtained results demonstrate the high quality of the data recorded from the CirPAD, which allows the proposal of its use to all scientific communities interested in performing experiments at the DiffAbs beamline.

Research infrastructures play a key role in launching a new generation of integrated long-Term, geographically distributed observation programmes designed to monitor climate change, better understand its impacts on global ecosystems, and evaluate possible mitigation and adaptation strategies. The pan-European Integrated Carbon Observation System combines carbon and greenhouse gas (GHG; CO 2 , CH 4 , N 2 O, H 2 O) observations within the atmosphere, terrestrial ecosystems and oceans. High-precision measurements are obtained using standardised methodologies, are centrally processed and openly available in a traceable and verifiable fashion in combination with detailed metadata. The Integrated Carbon Observation System ecosystem station network aims to sample climate and land-cover variability across Europe. In addition to GHG flux measurements, a large set of complementary data (including management practices, vegetation and soil characteristics) is collected to support the interpretation, spatial upscaling and modelling of observed ecosystem carbon and GHG dynamics. The applied sampling design was developed and formulated in protocols by the scientific community, representing a trade-off between an ideal dataset and practical feasibility. The use of open-Access, high-quality and multi-level data products by different user communities is crucial for the Integrated Carbon Observation System in order to achieve its scientific potential and societal value.

BackgroundIn the phase 3 SOLO2 trial (ENGOT Ov-21), maintenance therapy with olaparib tablets significantly prolonged progression-free survival (primary endpoint) compared with placebo in patients with a germline BRCA1 or BRCA2 (BRCA1/2) mutation and platinum-sensitive, relapsed ovarian cancer who had received two or more lines of previous chemotherapy. The most common subjective adverse effects included fatigue, nausea, and vomiting, which were typically low grade and self-limiting. Our a-priori hypothesis was that maintenance olaparib would not negatively affect health-related quality of life (HRQOL) and additionally that the prolongation of progression-free survival with olaparib would be underpinned by additional patient-centred benefits.MethodsIn SOLO2, 196 patients were randomly assigned to olaparib tablets (300 mg twice daily) and 99 to placebo. Randomisation was stratified by response to previous chemotherapy (complete vs partial) and length of platinum-free interval (>6-12 vs >12 months). The prespecified primary HRQOL analysis evaluated the change from baseline in the Trial Outcome Index (TOI) score during the first 12 months of the study. To be assessable, patients had to have an evaluable score at baseline and at least one evaluable follow-up form. Secondary planned quality-of-life (QOL) analyses included the duration of good quality of life (defined as time without significant symptoms of toxicity [TWiST] and quality-adjusted progression-free survival [QAPFS]). Efficacy and QOL outcomes were analysed in all randomly assigned patients (the full analysis set), and safety outcomes were analysed in all randomly assigned patients who received at least one dose of study drug. This ongoing study is registered with ClinicalTrials.gov, number NCT01874353, and is closed to new participants.FindingsThe adjusted average mean change from baseline over the first 12 months in TOI was -2·90 (95% CI -4·13 to -1·67) with olaparib and -2·87 (-4·64 to -1·10) with placebo (estimated difference -0·03; 95% CI -2·19 to 2·13; p=0·98). Mean QAPFS (13·96 [SD 10·96] vs 7·28 [5·22] months; difference 6·68, 95% CI 4·98-8·54) and mean duration of TWiST (15·03 [SD 12·79] vs 7·70 [6·42] months; difference 7·33, 95% CI 4·70-8·96) were significantly longer with olaparib than with placebo.InterpretationOlaparib maintenance therapy did not have a significant detrimental effect on HRQOL compared with placebo. There were clinically meaningful patient-centred benefits in both TWiST and QAPFS despite the adverse effects associated with olaparib. These patient-centred endpoints support the improvement in progression-free survival, the primary endpoint in SOLO2, and should be included in future trials of maintenance therapies.FundingAstraZeneca.

Correction for "Phylogenetic classification of the world's tropical forests, " by J. W. Ferry Slik, Janet Franklin, Víctor Arroyo- Rodríguez, Richard Field, Salomon Aguilar, Nikolay Aguirre, Jorge Ahumada, Shin-Ichiro Aiba, Luciana F. Alves, Anitha K, Andres Avella, Francisco Mora, Gerardo A. Aymard C., Selene B?ez, Patricia Balvanera, Meredith L. Bastian, Jean-François Bastin, Peter J. Bellingham, Eduardo van den Berg, Polyanna da Conceição Bispo, Pascal Boeckx, Katrin Boehning-Gaese, Frans Bongers, Brad Boyle, Fabian Brambach, Francis Q. Brearley, Sandra Brown, Shauna-Lee Chai, Robin L. Chazdon, Shengbin Chen, Phourin Chhang, George Chuyong, Corneille Ewango, Indiana M. Coronado, Jurgi Crist?bal-Azkarate, Heike Culmsee, Kipiro Damas, H. S. Dattaraja, Priya Davidar, Saara J. DeWalt, Hazimah Din, Donald R. Drake, Alvaro Duque, Giselda Durigan, Karl Eichhorn, Eduardo Schmidt Eler, Tsutomu Enoki, Andreas Ensslin, Adand? Belarmain Fandohan, Nina Farwig, Kenneth J. Feeley, Markus Fischer, Olle Forshed, Queila Souza Garcia, Satish Chandra Garkoti, Thomas W. Gillespie, Jean- Francois Gillet, Christelle Gonmadje, Iñigo Granzow-de la Cerda, Daniel M. Griffith, James Grogan, Khalid Rehman Hakeem, David J. Harris, Rhett D. Harrison, Andy Hector, Andreas Hemp, J?rgen Homeier, M. Shah Hussain, Guillermo Ibarra-Manríquez, I. Faridah Hanum, Nobuo Imai, Patrick A. Jansen, Carlos Alfredo Joly, Shijo Joseph, Kuswata Kartawinata, Elizabeth Kearsley, Daniel L. Kelly, Michael Kessler, Timothy J. Killeen, Robert M. Kooyman, Yves Laumonier, Susan G. Laurance, William F. Laurance, Michael J. Lawes, Susan G. Letcher, Jeremy Lindsell, Jon Lovett, Jose Lozada, Xinghui Lu, Anne Mette Lykke, Khairil Bin Mahmud, Ni Putu Diana Mahayani, Asyraf Mansor, Andrew R. Marshall, Emanuel H. Martin, Darley Calderado Leal Matos, Jorge A.Meave, Felipe P. L. Melo, Zhofre Huberto Aguirre Mendoza, Faizah Metali, Vincent P. Medjibe, Jean Paul Metzger, Thiago Metzker, D. Mohandass, Miguel A. Munguía-Rosas, Rodrigo Muñoz, Eddy Nurtjahy, Eddie Lenza de Oliveira, Onrizal, Pia Parolin, Marc Parren, N. Parthasarathy, Ekananda Paudel, Rolando Perez, Eduardo A. P?rez-García, Ulf Pommer, Lourens Poorter, Lan Qi, Maria Teresa F. Piedade, Jos? Roberto Rodrigues Pinto, Axel Dalberg Poulsen, John R. Poulsen, Jennifer S. Powers, Rama Chandra Prasad, Jean-Philippe Puyravaud, Orlando Rangel, Jan Reitsma, Diogo S. B. Rocha, Samir Rolim, Francesco Rovero, Andes Rozak, Kalle Ruokolainen, Ervan Rutishauser, Gemma Rutten, Mohd. NizamMohd. Said, Felipe Z. Saiter, Philippe Saner, Braulio Santos, João Roberto dos Santos, Swapan Kumar Sarker, Christine B. Schmitt, Jochen Schoengart, Mark Schulze, Douglas Sheil, Plinio Sist, Alexandre F. Souza, Wilson Roberto Spironello, Tereza Sposito, Robert Steinmetz, Tariq Stevart, Marcio Seiji Suganuma, Rahayu Sukri, Aisha Sultana, Raman Sukumar, Terry Sunderland, Supriyadi, H. S. Suresh, Eizi Suzuki, Marcelo Tabarelli, Jianwei Tang, Ed V. J. Tanner, Natalia Targhetta, Ida Theilade, Duncan Thomas, Jonathan Timberlake, M?rcio de Morisson Valeriano, Johan van Valkenburg, Tran Van Do, Hoang Van Sam, John H. Vandermeer, Hans Verbeeck, Ole Reidar Vetaas, Victor Adekunle, Simone A. Vieira, Campbell O.Webb, Edward L. Webb, Timothy Whitfeld, Serge Wich, John Williams, Susan Wiser, FlorianWittmann, Xiaobo Yang, C. Yves Adou Yao, Sandra L. Yap, Rakan A. Zahawi, Rahmad Zakaria, and Runguo Zang, which was first published February 5, 2018; 10.1073/pnas.1714977115 (Proc Natl Acad Sci USA 115:1837-1842). The authors note that, due to a printer's error, an author name published incorrectly. The author name Lan Qi should instead appear as Lan Qie. The online version has been corrected.

Knowledge about the biogeographic affinities of the world's tropical forests helps to better understand regional differences in forest structure, diversity, composition, and dynamics. Such understanding will enable anticipation of region-specific responses to global environmental change. Modern phylogenies, in combination with broad coverage of species inventory data, now allow for global biogeographic analyses that take species evolutionary distance into account. Here we present a classification of the world's tropical forests based on their phylogenetic similarity. We identify five principal floristic regions and their floristic relationships: (i) Indo-Pacific, (ii) Subtropical, (iii) African, (iv) American, and (v) Dry forests. Our results do not support the traditional neo- versus paleotropical forest division but instead separate the combined American and African forests from their Indo-Pacific counterparts. We also find indications for the existence of a global dry forest region, with representatives in America, Africa, Madagascar, and India. Additionally, a northern-hemisphere Subtropical forest region was identified with representatives in Asia and America, providing support for a link between Asian and American northern-hemisphere forests.

Measurement(s) preclinical phenotype • protein expression profiling • metabolite profiling Technology Type(s) phenotyping tests • mass spectrometry assay Factor Type(s) genotype • sex Sample Characteristic - Organism Mus musculus Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.15015273

Helness et al. show that GFI1/CHD4 complexes critically regulate chromatin accessibility and histone modifications to regulate target genes affecting diverse cellular processes in neutrophils. Their results provide further insight into the molecular network operated by GFI1 for neutrophil differentiation programs.

Background: Treatment and outcomes of patients with HER2-positive (HER2+) metastatic breast cancer (MBC) have dramatically improved over the past 20 years. This work evaluated treatment patterns and outcomes according to age. Methods: Women who initiated a treatment for HER2+ MBC between 2008 and 2016 in one of the 18 French comprehensive centers part of the ESME program were included. Objectives were the description of first-line treatment patterns, overall survival (OS), first-line progression-free survival (PFS), and prognostic factors among patients aged 70 years or more (70+), or less than 70 (

Abstract Summer diets are crucial for large herbivores in the subarctic and are affected by weather, harassment from insects and a variety of environmental changes linked to climate. Yet, understanding foraging behavior and diet of large herbivores is challenging in the subarctic because of their remote ranges. We used GPS video‐camera collars to observe behaviors and summer diets of the migratory Fortymile Caribou Herd (Rangifer tarandus granti) across Alaska, USA and the Yukon, Canada. First, we characterized caribou behavior. Second, we tested if videos could be used to quantify changes in the probability of eating events. Third, we estimated summer diets at the finest taxonomic resolution possible through videos. Finally, we compared summer diet estimates from video collars to microhistological analysis of fecal pellets. We classified 18,134 videos from 30 female caribou over two summers (2018 and 2019). Caribou behaviors included eating (mean = 43.5%), ruminating (25.6%), travelling (14.0%), stationary awake (11.3%) and napping (5.1%). Eating was restricted by insect harassment. We classified forage(s) consumed in 5,549 videos where diet composition (monthly) highlighted a strong tradeoff between lichens and shrubs; shrubs dominated diets in June and July when lichen use declined. We identified 63 species, 70 genus and 33 family groups of summer forages from videos. After adjusting for digestibility, monthly estimates of diet composition were strongly correlated at the scale of the forage functional type (i.e., forage groups composed of forbs, graminoids, mosses, shrubs and lichens; r = 0.79, p

Abstract Background Migrations in temperate systems typically have two migratory phases, spring and autumn, and many migratory ungulates track the pulse of spring vegetation growth during a synchronized spring migration. In contrast, autumn migrations are generally less synchronous and the cues driving them remain understudied. Our goal was to identify the cues that migrants use in deciding when to initiate migration and how this is updated while en route. Methods We analyzed autumn migrations of Arctic barren-ground caribou (Rangifer tarandus) as a series of persistent and directional movements and assessed the influence of a suite of environmental factors. We fitted a dynamic-parameter movement model at the individual-level and estimated annual population-level parameters for weather covariates on 389 individual-seasons across 9 years. Results Our results revealed strong, consistent effects of decreasing temperature and increasing snow depth on migratory movements, indicating that caribou continuously update their migratory decision based on dynamic environmental conditions. This suggests that individuals pace migration along gradients of these environmental variables. Whereas temperature and snow appeared to be the most consistent cues for migration, we also found interannual variability in the effect of wind, NDVI, and barometric pressure. The dispersed distribution of individuals in autumn resulted in diverse environmental conditions experienced by individual caribou and thus pronounced variability in migratory patterns. Conclusions By analyzing autumn migration as a continuous process across the entire migration period, we found that caribou migration was largely related to temperature and snow conditions experienced throughout the journey. This mechanism of pacing autumn migration based on indicators of the approaching winter is analogous to the more widely researched mechanism of spring migration, when many migrants pace migration with a resource wave. Such a similarity in mechanisms highlights the different environmental stimuli to which migrants have adapted their movements throughout their annual cycle. These insights have implications for how long-distance migratory patterns may change as the Arctic climate continues to warm.

Abstract Background The rice weevil Sitophilus oryzae is one of the most important agricultural pests, causing extensive damage to cereal in fields and to stored grains. S. oryzae has an intracellular symbiotic relationship (endosymbiosis) with the Gram-negative bacterium Sodalis pierantonius and is a valuable model to decipher host-symbiont molecular interactions. Results We sequenced the Sitophilus oryzae genome using a combination of short and long reads to produce the best assembly for a Curculionidae species to date. We show that S. oryzae has undergone successive bursts of transposable element (TE) amplification, representing 72% of the genome. In addition, we show that many TE families are transcriptionally active, and changes in their expression are associated with insect endosymbiotic state. S. oryzae has undergone a high gene expansion rate, when compared to other beetles. Reconstruction of host-symbiont metabolic networks revealed that, despite its recent association with cereal weevils (30 kyear), S. pierantonius relies on the host for several amino acids and nucleotides to survive and to produce vitamins and essential amino acids required for insect development and cuticle biosynthesis. Conclusions Here we present the genome of an agricultural pest beetle, which may act as a foundation for pest control. In addition, S. oryzae may be a useful model for endosymbiosis, and studying TE evolution and regulation, along with the impact of TEs on eukaryotic genomes.

Abstract Background Crohn’s disease (CD) is a chronic disorder with frequent complications. The objective of this study was to assess the predictive factors of finding a complication of CD using abdominopelvic CT-scan in patients with a visit to the emergency department. Methods Patients with at least one visit to the gastroenterology department of our University hospital during the year with a CD were retrospectively included. All visits to the emergency department of the hospital during the follow-up of these patients were identified. Results A total of 638 patients were included and 318 (49.8%) had at least one visit to the emergency department since the beginning of their follow-up. Abdominopelvic CT-scan was performed in 141 (23.7%) of the 595 visits for digestive symptoms. Only 4.3% of these CT-scans were considered as normal; there was luminal inflammation without complication in 24.8%, abscess, fistula or perforation in 22.7%, mechanical bowel obstruction in 36.9% and diagnosis unrelated to CD in 11.3%. In univariate analysis, stricturing phenotype (OR, 2.48; 95% CI, 1.16–5.29; p = 0.02) and previous surgery (OR, 2.90; 95% CI, 1.37–6.14; p = 0.005) were predictive factors of finding a complication of CD using abdominopelvic CT-scan, whereas no independent predictive factor was statistically significant in multivariate analysis. Conclusion In CD patients consulting in emergency department, CT-scan examination was performed in 24% of visits for digestive symptoms and complications of CD were found in 60%. Complications were more frequent in patients with stricturing phenotype and previous surgery.

Abstract Patients with multiple myeloma are at high risk of severe forms of COVID-19. Despite data showing diminished response to vaccine, the era of highly efficient mRNA vaccine might be a gamechanger. We sought to examine response to mRNA vaccine between healthy controls (n = 28) and multiple myeloma (MM) patients (n = 27). Response was analyzed 1 month after the second dose of anti-SARS-CoV-2 BNT162b2 vaccine. Multiple myeloma patients showed diminished levels of Anti-Spike IgG levels compared to controls, but with a high proportion of patients achieving a humoral response (89% vs. 97% in controls). Neutralizing antibodies were present in 74% of patients versus 96% of controls. Patients under current daratumumab treatment had neutralizing activity of anti-SARS-CoV-2 antibodies. Multiple myeloma patients show diminished response to SARS-COV-2 vaccine but with still high response rate. The main potential risk factor of non-response to COVID-19 vaccine was uncontrolled disease under treatment.

Abstract Background Self-efficacy, or patients’ confidence in their ability to control disease and its consequences, was recently prioritised in EULAR recommendations for inflammatory arthritis self-management strategies. However, it remains unclear which factors influence self-efficacy in early rheumatoid arthritis (RA). Methods Data were analysed from the 2-year RCT Care in early RA (CareRA), which studied remission-induction treatment regimens for early RA. Participants completed the Arthritis Self-Efficacy Scale (ASES), Short-Form 36 (SF-36), Revised Illness Perception Questionnaire (IPQ-R), Utrecht Coping List (UCL), RAQoL and Health Assessment Questionnaire (HAQ). Depending on time to first remission (DAS28-CRP < 2.6) and persistence of remission, treatment response was defined as persistent response, secondary failure, delayed response, late response or non-response. The association between ASES scores and clinical/psychosocial factors was explored with Spearman correlation and multivariate linear mixed models. Baseline predictors of week 104 ASES were identified with exploratory linear regression followed by multiple regression of significant predictors adjusted for DAS28-CRP, HAQ, treatment arm, treatment response, cumulative CRP/SJC28 and demographic/serologic confounders. Results All 379 patients had a recent diagnosis of RA and were DMARD-naïve at study initiation. Most patients were women (69%) and RF/ACPA-positive (66%), and the mean (SD) age was 52 (13) years. For all tested outcome measures, better perceived health correlated with higher self-efficacy. While patient-reported factors (HAQ, SF-36, RAQoL, IPQ-R, pain, fatigue and patient’s global assessment) showed moderate/strong correlations with ASES scores, correlations with physician-reported factors (physician’s global assessment, SJC28), TJC28 and DAS28-CRP were weak. Only more favourable outcomes on patient-reported factors and DAS28-CRP were associated with higher ASES scores at each time point. An earlier, persistent treatment response predicted higher ASES scores at both weeks 52 and 104. Significant baseline predictors of week 104 ASES included HAQ; SF-36 mental component score, vitality, mental health and role emotional; IPQ-R illness coherence, treatment control, emotional representations and consequences; UCL Passive reacting; and the RAQoL. Conclusions Patient-reported outcomes and treatment response were early determinants of long-term self-efficacy in an early RA trial. These results provide further relevance for the window of opportunity in an early treat-to-target strategy and could help to timely identify patients who might benefit from self-management interventions. Trial registration EudraCT 2008-007225-39

Abstract Background Germ cell tumors and sex cord stromal tumors are rare cancers of the ovary. They mainly affect young women and are associated with a high survival rate. The standard treatment mainly involves conservative surgery combined with chemotherapy [bleomycin, etoposide and cisplatin (BEP)] depending on the stage and the prognostic factors, as for testicular cancers. As reported in testicular cancer survivors, chemotherapy may induce sequelae impacting quality of life, which has not yet been evaluated in survivors of germ cell tumors and sex cord stromal tumors. The GINECO-VIVROVAIRE-Rare tumor study is a two-step investigation aiming to assess i) chronic fatigue and quality of life and ii) long-term side-effects of chemotherapy with a focus on cardiovascular and pulmonary disorders. Methods Using self-reported questionnaires, chronic fatigue and quality of life are compared between 134 ovarian cancer survivors (cancer-free ≥2 years after treatment) treated with surgery and chemotherapy and 2 control groups (67 ovarian cancer survivors treated with surgery alone and 67 age-matched healthy women). Medical data are collected from patient records. In the second step evaluating the long-term side-effects of chemotherapy, a subgroup of 90 patients treated with chemotherapy and 45 controls undergo the following work-up: cardiovascular evaluation (clinical examination, non-invasive cardiovascular tests to explore heart disease, blood tests), pulmonary function testing, audiogram, metabolic and hormonal blood tests. Costs of sequelae will be also assessed. Patients are selected from the registry of the INCa French Network for Rare Malignant Ovarian Tumors, and healthy women by the ‘Seintinelles’ connected network (collaborative research platform). Discussion This study will provide important data on the potential long-term physical side-effects of chemotherapy in survivors of Germ Cell Tumors (GCT) and Sex Cord Stromal Tumors (SCST), especially cardiovascular and pulmonary disorders, and neurotoxicity. The identification of long-term side-effects can contribute to adjusting the treatment of ovarian GCT or SCST patients and to managing follow-up with adapted recommendations regarding practices and chemotherapy regimens, in order to reduce toxicity while maintaining efficacy. Based on the results, intervention strategies could be proposed to improve the management of these patients during their treatment and in the long term. Trial registration This trial was registered at clinicaltrials.gov : 03418844 , on 1 February 2018. This trial was registered on 25 October 2017 under the unique European identification number (ID-RCB): 2017-A03028–45. Recruitment Status: Recruiting. Protocol version Version n° 4.2 dated from Feb 19, 2021. Trial sponsor Centre François Baclesse, 3 avenue du Général Harris, F-14076 Caen cedex 05, France.

Abstract Background The detection of environmental cues and signals via the sensory system directs behavioral choices in diverse organisms. Insect larvae rely on input from the chemosensory system, mainly olfaction, for locating food sources. In several lepidopteran species, foraging behavior and food preferences change across larval instars; however, the molecular mechanisms underlying such behavioral plasticity during larval development are not fully understood. Here, we hypothesize that expression patterns of odorant receptors (ORs) change during development, as a possible mechanism influencing instar-specific olfactory-guided behavior and food preferences. Results We investigated the expression patterns of ORs in larvae of the cotton leafworm Spodoptera littoralis between the first and fourth instar and revealed that some of the ORs show instar-specific expression. We functionally characterized one OR expressed in the first instar, SlitOR40, as responding to the plant volatile, β-caryophyllene and its isomer α-humulene. In agreement with the proposed hypothesis, we showed that first but not fourth instar larvae responded behaviorally to β-caryophyllene and α-humulene. Moreover, knocking out this odorant receptor via CRISPR-Cas9, we confirmed that instar-specific responses towards its cognate ligands rely on the expression of SlitOR40. Conclusion Our results provide evidence that larvae of S. littoralis change their peripheral olfactory system during development. Furthermore, our data demonstrate an unprecedented instar-specific behavioral plasticity mediated by an OR, and knocking out this OR disrupts larval behavioral plasticity. The ecological relevance of such behavioral plasticity for S. littoralis remains to be elucidated, but our results demonstrate an olfactory mechanism underlying this plasticity in foraging behavior during larval development.