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The early evolution of a supernova (SN) can reveal information about the environment and the progenitor star. When a star explodes in vacuum, the first photons to escape from its surface appear as a brief, hours-long shock-breakout flare1,2, followed by a cooling phase of emission. However, for stars exploding within a distribution of dense, optically thick circumstellar material (CSM), the first photons escape from the material beyond the stellar edge and the duration of the initial flare can extend to several days, during which the escaping emission indicates photospheric heating3. Early serendipitous observations2,4 that lacked ultraviolet (UV) data were unable to determine whether the early emission is heating or cooling and hence the nature of the early explosion event. Here we report UV spectra of the nearby SN 2023ixf in the galaxy Messier 101 (M101). Using the UV data as well as a comprehensive set of further multiwavelength observations, we temporally resolve the emergence of the explosion shock from a thick medium heated by the SN emission. We derive a reliable bolometric light curve that indicates that the shock breaks out from a dense layer with a radius substantially larger than typical supergiants.

Background: Acute right colic diverticulitis (ARD) is less frequent in Western countries than acute sigmoid diverticulitis (ASD). We aimed to compare the management of ARD and ASD operated on in emergency., Methods: All consecutive patients who had emergency surgery for ASD and ARD (2010-2021) were included in a retrospective, multicenter, cohort study. Patients were identified from databases in French centers that were members of the French Surgical Association. Emergency surgery was performed during the same hospitalization for peritonitis or after failure of conservative treatment. Early and late postoperative outcomes were studied., Results: A total of 2297 patients were included with 2256 (98.2%) ASD and 41 (1.8%) ARD patients. Baseline characteristics were similar. Overall, patients were rated Hinchey 3-4 (63.9%, n = 1468, p = 0.287). ARD was more often treated with resection and anastomosis, protected or not (53.7%, n = 22), whereas ASD was mainly treated with resection and terminal ostomy (62.5% (n = 1409), p < 0.001). Median operative time was shorter for ARD (120 vs 146 min, p = 0.04). The group of ARD patients showed a higher prevalence of Clavien III/IV complications compared to the group of ASD patients, although no statistically significant difference was observed (41.5%, n = 17 vs. 27.6%, n = 620, p = 0.054). However 90-day mortality only happened in ASD patients (9.8%, n = 223 vs 0, p = 0.03). ARD patients had more diverticulitis recurrence (46.3%, n = 19 vs 13.4%, n = 303, p < 0.001). Multivariate analysis identified female sex as a protective factor for recurrence [odds ratio (OR) 0.55, p < 0.001] and ARD as a risk factor (OR 8.85, p < 0.001)., Conclusion: Operated on in emergency, ARDs have more resection anastomosis, with a similar rate of complications, less mortality, and more recurrence of diverticulitis than ASD., (© 2024. Springer Nature Switzerland AG.)

The crop cycle of winter oilseed rape (WOSR) incorporates source-to-sink remobilisation during the vegetative stage as a principal factor influencing the ultimate seed yield. These processes are supported by the coordinated activity of the plant's central metabolism. However, climate change-induced drought will affect the metabolic acclimation of WOSR sink/source relationships at this vegetative stage, with consequences that remain to be determined. In this study, we subjected WOSR to severe soil dehydration for 18 days and analysed the physiological and metabolic acclimation of sink and source leaves along the kinetics in combination with measurements of enzymatic activities and transcript levels. Overall, the acclimation of WOSR to drought led to subtle regulations of central metabolism in relation to leaf growth and Pro-induced osmotic adjustment. Notably, sink leaves drastically reduced their growth and transiently accumulated starch. Subsequent starch degradation correlated with the induction of beta-amylases, sucrose transporters, pyrroline-5-carboxylate synthases and proline accumulation. The functioning of the tricarboxylic acid cycle was also altered in sink leaves, as evidenced by variations in citrate, malate and associated enzymatic activities. The metabolic origin of Pro in sink leaves is discussed in relation to Pro accumulation in source leaves and the up-regulation of amino acid permease 1 and glutamine synthetase genes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: Besides the high prevalence of HIV and HCV infections, people who inject drugs (PWID) have a cumulative risk of acquiring skin and soft tissue infections (SSTI) from, among other things, social precariousness, homelessness/unstable housing, and unhygienic injecting practices. We propose to evaluate whether a two-component educational hand hygiene intervention which combines training in hand-washing with the supply of a single-use alcohol-based hand rub, called MONO-RUB, is effective in reducing injection-related abscesses in the PWID population. Specifically, we shall implement a nationwide, two-arm, multi-centre, cluster randomised controlled trial to evaluate the effectiveness and cost-effectiveness of this intervention in PWID., Methods: HAWA is a community-based participatory research study to be conducted in 22 harm reduction centres (HR) in France (not yet recruiting); the latter will be randomised into two clusters: centres providing standard HR services and the intervention (i.e., intervention group) and those providing standard HR services only (i.e., control group). After randomization, each cluster will include 220 PWID, with an inclusion period of 12 months and an individual follow-up period of 6 months. For each participant, we will collect data at M0, M3 and M6 from photos of injection sites on the participant's body, a face-to-face injection-related SSTI questionnaire, and a CATI questionnaire. The primary outcome is the reduction in abscess prevalence between M0 and M6, which will be compared between the control and intervention arms, and measured from observed (photographs) and self-declared (SSTI questionnaire) data. We will also assess the cost-effectiveness of the intervention., Discussion: The HAWA trial will be the first cluster randomized controlled trial to improve hand hygiene among PWID with a view to reducing SSTI. If effective and cost-effective, the intervention combined with the distribution of MONO-RUBs (or a similar cleaning product) may prove to be an important HR tool, helping to reduce the enormous burden of infection-related deaths and diseases in PWID., Trial Registration: NCT06131788, received on 2 January 2024., (© 2024. The Author(s).)

Background: Mindfulness improves well-being, improves emotional regulation, reduces impulses to eat, and is linked to increased physical activity. Mindfulness interventions usually focus on 1 aspect but do not offer an approach to holistically improving lifestyle., Objective: This study aims to address this gap by designing and evaluating a holistic mindfulness intervention., Methods: Committing to a 12-week intervention with 2-hour sessions without knowing whether you will enjoy it can be a hindrance for someone completely unfamiliar with mindfulness. For this reason, we decided to design a mindfulness intervention with short sessions over a reduced number of weeks. The aim is to enable novices to discover different aspects of mindfulness while at the same time offering a satisfactory practice for people who are already practicing mindfulness. We designed and evaluated a web-based mindfulness intervention in 5 sessions of 5 to 10 minutes each on well-being, diet, and physical activity to support a healthier lifestyle. The first 2 sessions focus on formal mindfulness meditation to enable novices to discover mindfulness and its main principles. Then there are 2 sessions about food. The first session about food aims to develop a sense of satisfaction with the food we eat and to focus our attention on new sensations. The second session about food aims to develop the ability to resist the lure of unhealthy foods. Finally, there is a session on physical activity. The aim is to develop a particular awareness of the body during movement, to increase satisfaction with physical activity, and to develop regular exercise., Results: In total, 32 participants completed the intervention. After the intervention, we observed decreases in negative affect, anxiety, and emotional distress, and an increase in dispositional mindfulness. There was no effect on reported healthy eating habits and physical activity habits. Few participants repeated the exercises as recommended. The majority of our participants were new to mindfulness. The majority of our participants reported being satisfied with the different sessions. A few minor difficulties were mentioned, mainly related to the environment in which the participants carried out the sessions. Only 1 session was less satisfactory for one-third of the participants. The session on resistance to unhealthy foods was formulated too strictly and the idea of banning certain foods was a hindrance for one-third of the participants. A reformulation is needed., Conclusions: The mindfulness exercises were well accepted and promoted a state of mindfulness. It would be interesting to provide easier technical access to the exercises via a mobile app so that they can be repeated easily., (©Morghane Aubert, Céline Clavel, Christine Le Scanff, Jean-Claude Martin. Originally published in JMIR Formative Research (https://formative.jmir.org), 15.10.2024.)

Background: Cystic Fibrosis (CF) is a monogenic disease caused by mutations in the gene coding the Cystic Fibrosis Transmembrane Regulator (CFTR) protein, but its overall physio-pathology cannot be solely explained by the loss of the CFTR chloride channel function. Indeed, CFTR belongs to a yet not fully deciphered network of proteins participating in various signalling pathways., Methods: We propose a systems biology approach to study how the absence of the CFTR protein at the membrane leads to perturbation of these pathways, resulting in a panel of deleterious CF cellular phenotypes., Results: Based on publicly available transcriptomic datasets, we built and analyzed a CF network that recapitulates signalling dysregulations. The CF network topology and its resulting phenotypes were found to be consistent with CF pathology., Conclusion: Analysis of the network topology highlighted a few proteins that may initiate the propagation of dysregulations, those that trigger CF cellular phenotypes, and suggested several candidate therapeutic targets. Although our research is focused on CF, the global approach proposed in the present paper could also be followed to study other rare monogenic diseases., (© 2024. The Author(s).)

Gene drives are genetic modifications designed to propagate efficiently through a population. Most applications rely on homologous recombination during sexual reproduction in diploid organisms such as insects, but we recently developed a gene drive in herpesviruses that relies on co-infection of cells by wild-type and engineered viruses. Here, we report on a viral gene drive against human herpes simplex virus 1 (HSV-1) and show that it propagates efficiently in cell culture and during HSV-1 infection in mice. We describe high levels of co-infection and gene drive-mediated recombination in neuronal tissues during herpes encephalitis as the infection progresses from the site of inoculation to the peripheral and central nervous systems. In addition, we show evidence that a superinfecting gene drive virus could recombine with wild-type viruses during latent infection. These findings indicate that HSV-1 achieves high rates of co-infection and recombination during viral infection, a phenomenon that is currently underappreciated. Overall, this study shows that a viral gene drive could spread in vivo during HSV-1 infection, paving the way toward therapeutic applications., (© 2024. The Author(s).)

Given the multiple challenges that agriculture faces, collective action is a potential pathway towards more sustainable agriculture. This article aims to contribute to the literature by assessing the extent to which collective action can meet the objective of both healthy and profitable production in the French West Indies. To do so, we call on the theory of collective action and emphasise the role of formal and informal collectives in achieving the objectives of improving income and implementing agroecological practices. We use original data collected in 2022 from 409 vegetable farmers in Martinique and Guadeloupe. We consider the interdependence between farmers' economic and environmental objectives through a simultaneous equations model. We characterise the diversity of collectives according to their degree of formalisation and to the adequacy between the objectives pursued by these collectives and the individual objectives of their members. Our results show that the achievement of an individual objective is fostered by its adequacy with the objective set by the collective and also, to a certain extent, by the degree of formalisation of this collective. It appears that achieving individual objectives is based on sharing common objectives as well as having collective rules. More particularly, we find that producer organisations - collectives considered to be the most formal - best meet the objectives of improving income and adopting agroecological practices. However, in the French West Indies, the instability of such collectives and the organisational deficiencies of the sector call into question their real long-term impact. These findings contribute to a better understanding of farmers' decision-making and provide relevant policy implications for supporting agricultural collectives in managing and federating producers towards achieving a more healthy and profitable production., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: In women, ovarian cancer is the eighth most frequent cancer in incidence and mortality. It is often diagnosed at advanced stages; relapses are frequent, with a poor prognosis. When platinum resistant, subsequent lines of chemotherapy are of limited effect and often poorly tolerated, leading to quality of life deterioration. Various studies suggest a hormonal role in ovarian carcinogenesis, with a rationale for endocrine therapy in these cancers., Patients and Methods: This multicenter, retrospective study assessed the use of endocrine treatment for high-grade ovarian epithelial carcinomas treated between 2010 and 2020., Results: Eighty-one patients with ovarian cancers were included. The median duration of platinum sensitivity was 29 months. We observed a 35% disease control rate with endocrine therapy, and 10% reported symptom improvement. For 19 patients (23.5%), the disease was stabilized for more than 6 months. Median overall survival from diagnosis was 62.6 months. Regarding endocrine therapy predictive factors of response, in a multivariate analysis, 3 factors were statistically significant in favoring progression-free survival: platinum sensitivity (P = .021), an R0 surgical resection (P = .020), and the indication for hormone therapy being maintenance therapy (P = .002)., Conclusion: This study shows real-life data on endocrine therapy in ovarian cancer. As it is a low-cost treatment with many advantages such as its oral administration and its safety, it may be an option to consider. A perspective lies in the search for cofactors to aim as future therapeutic targets to improve the effectiveness of hormone treatment by means of combination therapy., (© The Author(s) 2024. Published by Oxford University Press.)

Previous dating research indicated that the Indonesian island of Sulawesi is host to some of the oldest known rock art 1-3 . That work was based on solution uranium-series (U-series) analysis of calcite deposits overlying rock art in the limestone caves of Maros-Pangkep, South Sulawesi 1-3 . Here we use a novel application of this approach-laser-ablation U-series imaging-to re-date some of the earliest cave art in this karst area and to determine the age of stylistically similar motifs at other Maros-Pangkep sites. This method provides enhanced spatial accuracy, resulting in older minimum ages for previously dated art. We show that a hunting scene from Leang Bulu' Sipong 4, which was originally dated using the previous approach to a minimum of 43,900 thousand years ago (ka) 3 , has a minimum age of 50.2 ± 2.2 ka, and so is at least 4,040 years older than thought. Using the imaging approach, we also assign a minimum age of 53.5 ± 2.3 ka to a newly described cave art scene at Leang Karampuang. Painted at least 51,200 years ago, this narrative composition, which depicts human-like figures interacting with a pig, is now the earliest known surviving example of representational art, and visual storytelling, in the world 3 . Our findings show that figurative portrayals of anthropomorphic figures and animals have a deeper origin in the history of modern human (Homo sapiens) image-making than recognized to date, as does their representation in composed scenes., (© 2024. The Author(s).)

Aim: The aim of this work was to investigate the association between early postoperative anastomotic leakage or pelvic abscess (AL/PA) and symptomatic anastomotic stenosis (SAS) in patients after surgery for left colonic diverticulitis., Method: This is a retrospective study based on a national cohort of diverticulitis surgery patients carried out by the Association Française de Chirurgie. The assessment was performed using path analyses. The database included 7053 patients operated on for colonic diverticulitis, with surgery performed electively or in an emergency, by open access or laparoscopically. Patients were excluded from the study analysis where there was (i) right-sided diverticulitis (the initial database included all consecutive patients operated on for colonic diverticulitis), (ii) no anastomosis was performed during the first procedure or (iii) missing information about stenosis, postoperative abscess or anastomotic leakage., Results: Of the 4441 patients who were included in the final analysis, AL/PA occurred in 327 (4.6%) and SAS occurred in 82 (1.8%). AL/PA was a significant independent factor associated with a risk for occurrence of SAS (OR = 3.41, 95% CI = 1.75-6.66), as was the case for diverting stoma for ≥100 days (OR = 2.77, 95% CI = 1.32-5.82), while central vessel ligation proximal to the inferior mesenteric artery was associated with a reduced risk (OR = 0.41; 95% CI = 0.19-0.88). Diverting stoma created for <100 days or ≥100 days was also a factor associated with a risk for AL/PA (OR = 3.08, 95% CI = 2-4.75 and OR = 12.95, 95% CI = 9.11-18.50). Interestingly, no significant association between radiological drainage or surgical management of AL/PA and SAS could be highlighted., Conclusion: AL/PA was an independent factor associated with the risk for SAS. The treatment of AL/PA was not associated with the occurrence of anastomotic stenosis. Diverting stoma was associated with an increased risk of both AL/PA and SAS, especially if it was left for ≥100 days. Physicians must be aware of this information in order to decide on the best course of action when creating a stoma during elective or emergency surgery., (© 2024 The Author(s). Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Background: Pilonidal disease (PD) is a common condition for which the global incidence is increasing. Surgery is the currently preferred approach to treatment but there is a growing interest in new minimally invasive techniques, such as sinus laser therapy (SiLaT)., Aim: Our primary objective was to assess the efficacy of SiLaT for the treatment of pilonidal disease. The secondary objectives were to evaluate morbidity and patient satisfaction and identify predictive factors of success., Methods: All adult patients, who underwent SiLaT in our department for a primary or recurrent pilonidal sinus from June 1, 2018, to December 31, 2020, were included in the study. Healing was defined as the closure of cutaneous orifices and the absence of seepage or abscesses., Results: In total, 111 consecutive patients, for whom the male/female sex ratio was 2.1 and the mean age 28.8 (± 9.4) years, were included in this study. Eighteen (16.2%) patients had already undergone prior surgery for PD. The mean follow-up was 339.2 (± 221.4) days. A healing rate of 78.4% was observed, with a median time to healing of 20.0 days (15.0-30.0). The median time to return to usual activities was three days (1-7). The only postoperative complication was bleeding, which occurred for two patients (1.8%). Eighty-two patients (88.2%) reported being "very satisfied" with the treatment. Multivariate analysis showed no predictive factors for healing among the studied variables., Conclusion: SiLaT is an efficient and safe procedure for the treatment of PD, with a high level of patient satisfaction. It will now be necessary to position it within the therapeutic algorithm., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Anti-HSV therapies are only suppressive because they do not eliminate latent HSV present in ganglionic neurons, the source of recurrent disease. We have developed a potentially curative approach against HSV infection, based on gene editing using HSV-specific meganucleases delivered by adeno-associated virus (AAV) vectors. Gene editing performed with two anti-HSV-1 meganucleases delivered by a combination of AAV9, AAV-Dj/8, and AAV-Rh10 can eliminate 90% or more of latent HSV DNA in mouse models of orofacial infection, and up to 97% of latent HSV DNA in mouse models of genital infection. Using a pharmacological approach to reactivate latent HSV-1, we demonstrate that ganglionic viral load reduction leads to a significant decrease of viral shedding in treated female mice. While therapy is well tolerated, in some instances, we observe hepatotoxicity at high doses and subtle histological evidence of neuronal injury without observable neurological signs or deficits. Simplification of the regimen through use of a single serotype (AAV9) delivering single meganuclease targeting a duplicated region of the HSV genome, dose reduction, and use of a neuron-specific promoter each results in improved tolerability while retaining efficacy. These results reinforce the curative potential of gene editing for HSV disease., (© 2024. The Author(s).)

Aim: Digestive stoma are frequently performed. The last French guidelines have been published twenty years ago. Our aim was to update French clinical practice guidelines for the perioperative management of digestive stoma and stoma-related complications., Methods: A systematic literature review of French and English articles published between January 2000 and May 2022 was performed. Only digestive stoma for fecal evacuation in adults were considered. Stoma in children, urinary stoma, digestive stoma for enteral nutrition, and rare stoma (Koch, perineal) were not included., Results: Guidelines include the surgical landmarks to create digestive stoma (ideal location, mucocutaneous anastomosis, utility of support rods, use of prophylactic mesh), the perioperative clinical practice guidelines (patient education, preoperative ostomy site marking, postoperative equipment, prescriptions, and follow-up), the management of early stoma-related complications (difficulties for nursing, high output, stoma necrosis, retraction, abscess and peristomal skin complications), and the management of late stoma-related complications (stoma prolapse, parastomal hernia, stoma stenosis, late stoma retraction). A level of evidence was assigned to each statement., Conclusion: These guidelines will be very useful in clinical practice, and allow to delete some outdated dogma., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

In the context of climate change and the reduction of mineral nitrogen (N) inputs applied to the field, winter oilseed rape (WOSR) will have to cope with low-N conditions combined with water limitation periods. Since these stresses can significantly reduce seed yield and seed quality, maintaining WOSR productivity under a wide range of growth conditions represents a major goal for crop improvement. N metabolism plays a pivotal role during the metabolic acclimation to drought in Brassica species by supporting the accumulation of osmoprotective compounds and the source-to-sink remobilization of nutrients. Thus, N deficiency could have detrimental effects on the acclimation of WOSR to drought. Here, we took advantage of a previously established experiment to evaluate the metabolic acclimation of WOSR during 14 days of drought, followed by 8 days of rehydration under high- or low-N fertilization regimes. For this purpose, we selected three leaf ranks exhibiting contrasted sink/source status to perform absolute quantification of plant central metabolites. Besides the well-described accumulation of proline, we observed contrasted accumulations of some "respiratory" amino acids (branched-chain amino acids, lysineand tyrosine) in response to drought under high- and low-N conditions. Drought also induced an increase in sucrose content in sink leaves combined with a decrease in source leaves. N deficiency strongly decreased the levels of major amino acids and subsequently the metabolic response to drought. The drought-rehydration sequence identified proline, phenylalanine, and tryptophan as valuable metabolic indicators of WOSR water status for sink leaves. The results were discussed with respect to the metabolic origin of sucrose and some amino acids in sink leaves and the impact of drought on source-to-sink remobilization processes depending on N nutrition status. Overall, this study identified major metabolic signatures reflecting a similar response of oilseed rape to drought under low- and high-N conditions.

Introduction: 'Highly effective' modulator therapies (HEMTs) have radically changed the Cystic Fibrosis (CF) therapeutic landscape., Areas Covered: A comprehensive search strategy was undertaken to assess impact of HEMT in life of pwCF, treatment challenges in specific populations such as very young children, and current knowledge gaps., Expert Opinion: HEMTs are prescribed for pwCF with definite genotypes. The heterogeneity of variants complicates treatment possibilities and around 10% of pwCF worldwide remains ineligible. Genotype-specific treatments are prompting theratyping and personalized medicine strategies. Improvement in lung function and quality of life increase survival rates, shifting CF from a pediatric to an adult disease. This implies new studies addressing long-term efficacy, side effects, emergence of adult co-morbidities and possible drug-drug interactions. More sensitive and predictive biomarkers for both efficacy and toxicity are warranted. As HEMTs cross the placenta and are found in breast milk, studies addressing the potential consequences of treatment during pregnancy and breastfeeding are urgently needed. Finally, although the treatment and expected outcomes of CF have improved dramatically in high- and middle-income countries, lack of access in low-income countries to these life-changing medicines highlights inequity of care worldwide.

Redesigning agrosystems to include more ecological regulations can help feed a growing human population, preserve soils for future productivity, limit dependency on synthetic fertilizers, and reduce agriculture contribution to global changes such as eutrophication and warming. However, guidelines for redesigning cropping systems from natural systems to make them more sustainable remain limited. Synthetizing the knowledge on biogeochemical cycles in natural ecosystems, we outline four ecological systems that synchronize the supply of soluble nutrients by soil biota with the fluctuating nutrient demand of plants. This synchrony limits deficiencies and excesses of soluble nutrients, which usually penalize both production and regulating services of agrosystems such as nutrient retention and soil carbon storage. In the ecological systems outlined, synchrony emerges from plant-soil and plant-plant interactions, eco-physiological processes, soil physicochemical processes, and the dynamics of various nutrient reservoirs, including soil organic matter, soil minerals, atmosphere, and a common market. We discuss the relative importance of these ecological systems in regulating nutrient cycles depending on the pedoclimatic context and on the functional diversity of plants and microbes. We offer ideas about how these systems could be stimulated within agrosystems to improve their sustainability. A review of the latest advances in agronomy shows that some of the practices suggested to promote synchrony (e.g., reduced tillage, rotation with perennial plant cover, crop diversification) have already been tested and shown to be effective in reducing nutrient losses, fertilizer use, and N 2 O emissions and/or improving biomass production and soil carbon storage. Our framework also highlights new management strategies and defines the conditions for the success of these nature-based practices allowing for site-specific modifications. This new synthetized knowledge should help practitioners to improve the long-term productivity of agrosystems while reducing the negative impact of agriculture on the environment and the climate., (© 2023 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)