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Abstract Over the last two decades, an increase in bed bug infestations has been observed worldwide. Although their definitive role as vectors of infectious agents has not yet been demonstrated, bed bugs have a direct effect on human health through dermatological reactions to their bites and psychological disorders linked to domestic infestations. In this study, the effectiveness of using MALDI-TOF MS to correctly identify these two bed bug species at immature stages was assessed, as well as it effectiveness as discriminating between the immature stages (IS) of C. lectularius and C. hemipterus and their associated developmental stages. A total of 305 specimens were subjected to MALDI-TOF MS analysis, including 153 C. lectularius (28 eggs and 25 nymphs per stage from IS1 to IS5) and 152 C. hemipterus (27 eggs and 25 nymphs per stage from IS1 to IS5). ). MALDI-TOF MS analysis enabled us to obtain 84.97% (130/153) of high-quality MS spectra in terms of reproducibility and profile intensity. Twenty-four spectra including two per stage, from egg to IS5, and per bed bug species - were added to our in-house MS reference arthropod spectra database. All specimens were correctly identified at the species level, independently of the developmental stage, with log score values (LSVs) ranging from 1.75 to 2.79 (mean = 2.29 ± 0.12) and 1.81 to 2.71 (mean = 2.37 ± 0.03) for C. lectularius and C. hemipterus, respectively. MALDI-TOF MS correctly classified 53,33% (104/195) of the Cimex at the correct immature stage. Conversely, an accurate comparison of the profiles with a Genetic Algorithm model underlined that grouping the immature stages in two groups, early (IS1-IS2) and late (IS3-IS4-IS5), made it possible to obtain a cross validation (CV) and recognition capability (RC) greater than 92% and 94%, respectively, for both species. This study holds great promise for the management of bed bug infestations.

In this contribution, new data concerning algae, bryophytes, fungi and lichens of the Italian flora are presented. It includes new records, confirmations or exclusions for the algal genera Chara and Tolypella, the bryophyte genera Pogonatum, Pseudephemerum, and Riella, the fungal genera Arrhenia, Arthonia, Buchwaldoboletus, Dacampia, Hebeloma, Inocybe, and Trechispora, and the lichen genera Aspicilia, Bellemerea, Cladonia, Hypotrachyna, Maronea, Parvoplaca, Polyozosia, Schismatomma, Solenopsora, Trapelia, and Zwackhia.

Objective: Subclinical hyperthyroidism (SCH) is common and associated with atrial fibrillation (AF) risk in the elderly. Current guidelines rely on a low level of evidence. Methods: Randomized clinical trial including patients 50 years and older, with thyroid-stimulating hormone (TSH) 65 years or TSH < 0.1mU/L. Of 94 patients treated using radioiodine, 25% developed hypothyroidism during follow-up. Conclusion: Due to recruitment difficulties, this study failed to demonstrate that SCH treatment can significantly reduce the incidence of AF in patients older than 50 years with thyroid autonomy even if all the patients who developed AF maintained TSH

DNA collections are a valuable type of Natural Science collection, enabling the validation of past research, serving as a source for new genomic studies and supporting ex situ conservation. The DiSSCo Flanders DNA collection working group, aiming to advance and "unlock" their DNA collections, identified the need for: 1) actively sharing best practices regarding the management of DNA collections; and 2) providing guidance on how to bring theory into practice. By combining best practice examples from within the working group with available literature and brainstorming ideas, the working group co-created two outputs, referred to as: the "Challenges" and the "Key". The Challenges are a list of obstacles to DNA collection management, which shape the structure of the linked Key and can also be used to spark discussion amongst stakeholders. The Key is a tool that guides users through the maturation process of their DNA collection in a standardised way. It stimulates holistic growth, breaks down the needed work into manageable steps and helps to decide priorities during the process. Furthermore, the Key facilitates communication with both internal stakeholders and external DNA collection managers. The Key distinguishes itself from other self-assessment tools in several ways: it includes (re)investigation of the collection’s purpose and context; it is specialised for DNA collections; it delivers concrete goals linked to relevant information and shared experience; and it is inclusive, targeting all Natural Science DNA collections, regardless of their context or size.

Abstract Metabolic dysfunction-associated steatotic liver disease (MASLD) is common in individuals with obesity. Sexual dimorphism is present in MASLD. A noninvasive test to diagnose the severity of the disease, in particular the presence of Metabolic dysfunction-associated steatohepatitis (MASH), is lacking. This European multicenter prospective study uses a blood test based on mid-infrared (MIR) metabolic fingerprinting of individuals with severe or morbid obesity to diagnose MASH. Three hundred eighty-two individuals with severe or morbid obesity undergoing bariatric surgery were enrolled prospectively. Liver biopsies were obtained during surgery and assessed centrally. An algorithm was defined to calculate a score from the recorded MIR spectrum and to establish a diagnostic threshold to classify patients with MASH. Among the women (n = 217), MASH was diagnosed in 14.3% of cases. For women, the performance in terms of AUC were 0.83 and 0.82 in the calibration and validation groups, respectively. For a threshold of 0.1817, sensitivities were 86% and 70%, specificities were 81% and 75%, PPV were 43% and 32%, NPV were 97% and 94% and ACC were 82% and 74% for the calibration and validation groups, respectively. For men (n = 78; MASH: 33.3%), the performance of the spectral model was poor. The metabolic fingerprint obtained by MIR spectroscopy can rule out MASH in women with severe or morbid obesity. Its value in men needs new studies. Trial registration: ClinicalTrials.gov identifier: ClinicalTrials.gov identifier: NCT03978247 (04/06/2019)

Abstract Background The present study assessed physical activity (PA) and sedentary behavior (SB) levels and their motivational and emotional health-related correlates, in outpatients following a cardiovascular rehabilitation (CR) program, and compared these variables with those of a healthy control group. Methods The study included 119 participants: 68 CR outpatients (M age 57.76 ± 10.76; 86.76% males) and 51 control participants matched on age (M age 57.35 ± 6.33 years; 45.10% males). PA and SB were assessed using accelerometers during the first week post-discharge for outpatients and during a typical week for controls. Motivational (i.e., perceived capabilities, affective and instrumental attitudes, intention, approach-avoidance tendencies) and emotional health-related variables (i.e., anxiety, depressive symptoms, fatigue, pain intensity) were measured using validated scales. PA and SB data from 17 outpatients and 42 controls were valid for analysis, resulting in a final sample of 59 participants. Results CR outpatients engaged an average of 60.21 (± 34.79) min of moderate-to-vigorous PA (MVPA), and 548.69 (± 58.64) min of SB per day, with 18 more minutes of MVPA per day than controls (p = .038). Univariate and multivariate regressions indicated that positive affective attitudes were associated with higher MVPA (b = 10.32, R2 = 0.07, p = .029), and that males spent more time in SB than females (b = 40.54, R2 = 0.09, p = .045). Univariate and multivariate logistic regressions showed that meeting the World Health Organization’s weekly guidelines for MVPA was associated with higher perceived capabilities toward PA and more positive affective attitudes (OR = 1.17, p = .030; OR = 1.26, p

Abstract The structural basis for the allosteric interactions within G protein-coupled receptors (GPCRs) heterodimers remains largely unknown. The metabotropic glutamate (mGlu) receptors are complex dimeric GPCRs important for the fine tuning of many synapses. Heterodimeric mGlu receptors with specific allosteric properties have been identified in the brain. Here we report four cryo-electron microscopy structures of mGlu2-4 heterodimer in different states: an inactive state bound to antagonists, two intermediate states bound to either mGlu2 or mGlu4 agonist only and an active state bound to both glutamate and a mGlu4 positive allosteric modulator (PAM) in complex with Gi protein. In addition to revealing a unique PAM binding pocket among mGlu receptors, our data bring important information for the asymmetric activation of mGlu heterodimers. First, we show that agonist binding to a single subunit in the extracellular domain is not sufficient to stabilize an active dimer conformation. Single-molecule FRET data show that the monoliganded mGlu2-4 can be found in both intermediate states and an active one. Second, we provide a detailed view of the asymmetric interface in seven-transmembrane (7TM) domains and identified key residues within the mGlu2 7TM that limits its activation leaving mGlu4 as the only subunit activating G proteins.

Interstitial lung disease (ILD) is a frequent manifestation of rheumatoid arthritis (RA) that is associated with high mortality. RA‐ILD may initially be asymptomatic, and lung function may be markedly impaired by the time it is diagnosed. The course of RA‐ILD is highly variable, with some patients experiencing no discernable progression or a slow decline, whereas others experience more rapid deterioration. Some patients develop progressive pulmonary fibrosis, which is associated with high mortality. Although risk factors for the progression of RA‐ILD have been identified, including older age, worse lung function, and a usual interstitial pneumonia pattern on high‐resolution computed tomography, it is not possible to predict the course of RA‐ILD in an individual patient. The association between RA disease activity and progression of RA‐ILD remains unclear. Regular monitoring is important to enable the prompt identification of progression and early intervention to preserve lung function. The management of RA‐ILD requires a multidisciplinary and individualized approach, taking account of the severity and progression of articular and lung disease, risk factors for the progression of RA‐ILD, and the patient's preferences, and may include immunosuppression, antifibrotic therapy, and supportive care.

Abstract Objective This systematic review aims to describe the involvement of persons with epilepsy (PWE), healthcare professionals (HP) and caregivers (CG) in the design and development of medical devices is epilepsy. Methods A systematic review was conducted, adhering to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Eligibility criteria included peer‐reviewed research focusing on medical devices for epilepsy management, involving users (PWE, CG, and HP) during the MDD process. Searches were performed on PubMed, Web of Science, and Scopus, and a total of 55 relevant articles were identified and reviewed. Results From 1999 to 2023, there was a gradual increase in the number of publications related to user involvement in epilepsy medical device development (MDD), highlighting the growing interest in this field. The medical devices involved in these studies encompassed a range of seizure detection tools, healthcare information systems, vagus nerve stimulation (VNS) and electroencephalogram (EEG) technologies reflecting the emphasis on seizure detection, prediction, and prevention. PWE and CG were the primary users involved, underscoring the importance of their perspectives. Surveys, usability testing, interviews, and focus groups were the methods used for capturing user perspectives. User involvement occurs in four out of the five stages of MDD, with production being the exception. Significance User involvement in the MDD process for epilepsy management is an emerging area of interest holding a significant promise for improving device quality and patient outcomes. This review highlights the need for broader and more effective user involvement, as it currently lags in the development of commercially available medical devices for epilepsy management. Future research should explore the benefits and barriers of user involvement to enhance medical device technologies for epilepsy. Plain Language Summary This review covers studies that have involved users in the development process of medical devices for epilepsy. The studies reported here have focused on getting input from people with epilepsy, their caregivers, and healthcare providers. These devices include tools for detecting seizures, stimulating nerves, and tracking brain activity. Most user feedback was gathered through surveys, usability tests, interviews, and focus groups. Users were involved in nearly every stage of device development except production. The review highlights that involving users can improve device quality and patient outcomes, but more effective involvement is needed in commercial device development. Future research should focus on the benefits and challenges of user involvement.

Abstract Aims The indication for implantable cardioverter defibrillator (ICD) for sudden cardiac death (SCD) prevention relies mostly on left ventricular ejection fraction (LVEF) ≤ 35%. The use of a wearable cardioverter defibrillator (WCD) in the case of dynamic alterations of LVEF may help avoid an improper early ICD implant when a favourable evolution in the post‐acute phase is observed and may help reduce costs. Methods This parallel cohort retrospective study included patients with heart failure with reduced ejection fraction (HFrEF) at high risk of arrhythmias recruited in the acute phase and divided into an early ICD cohort and a WCD cohort for primary prevention during the waiting period established by European Society of Cardiology guidelines. Results A total of 41 consecutive patients were enrolled: 26 in the WCD group and 15 in the early ICD group. Age, LVEF at baseline, causes of HFrEF and drug therapy in the two cohorts were similar. During the waiting period after the inclusion, three patients (11.5%) in the WCD cohort and four (26.7%) in the early ICD cohort developed relevant ventricular arrhythmias (P = 0.22); none of them had subsequent LVEF recovery. At the end of the waiting period, 13 patients (50%) in the WCD group and 7 (46.7%) in the early ICD group experienced LVEF recovery (P = 0.84). The average cost per patient at the end of the waiting period was €23 934 in the early ICD cohort versus €19 167 in the WCD cohort (−19.9%). This cost savings from WCD use appears even higher when projected over a 10 year period (−41.2%). Conclusions WCD may represent a cost‐effective strategy to more accurately select candidates for the primary prevention ICD implant among high‐risk patients with HFrEF. ICD use provides effective protection from SCD and reduces costs compared with an extensive early ICD implant.

Abstract Taxanes, such as paclitaxel (PTX), stabilize microtubules and are used as a first-line therapy in multiple cancer types. Disruption of microtubule equilibrium, which plays an essential role in mitosis and cell homeostasis, ultimately results in cell death. Even though PTX is a very potent chemotherapy, its use is associated with major side effects and therapy resistance. Pelophen B (PPH), a synthetic analog of peloruside A, stabilizes microtubules through interaction with a non-taxoid binding site of β-tubulin. We evaluated the anticancer effect of PPH in a variety of tumor types by using established cell lines, early-passage cultures and ex vivo tumor-derived cultures that preserve the 3D architecture of the tumor microenvironment. PPH significantly blocks colony formation capacity, reduces viability and exerts additivity with PTX. Interestingly, PPH overcomes resistance to PTX. Mechanistically, PPH induces a G2/M cell cycle arrest and increases the presence of tubulin polymerization promoting protein (TPPP), inducing lysine 40 acetylation of α-tubulin. Although, results induced by paclitaxel or PPH are concordant, PPH’s unique microtubule binding mechanism enables PTX additivity and ensures overcoming PTX-induced resistance. In conclusion, PPH results in remarkable anti-cancer activity in a range of preclinical models supporting further clinical investigation of PPH as a therapeutic anticancer agent.

Abstract Background Osteoarthritis is a leading cause of pain and retirement in athletic horses. Hydro-expansive functionalized nanogels, acting as Drug Delivery Systems, constitute one of the current therapeutic prospects. These nanogels have the potential to combine mechanical benefits through polymers with the biological effect of prolonged release of bioactive molecules. The purpose of this double-blinded randomized tolerance study versus negative control was to evaluate the response of healthy joints to a single injection of the expected efficient dose (further referred to as the trial dose) and overdose of nanogels composed of chitosan and hyaluronic acid and featuring a type A endothelin receptor antagonist and a type B1 bradykinin receptor antagonist. The metacarpophalangeal joints of 8 healthy horses were randomly injected with 2.4 mL of functionalized nanogels and 2.4 mL of saline as control on the contralateral limb. Injections were repeated twice at one-week intervals, followed by injection of a triple dose of nanogel on week four. Clinical, ultrasonographic and synovial fluid cellular and biochemical follow-ups were performed up to three months following the first injection. Results No change in general clinical parameters, lameness or sensitivity to passive flexion of the fetlocks was noted. Mild to moderate synovitis was noted on the day following injection in the treated group, with a significant difference (p

Abstract Introduction Adolescents face unique challenges in accessing appropriate information and services regarding sexuality and reproductive health (SRH). This poor access can lead to sexual behaviours that could put them at risk of unintended pregnancies and sexually transmitted infections. Adolescents living with HIV (ALHIV) have specific SRH needs that remain unmet. We explored the SRH knowledge, practices and needs of ALHIV in Abidjan, Côte d’Ivoire. Methods Between April and September 2023, a qualitative study using semi-structured individual interviews was conducted with nine male and nine female ALHIV without previous pregnancies, and eight ALHIV who became pregnant. All consented and were ALHIV acquired perinatally, aged 15–19 years, informed of their HIV status, and followed in three paediatric HIV care centres in Abidjan. participating in the paediatric IeDEA West African Cohort and enrolled in the ANRS12390 OPTIMISE-AO project aimed at improving HIV disclosure process and adherence to antiretroviral treatment. A focus group discussion was conducted with five peer-educators, aged 23–31 years, participating in the OPTIMISE-AO project to gather their perspectives on adolescent SRH. Interviews were conducted in French, and a thematic analysis was performed. Results All participants expressed difficulty in talking about SRH with their parents or health professionals and turned to their friends for advice. All feared transmitting HIV. One-third of female participants reported having experienced non-consensual sex and sexual violence. Participants reported low levels of condom use, despite having good knowledge of its purpose. Reasons for not using condoms included difficulties in negotiating for girls, as well as having an undetectable viral load, which was seen by adolescents as a condition for waiving condom use. As hormonal contraceptives were subject to many negative beliefs justifying their non-use, alternative methods, such as emergency contraceptive pills or traditional plants, were used to prevent pregnancy. Conclusion ALHIV reported unmet SRH needs, particularly in terms of accessing reliable information and appropriate support. Integrating SRH care into paediatric HIV care, organising SRH discussion groups led by peer-educators, and improving access to a range of contraceptives may address these needs to enhance SRH outcomes for ALHIV.

Abstract Background Existing evidence for associations of per- and polyfluoroalkyl substances (PFASs) with blood lipids, lipoproteins and apolipoproteins (apo), and coronary heart disease (CHD) risk is limited and inconsistent. This study aims to explore associations between plasma PFASs, blood lipoprotein subspecies defined by apolipoproteins, and CHD risk. Methods A case–control study of CHD was conducted in the Health Professionals Follow-Up Study (HPFS) and Nurses' Health Study (NHS). Among participants initially free of cardiovascular disease at blood collection in 1994 (HPFS) or 1990 (NHS), 101 participants who developed non-fatal myocardial infarction or fatal CHD were identified and confirmed. A healthy control was matched to each case for age, smoking status, and date of blood draw. Plasma levels of perfluorohexane sulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), total perfluorooctane sulfonic acid (PFOS), branched PFOS (brPFOS), linear PFOS (nPFOS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were measured. Conditional logistic regression and cubic spline regression models were used to examine associations between baseline PFASs and CHD risk. Linear regression models were applied to study PFAS associations with lipids and their subfractions. Results After multivariate adjustments, total PFOS, brPFOS and nPFOS were significantly associated with increased risk of developing CHD, and HRs (95% CIs) per log(ng/mL) increment of PFASs were 3.66 (1.36–9.89), 3.68 (1.55–8.76), and 3.01 (1.16–7.86), respectively. Significant positive dose–response relationships were identified for these PFASs (P linearity = 0.01, 0.002, 0.02, respectively). Other PFASs were not associated with CHD risk. PFNA and PFDA were positively associated with total apoE levels among HDL particles with or without apoC-III. No associations were observed for other PFASs with blood lipid subspecies. Blood lipid subfractions did not explain the association between PFOS and CHD risk. Conclusions Plasma PFOS and its isomers were positively associated with CHD risk. These findings suggest that PFOS exposure causes public health risks that are greater than hitherto believed.

Abstract Background PROMISE-EPI trial evaluated a combination of interventions to prevent HIV transmission during breastfeeding. It showed a reduced postnatal transmission compared to the standard of care. The intervention combined identification of infants at high risk of infection using a point of care assay (POC) for early infant diagnosis and monitoring maternal viral load (VL) at 6 weeks and 6 months. A single-drug post-natal prophylaxis (PNP) was immediately initiated for high risk infants (maternal VL ≥ 1000 cp/mL). In Zambia, the national guidelines standard of care differs by 1) using three-drug PNP; 2) quarterly monitoring of maternal VL; 3) maternal VL testing in central labs. We explored the facilitators and barriers of this innovative prevention package to guide future scale-up. Methods Qualitative methods were used to gather information on PROMISE-EPI trial delivery, context, and behaviors. PROMISE-EPI intervention and control participants, staff members and health care professionals were interviewed. Verbatim transcripts were coded using a priori and emerging codes. Analysis was conducted using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework. The determinants were categorized into the 5 domains of the Consolidated Framework for Implementation Research (CFIR) to better identify the causes of intervention success or failure among the 5 RE-AIM components. Results A total of 37 individual interviews and 15 focus group discussions were conducted. Facilitators included the importance of the connection between the key elements of the intervention (POC and PNP) for immediate clinical action. Rapid maternal VL results induce several positive downstream behaviors in mothers and healthcare professionals, including increased trust in health care system. These can be quickly reversed when point of care testing is sub-optimal, as during the COVID-19 pandemic. Furthermore, the secondary elements of the intervention beyond POC and PNP; namely a warm welcome, a dedicated space, detailed and dedicated counselling, reimbursement for transport, solar panels and batteries, reminders and additional staff; were identified as facilitating its acceptability and fidelity. Conclusion This study provides new elements to better understand the reduced HIV transmission with the PROMISE-EPI intervention. It also highlights potential gaps between the package proposed in the trial and what can be applied in less controlled, ‘real life’ settings.

Abstract Following the global progressive deployment of 5G networks, considerable attention has focused on assessing their potential impact on human health. This study aims to investigate autonomous nervous system changes by exploring skin temperature and electrodermal activity (EDA) among 44 healthy young individuals of both sexes during and after exposure to 3.5 GHz antenna‐emitted signals, with an electrical field intensity ranging from 1 to 2 V/m. The study employed a randomized, cross‐over design with triple‐blinding, encompassing both ‘real’ and ‘sham’ exposure sessions, separated by a maximum interval of 1 week. Each session comprised baseline, exposure and postexposure phases, resulting in the acquisition of seven runs. Each run initiated with a 150 s segment of EDA recordings stimulated by 10 repeated beeps. Subsequently, the collected data underwent continuous decomposition analysis, generating specific indicators assessed alongside standard metrics such as trough‐to‐peak measurements, global skin conductance and maximum positive peak deflection. Additionally, non‐invasive, real‐time skin temperature measurements were conducted to evaluate specific anatomical points (hand, head and neck). The study suggests that exposure to 3.5 GHz signals may potentially affect head and neck temperature, indicating a slight increase in this parameter. Furthermore, there was a minimal modulation of certain electrodermal metrics after the exposure, suggesting a potentially faster physiological response to auditory stimulation. However, while the results are significant, they remain within the normal physiological range and could be a consequence of an uncontrolled variable. Given the preliminary nature of this pilot study, further research is needed to confirm the effects of 5G exposure.

Abstract A LoRa self‐jamming scheme that enables secure and covert communications by adding jamming symbols when transmitting is proposed. The scheme has been validated in simulations. The work is continued by evaluating the scheme on real‐world software defined radio (SDR) equipment. Experiments immediately showed that a demodulation is impossible as the received signal is highly distorted. This comes from the fact that adding symbols at transmission actually generates high peak‐to‐average power ratio (PAPR) preventing proper waveform generation by the equipment's hardware. This paper presents a PAPR correction scheme that modifies the waveform. The properties of this modified waveform are analysed and the performances are assessed in simulations with realistic time and frequency synchronization assumption. For the ideal 0 dB PAPR corrected output, the SER performances are close to that of a legacy LoRa communication, while preserving the physical layer security capabilities of the self‐jamming scheme. It is finally shown that our PAPR correction scheme effectively recovers the self‐jamming properties on SDR devices.

Abstract Marine microbes are strongly interrelated to trace metals in the ocean. How the availability of trace metals selects for prokaryotic taxa and the potential feedback of microbial processes on the trace metal distribution in the ocean remain poorly understood. We investigate here the potential reciprocal links between diverse prokaryotic taxa and iron (Fe), manganese (Mn), copper (Cu), and nickel (Ni) as well as apparent oxygen utilization (AOU) across 12 well‐defined water masses in the Southern Indian Ocean (SWINGS—South West Indian Ocean GEOTRACES GS02 Section cruise). Applying partial least square regression (PLSR) analysis, we show that the water masses are associated with particular latent vectors that are a combination of the spatial distribution of prokaryotic taxa, trace elements, and AOU. This approach provides novel insights on the potential interactions between prokaryotic taxa and trace metals in relation to organic matter remineralization in distinct water masses of the ocean.

Primary metastatic prostate cancer to the orbit is exceedingly rare. Benign lesions, including meningioma, have demonstrated PSMA expression and can be visualized using PSMA-based PET tracers. We report the findings of 18F-PSMA-1007 PET/CT in a 76-year-old man with progressive confusion and long-standing blindness of the left eye. PET/CT scan revealed increased uptake of PSMA in the orbital and temporal region, and other sites throughout the body. Histopathological examination after biopsy of the left orbit showed adenocarcinoma of the prostate. This case substantiates the diverse clinical and radiological presentations of metastatic prostate cancer and underscores the diagnostic significance of targeted biopsy.

We consider state and parameter estimation for compartmental models having both time-varying and time-invariant parameters. In this manuscript, we first detail a general Bayesian computational framework as a continuation of our previous work. Subsequently, this framework is specifically tailored to the susceptible-infectious-removed (SIR) model which describes a basic mechanism for the spread of infectious diseases through a system of coupled nonlinear differential equations. The SIR model consists of three states, namely, the susceptible, infectious, and removed compartments. The coupling among these states is controlled by two parameters, the infection rate and the recovery rate. The simplicity of the SIR model and similar compartmental models make them applicable to many classes of infectious diseases. However, the combined assumption of a deterministic model and time-invariance among the model parameters are two significant impediments which critically limit their use for long-term predictions. The tendency of certain model parameters to vary in time due to seasonal trends, non-pharmaceutical interventions, and other random effects necessitates a model that structurally permits the incorporation of such time-varying effects. Complementary to this, is the need for a robust mechanism for the estimation of the parameters of the resulting model from data. To this end, we consider an augmented state vector, which appends the time-varying parameters to the original system states whereby the time evolution of the time-varying parameters are driven by an artificial noise process in a standard manner. Distinguishing between time-varying and time-invariant parameters in this fashion limits the introduction of artificial dynamics into the system, and provides a robust, fully Bayesian approach for estimating the time-invariant system parameters as well as the elements of the process noise covariance matrix. This computational framework is implemented by leveraging the robustness of the Markov chain Monte Carlo algorithm permits the estimation of time-invariant parameters while nested nonlinear filters concurrently perform the joint estimation of the system states and time-varying parameters. We demonstrate performance of the framework by first considering a series of examples using synthetic data, followed by an exposition on public health data collected in the province of Ontario.

In anticipation of potential future pandemics, we examined the challenges and opportunities presented by the COVID-19 outbreak. This analysis highlights how artificial intelligence (AI) and predictive models can support both patients and clinicians in managing subsequent infectious diseases, and how legislators and policymakers could support these efforts, to bring learning healthcare system (LHS) from guidelines to real-world implementation. This report chronicles the trajectory of the COVID-19 pandemic, emphasizing the diverse data sets generated throughout its course. We propose strategies for harnessing this data via AI and predictive modelling to enhance the functioning of LHS. The challenges faced by patients and healthcare systems around the world during this unprecedented crisis could have been mitigated with an informed and timely adoption of the three pillars of the LHS: Knowledge, Data and Practice. By harnessing AI and predictive analytics, we can develop tools that not only detect potential pandemic-prone diseases early on but also assist in patient management, provide decision support, offer treatment recommendations, deliver patient outcome triage, predict post-recovery long-term disease impacts, monitor viral mutations and variant emergence, and assess vaccine and treatment efficacy in real-time. A patient-centric approach remains paramount, ensuring patients are both informed and actively involved in disease mitigation strategies.

Myotonic dystrophy type 1 (DM1) is a rare autosomal dominant genetic disorder. Although DM1 is primarily characterized by progressive muscular weakness, it exhibits many multisystemic manifestations, such as cognitive deficits, cardiac conduction abnormalities, and cataracts, as well as endocrine and reproductive issues. Additionally, the gastrointestinal (GI) tract is frequently affected, encompassing the entire digestive tract. However, the underlying causes of these GI symptoms remain uncertain, whether it is biomechanical problems of the intestine, involvement of bacterial communities, or both. The primary objective of this study is to investigate the structural changes in the gut microbiome of DM1 patients. To achieve this purpose, 35 patients with DM1 were recruited from the DM-Scope registry of the neuromuscular clinic in the Saguenay–Lac-St-Jean region of the province of Québec, Canada. Stool samples from these 35 patients, including 15 paired samples with family members living with them as controls, were collected. Subsequently, these samples were sequenced by 16S MiSeq and were analyzed with DADA2 to generate taxonomic signatures. Our analysis revealed that the DM1 status correlated with changes in gut bacterial community. Notably, there were differences in the relative abundance of Bacteroidota, Euryarchaeota, Fusobacteriota, and Cyanobacteria Phyla compared to healthy controls. However, no significant shift in gut microbiome community structure was observed between DM1 phenotypes. These findings provide valuable insights into how the gut bacterial community, in conjunction with biomechanical factors, could potentially influence the gastrointestinal tract of DM1 patients.

Abstract To have effective water resource management, the distributed hydrological models are commonly applied for supporting the decision‐making processes. Among different inputs, the spatial distributed rainfall plays significant role in those model simulations. Many interpolation methods have been developed for generating distributed rainfall based on measurement samples. However, depending on the catchment characteristics and data availability, the suitable interpolation algorithm is case‐dependent. This paper presents one operational approach for determining the resonable interpolation algorithm in a complex large catchment (Var catchment, France). Based on the daily rainfall data (2008–2014) collected from 16 stations in the Var catchment, six different interpolation approaches including: inverse distance weight (IDW), spline, kriging with linear and spherical semi‐variogram models and geographically weighted regression considering elevation effects and the combined impacts of elevation and distance to the sea were tested. Integrated the results of statistical and modeling assessments, the 400 m resolution distributed rainfall generated by IDW algorithm shows high preference in generating distributed rainfall in the Var catchment. Moreover, the strategy described in the article also shows promising acceptability for other catchments.

Abstract The western Alpine belt is the focal point of moderate but constant seismic activity. Numerous geodynamic and seismological studies underline the many scientific questions linked to Alpine dynamic processes and the associated rate of deformation resulting from late continental collision phases, and the assessment of seismic hazard and its associated risks. Seismic monitoring in the northern French Alps was launched in 1987 with the installation of the first seismological network, hosted by the Earth Science Observatory at Grenoble Alpes University. Since then, the network has been updated over the years, keeping pace with technical developments in seismic instrumentation, monitoring and data management. The homogenization of information described in this scientific data paper is motivated by the need for a single instrumental seismic catalogue, consisting in arrival times picks and hypocenters using the same velocity model. The final catalogue SISMalp-1987–2023 (CC-BY-4.0) contains 50,822 weak-to-moderate earthquakes with local magnitude between −1.8 and 5.0; it can serve as a basis for all general seismotectonic and risk assessment studies in the region.

Abstract The International Staging System for multiple myeloma recently underwent a second revision (R2-ISS) to include gain/amplification of 1q21 and account for the additive prognostic significance of multiple high-risk features. The phase 3 ICARIA-MM (isatuximab–pomalidomide–dexamethasone vs. pomalidomide–dexamethasone) and IKEMA (isatuximab–carfilzomib–dexamethasone vs. carfilzomib–dexamethasone) studies provide large datasets for retrospectively validating the prognostic value of the R2-ISS in relapsed/refractory multiple myeloma. Of 609 pooled patients, 68 (11.2%) were reclassified as R2-ISS stage I, 136 (22.3%) as R2-ISS stage II, 204 (33.5%) as R2-ISS stage III, 55 (9.0%) as stage IV, and 146 (24.0%) “Not classified”. Median progression-free survival was shorter among those reclassified as R2-ISS stage II (HR 1.52, 95% CI 0.979–2.358), stage III (HR 2.59, 95% CI 1.709–3.923), and stage IV (HR 3.51, 95% CI 2.124–5.784) versus stage I. Adding isatuximab led to longer progression-free survival versus doublet therapy (adjusted HR 0.544 [95% CI 0.436–0.680]), with a consistent treatment effect observed across all R2-ISS stages. This is the first study to validate the R2-ISS with novel agents, including anti-CD38 monoclonal antibodies, and to show that R2-ISS, as a prognostic scoring system, can be applied to patients with relapsed/refractory multiple myeloma.

Abstract Background The Abdominal Compartment Society (WSACS) established consensus definitions and recommendations for the management of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) in 2006, and they were last updated in 2013. The WSACS conducted an international survey between 2022 and 2023 to seek the agreement of healthcare practitioners (HCPs) worldwide on current and new candidate statements that may be used for future guidelines. Methods A self-administered, online cross-sectional survey was conducted under the auspices of the WSACS to assess the level of agreement among HCPs over current and new candidate statements. The survey, distributed electronically worldwide, collected agreement or disagreement with statements on the measurement of intra-abdominal pressure (IAP), pathophysiology, definitions, and management of IAH/ACS. Statistical analysis assessed agreement levels, expressed in percentages, on statements among respondents, and comparisons between groups were performed according to the respondent’s education status, base specialty, duration of work experience, role (intensivist vs non-intensivist) and involvement in previous guidelines. Agreement was considered to be reached when 80% or more of the respondents agreed with a particular statement. Results A total of 1042 respondents from 102 countries, predominantly physicians (73%), of whom 48% were intensivists, participated. Only 59% of HCPs were aware of the 2013 WSACS guidelines, and 41% incorporated them into practice. Despite agreement in most statements, significant variability existed. Notably, agreement was not reached on four new candidate statements: “normal intra-abdominal pressure (IAP) is 10 mmHg in critically ill adults” (77%), “clinical assessment and estimation of IAP is inaccurate” (65.2%), “intragastric can be an alternative to the intravesical route for IAP measurement” (70.4%), and “measurement of IAP should be repeated in the resting position after measurement in a supine position” (71.9%). The survey elucidated nuances in clinical practice and highlighted areas for further education and standardization. Conclusion More than ten years after the last published guidelines, this worldwide cross-sectional survey collected feedback and evaluated the level of agreement with current recommendations and new candidate statements. This will inform the consensus process for future guideline development.

Abstract There has been a significant interest in venous congestion in recent years, among which the VExUS score has been prominent, both in clinical practice and research efforts. We have noted some recurrent misconceptions among clinicians which are also reflected in certain research efforts. Notably, the misguided attempt to correlate VExUS to volume status, which is only one of the factors influencing it, as well as attempts to re-interpret VExUS in the context of certain pathologies, which reflects a fundamental misunderstanding of its circulatory perspective. In this article we review the physiological basis of the VExUS assessment as a measure and marker of venous congestion from the organs’ standpoint and its role as part of the emerging concept of fluid tolerance, in hopes to address these misconceptions for clinicians and for important further studies.

Abstract China’s commitment to carbon neutrality by 2060 relies on the Land Use, Land-Use Change, and Forestry (LULUCF) sector, with forestation targets designed to enhance carbon removal. However, the exact sequestration potential of these initiatives remains uncertain due to differing accounting conventions between national inventories and scientific assessments. Here, we reconcile both estimates and reassess LULUCF carbon fluxes up to 2100, using a spatially explicit bookkeeping model, state-of-the-art historical data, and national forestation targets. We simulate a carbon sink of −0.24 ± 0.03 Gt C yr−1 over 1994–2018 from past forestation efforts, aligned well with the national inventory. Should the official forestation targets be followed and extended, this could reach −0.35 ± 0.04 Gt C yr−1 in 2060, offsetting 43 ± 4% of anticipated residual fossil CO2 emissions. Our findings confirm the key role of LULUCF in carbon sequestration, but its potential will decline if forestation efforts cease, highlighting the necessity for emission reductions in other sectors to achieve carbon neutrality.

Abstract Bubbles are ubiquitous in many research applications ranging from ultrasound imaging and drug delivery to the understanding of volcanic eruptions and water circulation in vascular plants. From an acoustic perspective, bubbles are resonant scatterers with remarkable properties, including a large scattering cross-section and strongly sub-wavelength dimensions. While it is known that the resonance properties of bubbles depend on their local environment, it remains challenging to probe this interaction at the single-bubble level due to the difficulty of manipulating a single resonating bubble in a liquid. Here, we confine a cubic bubble inside a cage using 3D printing technology, and we use this bubble as a local probe to perform scanning near-field acoustic microscopy—an acoustic analog of scanning near-field optical microscopy. By probing the acoustic interaction between a single resonating bubble and its local environment, we demonstrate near-field imaging of complex structures with a resolution that is two orders of magnitudes smaller than the wavelength of the acoustic field. As a potential application, our approach paves the way for the development of low-cost acoustic microscopes based on caged bubbles.

Abstract Eukaryotes must balance the need for gene transcription by RNA polymerase II (Pol II) against the danger of mutations caused by transposable element (TE) proliferation. In plants, these gene expression and TE silencing activities are divided between different RNA polymerases. Specifically, RNA polymerase IV (Pol IV), which evolved from Pol II, transcribes TEs to generate small interfering RNAs (siRNAs) that guide DNA methylation and block TE transcription by Pol II. While the Pol IV complex is recruited to TEs via SNF2-like CLASSY (CLSY) proteins, how Pol IV partners with the CLSYs remains unknown. Here, we identified a conserved CYC-YPMF motif that is specific to Pol IV and is positioned on the complex exterior. Furthermore, we found that this motif is essential for the co-purification of all four CLSYs with Pol IV, but that only one CLSY is present in any given Pol IV complex. These findings support a “one CLSY per Pol IV” model where the CYC-YPMF motif acts as a CLSY-docking site. Indeed, mutations in and around this motif phenocopy pol iv null and clsy quadruple mutants. Together, these findings provide structural and functional insights into a critical protein feature that distinguishes Pol IV from other RNA polymerases, allowing it to promote genome stability by targeting TEs for silencing.

Abstract Background DPANN archaea, including Woesearchaeota, encompass a large fraction of the archaeal diversity, yet their genomic diversity, lifestyle, and role in natural microbiomes remain elusive. With an archaeal assemblage naturally enriched in Woesearchaeota and steep vertical geochemical gradients, Lake Dziani Dzaha (Mayotte) provides an ideal model to decipher their in-situ activity and ecology. Results Using genome-resolved metagenomics and phylogenomics, we identified highly diversified Woesearchaeota populations and defined novel halophilic clades. Depth distribution of these populations in the water column showed an unusual double peak of abundance, located at two distinct chemoclines that are hotspots of microbial diversity in the water column. Genome-centric metatranscriptomics confirmed this vertical distribution and revealed a fermentative activity, with acetate and lactate as end products, and active cell-to-cell processes, supporting strong interactions with other community members at chemoclines. Our results also revealed distinct Woesearchaeota ecotypes, with different transcriptional patterns, contrasted lifestyles, and ecological strategies, depending on environmental/host conditions. Conclusions This work provides novel insights into Woesearchaeota in situ activity and metabolism, revealing invariant, bimodal, and adaptative lifestyles among halophilic Woesearchaeota. This challenges our precepts of an invariable host-dependent metabolism for all the members of this taxa and revises our understanding of their contributions to ecosystem functioning and microbiome assemblage. Video Abstract

Abstract The Neotropical realm, one of the most biodiverse regions on Earth, houses a broad range of zoonoses that pose serious public health threats. Protozoan parasites of the Leishmania (Viannia) braziliensis clade cause zoonotic leishmaniasis in Latin America with clinical symptoms ranging from simple cutaneous to destructive, disfiguring mucosal lesions. We present the first comprehensive genome-wide continental study including 257 cultivated isolates representing most of the geographical distribution of this major human pathogen. The L. braziliensis clade is genetically highly heterogeneous, consisting of divergent parasite groups that are associated with different environments and vary greatly in diversity. Apart from several small ecologically isolated groups with little diversity, our sampling identifies two major parasite groups, one associated with the Amazon and the other with the Atlantic Forest biomes. These groups show different recombination histories, as suggested by high levels of heterozygosity and effective population sizes in the Amazonian group in contrast to high levels of linkage and clonality in the Atlantic group. We argue that these differences are linked to strong eco-epidemiological differences between the two regions. In contrast to geographically focused studies, our study provides a broad understanding of the molecular epidemiology of zoonotic parasites circulating in tropical America.

In Western France, rapeseed (Brassica napus) cultivation faces substantial yield losses due to the root holoparasitic plant Phelipanche ramosa. However, recent observations have shown a reduction in parasitism within previously heavily infested fields. This study investigates two neighboring rapeseed soils with distinct levels of parasitic infestation, considered suppressive and conducive. Using a cocultivation system of Brassica napus and P. ramosa, we comprehensively examined rhizosphere exudates, parasitic plant attachment, and rhizosphere soil microbiota. Our findings revealed that the suppressive soil effectively reduced parasitism by impeding broomrape attachment and development, as well as inducing necrosis of tubercles. This suppressive effect was specific to postattachment stages, leaving germination and haustoriogenesis preattachment stages unaffected. Analysis of microbial structures suggested that the suppression of parasitism is predominantly of fungal rather than bacterial origin. Correlation network analyses identified three groups of amplicon sequence variants (ASVs) associated with suppression. Notably, seven ASVs were inversely correlated with parasitic attachments, and only one ASV, identified as Berkeleyomyces, a necrotrophic fungus responsible for black root rot, was positively correlated with necrosis and was more abundant in the suppressive soil. This study demonstrates the contrasting parasitic plant development on two physicochemically similar soils, highlighting the central role of fungal dynamics in the rhizosphere. These results provide valuable insights into the mechanisms underlying soil-mediated suppression of P. ramosa, offering potential strategies for mitigating the impact of this root holoparasite on rapeseed yields in the region.

Abstract Background and Aims Interstitial lung diseases (ILDs), encompassing both pediatric and adult cases, present a diverse spectrum of chronic conditions with variable prognosis. Despite limited therapeutic options beyond antifibrotic drugs and immunosuppressants, accurate diagnosis is challenging, often necessitating invasive procedures that may not be feasible for certain patients. Drawn against this background, experts across pediatric and adult ILD fields have joined forces in the RARE-ILD initiative to pioneer novel non-invasive diagnostic algorithms and biomarkers. Collaborating with the RARE-ILD consortium, the eurILDreg aims to comprehensively describe different ILDs, analyze genetically defined forms across age groups, create innovative diagnostic and therapeutic biomarkers, and employ artificial intelligence for data analysis. Methods The foundation of eurILDreg is built on a comprehensive parameter list developed and adopted by clinical experts, encompassing over 1,800 distinct parameters related to patient history, clinical examinations, diagnosis, lung function and biospecimen collection. This robust dataset is further enriched with daily assessments captured through the patientMpower app, including handheld spirometry and exercise tests, conducted on approximately 350 patients over the course of a year. This approach involves app-based daily assessments of quality of life, symptom tracking, handheld spirometry, saturation measurement, and the 1-min sit-to-stand test (1-STST). Additionally, pediatric data from the ChILD-EU registry will be integrated into the RARE-ILD Data Warehouse, with the ultimate goal of including a total of 4.000 ILD patients and over 100.000 biospecimen. Discussion The collaborative efforts within the consortium are poised to streamline research endeavors significantly, promising to advance patient-centered care, foster innovation, and shape the future landscape of interstitial lung disease research and healthcare practices. Trial Registration EurILDreg is registered in the German Clinical Trials Register (DRKS 00028968, 26.07.2022), and eurIPFreg is registered in ClinicalTrials.gov (NCT02951416).

Abstract This study aimed to assess sand and dust storm (SDS) risks in arid Central Asia during 2001–2021 from a multisectoral (environment, society, and agriculture) and comprehensive perspective on the Google Earth Engine (GEE) platform. The results show that the areas with moderate or greater SDS risk accounted for 18.75% of the total area of arid Central Asia. The high SDS risk areas are mainly concentrated in the oases around the desert and are most widely distributed in spring and summer. The SDS risk in the oasis area of southern Xinjiang increased significantly, while the SDS risk in the northeastern Aral Sea region and the Kazakh hilly region decreased significantly over the 21 years. Khwarazm of Uzbekistan, located in the Amu Darya River Delta, is the administrative district with the highest comprehensive risk of sandstorms, and the Balkan State of Turkmenistan and Kashi City and Zepu County in China are the administrative districts with the highest multisectoral risk of sandstorms. The results of this study provide a complete picture of SDS risks in the arid Central Asia region and will provide some guidance to policymakers and local authorities in SDS risk mitigation.

Abstract Background Ticks are significant vectors of pathogens, including viruses, bacteria, and protozoa. With approximately 900 tick species worldwide, many are expanding their geographical range due to changing socioeconomic and climate factors. The Danube Delta, one of Europe’s largest wetlands, is an ecosystem that, despite its ecological importance, remains understudied concerning the risk of introducing new tick-borne viruses. This region serves as a critical habitat for migratory birds, which can carry ticks over long distances, potentially introducing exotic tick species and their pathogens into the local ecosystem. Hyalomma marginatum ticks, the primary vector of Crimean-Congo hemorrhagic fever virus (CCHFV), are of particular concern due to their expanding presence in Europe and potential to spread other arboviruses. In addition to being the primary vector for CCHFV, Hyalomma sp. ticks are capable of transmitting other pathogens of medical and veterinary importance, including Dugbe virus, West Nile virus, African horse sickness virus, and Kyasanur forest disease virus. Therefore, it is essential to monitor the presence of Hyalomma sp. ticks while simultaneously surveilling arbovirus circulation in tick populations to mitigate the risk of arboviral outbreaks. Methods In this work, we used an RNA sequencing technique to analyze the virome of H. marginatum ticks collected from the Danube Delta Biosphere Reserve, Romania, one of the major bird migration hubs from Africa to Europe. Results Among the viral taxa detected in H. marginatum ticks, sequences belonging to Volzhskoe tick virus (VTV), Balambala tick virus (BMTV) and Bole tick virus 4 (BTV4) were identified. In addition, we report the first identification of a novel Rhabdoviridae-related virus, Hyalomma marginatum rhabdovirus (HMRV). No CCHFV or any CCHFV-related nairovirus were detected in this study. Conclusions To summarize, detecting new viruses is essential for monitoring potential viral outbreaks. Our research expands the understanding of virus diversity in Eastern Europe, including the identification of novel viruses. This insight is crucial for monitoring viruses that may pose risks to both animal and human health, such as CCHFV. Graphical Abstract

Abstract Venous congestion, often associated with elevated right atrial pressure presents a clinical challenge due to its varied manifestations and potential organ damage. Recognizing the manifestations of venous congestion through bedside physical examination or laboratory tests can be challenging. Point-of-care ultrasound (POCUS) is emerging as a valuable bedside tool for assessing venous congestion, with the Venous Excess Ultrasound (VExUS) technique gaining prominence. VExUS facilitates non-invasive quantification of venous congestion, relying on measurements of the inferior vena cava (IVC) size and Doppler assessments of the hepatic vein (HV), portal vein (PV), and intrarenal vein, thereby providing real-time insights into hemodynamic status and guiding therapeutic interventions. The grading system outlined in VExUS aids in stratifying the severity of congestion. However, achieving proficiency in VExUS requires a comprehensive understanding of Doppler techniques and their clinical applications. This review article provides practical guidance on performing VExUS, encompassing equipment requirements, preparation, machine settings, and examination techniques for assessing the inferior vena cava (IVC), hepatic vein (HV), portal vein (PV), and intrarenal vein. Potential pitfalls and troubleshooting strategies are discussed to ensure accurate interpretation of Doppler waveforms.

Abstract Perovskite solar cells (PSCs) offer an efficient, inexpensive alternative to current photovoltaic technologies, with the potential for manufacture via high-throughput coating methods. However, challenges for commercial-scale solution-processing of metal-halide perovskites include the use of harmful solvents, the expense of maintaining controlled atmospheric conditions, and the inherent instabilities of PSCs under operation. Here, we address these challenges by introducing a high volatility, low toxicity, biorenewable solvent system to fabricate a range of 2D perovskites, which we use as highly effective precursor phases for subsequent transformation to α-formamidinium lead triiodide (α-FAPbI3), fully processed under ambient conditions. PSCs utilising our α-FAPbI3 reproducibly show remarkable stability under illumination and elevated temperature (ISOS-L-2) and “damp heat” (ISOS-D-3) stressing, surpassing other state-of-the-art perovskite compositions. We determine that this enhancement is a consequence of the 2D precursor phase crystallisation route, which simultaneously avoids retention of residual low-volatility solvents (such as DMF and DMSO) and reduces the rate of degradation of FA+ in the material. Our findings highlight both the critical role of the initial crystallisation process in determining the operational stability of perovskite materials, and that neat FA+-based perovskites can be competitively stable despite the inherent metastability of the α-phase.

Abstract Genetic effects on changes in human traits over time are understudied and may have important pathophysiological impact. We propose a framework that enables data quality control, implements mixed models to evaluate trajectories of change in traits, and estimates phenotypes to identify age-varying genetic effects in GWAS. Using childhood BMI as an example trait, we included 71,336 participants from six cohorts and estimated the slope and area under the BMI curve within four time periods (infancy, early childhood, late childhood and adolescence) for each participant, in addition to the age and BMI at the adiposity peak and the adiposity rebound. GWAS of the 12 estimated phenotypes identified 28 genome-wide significant variants at 13 loci, one of which (in DAOA) has not been previously associated with childhood or adult BMI. Genetic studies of changes in human traits over time could uncover unique biological mechanisms influencing quantitative traits.

Abstract Assessing mitigation strategies for aviation is a critical issue for the aviation stakeholders, while the debate continues on the most appropriate CO2-equivalence metrics to address non-CO2 effects. Here, we propose two lightweight climate models that can be parameterised to assess these strategies and move beyond the CO2-equivalence metrics debate. A first approach relies on the use of the GWP* method, while a second one uses the FaIR climate emulator. These lightweight models, which should be considered as a new family of climate models for aviation that facilitate parametric studies, provide a straightforward and consistent means of evaluating mitigation strategies at the temperature level, although they are still limited for informing policymakers due to the significant uncertainties involved. They bypass the need for CO2-equivalence metrics for comparing strategies. The latter should rather be used for other applications, such as policy mechanisms to encourage the emergence of strategies, as they are not suitable for assessing temperature changes from aviation. The debate on the choice of CO2-equivalence metrics could then focus on methodological and ethical criteria. However, this paper demonstrates that the higher the traffic, the more appropriate it is to choose CO2-equivalence metrics with high values for consistency with temperature estimates.

Purpose – In the Global South where humanitarian responses to disasters are often hampered by systemic gaps, community-based humanitarian actors play a crucial but underexplored role in mediating aid to vulnerable populations. This study explores the everydayness of humanitarian action through the lived experiences of urban community leaders during the COVID-19 Pandemic in the Philippines. Specifically, it sheds light on their engagement with national-level responders, the typologies of humanitarian activities they undertook and the contextual factors influencing their decision-making. Design/methodology/approach – Using a qualitative approach, this study presents interviews with 35 community-based humanitarian leaders in urban poor areas of Metro Manila, Philippines. Analytical themes were developed inductively from the transcripts. Findings – Due to mobility restrictions from quarantine protocols, the typologies of humanitarian action shifted to accommodate arising challenges from pandemic management. Engagement with formal humanitarian actors were premised on pre-existing relationships. The study further reveals that, despite lacking formal training, community leaders utilized preexisting networks of care while subscribing to Filipino communal values of bayanihan (working together), malasakit (care) and pagkakaisa (unity). The findings underscore the need for discourse on the realities faced by community leaders and highlight the importance of holistic and gendered capacity building for effective disaster response in vulnerable communities. Originality/value – This study contributes to understanding the intricate dynamics of humanitarian coordination, particularly in areas where community leaders act as critical intermediaries between their constituents and external support providers and concludes with critical take on localization as a form of community resilience to disaster events.

Abstract Tryptophan-2,3-dioxygenase (TDO2) and indoleamine-2,3-dioxygenase (IDO1) are structurally distinct heme enzymes that catalyze the conversion of L-tryptophan to N-formyl-kynurenine, and play important roles in metabolism, inflammation, and tumor immune surveillance. The enzymes can adopt an inactive, heme-free (apo) state or an active, heme-containing (holo) state, with the balance between them varying dynamically according to biological conditions. Inhibitors of holo-TDO2 are known but, despite several advantages of the heme-free state as a drug target, no inhibitors of apo-TDO2 have been reported. We describe the discovery of the first apo-TDO2 binding inhibitors, to our knowledge, and their inhibition of cellular TDO2 activity at low nanomolar concentrations. The crystal structure of a potent, small molecule inhibitor bound to apo-TDO2 reveals its detailed binding interactions within the large, hydrophobic heme binding pocket of the active site.

Abstract Background: As fat grafting is commonly used as a filler, Adipose-derived stem/stromal cells (ASC) have been reported to be key player in retention rate. Paracrine and differentiation potential of those cells confer them strong pro-angiogenic capacities. However, a full characterization of the influence of aging on ASC has not been reported yet. Here we’ve investigated the effect of age on paracrine function, stemness and angiogenic potential of ASC. Methods: ASC were extracted from young and old adult donors. We assessed stromal vascular fraction cell populations repartition, ASC stemness potential, capability to differentiate into mesenchymal lineages as well as their secretome. Angiogenic potential was assessed using a sprouting assay, an indirect co-culture of ASC and dermal microvascular endothelial cells (EC). Total vascular sprout length was measured, and co-culture soluble factors were quantified. Pro-angiogenic factors alone or in combination as well as ASC-conditioned medium (CM) were added to EC to assess sprouting induction. Results: Decrease of endothelial cells yield and percentage is observed in cells extracted from adipose tissue of older patients, whereas ASC percentage increased with age. Clonogenic potential of ASC is stable with age. ASC can differentiate into adipocytes, chondrocytes and osteoblasts, and aging does not alter this potential. Among the 25 analytes quantified, high levels of pro-angiogenic factors were found, but none is significantly modulated with age. ASC induce a significantly longer vascular sprouts compared to fibroblasts, and no difference was found between young and old ASC donors on that parameter. Higher concentrations of FGF-2, G-CSF, HGF and IL-8, and lower concentrations of VEGF-C were quantified in EC/ASC co-cultures compared to EC/fibroblasts co-cultures. EC/ASC from young donors secrete higher levels of VEGF-A compared to old ones. Neither soluble factor nor CM without cells are able to induce organized sprouts, highlighting the requirement of cell communication for sprouting. CM produced by ASC supporting development of long vascular sprouts promote sprouting in co-cultures that establish shorter sprouts. Conclusion: Our results show cells from young and old donors exhibit no difference in all assessed parameters, suggesting all patients could be included in clinical applications. We emphasized the leading role of ASC in angiogenesis, without impairment with age, where secretome is a key but not sufficient actor.

Abstract Caenorhabditis elegans is highly important in current research, serving as a pivotal model organism that has greatly advanced the understanding of fundamental biological processes such as development, cellular biology, and neurobiology, helping to promote major advances in various fields of science. In this context, the survival of a nematode under various conditions is commonly investigated via statistical survival analysis, which is typically based on hypothesis testing, providing valuable insights into the factors influencing its longevity and response to various environmental factors. The extensive reliance on hypothesis testing is acknowledged as a concern in the scientific analysis process, emphasizing the need for a comprehensive evaluation of alternative statistical approaches to ensure a rigorous and unbiased interpretation of research findings. In this work, we propose an alternative method to hypothesis testing for evaluating differences in nematode survival. Our approach relies on a clustering technique that takes into account the complete structure of survival curves, enabling a more comprehensive assessment of survival dynamics. The proposed methodology helps to identify complex effects on nematode survival and enables us to derive the probability that treatment induces a specific effect. To highlight the application and benefits of the proposed methodology, it is applied to two different datasets, one simple and one more complex.

Abstract Cellular senescence occurs through the accumulation of many kinds of stresses. Senescent cells in tissues also cause various age-related disorders. Therefore, detecting them without labeling is beneficial for medical research and developing diagnostic methods. However, existing biomarkers have limitations of requiring fixation and labeling, or their molecular backgrounds are uncertain. Coherent anti-Stokes Raman scattering (CARS) spectroscopic imaging is a novel option because it can assess and visualize molecular structures based on their molecular fingerprint. Here, we present a new label-free method to visualize cellular senescence using CARS imaging in nucleoli. We found the peak of the nucleolar amide I band shifted to a higher wavenumber in binuclear senescent cells, which reflects changes in the protein secondary structure from predominant α-helices to β-sheets originating from amyloid-like aggregates. Following this, we developed a procedure that can visualize the senescent cells by providing the ratios and subtractions of these two components. We also confirmed that the procedure can visualize nucleolar aggregates due to unfolded/misfolded proteins produced by proteasome inhibition. Finally, we found that this method can help visualize the nucleolar defects in naïve cells even before binucleation. Thus, our method is beneficial to evaluate ongoing cellular senescence through label-free imaging of nucleolar defects.

Abstract Background Multiple studies have evaluated fecal microbiota transfer (FMT) in patients with ulcerative colitis (UC) using single-donor (SDN) and multidonor (MDN) products. Systematic review and meta-analysis were performed to compare the safety of SDN and MDN products. Methods Systematic searches were performed in Web of Science, Scopus, PubMed, and Orbit Intelligence to identify studies that compared FMT products manufactured using SDN or MDN strategies against control treatment in patients with UC. Fifteen controlled studies were selected for meta-analysis (11 randomized controlled trials and 4 controlled cohort trials). Safety of each treatment type was assessed using the counts of adverse events and serious adverse events using fixed- and random-effects models. Significance of the indirect difference between FMT preparations was assessed using a network approach. Benefit-risk ratios were calculated by multiplicative utility model, incorporating geometric mean of risk ratios (RRs) of efficacy and safety. Results Safety data was collected for a total of 587 patients (193 exposed to SDN products, 114 exposed to MDN products and 280 exposed to control treatment). The 12 studies showed similar overall safety event counts for MDN and SDN versus placebo (RRs: 0.90 and 1.09, respectively [P = 0.206 and P = 0.420, respectively]). Results indicated similar risk of safety events for MDN compared to SDN (RR: 0.83, P = 0.159). Positive benefit-risk ratios were demonstrated for MDN and SDN versus placebo (RRs: 1.70 and 1.16, respectively [P = 0.003 and P = 0.173, respectively]). MDN had a greater benefit-risk ratio compared to SDN (RR: 1.46, P = 0.072). Conclusion Similar safety profiles were observed for MDN and SDN strategies. Alongside previously described superior efficacy, treatment with MDN has greater benefit-risk ratio than SDN in patients with UC. Further development of MDN FMT treatment for UC should be considered.

Abstract H5N1 high pathogenicity avian influenza virus has killed thousands of marine mammals in South America since 2022. Here we report epidemiological data and full genome characterization of clade 2.3.4.4b H5N1 HPAI viruses associated with a massive outbreak in southern elephant seals (Mirounga leonina) at Península Valdés, Argentina, in October 2023. We also report on H5N1 viruses in concurrently dead terns. Our genomic analysis shows that viruses from pinnipeds and terns in Argentina form a distinct clade with marine mammal viruses from Peru, Chile, Brazil and Uruguay. Additionally, these marine mammal clade viruses share an identical set of mammalian adaptation mutations which were also present in tern viruses. Our combined ecological and phylogenetic data support mammal-to-mammal transmission and occasional mammal-to-bird spillover and suggest multinational transmission of H5N1 viruses in mammals. We reflect that H5N1 viruses becoming more evolutionary flexible and adapting to mammals in new ways could have global consequences for wildlife, humans, and/or livestock.

Abstract Phasic variations in dopamine levels are interpreted as a teaching signal reinforcing rewarded behaviors. However, behavior also depends on the motivational, neuromodulatory effect of phasic dopamine. In this study, we reveal a neurodynamical principle that unifies these roles in a recurrent network-based decision architecture embodied through an action-perception loop with the task space, the MAGNet model. Dopamine optogenetic conditioning in mice was accounted for by an embodied network model in which attractors encode internal goals. Dopamine-dependent synaptic plasticity created “latent” attractors, to which dynamics converged, but only locally. Attractor basins were widened by dopamine-modulated synaptic excitability, rendering goals accessible globally, i.e. from distal positions. We validated these predictions optogenetically in mice: dopamine neuromodulation suddenly and specifically attracted animals toward rewarded locations, without off-target motor effects. We thus propose that motivational dopamine reveals dopamine-built attractors representing potential goals in a behavioral landscape.