In adults with COVID-19 and severe hypoxemia, lower vs. higher oxygenation targets increased days alive without life support.

SOURCE CITATION: Nielsen FM, Klitgaard TL, Siegemund M, et al; HOT-COVID Trial Group. Lower vs higher oxygenation target and days alive without life support in COVID-19: the HOT-COVID randomized clinical trial. JAMA. 2024;331:1185-1194. 38501214.

Multinational Drug Survival Study of Omalizumab in Patients With Chronic Urticaria and Potential Predictors for Discontinuation.

Importance: Treating patients with chronic urticaria using omalizumab has been shown to be safe and effective in randomized clinical trials. Multinational studies on long-term omalizumab performance in chronic urticaria in clinical practice settings are lacking, especially on drug survival. Drug survival, which refers to the length of time that patients are treated with a specific drug, is a comprehensive outcome covering effectiveness, safety, and patient and physician preferences. Furthermore, little is known about the reasons and potential predictors for omalizumab discontinuation. Objective: To investigate omalizumab drug survival as well as reasons and potential predictors for discontinuation in a large, diverse population. Design, Setting, and Participants: This international multicenter cohort study was conducted at 14 Urticaria Centers of Reference and Excellence in 10 countries, including all patients with chronic urticaria from these centers who were ever treated with omalizumab. Main Outcomes and Measures: Drug survival analysis was performed to assess time to discontinuation. Patient characteristics and treatment protocols were investigated by Cox regression analysis to identify potential predictors for omalizumab discontinuation. Results: In 2325 patients with chronic urticaria who started omalizumab between June 2009 and July 2022, the mean (SD) age of the cohort was 42 (6) years, and 1650 participants (71%) were female. Overall omalizumab survival rates decreased from 76% to 39% after 1 to 7 years, respectively (median survival time, 3.3 [95 % CI, 2.9-4.0] years), primarily due to discontinuation from well-controlled disease in 576 patients (65%). Ineffectiveness and adverse effects were reasons for discontinuation in a far smaller proportion of patients, totaling 164 patients (18%) and 31 patients (4%), respectively. Fast treatment response was associated with higher rates of omalizumab discontinuation due to well-controlled disease (hazard ratio, 1.45 [95% CI, 1.20-1.75]), and disease duration of more than 2 years was associated with lower rates of discontinuation due to well-controlled disease (HR, 0.81 [95% CI, 0.67-0.98]). Immunosuppressive cotreatment at the start of omalizumab and autoimmune disease was associated with a higher risk for discontinuation due to ineffectiveness (HR, 1.65 [95% CI, 1.12-2.42]). The presence of spontaneous wheals (HR, 0.62 [95% CI, 0.41-0.93]) and access to higher dosages (HR, 0.40 [95% CI, 0.27-0.58) were both associated with a lower risk for discontinuation of omalizumab due to ineffectiveness. Conclusion and Relevance: This multinational omalizumab drug survival cohort study demonstrated that treatment of chronic urticaria with omalizumab in a clinical setting is effective and safe, and well-controlled disease is the main reason for treatment discontinuation. These findings on omalizumab drug survival rates and reasons and potential predictors for discontinuation may guide patients and physicians in clinical decision-making and expectation management. These results may call for the identification of biomarkers for chronic urticaria remission in complete responders to omalizumab treatment.

Biomarkers in pulmonary infections: a clinical approach.

Severe acute respiratory infections, such as community-acquired pneumonia, hospital-acquired pneumonia, and ventilator-associated pneumonia, constitute frequent and lethal pulmonary infections in the intensive care unit (ICU). Despite optimal management with early appropriate empiric antimicrobial therapy and adequate supportive care, mortality remains high, in part attributable to the aging, growing number of comorbidities, and rising rates of multidrug resistance pathogens. Biomarkers have the potential to offer additional information that may further improve the management and outcome of pulmonary infections. Available pathogen-specific biomarkers, for example, Streptococcus pneumoniae urinary antigen test and galactomannan, can be helpful in the microbiologic diagnosis of pulmonary infection in ICU patients, improving the timing and appropriateness of empiric antimicrobial therapy since these tests have a short turnaround time in comparison to classic microbiology. On the other hand, host-response biomarkers, for example, C-reactive protein and procalcitonin, used in conjunction with the clinical data, may be useful in the diagnosis and prediction of pulmonary infections, monitoring the response to treatment, and guiding duration of antimicrobial therapy. The assessment of serial measurements overtime, kinetics of biomarkers, is more informative than a single value. The appropriate utilization of accurate pathogen-specific and host-response biomarkers may benefit clinical decision-making at the bedside and optimize antimicrobial stewardship.

Prospective Follow-Up of Adolescents With and at Risk for Depression: Protocol and Methods of the Identifying Depression Early in Adolescence Risk Stratified Cohort Longitudinal Assessments.

Objective: To present the protocol and methods for the prospective longitudinal assessments-including clinical and digital phenotyping approaches-of the Identifying Depression Early in Adolescence Risk Stratified Cohort (IDEA-RiSCo) study, which comprises Brazilian adolescents stratified at baseline by risk of developing depression or presence of depression. Method: Of 7,720 screened adolescents aged 14 to 16 years, we recruited 150 participants (75 boys, 75 girls) based on a composite risk score: 50 with low risk for developing depression (LR), 50 with high risk for developing depression (HR), and 50 with an active untreated major depressive episode (MDD). Three annual follow-up assessments were conducted, involving clinical measures (parent- and adolescent-reported questionnaires and psychiatrist assessments), active and passive data sensing via smartphones, and neurobiological measures (neuroimaging and biological material samples). Retention rates were 96% (Wave 1), 94% (Wave 2), and 88% (Wave 3), with no significant differences by sex or group (p > .05). Participants highlighted their familiarity with the research team and assessment process as a motivator for sustained engagement. Discussion: This protocol relied on novel aspects, such as the use of a WhatsApp bot, which is particularly pertinent for low- to-middle-income countries, and the collection of information from diverse sources in a longitudinal design, encompassing clinical data, self-reports, parental reports, Global Positioning System (GPS) data, and ecological momentary assessments. The study engaged adolescents over an extensive period and demonstrated the feasibility of conducting a prospective follow-up study with a risk-enriched cohort of adolescents in a middle-income country, integrating mobile technology with traditional methodologies to enhance longitudinal data collection.

This article details the study protocol and methods used in the longitudinal assessment of 150 Brazilian teenagers with depression and at risk for depression as part of the Identifying Depression Early in Adolescence Risk Stratified Cohort (IDEA-RiSCo). Over 3 years, the authors collected clinical and digital data using innovative mobile technology, including a WhatsApp bot. Most adolescents participated in all the study phases, showing feasibility of prospective follow-up in a middle-income country. This approach allowed for a deeper understanding of depression in young populations, particularly in areas where mental health research is scarce.

Flow Cytometry Coupled with Resuscitation Assays As a High-Resolution Tool to Inform Environmental Management and Disinfection of Settings Affected by Tuberculous Mycobacteria.

Environmental decontamination and water disinfection practices are hallmarks of disease prevention and control in agricultural and public health settings. Informed fit-to-purpose biocontainment is thus dependent on methodologies accurately assessing microbial burden and viability. Also, rigorous evaluation of the efficacy of biocontrol measures implies monitoring microbial inactivation after decontamination/disinfection procedures. In this study, we used flow cytometry coupled with a resuscitation protocol to monitor the metabolic inactivation of bacteria capable of entering non-cultivable states, after the application of a chlorine-based water disinfectant. For this purpose, we used Mycobacterium bovis BCG as a model of slow-growing bacteria able to enter dormancy and representing a multi-host pathogen in a zoonotic disease system-animal tuberculosis-thriving both across temperate and semi-arid regions and involving environmental contamination. The biocide activity of a commercial sodium dichloroisocyanurate (NaDCC) disinfectant against M. bovis BCG was evaluated through mock environmental matrix tests. Using the manufacturer-recommended dosage of NaDCC, BCG cells were apparently inactivated after 24 h upon exposure. However, we show via flow cytometry that, upon exposure to optimal growth conditions, mycobacterial cells were able to regain metabolic activity shortly after, highlighting a sublethal effect of NaDCC at the recommended commercial dosage due to reversible BCG cell damage. In contrast, increasing twice the disinfectant dosage completely inactivated BCG cells after 24 h of exposure, with full irreversible loss of metabolic activity. Methodological workflows based on conventional culture or PCR would have missed the detection of these dormant subpopulations that were in fact able to resume growth when following the recommendations of a commercial disinfectant. This study highlights the superior, high-resolution value of single-cell approaches, such as flow cytometry, to accurately assess the activity of biocides against metabolically heterogeneous and dormant pathogenic bacteria with environmental cycles, supporting data-driven prioritization of environmental management and disinfection options in contaminated vulnerable settings.

Sepsis phenotypes, subphenotypes, and endotypes: are they ready for bedside care?

PURPOSE OF REVIEW: Sepsis remains a leading global cause of morbidity and mortality, and despite decades of research, no effective therapies have emerged. The lack of progress in sepsis outcomes is related in part to the significant heterogeneity of sepsis populations. This review seeks to highlight recent literature regarding sepsis phenotypes and the potential for further research and therapeutic intervention. RECENT FINDINGS: Numerous recent studies have elucidated various phenotypes, subphenotypes, and endotypes in sepsis. Clinical parameters including vital sign trajectories and microbial factors, biomarker investigation, and genomic, transcriptomic, proteomic, and metabolomic studies have illustrated numerous differences in sepsis populations with implications for prediction, diagnosis, treatment, and prognosis of sepsis. SUMMARY: Sepsis therapies including care bundles, fluid resuscitation, and source control procedures may be better guided by validated phenotypes than universal application. Novel biomarkers may improve upon the sensitivity and specificity of existing markers and identify complications and sequelae of sepsis. Multiomics have demonstrated significant differences in sepsis populations, most notably expanding our understanding of immunosuppressed sepsis phenotypes. Despite progress, these findings may be limited by modest reproducibility and logistical barriers to clinical implementation. Further studies may translate recent findings into bedside care.

Remdesivir is Associated with Reduced Mortality in Patients Hospitalized for COVID-19 Not Requiring Supplemental Oxygen.

Background: Remdesivir has demonstrated benefit in some hospitalized patients with coronavirus disease 2019 (COVID-19) on supplemental oxygen and in nonhospitalized patients breathing room air. The durability of this benefit across time periods with different circulating severe acute respiratory syndrome coronavirus 2 variants of concern (VOC) is unknown. This comparative effectiveness study in patients hospitalized for COVID-19 and not receiving supplemental oxygen at admission compared those starting remdesivir treatment in the first 2 days of admission with those receiving no remdesivir during their hospitalization across different VOC periods. Method: Using a large, multicenter US hospital database, in-hospital mortality rates were compared among patients hospitalized for COVID-19 but not requiring supplemental oxygen at admission between December 2020 and April 2022. Patients receiving remdesivir at hospital admission were matched 1:1 to those not receiving remdesivir during hospitalization, using propensity score matching. Cox proportional hazards models were used to assess 14- and 28-day in-hospital mortality rates or discharge to hospice. Results: Among the 121 336 eligible patients, 58 188 remdesivir-treated patients were matched to 17 574 unique patients not receiving remdesivir. Overall, 5.4% of remdesivir-treated and 7.3% in the non-remdesivir group died within 14 days, and 8.0% and 9.8%, respectively, died within 28 days. Remdesivir treatment was associated with a statistically significant reduction in the in-hospital mortality rate compared with non-remdesivir treatment (14-day and 28-day adjusted hazard ratios [95% confidence interval], 0.75 [0.68-0.83] and 0.83 [0.76-0.90], respectively). This significant mortality benefit endured across the different VOC periods. Conclusions: Remdesivir initiation in patients hospitalized for COVID-19 and not requiring supplemental oxygen at admission was associated with a significantly reduced in-hospital mortality rate. These findings highlight a potential survival benefit when clinicians initiated remdesivir on admission across the dominant variant eras of the evolving pandemic.

Genetic parameters for novel climatic resilience indicators derived from automatically-recorded vaginal temperature in lactating sows under heat stress conditions.

BACKGROUND: Longitudinal records of automatically-recorded vaginal temperature (TV) could be a key source of data for deriving novel indicators of climatic resilience (CR) for breeding more resilient pigs, especially during lactation when sows are at an increased risk of suffering from heat stress (HS). Therefore, we derived 15 CR indicators based on the variability in TV in lactating sows and estimated their genetic parameters. We also investigated their genetic relationship with sows' key reproductive traits. RESULTS: The heritability estimates of the CR traits ranged from 0.000 ± 0.000 for slope for decreased rate of TV (SlopeDe) to 0.291 ± 0.047 for sum of TV values below the HS threshold (HSUB). Moderate to high genetic correlations (from 0.508 ± 0.056 to 0.998 ± 0.137) and Spearman rank correlations (from 0.431 to 1.000) between genomic estimated breeding values (GEBV) were observed for five CR indicators, i.e. HS duration (HSD), the normalized median multiplied by normalized variance (Nor_medvar), the highest TV value of each measurement day for each individual (MaxTv), and the sum of the TV values above (HSUA) and below (HSUB) the HS threshold. These five CR indicators were lowly to moderately genetically correlated with shoulder skin surface temperature (from 0.139 ± 0.008 to 0.478 ± 0.048) and respiration rate (from 0.079 ± 0.011 to 0.502 ± 0.098). The genetic correlations between these five selected CR indicators and sow reproductive performance traits ranged from - 0.733 to - 0.175 for total number of piglets born alive, from - 0.733 to - 0.175 for total number of piglets born, and from - 0.434 to - 0.169 for number of pigs weaned. The individuals with the highest GEBV (most climate-sensitive) had higher mean skin surface temperature, respiration rate (RR), panting score (PS), and hair density, but had lower mean body condition scores compared to those with the lowest GEBV (most climate-resilient). CONCLUSIONS: Most of the CR indicators evaluated are heritable with substantial additive genetic variance. Five of them, i.e. HSD, MaxTv, HSUA, HSUB, and Nor_medvar share similar underlying genetic mechanisms. In addition, individuals with higher CR indicators are more likely to exhibit better HS-related physiological responses, higher body condition scores, and improved reproductive performance under hot conditions. These findings highlight the potential benefits of genetically selecting more heat-tolerant individuals based on CR indicators.

BioPrediction-RPI: Democratizing the prediction of interaction between non-coding RNA and protein with end-to-end machine learning.

Machine Learning (ML) algorithms have been important tools for the extraction of useful knowledge from biological sequences, particularly in healthcare, agriculture, and the environment. However, the categorical and unstructured nature of these sequences requiring usually additional feature engineering steps, before an ML algorithm can be efficiently applied. The addition of these steps to the ML algorithm creates a processing pipeline, known as end-to-end ML. Despite the excellent results obtained by applying end-to-end ML to biotechnology problems, the performance obtained depends on the expertise of the user in the components of the pipeline. In this work, we propose an end-to-end ML-based framework called BioPrediction-RPI, which can identify implicit interactions between sequences, such as pairs of non-coding RNA and proteins, without the need for specialized expertise in end-to-end ML. This framework applies feature engineering to represent each sequence by structural and topological features. These features are divided into feature groups and used to train partial models, whose partial decisions are combined into a final decision, which, provides insights to the user by giving an interpretability report. In our experiments, the developed framework was competitive when compared with various expert-created models. We assessed BioPrediction-RPI with 12 datasets when it presented equal or better performance than all tools in 40% to 100% of cases, depending on the experiment. Finally, BioPrediction-RPI can fine-tune models based on new data and perform at the same level as ML experts, democratizing end-to-end ML and increasing its access to those working in biological sciences.

Poor sleep quality is an important modifiable risk factor for dementia: Population attributable fraction of poor sleep in a Brazilian population-based study.

OBJECTIVES: The populational impact of poor sleep quality and the risk of dementia is unclear. We analyzed the Population Attributable Fraction (PAF) of poor sleep quality for dementia, and its association with other two sleep parameters through self-reported and single questions collected in a large-scale Brazilian cohort (ELSI-Brazil). METHODS: A subset of the ELSI-Brazil with complete responses to sleep quality was retrieved for this study. This is a large representative sample of the Brazilian elderly population with an extensive assessment of sociodemographic and health risk variables. Prevalence of poor sleep quality was estimated according to the complex sample design, and its PAF was measured using a meta-analytic relative risk. A total of 6024 (56.3% women, mean 62.8 ± 9.5 years of age) individuals had complete responses. RESULTS: The prevalence of poor sleep quality was 24.9% (95%CI 23%-26%), and the PAF of poor sleep quality including other 10 modifiable risk factors of dementia was 52.5% in Brazil. Secondary analyses identified that sleep quality, restorative sleep and sleep drug usage varied considerably according to age ranges, race, and gender. CONCLUSIONS: Poor sleep quality is an important populational modifiable risk factor for dementia in Brazil. Targeted interventions may provide an important impact in preventing dementia in low- and middle-income countries.

Is stimulation of browning of human adipose tissue a relevant therapeutic target?

Brown adipose tissue (BAT) and beige adipose tissues are important contributors to cold-induced whole body thermogenesis in rodents. The documentation in humans of cold- and ß-adrenergic receptor agonist-stimulated BAT glucose uptake using positron emission tomography (PET) and of a decrease of this response in individuals with cardiometabolic disorders led to the suggestion that BAT/beige adipose tissues could be relevant targets for prevention and treatment of these conditions. In this brief review, we will critically assess this question by first describing the basic rationale for this affirmation, second by examining the evidence in human studies, and third by discussing the possible means to activate the thermogenic response of these tissues in humans.

Adiposity, type 2 diabetes and atherosclerotic cardiovascular disease risk: Use and abuse of the body mass index.

The worldwide prevalence of individuals with an elevated body weight has increased steadily over the past five decades. Billions of research dollars have been invested to improve our understanding of the causes and consequences of having an elevated body weight. All this knowledge has, however, failed to influence populational body weight trajectories of most countries around the world. Research on the definition of "obesity" has also evolved. Body mass index (BMI), the most commonly used tool to make its diagnosis, has major limitations. In this review article, we will highlight evidence from observational studies, genetic association studies and randomized clinical trials that have shown the remarkable inter-individual differences in the way humans store energy as body fat. Increasing evidence also suggests that, as opposed to weight inclusive, lifestyle-based approaches, weight-centric approaches advising people to simply eat less and move more are not sustainable for most people for long-term weight loss and maintenance. It is time to recognize that this outdated approach may have produced more harm than good. On the basis of pathophysiological, genetic and clinical evidence presented in this review, we propose that it may be time to shift away from the traditional clinical approach, which is BMI-centric. Rather, emphasis should be placed on actionable lifestyle-related risk factors aiming at improving overall diet quality and increasing physical activity level in the general population.

Neoadjuvant immunotherapy in microsatellite instability-high (MSI-H) duodenal adenocarcinoma leads to pathological complete response and paves the way for new strategies.

Duodenal adenocarcinoma is a rare digestive cancer, often diagnosed at a late stage and harbours a poor prognosis. The arrival of immunotherapy has changed the prognosis of many neoplasia, including digestive adenocarcinomas with MSI-H status. Hereby, we describe three cases of MSI-H locally advanced duodenal adenocarcinoma who received neoadjuvant treatment with a PD1 inhibitor, pembrolizumab. A partial metabolic and endoscopic response was observed in all patients after 2 cycles. Duodenopancreatectomy was performed at the end of treatment (4-6 cycles), and anatomopathological analysis demonstrated pathological complete response in all patients. Our case series paves the way for prospectively exploring neoadjuvant immunotherapy in duodenal MSI-H adenocarcinoma and raises the question of organ sparing surgery in case of complete clinical response as observed in gastric and colo-rectal adenocarcinomas.

Acute exposure and biomarkers assessment in rainbow trout exposed to selected pharmaceuticals.

Pharmaceuticals released from municipal effluents discharges pose a risk to aquatic organisms. The toxicity of 5 pharmaceuticals with distinct therapeutic actions were assessed in rainbow trout: olanzapine (antipsychotic), erythromycin (antibiotic), mycophenoate (immunosuppression), pinaverium (anti-inflammatory) and trazodone (sedative). Juveniles were exposed to these drugs for 96 h at concentrations between 64 µg/L up to 40 mg/L to reach lethality. Survival was determined and a suite of biomarkers was analyzed for drug biotransformation, oxidative stress/damage and metabolic activity at sublethal concentrations. The data revealed the following toxicity: olanzapine >trazodone>mycophenolate>pinaverium∼erythromycin based on mortality. The data also revealed that toxicity was associated to mass, pKa and hydrophobicity and the following sublethal effects: GST, LPO and DNA strand breaks. Pharmaceuticals with lower molecular weight, physiological pKa, moderate hydrophobicity, low biotransformation and DNA strand breaks were generally more toxic to fish. However, this should be considered as a general guide in identifying toxic pharmaceuticals in non-target organisms.

Population structure and history of Mycobacterium bovis European 3 clonal complex reveal transmission across ecological corridors of unrecognized importance in Portugal.

Mycobacterium bovis causes animal tuberculosis in livestock and wildlife, with an impact on animal health and production, wildlife management, and public health. In this work, we sampled a multi-host tuberculosis community from the official hotspot risk area of Portugal over 16 years, generating the largest available data set in the country. Using phylogenetic and ecological modeling, we aimed to reconstruct the history of circulating lineages across the livestock-wildlife interface to inform intervention and the implementation of genomic surveillance within the official eradication plan. We find evidence for the co-circulation of M. bovis European 1 (Eu1), Eu2, and Eu3 clonal complexes, with Eu3 providing sufficient temporal signal for further phylogenetic investigation. The Eu3 most recent common ancestor (bovine) was dated in the 1990s, subsequently transitioning to wildlife (red deer and wild boar). Isolate clustering based on sample metadata was used to inform phylogenetic inference, unravelng frequent transmission between two clusters that represent an ecological corridor of previously unrecognized importance in Portugal. The latter was associated with transmission at the livestock-wildlife interface toward locations with higher temperature and precipitation, lower agriculture and road density, and lower host densities. This is the first analysis of M. bovis Eu3 complex in Iberia, shedding light on background ecological factors underlying long-term transmission and informing where efforts could be focused within the larger hotspot risk area of Portugal. IMPORTANCE: Efforts to strengthen surveillance and control of animal tuberculosis (TB) are ongoing worlwide. Here, we developed an eco-phylodynamic framework based on discrete phylogenetic approaches informed by M. bovis whole-genome sequence data representing a multi-host transmission system at the livestock-wildlife interface, within a rich ecological landscape in Portugal, to understand transmission processes and translate this knowledge into disease management benefits. We find evidence for the co-circulation of several M. bovis clades, with frequent transmission of the Eu3 lineage among cattle and wildlife populations. Most transition events between different ecological settings took place toward host, climate and land use gradients, underscoring animal TB expansion and a potential corridor of unrecognized importance for M. bovis maintenance. Results stress that animal TB is an established wildlife disease without ecological barriers, showing that control measures in place are insufficient to prevent long-distance transmission and spillover across multi-host communities, demanding new interventions targeting livestock-wildlife interactions.

Alkylresorcinol detection and identification in archaeological pottery using ultra-high-performance liquid chromatography-quadrupole/Orbitrap mass spectrometry.

RATIONALE: Alkylresorcinols (AR) are cereal-specific biomarkers and have recently been found in archaeological pots. However, their low concentrations and high susceptibility to degradation make them difficult to detect using conventional gas chromatography mass spectrometry (GC/MS). Here we describe the development of a more sensitive liquid chromatography mass spectrometry (LC/MS) method to detect these compounds. METHOD: A method based on the use of ultra-high-performance liquid chromatography (UHPLC) coupled to an Orbitrap mass analyser was established and validated for the detection of low-concentration ARs in pottery. During the preliminary experiments, UHPLC-Q/Orbitrap MS (ultra-high-performance liquid chromatography-quadrupole/Orbitrap mass spectrometry) was demonstrated to be more sensitive, and a wide range of AR homologues in cereal extracts were detected, unlike UHPLC-QTOFMS (ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry) and GC/MS. The developed method was utilised to profile AR homologue distribution in modern cereal samples and reanalyse AR-containing pots from the archaeological site of Must Farm. RESULTS: A highly sensitive LC/MS method with a limit of detection (LOD) of 0.02 µg/g and a limit of quantification (LOQ) of 0.06 µg/g was used to profile ARs in five modern cereal grains. The obtained LOD is 250 times lower than that obtained using the conventional GC/MS approach. AR 21:0 was the most abundant homologue in all four Triticum spp.-einkorn, emmer, Khorasan wheat and common wheat. Meanwhile, AR 25:0 was the predominant homologue in barley, potentially enabling differentiation between wheat and barley. The developed LC/MS-based method was successfully used to analyse ARs extracted from Must Farm potsherds and identified the cereal species most likely processed in the pots-emmer wheat. CONCLUSION: The described method offers an alternative and more sensitive approach for detecting and identifying ARs in ancient pottery. It has been successfully utilised to detect AR homologues in archaeological samples and discriminate which cereal species-wheat and barley-were processed in the pots.

First time whole genome sequencing of Mycobacterium bovis from the environment supports transmission at the animal-environment interface.

Spreading of Mycobacterium bovis causing animal tuberculosis (TB) at livestock-wildlife-environment interfaces remains a significant problem. Recently, we provided evidence of widespread environmental contamination of an endemic animal TB setting with viable and dormant M. bovis cells able to recover metabolic activity, making indirect transmission via environmental contamination plausible. We now report the first whole genome sequences of M. bovis recovered from the environment. We establish epidemiological links at the environment-animal interface by phylogenomic comparison of these M. bovis genomes with those isolated from livestock and wild ungulates from the same area. Environmental and animal genomes are highly intertwined and distribute similarly into the same M. bovis lineages, supporting several instances of environmental contamination. This study provides compelling evidence of M. bovis excretion into the environment and viability maintenance, supporting the environment as a potential source of new infection. These insights have clear implications for policy formulation, advocating environmental surveillance and an ecosystem perspective in TB control programs. ENVIRONMENTAL IMPLICATION: We report the first whole genome sequences of M. bovis from the environment and establish epidemiological links at the environment-animal interface, demonstrating close phylogenomic relatedness of animal and environmental M. bovis. Definitive evidence of M. bovis excretion into the environment with viability maintenance is provided, supporting the environment as a potential source of new infection. Implications of this work include methodological innovations offering a tool to resolve indirect transmission chains and support customized biosecurity measures. Policy formulation aiming at the control of animal tuberculosis and cost mitigation should consider these findings, encouraging environmental surveillance in official eradication programmes.