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Understanding large carnivore demography on human-dominated lands is a priority to inform conservation strategies, yet few studies examine long-term trends. Jaguars (Panthera onca) are one such species whose population trends and survival rates remain unknown across working lands. We integrated nine years of camera trap data and tourist photos to estimate jaguar density, survival, abundance, and probability of tourist sightings on a working ranch and tourism destination in Colombia. We found that abundance increased from five individuals in 2014 to 28 in 2022, and density increased from 1.88 ± 0.87 per 100 km2 in 2014 to 3.80 ± 1.08 jaguars per 100 km2 in 2022. The probability of a tourist viewing a jaguar increased from 0% in 2014 to 40% in 2020 before the Covid-19 pandemic. Our results are the first robust estimates of jaguar survival and abundance on working lands. Our findings highlight the importance of productive lands for jaguar conservation and suggest that a tourism destination and working ranch can host an abundant population of jaguars when accompanied by conservation agreements and conflict interventions. Our analytical model that combines conventional data collection with tourist sightings can be applied to other species that are observed during tourism activities. Entender los patrones demográficos de los grandes carnívoros al interior de paisajes antrópicos es fundamental para el diseño de estrategias de conservación efectivas. En el Neotrópico, el jaguar (Panthera onca) es una de estas especies cuyas tendencias poblacionales y tasas de supervivencia en paisajes productivos son desconocidas. Para entender mejor estas dinámicas, integramos nueve años de fototrampeo junto a fotos de turistas para estimar la densidad, supervivencia, abundancia y probabilidad de avistamiento de esta especie en una finca ganadera y destino turístico en Colombia. Entre 2014 y 2022 encontramos que la abundancia incrementó de cinco a 28 individuos y la densidad de 1.88 ± 0.87 jaguares/ 100 km2 a 3.80 ± 1.08 jaguares/ 100 km2. La probabilidad de avistamiento por turistas aumentó de 0% en 2014 a 40% en 2020 antes de la pandemia del Covid-19. Nuestros resultados presentan las primeras estimaciones robustas de abundancia y supervivencia de este felino en paisajes antrópicos dónde el manejo de sistemas productivos combinados con turismo e intervenciones para la mitigación del conflicto puede albergar poblaciones abundantes de jaguares, demostrando su importancia para la conservación de esta especie. Nuestro modelo, al combinar datos convencionales con avistamientos, podría ser aplicado a otras especies observadas durante actividades turísticas. [ABSTRACT FROM AUTHOR]

Background: Quality of life (QoL) is commonly impaired among people with multiple sclerosis (PwMS). The aim of this study was to evaluate via meta-analysis the efficacy of Mindfulness-based interventions (MBIs) for improving QoL in PwMS. Methods: Eligible randomized controlled trials (RCTs) were identified via searching six major electronic databases (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, AMED, and PsycINFO) in April 2022. The primary outcome was QoL. Study quality was determined using the Cochrane Collaboration risk of bias tool. Meta-analysis using a random effects model was undertaken. Effect sizes are reported as Standardized Mean Difference (SMD). Prospero ID: 139835. Results: From a total of 1312 individual studies, 14 RCTs were eligible for inclusion in the meta-analysis, total participant n = 937. Most studies included PwMS who remained ambulatory. Cognitively impaired PwMS were largely excluded. Comorbidities were inconsistently reported. Most MBIs were delivered face-to face in group format, but five were online. Eight studies (n = 8) measured MS-specific QoL. In meta-analysis, overall effect size (SMD) for any QoL measure (n = 14) was 0.40 (0.18–0.61), p = 0.0003, I2 = 52%. SMD for MS-specific QoL measures (n = 8) was 0.39 (0.21–0.57), p < 0.0001, I2 = 0%. MBI effect was largest on subscale measures of mental QoL (n = 8), SMD 0.70 (0.33–1.06), p = 0.0002, I2 = 63%. Adverse events were infrequently reported. Conclusions: MBIs effectively improve QoL in PwMS. The greatest benefits are on mental health-related QoL. However, more research is needed to characterize optimal formatting, mechanisms of action, and effects in PwMS with more diverse social, educational, and clinical backgrounds. [ABSTRACT FROM AUTHOR]

The co-occurrence of mental and physical chronic conditions is a growing concern and a largely unaddressed challenge in low-and-middle-income countries. This study aimed to investigate the independent and multiplicative effects of depression and physical chronic conditions on health-related quality of life (HRQoL) in China, and how it varies by age and gender. We used two waves of the China Health and Retirement Longitudinal Study (2011, 2015), including 9227 participants aged ≥ 45 years, 12 physical chronic conditions and depressive symptoms. We used mixed-effects linear regression to assess the effects of depression and physical multimorbidity on HRQoL, which was measured using a proxy measure of Physical Component Scores (PCS) and Mental Component Scores (MCS) of the matched SF-36 measure. We found that each increased number of physical chronic conditions, and the presence of depression were independently associated with lower proxy PCS and MCS scores. There were multiplicative effects of depression and physical chronic conditions on PCS (− 0.83 points, 95% CI − 1.06, − 0.60) and MCS scores (− 0.50 points, 95% CI − 0.73, − 0.27). The results showed that HRQoL decreased markedly with multimorbidity and was exacerbated by the presence of co-existing physical and mental chronic conditions. [ABSTRACT FROM AUTHOR]

Characterising associations between the methylome, proteome and phenome may provide insight into biological pathways governing brain health. Here, we report an integrated DNA methylation and phenotypic study of the circulating proteome in relation to brain health. Methylome-wide association studies of 4058 plasma proteins are performed (N = 774), identifying 2928 CpG-protein associations after adjustment for multiple testing. These are independent of known genetic protein quantitative trait loci (pQTLs) and common lifestyle effects. Phenome-wide association studies of each protein are then performed in relation to 15 neurological traits (N = 1,065), identifying 405 associations between the levels of 191 proteins and cognitive scores, brain imaging measures or APOE e4 status. We uncover 35 previously unreported DNA methylation signatures for 17 protein markers of brain health. The epigenetic and proteomic markers we identify are pertinent to understanding and stratifying brain health. Characterising associations between the methylome, proteome and phenome may provide insight into biological pathways governing brain health. Here, blood protein markers of brain health are integrated with omics data to reveal DNA methylation differences that associate with these protein markers. [ABSTRACT FROM AUTHOR]

Wire arc additive manufacturing (WAAM) appears as one of the most promising technologies due to its capacity to process all types of materials used in welding, its high production rate, and capacity to process large geometries of particular interest in the aeronautical industry. Since this technology is still under investigation, it is important to determine the efficiency of the process; in this sense, the melting efficiency stands out not only as a parameter of interest in energy terms but also as a measure of the stability of the process. For calculating melting efficiency, it is necessary to use tailored colorimeters or apply models requiring specific dimensions that involve destructive testing. For this reason, in the development of this work, the melting efficiency is evaluated through machine learning algorithms. Processing parameters such as wire diameter, wire feed speed, travel speed, and net power are used to determine melting efficiency. In addition, a simplified analytical model was developed to compare the results. The average melting efficiency analytically calculated was 44.56 ± 5.48%, while the predicted value reaches a comparable value of 44.32 ± 4.79% obtained with the Gaussian process regressor, which shows the highest accuracy. Moreover, the known relationship with travel speed was verified. [ABSTRACT FROM AUTHOR]

Species reintroductions are growing in popularity, and example motivations include supporting species populations or the restoration of ecosystem function. Interactions between humans and the reintroduced species are likely to occur post-reintroduction. Coexistence between humans and wildlife is adaptive and dynamic, in part requiring management of conflicts between humans and wildlife, or of conflicts between humans over wildlife management. We seek to learn from the experiences of steering group members in a Eurasian beaver (Castor fiber) project in England and identify how governance of coexistence with reintroduced species may differ from the governance of coexistence with species that are already present in the landscape. Using a qualitative thematic analysis of an online survey, we identify a series of lessons in six key areas: (1) project governance, (2) stakeholder engagement, (3) research and monitoring programme, (4) strategy to manage arising conflicts, (5) public engagement, and (6) broad perspectives on reintroduction trials. We advocate for reflective evaluation as an essential component of reintroduction projects to enable knowledge-sharing from experiences, leading to improved practices in the future. Reflecting on our analysis, we identify and define 'Renewed Coexistence'—a new term that draws on pre-existing coexistence knowledge but identifies the unique elements that relate to governing coexistence with reintroduced species. [ABSTRACT FROM AUTHOR]

Linking epigenetic marks to clinical outcomes improves insight into molecular processes, disease prediction, and therapeutic target identification. Here, a statistical approach is presented to infer the epigenetic architecture of complex disease, determine the variation captured by epigenetic effects, and estimate phenotype-epigenetic probe associations jointly. Implicitly adjusting for probe correlations, data structure (cell-count or relatedness), and single-nucleotide polymorphism (SNP) marker effects, improves association estimates and in 9,448 individuals, 75.7% (95% CI 71.70–79.3) of body mass index (BMI) variation and 45.6% (95% CI 37.3–51.9) of cigarette consumption variation was captured by whole blood methylation array data. Pathway-linked probes of blood cholesterol, lipid transport and sterol metabolism for BMI, and xenobiotic stimuli response for smoking, showed >1.5 times larger associations with >95% posterior inclusion probability. Prediction accuracy improved by 28.7% for BMI and 10.2% for smoking over a LASSO model, with age-, and tissue-specificity, implying associations are a phenotypic consequence rather than causal. Linking epigenetic marks to clinical outcomes promises insight into the underlying processes. Here, the authors introduce a statistical approach to estimate associations between a phenotype and all epigenetic probes jointly, and to estimate the proportion of variation captured by epigenetic effects. [ABSTRACT FROM AUTHOR]

Excessive insulin signaling through the insulin receptor (IR) may play a role in the pathogenesis of diet-induced metabolic disease, including obesity and type 2 diabetes. Here we investigate whether heterozygous impairment of insulin receptor (IR) expression limited to peripheral, i.e. non-CNS, tissues of adult mice impacts the development of high-fat diet-induced metabolic deterioration. While exhibiting some features of insulin resistance, PerIRKO+/− mice display a hepatic energy deficit accompanied by induction of energy-sensing AMPK, mitochondrial biogenesis, PPARα, unexpectedly leading to protection from, and reversal of hepatic lipid accumulation (steatosis hepatis, NAFLD). Consistently, and unlike in control mice, the PPARα activator fenofibrate fails to further affect hepatic lipid accumulation in PerIRKO+/− mice. Taken together, and opposing previously established diabetogenic features of insulin resistance, incomplete impairment of insulin signaling may mimic central aspects of calorie restriction to limit hepatic lipid accumulation during conditions of metabolic stress. Hyper-insulinemia associated with excess calorie intake may cause metabolic dysfunction. Here the authors report that mice with partially reduced insulin receptor expression in peripheral tissues are protected from and experience reversal of fatty liver disease. [ABSTRACT FROM AUTHOR]

Medium and large carnivores coexist with people in urban areas globally, occasionally resulting in negative interactions that prompt questions about how to reduce human-wildlife conflict. Hazing, i.e., scaring wildlife, is frequently promoted as an important non-lethal means for urbanites to reduce conflict but there is limited scientific evidence for its efficacy. We used a population of captive coyotes (Canis latrans) to simulate urban human-coyote interactions and subsequent effects of hazing on coyote behavior. Past experiences with humans significantly affected the number of times a coyote approached a human to necessitate hazing. Coyotes that had been hand fed by adults had to be more frequently hazed than coyotes with other or no past experiences with adults. Past experience with children had no impact on the number of hazing events. The number of times a coyote approached an adult or child was reduced across days based on the accumulative number of times hazed, suggesting coyotes learn to avoid behaviors warranting hazing and that this could be used as a non-lethal management tool. However, prior experience and whether the interaction is with an adult or child can alter the outcomes of hazing and must be considered in determining the efficacy of hazing programs. [ABSTRACT FROM AUTHOR]

Objectives: Incarcerated young men commonly experience problems with impulsivity and emotional dysregulation. Mindfulness training could help but the evidence is limited. This study developed and piloted an adapted mindfulness-based intervention for this group (n = 48). Methods: Feasibility of recruitment, retention, and data collection were assessed, and the effectiveness of mindfulness training measured using validated questionnaires. Twenty-five qualitative interviews were conducted to explore experiences of the course, and barriers and facilitators to taking part. Results: The findings indicated that recruitment and retention to mindfulness training groups was a challenge despite trying various adaptive strategies to improve interest, relevance, and acceptability. Quantitative data collection was feasible at baseline and post-course. There were significant improvements following training in impulsivity (effect size [ES] 0.72, 95% CI 0.32–1.11, p = 0.001), mental wellbeing (ES 0.50; 95% CI 0.18–0.80; p = 0.003), inner resilience (comprehensibility ES 0.35; 95% CI − 0.02–0.68; p = 0.03), and mindfulness (ES 0.32; 95% CI 0.03–0.60; p = 0.03). The majority (70%) of participants reported finding the course uncomfortable or disconcerting at first but if they chose to remain, this changed as they began to experience benefit. The body scan and breathing techniques were reported as being most helpful. Positive experiences included better sleep, less stress, feeling more in control, and improved relationships. Conclusions: Developing and delivering mindfulness training for incarcerated young men is feasible and may be beneficial, but recruitment and retention may limit reach. Further studies are required that include a control group. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

In the original version of this Article, the legend in the upper panel of Figure 2 incorrectly read 'paternal imprinting' and should have read 'maternal imprinting'. This has been corrected in both the PDF and HTML versions of the Article. [ABSTRACT FROM AUTHOR]

Parent-of-origin effects (POE) exist when there is differential expression of alleles inherited from the two parents. A genome-wide scan for POE on DNA methylation at 639,238 CpGs in 5,101 individuals identifies 733 independent methylation CpGs potentially influenced by POE at a false discovery rate ≤ 0.05 of which 331 had not previously been identified. Cis and trans methylation quantitative trait loci (mQTL) regulate methylation variation through POE at 54% (399/733) of the identified POE-influenced CpGs. The combined results provide strong evidence for previously unidentified POE-influenced CpGs at 171 independent loci. Methylation variation at 14 of the POE-influenced CpGs is associated with multiple metabolic traits. A phenome-wide association analysis using the POE mQTL SNPs identifies a previously unidentified imprinted locus associated with waist circumference. These results provide a high resolution population-level map for POE on DNA methylation sites, their local and distant regulators and potential consequences for complex traits. Parent-of-origin effects (POE) are observed when there are different effects from alleles inherited from the two parents on phenotypic measures. Here, Zeng et al. study POE on DNA methylation in 5,101 individuals and identify genetic variants that associate with methylation variation via POE and their potential phenotypic consequences. [ABSTRACT FROM AUTHOR]

Coyotes (Canis latrans) are highly adaptable, medium-sized carnivores that now inhabit nearly every large city in the United States and Canada. To help understand how coyotes have adapted to living in urban environments, we compared two ecologically and evolutionarily important behavioral traits (i.e., bold-shy and exploration-avoidance behavior) in two contrasting environments (i.e., rural and urban). Boldness is an individual's reaction to a risky situation and exploration is an individual's willingness to explore novel situations. Our results from both tests indicate that urban coyotes are bolder and more exploratory than rural coyotes and that within both populations there are individuals that vary across both spectrums. Bolder behavior in urban coyotes emerged over several decades and we speculate on possible processes (e.g., learning and selection) and site differences that could be playing a role in this behavioral adaptation. We hypothesize that an important factor is how people treat coyotes; in the rural area coyotes were regularly persecuted whereas in the urban area coyotes were rarely persecuted and sometimes positively rewarded to be in close proximity of people. Negative consequences of this behavioral adaptation are coyotes that become bold enough to occasionally prey on pets or attack humans. [ABSTRACT FROM AUTHOR]

Inhibition of cancer-promoting kinases is an established therapeutic strategy for the treatment of many cancers, although resistance to kinase inhibitors is common. One way to overcome resistance is to target orthogonal cancer-promoting pathways. Bromo and Extra-Terminal (BET) domain proteins, which belong to the family of epigenetic readers, have recently emerged as promising therapeutic targets in multiple cancers. The development of multitarget drugs that inhibit kinase and BET proteins therefore may be a promising strategy to overcome tumor resistance and prolong therapeutic efficacy in the clinic. We developed a general computational screening approach to identify novel dual kinase/bromodomain inhibitors from millions of commercially available small molecules. Our method integrated machine learning using big datasets of kinase inhibitors and structure-based drug design. Here we describe the computational methodology, including validation and characterization of our models and their application and integration into a scalable virtual screening pipeline. We screened over 6 million commercially available compounds and selected 24 for testing in BRD4 and EGFR biochemical assays. We identified several novel BRD4 inhibitors, among them a first in class dual EGFR-BRD4 inhibitor. Our studies suggest that this computational screening approach may be broadly applicable for identifying dual kinase/BET inhibitors with potential for treating various cancers. [ABSTRACT FROM AUTHOR]