Individual Variation In Response Research Articles

Ventricular Fibrillation Prediction and Detection: A Comprehensive Review of Modern Techniques

This review offers a detailed examination of modern ECG signal processing techniques employed in the prediction and detection of ventricular fibrillation (VF). It contains a thorough analysis of recent advancements in the field, exploring the strengths, limitations, and real-world applications of these techniques. By evaluating the current state of research, the review seeks to identify the most effective approaches and highlight key areas where further investigation is needed, ultimately guiding future research efforts toward improving VF prediction and detection. Overall, AI has shown significant potential in a range of VF-related tasks. However, real-world implementation encounters several challenges, including difficulties in accurately interpreting ECG signals, the variability in individual physiological responses, and the infrequency of ventricular fibrillation events. Additionally, there are issues related to the critical timing required for detecting VF, the presence of similar arrhythmias, the need for adaptation to new ECG devices, energy consumption concerns, and the complex process of obtaining regulatory and legislative approvals for integrating software components into medical equipment. We consider that the present work might be useful in approaching the above challenges.

Clinical and physiological effects of high-intensity aerobic training on metabolic syndrome: understanding the individual exercise response variability.

We analyzed the interindividual heterogeneity in health responses to a supervised high-intensity interval training (HIIT) program in individuals with metabolic syndrome (MetS). Two-hundred and sixty-four adults with overweight/obesity (56.3±7.3 y, body mass index, 32.3±4.7 kg·m-2), and MetS were randomized to a standard health care non-exercise group (CONT group, N=58) or standard health care plus HIIT (EXER group, N=206). HIIT intervention was performed on a cycloergometer thrice a week (43 min·session-1). The change in MetS components (i.e., MetS z score), cardiorespiratory fitness (VO2PEAK), maximal cycling power (WPEAK), and body weight/composition was assessed in both groups before (0 weeks) and after the intervention (16 weeks). Individual responses in the EXER group were considered attributable to HIIT when the improvements were larger than twice the typical error (>2 TE). TE was calculated using pre- and post-intervention data from the time-matched CONT group. The percent of participants that improved MetS z score beyond 2TE was 51% driven by reductions in blood pressure (45%) and waist circumference (48%). Blood lipids and glucose response were only 21% and 16% (participants improving beyond 2TE). Sixty percent of individuals that improved MetS z score, also improved VO2PEAK (r=-0.013; P=0.86) while 85% of individuals improving MetS z score also improved WPEAK (r=0.151; P=0.03). In summary, health providers can expect that a 16- week HIIT program would indisputably improve MetS in approximately 50% of individuals completing the program. Lastly, WPEAK better predicts which individuals would improve MetS than VO2PEAK when the direct assessment of the five MetS factors is not feasible.

The Role of Exogenous Ketones in Road Cycling: Evidence, Mechanisms, and Performance Claims

The Role of Exogenous Ketones in Road Cycling: Evidence, Mechanisms, and Performance Claims

Cortical effects of dopamine replacement account for clinical response variability in Parkinson's disease.

Individual variability in clinical response to dopaminergic replacement therapy (DRT) is a key barrier to efficacious treatment for patients with Parkinson's disease (PD). A better understanding of the neurobiological sources of such inter-individual differences is necessary to inform future clinical interventions and motivate translational research. One potential source of this variability is an unintended secondary activation of extra-nigrostriatal dopamine systems by DRT, particularly in the neocortex. In this study, we use magnetoencephalography data collected from patients with PD before and after DRT to map their individual cortical neurophysiological responses to dopaminergic pharmacotherapy. By combining these DRT response maps with normative atlases of cortical dopamine receptor and transporter densities, we link the variable enhancement of rhythmic beta activity by DRT to dopamine-rich cortical regions. Importantly, patients who exhibited a larger dopaminergic beta cortical enhancement showed a smaller clinical improvement from DRT, indicating a potential source of individual variability in medication response for patients with PD. We conclude that these findings inform our understanding of the dopaminergic basis of neurophysiological variability often seen in patients with PD, and indicate that our methodological approach may be useful for data-driven contextualization of medication effects on cortical neurophysiology in future research and clinical applications.

Assessing Changes in Motor Function and Mobility in Individuals with Parkinson's Disease After 12 Sessions of Patient-Specific Adaptive Dynamic Cycling.

This pilot randomized controlled trial evaluated the effects of 12 sessions of patient-specific adaptive dynamic cycling (PSADC) versus non-adaptive cycling (NA) on motor function and mobility in individuals with Parkinson's disease (PD), using inertial measurement unit (IMU) sensors for objective assessment. Twenty-three participants with PD (13 in the PSADC group and 10 in the NA group) completed the study over a 4-week period. Motor function was measured using the Kinesia™ sensors and the MDS-UPDRS Motor III, while mobility was assessed with the TUG test using OPAL IMU sensors. The PSADC group showed significant improvements in MDS-UPDRS Motor III scores (t = 5.165, p < 0.001) and dopamine-sensitive symptoms (t = 4.629, p = 0.001), whereas the NA group did not improve. Both groups showed non-significant improvements in TUG time. IMU sensors provided continuous, quantitative, and unbiased measurements of motor function and mobility, offering a more precise and objective tracking of improvements over time. PSADC demonstrated enhanced treatment effects on PD motor function compared to NA while also reducing variability in individual responses. The integration of IMU sensors was essential for precise monitoring, supporting the potential of a data-driven, individualized exercise approach to optimize treatment outcomes for individuals with PD.

Towards Precision Sports Nutrition for Endurance Athletes: A Scoping Review of Application of Omics and Wearables Technologies.

Endurance athletes require tailored nutrition strategies to optimize performance, recovery, and training adaptations. While traditional sports nutrition guidelines provide a foundational framework, individual variability in metabolic responses underscores the need for precision nutrition, informed by genetic, biological, and environmental factors. This scoping review evaluates the application of systems biology-driven sports nutrition for endurance athletes, focusing on 'omics' and wearable technologies. A scoping review of the literature was conducted in PubMed, Scopus, and Web of Science in accordance with the PRISMA-ScR checklist. Research questions, search strategies, and eligibility criteria were guided by the Population-Concept-Context framework with the following inclusion criteria: original research in English, involving endurance athletes, systems biology approaches, and nutritional interventions or continuous glucose monitoring (CGM). Fifty-two studies were included, with distance runners as the most studied cohort. Eleven studies used metagenomics, eleven CGM, ten nutrigenetics, ten metabolomics, seven multi-omics, one proteomics, one epigenomics, and one lipidomics. Over half (n = 31; 60%) were randomized controlled trials (RCTs) with generally high methodological quality. Most studies were proof-of-concept investigations aimed at assessing biomarkers; however, the evidence linking these biomarkers to performance, recovery, and long-term health outcomes in endurance athletes remains insufficient. Future research should focus on well-powered replicated crossover RCTs, multivariate N-of-1 clinical trials, 360-degree systems-wide approaches, and the validation of genetic impacts on nutritional interventions to refine dietary guidelines.

L-arginine Supplementation in Endurance Athletes: A Systematic Review of Recovery Mechanisms and Performance Enhancement

L-arginine, a semi-essential amino acid, has garnered significant attention for its potential to enhance athletic performance, particularly within endurance sports. Recognized for its multifaceted roles in cardiovascular, immune, and metabolic functions, L-arginine serves as a precursor to biologically active molecules, including nitric oxide (NO), creatine, and polyamines, which are integral to muscle function and recovery. Through its ability to stimulate NO production, L-arginine promotes vasodilation, enhancing blood flow and oxygen delivery to active muscles, thereby improving exercise efficiency and endurance. Additionally, L-arginine influences muscle protein synthesis (MPS) via activation of the mTOR signaling pathway, aids in ammonia detoxification within the urea cycle, and supports cellular energetics by facilitating ATP production. These mechanisms collectively underscore its potential to support prolonged physical exertion, reduce muscle fatigue, and expedite post-exercise recovery. This systematic review examines current evidence on L-arginine supplementation in endurance athletes, focusing on its physiological impacts, mechanisms of action, and potential to enhance recovery and performance. Despite promising findings, variability in individual responses and mixed results across studies highlight the need for refined dosing strategies and further research into long-term safety and efficacy. This review provides a comprehensive overview of L-arginine's potential as a supplement in sports nutrition, aiming to inform evidence-based recommendations for its application in endurance training and recovery strategies.

Efficacy and Safety of Lithium for Suicide and Suicide-Related Behaviors in Youth: A Review of the Literature.

This systematic review evaluates the anti-suicidal properties of Lithium in children and adolescents with Bipolar Disorder (BD), addressing gaps in evidence regarding its efficacy and safety in reducing suicidality and self-harming behaviors. A comprehensive literature search was conducted across PubMed, Web of Science, and Scopus up to February 2024. Eligible studies were those focusing on patients aged 25 years or younger, examining Lithium therapy and its impact on suicidal ideation and behaviors. The review included randomized controlled trials, longitudinal prospective and retrospective studies, and cross-sectional studies, while excluding expert opinions and case reports. Evidence generally supports the efficacy of Lithium in reducing suicidal ideation and self-harming behaviors in youth with BD, though results are mixed. Randomized controlled trials demonstrated its effectiveness in mitigating suicidal thoughts during acute manic episodes, with effects persisting post-treatment. Longitudinal studies suggested that Lithium might offer superior outcomes compared to other mood stabilizers, although its specific impact on suicidality remains inconclusive. Cross-sectional studies and retrospective analyses reveal associations between Lithium use and reduced self-harming behaviors, but causality remains uncertain. While mood-stabilizing effects of Lithium offer potential benefits for reducing suicidality in youth, evidence on its direct impact on emotional dysregulation (ED) and long-term efficacy is limited. Variability in individual responses and adherence issues underscore the need for further research. Future studies should include larger, diverse samples, focus on ED symptoms, and explore Lithium mechanisms in suicidality prevention. Lithium remains a promising treatment for mood stabilization and reduction in suicidality in youth with BD.

Influence of intestinal microbiota on the metabolism of main cardiotropic drugs

The intestinal microbiota is one of the most important pathogenetic links in the development of cardiovascular diseases. Every year the world scientific community finds new interactions at the level of signaling molecules, metabolites and microorganisms, identifying more and more patterns and cause-and-effect relationships which indicate the commonality of the intestinal microbiota (GM) and cardiovascular diseases. The state of the host's intestinal community, its qualitative and quantitative composition, directly and indirectly affects the fundamental pathogenetic mechanisms of the development of cardiovascular diseases. Despite the fact that there are scientifically based methods of treatment, cardiovascular diseases remain the leading cause of death in the world. This phenomenon is partly due to wide variations in individual response to cardiovascular drugs. The pharmacological effects of cardiotropic drugs are quite different even within groups of patients comparable in age and gender. Every year intestinal microbiota is more and more evident to be responsible for this intraspecific variability. Gut microbes influence drug metabolism in several pharmacokinetic ways, and conversely, drugs can have significant effects on the microbiome and therefore pharmacodynamic processes. Drugs can alter the gut microenvironment and microbial metabolism, influence bacterial growth, thereby changing the composition and functions of the microbial community. One of the most important functions of GM, related to “intestinal-cardiovascular system”, is participation in the metabolism of major cardiotropic medications, such as digoxin, statins, ezetimibe, antithrombotic drugs, calcium channel blockers (CCBs), beta blockers (BB), gliflozins and inhibitors of the renin-angiotensin-aldosterone system (RAAS).

Progress in the study of toxic effects of drugs on the male reproductive system

This paper provides a comprehensive summary of the toxic effects of drugs on the male reproductive system, with a special focus on the mechanisms of testicular and sperm damage caused by chemotherapeutic agents, antibiotics, and immunosuppressants. Drug-induced reproductive toxicity usually manifests through multiple pathways including direct injury, interference with hormone regulation, oxidative stress, and DNA damage. These mechanisms can lead to impaired spermatogenesis, decreased testicular function, and long-term infertility, thereby seriously affecting male reproductive health. Specifically, chemotherapeutic drugs, such as cisplatin and cyclophosphamide, have been widely documented to cause direct damage to the testes, leading to significant decreases in sperm quantity and quality. Antibiotics and nonsteroidal anti-inflammatory drugs also negatively affect reproductive function by affecting mitochondrial function and inducing oxidative stress in the testicular cells. Although important advances have been made in recent years in the study of drug-induced reproductive toxicity, further exploration is needed to assess the variability of individual responses to drugs and develop long-term protective measures. Future research should focus on developing accurate toxicity assessment methods, customized therapeutic regimens, and enhanced fertility protection strategies, such as the use of antioxidants and methods for the cryopreservation of testes and sperm. Interdisciplinary collaboration will provide new solutions for balancing disease treatment and fertility preservation, especially in the use of high-risk drugs, such as anticancer therapies, where achieving both efficacy and reproductive health will be an important clinical challenge.

NASA’s Top Human System Research and Technology Needs for Mars

NASA is working with industry and international partners to return humans to the Moon and to eventually enable humans to explore Mars. Within NASA, several organizations work together to identify, prioritize, fund, execute, and operationalize the research and technology development (R&TD) that will be necessary to enable crew health and performance (CHP) during these future missions. These organizations include flight programs, the Health and Medical Technical Authority (HMTA), the Human Research Program, the Space Technology Mission Directorate, System Capability Leadership Teams, and other organizations, many of which existed for several years prior to the creation of the Moon-to-Mars (M2M) Program Office in 2023. A variety of constructs, vocabularies, and processes exist for managing risks and supporting strategic planning across these organizations. For example, M2M objectives, program risks, human system risks, human research gaps, capability gaps, and envisioned futures are all constructs currently used within NASA to identify and prioritize R&TD needs. These strategic planning constructs are evolving to allow M2M objectives and R&TD investments to be aligned and traced at a detailed level. A recognized need exists among stakeholder organizations to identify and communicate the highest CHP R&TD priorities in a unified and digestible way that addresses the perspectives of NASA’s CHP community. To achieve this, the HMTA arranged a series of discussions with representatives of NASA’s CHP community, during which the 8 highest priority CHP capabilities that will enable human missions to Mars, referred to as the “top human system capability needs for Mars”, were identified. The list includes Earth-independent human operations; Mars-duration food system; Mars-duration effects on human physiology; risk mitigations for vehicle atmospheres; computational injury and anthropometric models; exploration exercise countermeasures; individual variability in responses to spaceflight; and sensorimotor countermeasures. Existing tools and processes for strategic planning and risk management were evaluated, as well as the technical practicalities, cost, and schedule feasibility associated with potential R&TD investments in different capability need areas. This capability needs report is not owned by any one NASA organization and does not replace existing strategic or program planning processes; rather it aims to complement and inform them with a unified set of community generated priorities. These top capability needs will be re-evaluated periodically based on R&TD progress and the evolving M2M architecture.

Genomic Study in Opioid-Treated Cancer Patients Identifies Variants Associated With Nausea-Vomiting

ContextOpioids are the mainstay therapy for patients affected by cancer pain. However, about 10%–20% of patients do not benefit from the received analgesic treatment or experience side effects. Genetic variability might account for the variation in individual responses to opioids, both in terms of efficacy and toxicity. ObjectivesThe aim of this genome-wide association study (GWAS) was to identify genetic markers of opioid toxicity, in terms of nausea-vomiting. MethodsCancer patients receiving morphine, oxycodone, buprenorphine, and fentanyl were recruited from different European countries. Data about toxicity (nausea-vomiting score, NVS) and other relevant clinical information were collected, as well as genotyping data. Regression analysis between genotypes of 2052 patients and NVS was performed, using appropriate covariates, with REGENIE software. ResultsWe found 65 variants associated with NVS (P-value < 1.0×10−5). Of note, 14 intronic variants on chromosome 2 were in NPAS2 gene, encoding a circadian transcription factor reported to play a role in another opioid side effect, the alteration of sleep. Some of these variants were previously identified as splicing quantitative trait loci of the NPAS2 gene. ConclusionsThis is the first GWAS, performed in more than two thousand individually genotyped patients treated with opioids for cancer pain, that investigated the genetic bases of opioid-induced nausea-vomiting. Although further studies are needed to confirm our findings and to characterize the functional role of the identified variants, our results emphasize the importance of performing large pharmacogenomic studies to identify germline variants associated with opioid response, with the ultimate goal of tailoring cancer pain therapies.

Are there compensatory behaviors in response to a sit-stand desk intervention?

Office workers represent one of the most sedentary groups. Alarmingly, more than a third of their sitting time during workdays occurs in prolonged bouts. Sit-stand desk (SSD) interventions have been found to be effective in reducing sitting time, but heterogeneity exists amongst studies, which may be due to compensations outside the workplace. This study aimed to assess the impact of a 6-month SSD intervention on office workers' sitting and standing times during the work shift and outside work (leisure time). A two-arm (1:1) clustered randomized controlled trial was conducted with 38 participants randomly assigned to either the intervention or control group. The intervention included a psychoeducational session, motivational prompts, and environmental modification (SSD implemented in the workplace). The waiting-list control group maintained the usual work conditions and only received the initial session. We employed repeated measures ANCOVA to compare changes between groups while adjusting for relevant covariates, with significance set at 5%. In the intervention group, there was a significant reduction in sitting time at work by 32.97 min, along with a notable increase in standing time by 27.88 min (p<0.05). Although not significant (p>0.05), there was an increase in sitting time in the leisure context of about 23.07 min. This study underscores the effectiveness of SSD as a key strategy to mitigate sitting time among office workers. However, future interventions should consider integrating comprehensive behavioral strategies beyond the workplace to sustain potential increases in sitting time during the leisure time and avoid compensatory behaviors. What is already known on this topic: Sedentary behavior, particularly in the workplace, is associated with increased risks of non-communicable diseases and premature mortality. Previous studies have shown that sit-stand desk (SSD) interventions can significantly reduce sitting time at work. However, uncertainties remain about whether these effects persist outside of the workplace and if compensatory behaviors occur during leisure time. This study demonstrated that a 6-month SSD intervention resulted in a significant reduction of 32.97 minutes in sitting time during work hours and a corresponding increase in standing time. However, a non-significant increase of 23.07 minutes in sitting time during leisure was observed, suggesting potential compensatory behaviors outside of work. Additionally, the response to the intervention varied among participants, highlighting the influence of individual factors. How this study might affect research, practice, or policy: The findings emphasize the importance of extending behavioral interventions beyond the workplace to maintain sustainable reductions in sedentary behavior. To maximize health benefits, future interventions should consider personalized strategies that address sedentary behavior in the workplace and during leisure time. Moreover, the variability in individual responses suggests that more tailored interventions may be necessary to ensure widespread effectiveness.

Association between 5-HTR1A gene C-1019G polymorphism and antidepressant response in patients with major depressive disorder: A meta-analysis.

Major depressive disorder (MDD) is a substantial global health concern, and its treatment is complicated by the variability in individual response to antidepressants. To consolidate research and clarify the impact of genetic variation on MDD treatment outcomes. Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic search across PubMed, EMBASE, Web of Science, and the Cochrane Library was conducted without date restrictions, utilizing key terms related to MDD, serotonin 1A receptor polymorphism (5-HTR1A), C-1019G polymorphism, and antidepressant response. Studies meeting inclusion criteria were thoroughly screened, and quality assessed using the Newcastle-Ottawa Scale. Statistical analyses, including χ 2 and I² values, were used to evaluate heterogeneity and fixed-effect or random-effect models were applied accordingly. The initial search yielded 1216 articles, with 11 studies meeting criteria for inclusion. Analysis of various genetic models showed no significant association between the 5-HTR1A C-1019G polymorphism and antidepressant efficacy. The heterogeneity was low to moderate, and no publication bias was detected through funnel plot symmetry and Egger's and Begg's tests. This meta-analysis does not support a significant association between the 5-HTR1A C-1019G polymorphism and the efficacy of antidepressant treatment in MDD. The findings call for further research with larger cohorts to substantiate these results and enhance the understanding of antidepressant pharmacogenetics.

Low-dose carbon monoxide inhalation to increase total hemoglobin mass and endurance performance: scientific evidence and implications.

Recently, chronic intermittent inhalation of low-dose carbon monoxide (CO) has been postulated as a practice to increase total hemoglobin mass with potential beneficial effects on endurance performance. In this perspective article, we discuss the potential performance enhancing capabilities as well as the safety concerns, which include individual variability in CO response, and acute and chronic health effects. It is also important to note that according to the World-Anti-Doping-Agency (WADA), CO inhalation could fall under "M1. Manipulation of Blood and Blood Components" and therefore could be considered a prohibited method if used as a non-diagnostic tool.

Evaluating Heat Stress Effects on Growth in Tunisian Local Kids: Enhancing Breeding Strategies for Arid Environments.

This study evaluates the impact of thermal load on the weights of Tunisian local kids using 24 models with cubic and quadratic Legendre polynomials, based on daily temperatures (Tmin, Tmax, and Tavg) on the day of weight recording and averaged over 7, 14, and 21 days before weighing. The deviance information criterion (DIC) consistently shows that cubic polynomial models offer a better fit than quadratic models, highlighting their superior accuracy in studying the effects of thermal load on kid weights. The models with the best fit utilized average or maximum temperatures over 14 or 21 days. The patterns of response were similar across the temperature variables and periods, showing a stable weight response at lower temperatures (thermoneutral region) followed by a decline as the temperatures increased. The weight loss was -125 g/°C beyond the moderate heat stress threshold (Tavg21 = 17.7 °C) and -450 g/°C beyond the severe heat stress threshold (Tavg21 = 25.3 °C) for Tavg21. The heat stress thresholds for moderate heat stress (HS1) were 8.6 °C for Tmin14, 27.4 °C for Tmax14, and 18.6 °C for Tavg14; moreover, for acute heat stress (HS2), they were 17.2 °C for Tmin14, 32.4 °C for Tmax14, and 25.5 °C for Tavg14. High variability in individual responses was observed, with differences in the slope of response ranging from 2.0 kg/°C for moderate heat stress to around 3.0 kg/°C for severe heat stress for Tavg. The correlations between the weights under different temperatures were low, indicating that rankings based on weight could change with varying heat conditions. The animals with larger weight levels generally demonstrated better heat tolerance, and those with good heat tolerance under moderate conditions were also likely to have good tolerance under severe conditions.

Longitudinal monitoring of hypertonia through a multimodal sensing glove

As clinical evaluations of neuromuscular disorders such as hypertonia mostly rely on perception-based scales, the imprecise subjective ratings make it difficult to accurately monitor treatment progress. To promote objective evaluation, this work used a multi-modal sensing glove in a double-blind study to enable sensitive monitoring of medication effects across 19 participants. The biomechanical measurements from the sensing glove effectively distinguished patient cohorts receiving a baclofen treatment or a placebo with 95% confidence. Consistent monitoring over a two-month period was demonstrated, closely tracking variations in individual responses to treatment. The biomechanical changes were correlated to neural activities as recorded by electromyography, verifying the medication effects. The sensing glove is shown to be a reliable tool for point-of-care settings to facilitate precise evaluation of hypertonia, essential for tailoring individual treatment choices and timely management of chronic symptoms.

Hierarchical Genomic Analysis of Susceptibility to Schizophrenia in Sudanese multi-case families

Background Schizophrenia, with its diverse and complex presentation, is a prime candidate for genetic investigation. Its heritability in both familial and sporadic cases, clinical overlap with other psychiatric conditions, and individual variations in response to treatment contribute to its complexity. Numerous genes and associated biochemical pathways show significant differences at the population, familial, and individual levels. Additionally, schizophrenia may represent an evolutionary trade-off for human brain development, creativity, and intellectual performance. Material and Methods This case pseudo-control study analyzed the whole genomes/exomes of seven Sudanese families with multiple siblings affected by schizophrenia. We examined shared variants among family members, including both cases and controls, and unique variants shared between patients but not controls. These variants were filtered based on their impact on protein function, expression levels, allele frequencies, ACMG classification for rare variants, and disease associations. Networks were created to identify central genes and common biological pathways. Results and Discussion The examination of this complex disorder in Sudanese families revealed numerous variants, both common and rare, showing differences between families and between our population and those reported in the literature. This highlights the challenge of accounting for the known heritability of the disease. Our hierarchical approach demonstrates that schizophrenia’s etiology involves the cumulative effect of various interacting variants in an ascending order of influence. Common variants are shared among all samples, while rare variants are shared among two or three families, most of which are associated with schizophrenia. In conclusion The significance lies not merely in the number of detected variants but in understanding their interactive roles, step by step, to reveal the complete picture of the disease’s phenotype.

Drivers of Wolf Activity in a Human-Dominated Landscape and Its Individual Variability Toward Anthropogenic Disturbance.

Wolves (Canis lupus) exhibit contrasted activity patterns along their distribution range. The shift from diurnal to nocturnal habits within and among populations appears to be primarily driven by localized levels of human activity, with ambivalent responses toward such disturbance reported among populations. Yet, the drivers and the underlying individual variability of temporal avoidance patterns toward human remains unexplored. We equipped 26 wolves with GPS-GSM collars, obtaining 54,721 locations. We used step lengths, turning angles, and accelerometer data from recorded locations to infer activity through hidden Markov models (Conners, M. G., T. Michelot, E. I. Heywood, et al. 2021. "Hidden Markov Models Identify Major Movement Modes in Accelerometer and Magnetometer Data From Four Albatross Species." Movement Ecology 9, no. 1: 1-16.). We further explored the probability of activity as a function of a set of proxies of anthropogenic disturbance at different spatial scales and its interaction with different periods of the day by fitting population-level and individual-based hidden Markov models. Wolves were predominantly active during dusk and night, yet variations in activity emerged among individuals across day periods. We did not find clear population-level effects of anthropogenic disturbance predictors, as these were masked by a wide range of individual-specific responses, which varied from positive to negative, with inter-individual variability in responses changing according to different predictors and periods of the day. Our results suggest a non-uniform strategy of wolves in adapting their behavior to human-dominated environments, further underscoring the role of vegetation patches acting as functional refuge cover for buffering the effects of anthropogenic disturbance and boosting the persistence of the species in human-dominated landscapes. This study, for the first time, reveals the individual variability in wolf responses to human disturbance. By fitting hidden Markov models to data from GPS-GSM collars deployed on 26 wolves, we found significant variation between individuals in their responses to different levels of anthropogenic pressure and across different times of day, highlighting a non-uniform strategy for coping with perturbations in human-dominated landscapes. Our findings underscore the diverse behavioral adjustments employed by wolves to persist in these environments and highlight the critical importance of vegetation patches serving as refuge cover.

Antibody response to SARS-CoV-2 mRNA vaccination in Danish adults exposed to perfluoroalkyl substances (PFASs): The ENFORCE study

IntroductionPer- and polyfluoroalkyl substances (PFASs) have immunotoxic effects in children while studies in adults, including recent studies on the SARS-CoV-2 vaccine response have been less consistent. In a cohort of 50–69-year-olds repeatedly vaccinated against COVID-19 in Denmark from early 2021, we aimed to assess the association between serum-PFAS concentrations and SARS-CoV-2 antibody responses. MethodsWe assessed serum-PFAS concentrations among 371 middle-aged adults from the National Cohort Study of Effectiveness and Safety of SARS-CoV-2 vaccines (ENFORCE) who had received their first vaccination against COVID-19. Following the second dose and the booster (third) Pfizer-BioNTech mRNA vaccination, we measured the specific spike IgG antibody response. Associations between serum-PFAS concentrations at inclusion and spike IgG antibody concentrations after vaccination were assessed using median regression, and analyses were adjusted for age, sex, presence of diabetes, number of vaccines received, and time since vaccination. We further examined the associations between serum-PFAS concentrations at inclusion and changes in spike IgG antibody concentration between the second dose and booster (third) vaccination. ResultsSerum-PFAS concentrations were not associated with spike IgG antibody concentrations after the SARS-CoV-2 vaccinations, but the increase in response after the booster (third) vaccination compared to after the second vaccination was consistently lower at higher serum-PFAS concentrations. Each doubling in the concentration of seven serum-PFASs was associated with a 802 BAU/mL lower median increase in spike IgG antibody response after the booster (third) vaccination (95% CI: −1812; 208) adjusted for confounders. DiscussionAs many adults were probably not immunological naïve prior to vaccination, our results were likely affected by individual variability in immune response to the vaccination. Despite this uncertainty, the diminished increase in SARS-CoV-2 spike antibody response after the booster (third) vaccination at higher PFAS exposure may potentially reflect an immunotoxic impact of the PFASs.