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Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. In the primary analysis of the global phase II ELIANA trial (ClinicalTrials.gov identifier: NCT02435849 ), tisagenlecleucel provided an overall remission rate of 81% in pediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), with 59% of responders remaining relapse-free at 12 months. Here, we report an update on efficacy, safety, and patient-reported quality of life in 79 pediatric and young adult patients with R/R B-ALL following a median follow-up of 38.8 months. The overall remission rate was 82%. The median event-free survival was 24 months, and the median overall survival was not reached. Event-free survival was 44% (95% CI, 31 to 57) and overall survival was 63% (95% CI, 51 to 73) at 3 years overall (most events occur within the first 2 years). The estimated 3-year relapse-free survival with and without censoring for subsequent therapy was 52% (95% CI, 37 to 66) and 48% (95% CI, 34 to 60), respectively. No new or unexpected long-term adverse events were reported. Grade 3/4 adverse events were reported in 29% of patients > 1 year after infusion; grade 3/4 infection rate did not increase > 1 year after infusion. Patients reported improvements in quality of life up to 36 months after infusion. These findings demonstrate favorable long-term safety and suggest tisagenlecleucel as a curative treatment option for heavily pretreated pediatric and young adult patients with R/R B-ALL.

center dot PURPOSE: To optimize artificial intelligence (AI) algo-rithms to integrate Scheimpflug-based corneal tomogra-phy and biomechanics to enhance ectasia detection.center dot DESIGN: Multicenter cross-sectional case-control ret-rospective study.center dot METHODS: A total of 3886 unoperated eyes from 3412 patients had Pentacam and Corvis ST (Oculus Op-tikgerate GmbH) examinations. The database included 1 eye randomly selected from 1680 normal patients (N) and from 1181 "bilateral" keratoconus (KC) patients, along with 551 normal topography eyes from patients with very asymmetric ectasia (VAE-NT), and their 474 unoperated ectatic (VAE-E) eyes. The current TBIv1 (tomographic-biomechanical index) was tested, and an optimized AI algorithm was developed for augmenting accuracy.center dot RESULTS: The area under the receiver operating char-acteristic curve (AUC) of the TBIv1 for discriminating clinical ectasia (KC and VAE-E) was 0.999 (98.5% sen-sitivity; 98.6% specificity [cutoff: 0.5]), and for VAE-NT, 0.899 (76% sensitivity; 89.1% specificity [cutoff: 0.29]). A novel random forest algorithm (TBIv2), devel-oped with 18 features in 156 trees using 10-fold cross -validation, had a significantly higher AUC (0.945; De -Long, P < .0001) for detecting VAE-NT (84.4% sen-sitivity and 90.1% specificity; cutoff: 0.43; DeLong, P < .0001) and a similar AUC for clinical ectasia (0.999; DeLong, P = .818; 98.7% sensitivity; 99.2% specificity [cutoff: 0.8]). Considering all cases, the TBIv2 had a higher AUC (0.985) than TBIv1 (0.974; DeLong, P < .0001).center dot CONCLUSIONS: AI optimization to integrate Scheimpflug-based corneal tomography and biome-chanical assessments augments accuracy for ectasia detection, characterizing ectasia susceptibility in the diverse VAE-NT group. Some patients with VAE may have true unilateral ectasia. Machine learning consider-ing additional data, including epithelial thickness or other parameters from multimodal refractive imaging, will con-tinuously enhance accuracy. NOTE: Publication of this article is sponsored by the American Ophthalmological Society. (Am J Ophthalmol 2023;251: 126-142. (c) 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ ))

Revision total knee arthroplasty (rTKA) and total hip arthroplasty (rTHA) procedures are more complex than primary TKA and THA, but their physiologic burden to the surgeon has not been quantified. While rTKA and rTHA have longer operative times, it is unknown whether differences exist in stress and strain compared to primary TKA and primary THA. The study was conducted to elicit whether differences exist in surgeon physiological response while performing rTKA and rTKA compared to primary TKA and primary THA.We evaluated a prospective cohort study of 70 consecutive cases (23 primary TKAs, 12 primary THAs, 16 rTKAs, and 19 rTHAs). Two high-volume fellowship-trained arthroplasty surgeons wore a smart vest that recorded cardiorespiratory data while performing primary THA, primary TKA, rTHA, and rTKA. Heart rate (beats/minute), stress index (correlates with sympathetic activation), respiratory rate (respirations/minute), minute ventilation (liters/minute), and energy expenditure (Calories) were collected for every case, along with patient body mass index (BMI; kilograms/meterCompared to primary TKA, performing rTKAs had a significantly higher surgeon stress index [17 vs. 15; p = 0.035), HR [104 vs. 99; p = 0.007], energy expenditure per case [409 vs. 297; p = 0.002], and a significantly lower HRV [11 vs. 12; p = 0.006]. Compared to primary THA, performing rTHA had a significantly higher energy expenditure per case [431 vs. 307; p = 0.007] and trended towards having a higher surgeon stress index [16 vs. 14; p = 0.272] and a lower HRV [11 vs. 12; p = 0.185], although it did not reach statistical significance.Surgeons experience higher physiological stress and strain when performing rTKA and rTHA compared to primary TKA and primary THA. This study provides objective data on what many surgeons feel and should promote further research on the specific stress and strain felt by surgeons who perform revision arthroplasty procedures.

The novel total left anterior descending devascularization (TLD) approach in a canine ischemic heart failure model limits collateral flow in the ischemic zone and provides excellent early survival and repeatable development of chronic ischemic heart failure in the canine heart. This work provides a consistent large animal model for investigating heart failure mechanisms and testing novel therapeutics.

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As a strong risk factor for mortality, individual differences in loneliness are of clear public health significance. Four of the Big Five traits have emerged as cross-sectional correlates, but the etiology of these links is unclear, as are relations with more specific personality facets. Thus, we estimated phenotypic, genetic, and environmental associations between loneliness and both broader and narrower personality dimensions. Traits that indexed Negative Emotionality (e.g., Neuroticism, Stress Reactivity, Alienation) and low Positive Emotionality (e.g., low Extraversion, low Well-Being) had the strongest associations with loneliness, though low Conscientiousness, low Agreeableness, and high Aggression were also implicated. These associations were explained by both genetic (0.30|r

Memory formation and maintenance is a dynamic process involving the modulation of the actin cytoskeleton at synapses. Understanding the signaling pathways that contribute to actin modulation is important for our understanding of synapse formation and function, as well as learning and memory. Here, we focused on the importance of the actin regulator, noncatalytic region of tyrosine kinase adaptor protein 1 (NCK1), in hippocampal dependent behaviors and development. We report that male mice lacking NCK1 have impairments in both short-term and working memory, as well as spatial learning. Additionally, we report sex differences in memory impairment showing that female mice deficient in NCK1 fail at reversal learning in a spatial learning task. We find that NCK1 is expressed in postmitotic neurons but is dispensable for neuronal proliferation and migration in the developing hippocampus. Morphologically, NCK1 is not necessary for overall neuronal dendrite development. However, neurons lacking NCK1 have lower dendritic spine and synapse densitiesin vitroandin vivo. EM analysis reveal increased postsynaptic density (PSD) thickness in the hippocampal CA1 region of NCK1-deficient mice. Mechanistically, we find the turnover of actin-filaments in dendritic spines is accelerated in neurons that lack NCK1. Together, these findings suggest that NCK1 contributes to hippocampal-dependent memory by stabilizing actin dynamics and dendritic spine formation.SIGNIFICANCE STATEMENTUnderstanding the molecular signaling pathways that contribute to memory formation, maintenance, and elimination will lead to a better understanding of the genetic influences on cognition and cognitive disorders and will direct future therapeutics. Here, we report that the noncatalytic region of tyrosine kinase adaptor protein 1 (NCK1) adaptor protein modulates actin-filament turnover in hippocampal dendritic spines. Mice lacking NCK1 show sex-dependent deficits in hippocampal memory formation tasks, have altered postsynaptic densities, and reduced synaptic density. Together, our work implicates NCK1 in the regulation of actin cytoskeleton dynamics and normal synapse development which is essential for memory formation.

Turbulent times have been prevalent throughout human history. Are these times somehow different? I expect we all have both similar and different perspectives. This talk will review turbulent times, past, today, and the future. As a scientist, my approach is to seek and organize facts. Our guide will be God’s creation, Word, and Holy Spirit. From these and His guidance let’s relate our times to God’s plan. Join me as the Lord leads us – to understanding and wisdom. I look forward to our time together – all disciples. Of special interest to me is the concluding discussion period. Opportunities for all of us to learn from each other.

Time spent working or caring for children may reduce the time available for undertaking time-intensive health behaviors. We test competing perspectives about how work hours and the number of children of specific ages will be associated with married or cohabiting men’s and women’s sleep duration and physical activity. We use data from the 2004 to 2017 waves of the National Health Interview Survey (N = 154,580). In support of the “time availability” perspective, longer work hours and children of any age are associated with shorter sleep hours. However, in support of the “time deepening” perspective, additional hours of work beyond 40 hours per week and children over the age of five are not associated with reduced physical activity. Contrary to our expectations, we did not find gender differences in support of our theories. Our results suggest that the economy of time works differently for sleep and exercise.

Purpose: Children with speech sound disorders (SSDs) often struggle with forming early representations for phonemes and words, which could impact their speech production as well as their lexical access. This difficulty may limit their ability to accurately identify nonexemplar productions of words, such as developmental misarticulations produced by peers. The purpose of this study was to examine word interpretation of misarticulated words by children with SSD. Method: Seventeen monolingual English-speaking preschoolers were assessed for language, phonological processing, and articulation skills. Participants heard three types of words: accurate productions (e.g., “leaf”), common misarticulated productions (e.g., “weaf”), uncommon misarticulated productions (e.g., “yeaf”), and unrelated nonwords (e.g., “gim”). Children were presented with these words aurally and asked to select the picture that matched what they heard—either a real object or a blank square. Results: The proportion of real object picture selections was calculated for each word type and compared within subjects. The findings indicate that children with SSD reliably associated common misarticulated words with pictured objects more frequently than they did in the uncommon misarticulation condition. These results were compared between subjects to typically developing (TD) peers' responses using a one-way analysis of variance. The results indicate that children with SSD identified common substitutions as real object pictures more often than TD peers. Conclusion: The results of this study suggest that children with SSD are sensitive to the commonness of misarticulations; however, they accept common substitutions as real object pictures significantly more often than TD peers.

Explicitly or implicitly, psychopathology is often defined in terms of statistical deviance, requiring that an affected individual is sufficiently distant from the norm in some dimension of psychological or neural function. In recent decades, the dominant paradigm in psychiatric research has focused primarily on deviance in neural function, treating psychopathology as disease of the brain. We argue that these conceptualizations are misguided. We recently proposed a novel theory of psychopathology, based in cybernetics and drawing additionally from neuroscience, psychometrics, and personality theory (DeYoung & Krueger, 2018a). In this theory, deviations from the norm in psychological and neural functioning serve as important risk factors for psychopathology but are not in themselves necessary or sufficient to identify psychopathology, which requires the presence of cybernetic dysfunction. Psychopathology is defined as persistent failure to move toward one’s goals, due to failure to generate effective new goals, interpretations, or strategies when existing ones prove unsuccessful. We argue that adopting a cybernetic theory to replace conceptualizations of psychopathology as statistical deviance or brain disease would facilitate improvements in measurement, diagnosis, prevention, and treatment of psychopathology.

Robust scientific knowledge is contingent upon replication of original findings. However, replicating researchers are constrained by resources, and will almost always have to choose one replication effort to focus on from a set of potential candidates. To select a candidate efficiently in these cases, we need methods for deciding which out of all candidates considered would be the most useful to replicate, given some overall goal researchers wish to achieve. In this article we assume that the overall goal researchers wish to achieve is to maximize the utility gained by conducting the replication study. We then propose a general rule for study selection in replication research based on the replication value of the set of claims considered for replication. The replication value of a claim is defined as the maximum expected utility we could gain by conducting a replication of the claim, and is a function of (a) the value of being certain about the claim, and (b) uncertainty about the claim based on current evidence. We formalize this definition in terms of a causal decision model, utilizing concepts from decision theory and causal graph modeling. We discuss the validity of using replication value as a measure of expected utility gain, and we suggest approaches for deriving quantitative estimates of replication value. Our goal in this article is not to define concrete guidelines for study selection, but to provide the necessary theoretical foundations on which such concrete guidelines could be built.Translational Abstract Replication-redoing a study using the same procedures-is an important part of checking the robustness of claims in the psychological literature. The practice of replicating original studies has been woefully devalued for many years, but this is now changing. Recent calls for improving the quality of research in psychology has generated a surge of interest in funding, conducting, and publishing replication studies. Because many studies have never been replicated, and researchers have limited time and money to perform replication studies, researchers must decide which studies are the most important to replicate. This way scientists learn the most, given limited resources. In this article, we lay out what it means to think about what is the most important thing to replicate, and we propose a general decision rule for picking a study to replicate. That rule depends on a concept we call replication value. Replication value is a function of the importance of the study, and how uncertain we are about the findings. In this article we explain how researchers can think precisely about the value of replication studies. We then discuss when and how it makes sense to use replication value as a measure of how valuable a replication study would be, and we discuss factors that funders, journals, or scientists could consider when determining how valuable a replication study is.

Given the key role of the IL-23/Th17 axis in the pathogenesis of moderate-to-severe plaque psoriasis, several specific inhibitors of the p19 subunit of IL-23 have been approved to treat this chronic inflammatory disease. Clinical data indicate that guselkumab, one such selective IL-23 inhibitor, achieves greater clinical efficacy compared with ustekinumab, which inhibits both IL-12 and IL-23 via binding their shared p40 subunit. To understand mechanisms underlying the enhanced efficacy observed with the p19 subunit of IL-23–specific inhibition, we explored cellular and molecular changes in skin of psoriasis patients treated with ustekinumab or guselkumab and in ustekinumab inadequate responders (Investigator’s Global Assessment of psoriasis score ≥ 2) subsequently treated with guselkumab (ustekinumab→guselkumab). Skin biopsies were collected pretreatment and posttreatment to assess histologic changes and molecular responses in ustekinumab- and guselkumab-treated patients. Serum cytokines and skin transcriptomics from the subset of ustekinumab→guselkumab-treated patients were also analyzed to characterize differential treatment effects. Ustekinumab and guselkumab demonstrated differential effects on secretion of pathogenic Th17-related cytokines induced by IL-23 in in vitro assays, which suggest guselkumab is a more potent therapeutic agent. Consistent with these findings, guselkumab elicited a significantly greater reduction in cellular and molecular psoriasis-related disease indicators than ustekinumab. In ustekinumab→guselkumab patients, suppression of serum IL-17A and IL-17F levels and neutralization of molecular scar and psoriasis-related gene markers in skin were significantly greater compared with patients continuing ustekinumab. This comparative study demonstrates that guselkumab inhibits psoriasis-associated pathology, suppresses Th17-related serum cytokines, and normalizes the psoriasis skin gene expression profile more effectively than ustekinumab.

by YannickGnipep-oo Pembouong, V&R Unipress, 2020. 474 pp. $ 64

The unanticipated COVID-19 pandemic renewed interest in the success of various pedagogic practices across populations to determine the universality of their importance. This article contrasts the findings of research conducted among Kazakhstan business students, and recently reported in the Journal Eastern European and Central Asian Research, to a population of business students at Texas A&M University-Kingsville. Our empirical sample survey of 112 undergraduate students reveals a.) a greater satisfaction with online education, b.) the potential for a longer attention span, c.) agreement on techniques to improve pedagogy, and d.) better perceived online experiences versus Kazakhstani findings. This report shares additional actionable suggestions for lessening the instances of low online involvement, as well as suggestions for improving asynchronous online education, which is again found to be preferred to a synchronous modality. Insights provided by students from a different culture and hemisphere enhance understanding of student perceptions and ways to improve the online learning experience.

In the central nervous system (CNS), insulin-like growth factor 1 (IGF-1) regulates myelination by oligodendrocyte (ODC) precursor cells and shows anti-apoptotic properties in neuronal cells in different in vitro and in vivo systems. Previous work also suggests that IGF-1 protects ODCs from cell death and enhances remyelination in models of toxin-induced and autoimmune demyelination. However, since evidence remains controversial, the therapeutic potential of IGF-1 in demyelinating CNS conditions is unclear. To finally shed light on the function of IGF1-signaling for ODCs, we deleted insulin-like growth factor 1 receptor (IGF1R) specifically in mature ODCs of the mouse. We found that ODC survival and myelin status were unaffected by the absence of IGF1R until 15 months of age, indicating that IGF-1 signaling does not play a major role in post-mitotic ODCs during homeostasis. Notably, the absence of IGF1R did neither affect ODC survival nor myelin status upon cuprizone intoxication or induction of experimental autoimmune encephalomyelitis (EAE), models for toxic and autoimmune demyelination, respectively. Surprisingly, however, the absence of IGF1R from ODCs protected against clinical neuroinflammation in the EAE model. Together, our data indicate that IGF-1 signaling is not required for the function and survival of mature ODCs in steady-state and disease.

The nephrotoxicity of cisplatin remains a major hurdle in the field of oncology. Thirty percent of patients treated with cisplatin develop acute kidney injury, and all patients are at risk for long-term impacts on kidney function. There are currently no Federal Drug Administration-approved agents to prevent or treat cisplatin-induced kidney injury. The dosing regimen used in preclinical models of nephrotoxicity may impact the success of therapeutic candidates in clinical trials. Here, we demonstrated that pharmacological inhibitors of autophagy have opposite effects when used as interventions in two different models of cisplatin-induced kidney injury. Eight-week-old male C57BL/6 mice were treated with either one dose of 20 mg/kg cisplatin or weekly doses of 9 mg/kg cisplatin for 4 wk or until body weight loss exceeded 30%. Concurrently, mice were administered multiple doses of 60 mg/kg chloroquine or 15 mg/kg 3-methyladenine attempting to globally inhibit autophagy. Mice that received a single high dose of cisplatin had worsened kidney function, inflammation, and cell death with the addition of chloroquine. 3-Methlyadenine did not impact the development of acute kidney injury in this model. In contrast, mice that received repeated low doses of cisplatin showed improved kidney function, reduced inflammation, and reduced fibrosis when treated with either chloroquine or 3-methyladenine. This study highlights how therapeutic candidates can have drastically different effects on the development of cisplatin-induced kidney injury depending on the dosing model used. This emphasizes the importance of choosing the appropriate model of injury for preclinical studies.

PurposeThis article aims to examine whether specific job tasks measured at the individual level or personality traits are associated with wages and whether the relationship between personality traits and wages differs depending on the job tasks that individuals perform.Design/methodology/approachThis study analyzes the association between job tasks and personality traits, and their interaction, with regard to wages using German employee data from 2017/2018.FindingsResults suggest that nonroutine manual, interactive or analytic tasks are associated with significantly higher wages compared to routine manual tasks, and while extraversion and emotional stability are related to higher wages, agreeableness and openness tend to be associated with lower wages also within occupations. Moreover, the association between personality traits and wages varies depending on the job task requirements at the workplace. A high degree of extraversion in particular is associated with higher wages when the employee performs nonroutine manual, interactive or analytic tasks.Originality/valueTo date, especially the interaction between individual job tasks and personality traits on wages has not been extensively studied because data on both job tasks and personality at the employee level are scarce. This study contributes to the understanding of wage differences among employees.

Workplace cultural diversity and community inclusion are two facets of a complex public issue that require a deliberative community-based problem-solving approach. This article reports findings from a qualitative analysis of fourteen focus groups (N = 83 participants) held in a rural Midwestern community that centered on community members’ experiences with workplace cultural diversity and community inclusion. Three themes emerged: (a) racism and micro-aggressions; (b) discomfort talking about and across cultural differences; and (c) lack of belonging. Of the 14 focus groups, five represented enclave groups with culturally diverse employees. By engaging with historically excluded groups, researchers communicated with affected stakeholders when framing the public issue and convening public meetings to discuss that issue. This use of enclave groups to make the initial stages of the deliberative cycle more inclusive has implications for practitioners of public deliberation, scholars of human communication, and citizens and their communities.

Species with temperature-dependent sex determination (TSD) exhibit significant variation in the relationship between incubation temperatures and the sex ratios they produce, making this an ideal system for comparing processes producing variation above and below the species level. Furthermore, a deeper mechanistic understanding of TSD macro- and microevolution may help reveal the currently unknown adaptive significance of this variation or of TSD as a whole. Here, we probe these topics by examining the evolutionary dynamics of this sex-determining mechanism in turtles. Our ancestral state reconstructions of discrete patterns of TSD suggest that producing females at cool incubation temperatures is derived and potentially adaptive. However, the ecological irrelevance of these cool temperatures and a strong genetic correlation across the sex-ratio reaction norm in Chelydra serpentina both contradict this interpretation. We further find the phenotypic consequence of this genetic correlation in C. serpentina reflected across all turtle species, suggesting that a single genetic architecture underlies both intra- and interspecific variation in TSD in this clade. This correlated architecture can explain the macroevolutionary origin of discrete TSD patterns without assigning cool-temperature female production an adaptive value. However, this architecture may also constrain adaptive microevolutionary responses to ongoing climate change.

OBJECTIVE A carefully selected subset of civilian cranial gunshot wound (CGSW) patients may be treated with simple wound closure (SWC) as a proactive therapy, but the appropriate clinical scenario for using this strategy is unknown. The aim of this study was to compare SWC and surgery patients in terms of their neurological outcomes and complications, including infections, seizures, and reoperations. METHODS This was a single-center, retrospective review of the prospectively maintained institutional traumatic brain injury and trauma registries. Included were adults who sustained an acute CGSW defined as suspected or confirmed dural penetration. Excluded were nonfirearm penetrating injuries, patients with an initial Glasgow Coma Scale (GCS) score of 3, patients with an initial GCS score of 4 and nonreactive pupils, and patients who died within 48 hours of presentation. RESULTS A total of 67 patients were included; 17 (25.4%) were treated with SWC and 50 (74.6%) were treated with surgery. The SWC group had a lower incidence of radiographic mass effect (3/17 [17.6%] SWC vs 31/50 [62%] surgery; absolute difference 44.4, 95% CI −71.9 to 16.8; p = 0.002) and lower incidence of involvement of the frontal sinus (0/17 [0%] SWC vs 14/50 [28%] surgery; absolute difference 28, 95% CI −50.4 to 5.6; p = 0.01). There were no differences in the frequency of Glasgow Outcome Scale–Extended scores ≥ 5 between the SWC and surgery groups at 30 days (4/11 [36.4%] SWC vs 12/35 [34.3%] surgery; OR 1.1, 95% CI 0.3–4.5; p > 0.99), 60 days (2/7 [28.6%] SWC vs 8/26 [30.8%] surgery; OR 0.9, 95% CI 0.3–3.4; p > 0.99), and 90 days (3/8 [37.5%] SWC vs 12/26 [46.2%] surgery; OR 0.7, 95% CI 0.1–3.6; p > 0.99). There were no differences in the incidence of infections (1/17 [5.9%] SWC vs 6/50 [12%] surgery; OR 0.5, 95% CI 0.1–4.1; p = 0.67), CSF fistulas (2/11 [11.6%] SWC vs 3/50 [6%] surgery; OR 2.1, 95% CI 0.3–13.7; p = 0.60), seizures (3/17 [17.6%] SWC vs 9/50 [18%] surgery; OR 1, 95% CI 0.2–4.1; p > 0.99), and reoperations (3/17 [17.6%] SWC vs 4/50 [8%] surgery; OR 2.5, 95% CI 0.5–12.4; p = 0.36) between the SWC and surgery groups. CONCLUSIONS There were important clinically relevant differences between the SWC and surgery groups. SWC can be considered a safe and efficacious proactive therapy in a carefully selected subset of civilian CGSW patients.

Background Atopic dermatitis (AD) is a heterogeneous, chronic inflammatory skin disease linked to skin microbiome dysbiosis with reduced bacterial diversity and elevated relative abundance of Staphylococcus aureus (S. aureus). Objectives We aimed to characterize the yet incompletely understood association between the skin microbiome and patients' demographic and clinical cofactors in relation to AD severity. Methods The skin microbiome in 48 adult moderate-to-severe AD patients was investigated using next-generation deep sequencing (16S rRNA gene, V1–V3 region) followed by denoising (DADA2) to obtain amplicon sequence variant (ASV) composition. Results In lesional skin, AD severity was associated with S. aureus relative abundance (rS = 0.53, p

Accelerated lakes eutrophication is one of the greatest challenges nowadays. To counteract its negative effects, large-scale restoration treatments are carried out worldwide. However, research in this field is mainly focused on the process effectiveness and there is a scarcity of studies concerning the impact of restoration treatments on water organisms and ecosystem homeostatsis. Our microcosm study presents the effects of a phosphorus coagulant (iron [III] chloride) on functional traits changes, oxidative stress and macro- and microelement stoichiometry disturbances in macrophyte Myriophyllum spicatum, a model species inhabiting eutrophic waters. Application of the coagulant to experimental vessels influenced the physicochemical and optical parameters of water and led to significant changes in biogeochemistry. Stoichiometric alterations were reflected by disturbances in the relative contents of macro- (C, N, P, Ca, Mg) and microelements (Fe, Zn, Cu, Co) and induced luxury consumption of available ions. Physicochemical and stoichiometric changes mutually exerted negative influence on M. spicatum functional traits. The parameters of oxidative stress remained at low levels, comparable to the untreated control whereas stoichiometric analysis revealed the activation of mechanisms responsible for minimizing low light stress. The ability of M. spicatum to maintain homeostasis of Cu and Co under simulated chemical water restoration was closely related to high concentrations of Fe and Zn ions, which simultaneously were not subjected to homeostasis control. Thus, chemical lake restoration treatments based on phosphorus coagulants are not as environmentally safe as previously considered and may have far-reaching consequences for the biogeochemical cycle and food web functioning.