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Cancer patients may encounter the onset of cardiovascular disease due to tumor advancement or chemotherapy, commonly known as "cardiotoxicity." In this respect, the conventional chemotherapy treatment protocol involves a mixture of different medications. These medications can be detrimental to cardiac tissue, consequently exposing the patient to the possibility of irreversible cardiac injury. The enhancement of oxidative stress and inflammation is an important mechanism of chemotherapeutic agents for developing cardiotoxicity. Regarding their dual pro- and anti-inflammatory functions, platelets can significantly influence the progression or suppression of cardiotoxicity. Therefore, the expression of platelet activatory markers can serve as valuable prognostic indicators for cardiotoxicity. The primary objective of this study is to examine the significance of platelets in cardiotoxicity and explore potential strategies that could effectively target malignant cells while minimizing their cytotoxic impact, such as cardiotoxicity and thrombosis., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Unionid mussels deposit growth rings (annuli) within the shell, which can be used to estimate age and growth. Thin-sectioning is a common technique for counting annuli, wherein a cross-section of a shell valve is taken and evaluated by multiple readers. Correctly identifying annuli can be challenging because ambiguous annuli can bias growth estimates. Staining with calcein, a fluorescent chemical, is a technique that has been used with marine and freshwater species to improve accuracy of growth estimates. This method chelates calcium, causing a permanent mark that fluoresces under ultraviolet light. Calcein has seen limited testing on unionid mussels so it remains unclear if this method has adverse effects on survival and growth. We evaluated calcein against 2 concentrations (125 mg L -1 and 250 mg L -1 ) at 2 exposure times (12 and 24 h) on Cyclonaias pustulosa, a common North American unionid. Survivorship remained above 80% 6 months post-immersion. Mark quality and retention for 250 mg L -1 were high for both 12- and 24-h immersions, although historical annuli were not highlighted. These findings corroborate studies indicating calcein immersion is generally safe and effective in juveniles and adults and suggest it may be useful in validating new growth., (© 2024. The Author(s).)

Several cross-sectional studies indicated a positive association between school bullying and homicidal ideation during early adolescence. However, few longitudinal studies investigated this association. This study examined whether a bi-directional relationship exists within the longitudinal association between bullying victimization or bullying perpetration and homicidal ideation among early adolescents using a Random Intercept Cross-Lagged Panel Model. A total of 1611 early adolescents (39.5% girls; M age  = 12.50 years, SD = 0.50) were recruited from the Chinese Early Adolescents Cohort study. Data on bullying victimization, bullying perpetration, and homicidal ideation collected during three time points (September 2019, September 2020, and September 2021) were used. Bullying victimization showed a significant positive association with homicidal ideation at the between-person level. Bullying victimization and bullying perpetration had a bi-directional relationship with homicidal ideation at the within-person level. Additionally, this study considered the impact of biological sex-based differences and bullying types on adolescents' homicidal ideation. Based on these findings, school bullying might exhibit unique reciprocal associations with homicidal ideation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Randomized response is an interview technique for sensitive questions designed to eliminate evasive response bias. Since this elimination is only partially successful, two models have been proposed for modeling evasive response bias: the cheater detection model for a design with two sub-samples with different randomization probabilities and the self-protective no sayers model for a design with multiple sensitive questions. This paper shows the correspondence between these models, and introduces models for the new, hybrid "ever/last year" design that account for self-protective no saying and cheating. The model for one set of ever/last year questions has a degree of freedom that can be used for the inclusion of a response bias parameter. Models with multiple degrees of freedom are introduced for extensions of the design with a third randomized response question and a second set of ever/last year questions. The models are illustrated with two surveys on doping use. We conclude with a discussion of the pros and cons of the ever/last year design and its potential for future research., (© 2024. The Author(s).)

Background: The therapeutic benefit of immuno-oncology (IO) therapy for patients with advanced non-clear-cell renal cell carcinoma (nccRCC) remains unclear., Patients and Methods: We reviewed clinical data from 93 patients with advanced nccRCC who received first-line systemic therapy including IO combination therapy and tyrosine kinase inhibitor (TKI) monotherapy at our affiliated institutions. Patients were divided based on the period when the treatment was implemented as the standard of care into the IO and TKI eras. Survival and tumor response outcomes were compared between the IO and TKI eras., Results: Of the 93 patients, 50 (54%) and 43 (46%) were categorized as IO era and TKI era groups, respectively. Progression-free survival (PFS) and overall survival (OS) were significantly longer in the IO era than in the TKI era (median PFS: 8.97 vs. 4.96 months, p = 0.0152; median OS: 38.4 vs. 13.5 months, p = 0.0001). After the adjustment using other covariates, the treatment era was an independent factor for PFS (hazard ratio: 0.59, p = 0.0235) and OS (hazard ratio: 0.27, p < 0.0001). Objective response and disease control rates was not significantly different between the treatment eras (26% vs. 16.3%, p = 0.268; 62% vs. 62.8%, p = 0.594)., Conclusion: The implementation of IO therapy was significantly associated with longer survival in the nccRCC population. Further studies are needed to establish a more effective treatment strategy in this population using multiple regimens of IO combination therapy., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Microphysiological systems (MPSs) reconstitute tissue interfaces and organ functions, presenting a promising alternative to animal models in drug development. However, traditional materials like polydimethylsiloxane (PDMS) often interfere by absorbing hydrophobic molecules, affecting drug testing accuracy. Additive manufacturing, including 3D bioprinting, offers viable solutions. GlioFlow3D, a novel microfluidic platform combining extrusion bioprinting and stereolithography (SLA) is introduced. GlioFlow3D integrates primary human cells and glioblastoma (GBM) lines in hydrogel-based microchannels mimicking vasculature, within an SLA resin framework using cost-effective materials. The study introduces a robust protocol to mitigate SLA resin cytotoxicity. Compared to PDMS, GlioFlow3D demonstrated lower small molecule absorption, which is relevant for accurate testing of small molecules like Temozolomide (TMZ). Computational modeling is used to optimize a pumpless setup simulating interstitial fluid flow dynamics in tissues. Co-culturing GBM with brain endothelial cells in GlioFlow3D showed enhanced CD133 expression and TMZ resistance near vascular interfaces, highlighting spatial drug resistance mechanisms. This PDMS-free platform promises advanced drug testing, improving preclinical research and personalized therapy by elucidating complex GBM drug resistance mechanisms influenced by the tissue microenvironment., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Metabolic dysfunction-associated liver disease (MASLD) and steatohepatitis (MASH) are becoming the most common causes of chronic liver disease in the United States and worldwide due to the obesity and diabetes epidemics. It is estimated that by 2030 close to 100 million people might be affected and patients with type 2 diabetes are especially at high risk. Twenty to 30% of patients with MASLD can progress to MASH, which is characterized by steatosis, necroinflammation, hepatocyte ballooning, and in advanced cases, fibrosis progressing to cirrhosis. Clinically, it is recognized that disease progression in diabetic patients is accelerated and the role of various genetic and epigenetic factors, as well as cell-matrix interactions in fibrosis and stromal remodeling, have recently been recognized. While there has been great progress in drug development and clinical trials for MASLD/MASH, the complexity of these pathways highlights the need to improve diagnosis/early detection and develop more successful antifibrotic therapies that not only prevent but reverse fibrosis., (© 2024 The New York Academy of Sciences.)

Purpose: Comprehensive geriatric assessment (CGA) is the cornerstone of high-quality care for older adults. There is no current gold standard to guide what should be included as the baseline measure for CGAs. We examined what metrics are being captured in CGA baseline assessments completed by community based integrated care teams in Ireland., Methods: CGA's care pathways in Ireland are usually initiated with a written document that establish patients baseline in various assessment areas. These documents were the focus of this study. We completed a cross-sectional study of the components captured in CGA baseline assessments completed in a community setting. We contacted operational leads in each of the community health organisations in Ireland and requested a copy of their current initial baseline screening document for CGA., Results: We reviewed 16 individual CGA baseline documents for analysis in this study. Common assessment areas in all documents included frailty (with the Rockwood Clinical frailty scale used in 94%, n = 15), cognition (4AT-56% of CGAs, MMSE-25%, MOCA-25%, AMTS-19%, AD8-19%, Addenbrookes-13%, 6CIT-13%, mini cog-6%), mobility (100%, n = 16), falls (100%, n = 16), continence (100% n = 16), nutrition (100% n = 16). Mood (94%, n = 15), pain (44%, n = 7), bone health (63%, n = 10), sleep (62%, n = 10) and skin integrity (56%, n = 9). Formal functional assessment was completed in 94% (n = 15) of CGAs with the Barthel index being the tool most used 81% (n = 13). Half of the CGAs included a section describing carer strain (50%, n = 8). The majority of CGAs included a patient centred question which was some variation of 'what matters most to me' (75% n = 11). 87.5% of assessments included a care plan summary (n = 14)., Conclusions: This report highlights that the core tenets of CGA are being assessed across different community based initial CGA screening instruments. There was significant variability in the discussion of challenging topics such as carer strain and social well-being. Our results should prompt a discussion about whether a minimum dataset should be developed for inclusion in nationwide initial baseline CGA document, aiming to improve standardisation of assessments, which will impact areas highlighted for intervention and ultimately guide population health policy., (© 2024. The Author(s).)

In various animal species conspecifics aggregate at sleeping sites. Such aggregations can act as information centres where individuals acquire up-to-date knowledge about their environment. In some species, communal sleeping sites comprise individuals from multiple groups, where each group maintains stable membership over time. We used GPS tracking to simultaneously record group movement in a population of wild vulturine guineafowl (Acryllium vulturinum) to investigate whether communal sleeping sites can facilitate the transfer of information among individuals across distinct groups. These birds live in large and stable groups that move both together and apart, often forming communal roosts containing up to five groups. We first test whether roosts provide the opportunity for individuals to acquire information from members of other groups by examining the spatial organization at roosts. The GPS data reveal that groups intermix, thereby providing an opportunity for individuals to acquire out-group information. We next conduct a field experiment to test whether naïve groups can locate novel food patches when co-roosting with knowledgeable groups. We find that co-roosting substantially increases the chances for the members of a naïve group to discover a patch known to individuals from other groups at the shared roost. Further, we find that the discovery of food patches by naïve groups subsequently shapes their space use and inter-group associations. We also draw on our long-term tracking to provide examples that demonstrate natural cases where communal roosting has preceded large-scale multi-group collective movements that extend into areas beyond the groups' normal ranges. Our findings support the extension of the information centre hypothesis to communal sleeping sites that consist of distinct social groups., (© 2024 The Author(s). Journal of Animal Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Society.)

Currently, there are no methods or tools available in clinical practice for classifying future knee osteoarthritis (KOA). In this study, we aimed to fill this gap by classifying future KOA into three severity grades: KL01 (healthy), KL2 (moderate), and KL34 (severe) based on the Kellgren-Lawrance scale. Due to the complex nature of multiclass classification, we used a two-stage method, which separates the classification task into two binary classifications (KL01 vs. KL234 in the first stage and KL2 vs. KL34 in the second stage). Our machine learning (ML) model used two Balanced Random Forest algorithms and was trained with gender, age, height, weight, and quantitative knee morphology obtained from magnetic resonance imaging. Our training dataset comprised longitudinal 8-year follow-up data of 1213 knees from the Osteoarthritis Initiative. Through extensive experimentation with various feature combinations, we identified KL baseline and weight as the most essential features, while gender surprisingly proved to be one of the least influential feature. Our best classification model generated a weighted F1 score of 79.0% and a balanced accuracy of 65.9%. The area under the receiver operating characteristic curve was 83.0% for healthy (KL01) versus moderate (KL2) or severe (KL34) KOA patients and 86.6% for moderate (KL2) versus severe (KL34) KOA patients. We found a statistically significant difference in performance between our two-stage classification model and the traditional single-stage classification model. These findings demonstrate the encouraging results of our two-stage classification model for multiclass KOA severity classification, suggesting its potential application in clinical settings in future., (© 2024. The Author(s).)

Background: Malnutrition in hospitalized patients is associated increased length of stay, cost, readmission, and death. No recent studies have examined trends in prevalence or outcomes of hospitalized patients with a diagnosis of malnutrition., Objectives: To study the prevalence of malnutrition diagnostic codes and associated hospital outcomes in the United States between 2016 and 2019., Methods: We conducted a retrospective trends study to identify use of malnutrition codes in hospitalizations in the National Inpatient Sample between 2016 and 2019. We used direct standardization by logistic regression to adjust outcomes of percutaneous gastrostomy tube placement, mechanical ventilation, and death for age, Gagne comorbidity score, and sex. We then used linear regression to test for trends over time by malnutrition type., Results: Across all hospitalizations, codes for diagnoses of non-severe malnutrition and severe malnutrition were present in 3.7% and 4.1% of hospitalizations, respectively. Codes for any malnutrition increased over time, from 6.6% in 2016 to 8.6% in 2018 (p = .03). Codes for severe malnutrition increased from 3.3% to 4.7% (p = .01). Among hospitalizations with coded severe malnutrition diagnoses, there was a statistically significant decrease in adjusted rate of death over time (-0.54% per year, p = .03) which was not seen in hospitalizations without coded malnutrition diagnoses., Conclusions: Use of malnutrition diagnosis codes increased significantly from 2016 to 2019. During this time, mortality among hospitalizations with a diagnosis code for severe malnutrition decreased. Though the increased prevalence of malnutrition codes may represent a change in the clinical characteristics of hospitalized patients, the decline in mortality suggests some of the increase may be due to lower threshold for coding and assignment of the diagnosis to less ill patients., (© 2024 The Author(s). Journal of Hospital Medicine published by Wiley Periodicals LLC on behalf of Society of Hospital Medicine.)

Predation is a dominant structuring force in ecological communities. In aquatic environments, predation on bivalves has long been an important focal interaction for ecological study because bivalves have central roles as ecosystem engineers, basal components of food webs, and commercial commodities. Studies of bivalves are common, not only because of bivalves' central roles, but also due to the relative ease of studying predatory effects on this taxonomic group. To understand patterns in the interactions of bivalves and their predators we synthesised data from 52 years of peer-reviewed studies on bivalve predation. Using a systematic search, we compiled 1334 studies from 75 countries, comprising 61 bivalve families (N = 2259), dominated by Mytilidae (29% of bivalves), Veneridae (14%), Ostreidae (8%), Unionidae (7%), and Dreissenidae and Tellinidae (6% each). A total of 2036 predators were studied, with crustaceans the most studied predator group (34% of predators), followed by fishes (24%), molluscs (17%), echinoderms (10%) and birds (6%). The majority of studies (86%) were conducted in marine systems, in part driven by the high commercial value of marine bivalves. Studies in freshwater ecosystems were dominated by non-native bivalves and non-native predator species, which probably reflects the important role of biological invasions affecting freshwater biodiversity. In fact, while 81% of the studied marine bivalve species were native, only 50% of the freshwater species were native to the system. In terms of approach, most studies used predation trials, visual analysis of digested contents and exclusion experiments to assess the effects of predation. These studies reflect that many factors influence bivalve predation depending on the species studied, including (i) species traits (e.g. behaviour, morphology, defence mechanisms), (ii) other biotic interactions (e.g. presence of competitors, parasites or diseases), and (iii) environmental context (e.g. temperature, current velocity, beach exposure, habitat complexity). There is a lack of research on the effects of bivalve predation at the population and community and ecosystem levels (only 7% and 0.5% of studies respectively examined impacts at these levels). At the population level, the available studies demonstrate that predation can decrease bivalve density through consumption or the reduction of recruitment. At the community and ecosystem level, predation can trigger effects that cascade through trophic levels or effects that alter the ecological functions bivalves perform. Given the conservation and commercial importance of many bivalve species, studies of predation should be pursued in the context of global change, particularly climate change, acidification and biological invasions., (© 2024 Cambridge Philosophical Society.)

Novel multihost pathogens can threaten endangered wildlife species, as well as humans and domestic animals. The zoonotic protozoan parasite Toxoplasma gondii is transmitted by members of Felidae and can infect a large number of animal species, including humans. This parasite can have significant health consequences for infected intermediate hosts and could further endanger wild carnivore populations of Madagascar. Building on an empirical characterization of the prevalence of the pathogen in local mammals, we used mathematical models of pathogen transmission in a multihost community to compare preventative measures that aim to limit the spread of this parasite in wild carnivores. Specifically, we examined the effect of hypothetical cat vaccination and population control campaigns on reducing the risk of infection by T. gondii in wild Eupleridae. Our model predicted that the prevalence of exposure to T. gondii in cats would be around 72% and that seroprevalence would reach 2% and 43% in rodents and wild carnivores, respectively. Reducing the rodent population in the landscape by half may only decrease the prevalence of T. gondii in carnivores by 10%. Similarly, cat vaccination and reducing the population of definitive hosts had limited impact on the prevalence of T. gondii in wild carnivorans of Madagascar. A significant reduction in prevalence would require extremely high vaccination, low turnover, or both in the cat population. Other potential control methods of T. gondii in endangered Eupleridae include targeted vaccination of wild animals but would require further investigation. Eliminating the threat entirely will be difficult because of the ubiquity of cats and the persistence of the parasite in the environment., (© 2024 The Authors. Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)

Thalidomide is a known teratogen that causes malformations especially in heart and limbs. Its mechanism of teratogenicity is still not fully elucidated. Recently, a new target of thalidomide was described, TBX5, and was observed a new interaction between HAND2 and TBX5 that is disrupted in the presence of thalidomide. Therefore, our study aimed to raise potential candidates for thalidomide teratogenesis, through systems biology, evaluating HAND2 and TBX5 interaction and heart and limbs malformations of thalidomide. Genes and proteins related to TBX5 and HAND2 were selected through TF2DNA, REACTOME, Human Phenotype Ontology, and InterPro databases. Networks were assembled using STRING © database. Network analysis were performed in Cytoscape © and R v3.6.2. Differential gene expression (DGE) analysis was performed through gene expression omnibus. We constructed a network for HAND2 and TBX5 interaction; a network for heart and limbs malformations of TE; and the two joined networks. We observed that EP300 protein seemed to be important in all networks. We also looked for proteins containing C2H2 domain in the assembled networks. ZIC3, GLI1, GLI3, ZNF148, and PRDM16 were the ones present in both heart and limbs malformations of TE networks. Furthermore, in the DGE analysis after treatment with thalidomide, we observed that FANCB, ESCO2, and XRCC2 were downregulated and present both in heart and limbs networks. Through systems biology, we were able to point to different new proteins and genes, and selected specially EP300, which was important in all the analyzed networks, to be further evaluated in the TE teratogenicity., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Despite evidence indicating a connection between inappropriate parenting styles and peer victimization, the dynamic processes and mechanisms underlying this link and whether it is consistent across genders and different developmental stages have yet to be explored. To address these gaps, the current 2-year longitudinal study explored the potential bidirectional associations between parental psychological control and peer victimization, as well as the mediating role of adolescent basic psychological need satisfaction. A total of 4,990 adolescents (49.4% boys, M age T1  = 12.21 years, SD age T1  = 2.60) across different developmental stages (early adolescents, N = 1,819, 49.2% boys, M age T1  = 9.34 years, SD age T1  = 0.62; middle adolescents, N = 1,525, 50.75% boys, M age T1  = 12.47 years, SD age T1  = 0.69; late adolescents, N = 1,646, 46.5% boys, M age T1  = 15.26 years, SD age T1  = 0.50) participated in this three-wave longitudinal survey. The results revealed that parental psychological control was bidirectionally associated with peer victimization. Additionally, basic psychological need satisfaction played the meditating role in this vicious cycle. Further analysis demonstrated interesting developmental differences. Parental psychological control was directly associated with subsequent peer victimization at all three developmental stages, and peer victimization was only directly associated with subsequent parental psychological control in the next year among early adolescents and middle adolescents. The mutual mediating role of basic psychological need satisfaction between parental psychological control and peer victimization was observed exclusively in early adolescents. Both male and female adolescents could be equally affected by these dynamics. This research underscores the reciprocal dynamics inherent in parent-child interactions, intervening in either of these processes (i.e., family, peers, and adolescent basic psychological need satisfaction) may break this destructive cycle., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Maternal experiences before pregnancy predict birth outcomes, a key indicator of health trajectories, but the timing and pathways for these effects are poorly understood. Here we test the hypothesis that maternal pre-adult growth patterns predict pregnancy glucose and offspring fetal growth in Cebu, Philippines., Methods: Using multiple regression and path analysis, gestational age-adjusted birthweight and variables reflecting infancy, childhood, and post-childhood/adolescent weight gain (conditional weights) were used to predict pregnancy HbA1c and offspring birth outcomes among participants in the Cebu Longitudinal Health and Nutrition Survey., Results: Maternal early/mid-childhood weight gain predicted birth weight, length, and head circumference in female offspring. Late-childhood/adolescent weight gain predicted birth length, birth weight, skinfold thickness, and head circumference in female offspring, and head circumference in male offspring. Pregnancy HbA1c did not mediate relationships between maternal growth and birth size parameters., Discussion: In Cebu, maternal growth patterns throughout infancy, childhood, and adolescence predict fetal growth via a pathway independent of circulating glucose, with stronger impacts on female than male offspring, consistent with a role of developmental nutrition on offspring fetal growth. Notably, the strength of relationships followed a pattern opposite to what occurs in response to acute pregnancy stress, with strongest effects on head circumference and birth length and weakest on skinfolds. We speculate that developmental sensitivities are reversed for stable, long-term nutritional cues that reflect average local environments. These findings are relevant to public health and life-history theory as further evidence of developmental influences on health and resource allocation across the life course., (© 2023 The Authors. American Journal of Biological Anthropology published by Wiley Periodicals LLC.)

The aging global population poses significant medical and social challenges, necessitating efforts to promote healthy aging. Comprehensive Geriatric Assessment (CGA) is a multidimensional diagnostic approach for older adults that aims to improve overall health. Remote CGA, facilitated by technological advancements, offers convenience and other potential advantages. It enables early disease detection, monitors chronic disease progression, delivers personalized care, and optimizes healthcare resources for better health outcomes in older individuals. However, remote CGA also has limitations, including technological requirements, data security, and the need for comprehensive evaluation and simplicity. Collaborative efforts are essential to developing a digital home-based CGA platform that addresses accessibility issues and tailors the assessment process to meet the needs of older adults. Continuous optimization of remote CGA can become a pivotal tool for advancing geriatric care and ensuring the well-being of the aging population. Geriatr Gerontol Int 2024; 24: 67-73., (© 2023 Japan Geriatrics Society.)

Aims: To identify the challenges and opportunities among primary health care nurses and general practitioners (GPs) in the care of older people with urinary incontinence (UI) and other chronic conditions in China., Background: UI is highly prevalent among community-dwelling older people with chronic conditions but is underreported and poorly managed. Understanding the factors that affect primary health care professionals' practices in their care for this population is imperative to foster nurse-led UI care services., Design: A qualitative descriptive study., Methods: Four focus groups were held with 24 primary health care nurses and GPs in Changsha, Hunan Province, China, between July and September 2021. A reflective thematic analysis was used to identify themes., Results: This study revealed misconceptions regarding older people living with UI and other chronic conditions in primary care health professional participants. Moreover, primary health care nurses had very limited autonomy in UI diagnosis and initiating care interventions for this patient population. By reflecting on practices, participants recognized various practical solutions to improve the detection and management of UI. Participants also identified barriers to accessing care services in older people with UI. They suggested changes in the health care system to achieve universal access to UI care services for older people., Conclusion: Nurse-led UI care services in primary health care for community-dwelling older people with chronic conditions are in high demand but are underdeveloped due to professional and health care system factors., Impact: Findings from this study provide new insights into challenges faced by primary health care professionals and illuminate practical solutions to address these challenges., Reporting Methods: Adherence to COREQ guidelines was maintained., Patient or Public Contribution: No patient or public contribution., (© 2023 The Authors. Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

Although a large amount of data consistently shows that genes affect immunometabolic characteristics and outcomes, epigenetic mechanisms are also heavily implicated. Epigenetic changes, including DNA methylation, histone modification, and noncoding RNA, determine gene activity by altering the accessibility of chromatin to transcription factors. Various factors influence these alterations, including genetics, lifestyle, and environmental cues. Moreover, acquired epigenetic signals can be transmitted across generations, thus contributing to early disease traits in the offspring. A closer investigation is critical in this aspect as it can help to understand the underlying molecular mechanisms further and gain insights into potential therapeutic targets for preventing and treating diseases arising from immuno-metabolic dysregulation. In this review, the role of chromatin alterations in the transcriptional modulation of genes involved in insulin resistance, systemic inflammation, macrophage polarization, endothelial dysfunction, metabolic cardiomyopathy, and nonalcoholic fatty liver disease (NAFLD), is discussed. An overview of emerging chromatin-modifying drugs and the importance of the individual epigenetic profile for personalized therapeutic approaches in patients with immuno-metabolic disorders is also presented., (© 2023 The Authors. Advanced Biology published by Wiley-VCH GmbH.)

Introduction: The CD34 + CD38 - population in bone marrow includes hematopoietic stem/progenitor cells. Recently, in acute myeloid leukemia, the focus has shifted to flow cytometry analysis targeting CD34 + CD38 - leukemic cells due to their effectiveness in minimal/measurable residual disease detection and prognosis prediction. Nevertheless, the immunophenotype and cell frequency of these cells in the bone marrow, in the absence of leukemic cells, remains unknown. We aimed to evaluate detailed characteristics of CD34 + CD38 - cells in both normal and leukemic cells by flow cytometry., Methods: We compared the cell frequency and immunophenotype of the CD34 + CD38 - fraction in the following groups: patients with idiopathic thrombocytopenic purpura and malignant lymphoma as controls (n = 17), post-treatment patients without abnormal blasts (n = 35), and patients with myeloid malignancies (n = 86). The comparison was based on the presence or absence of CD45RA expression, a marker commonly used to prospectively isolate lymphoid-primed cell populations within the CD34 + CD38 - fraction., Results: The CD34 + CD38 - CD45RA + cell population exhibited a significant expansion in bone marrow without leukemic cells 1 month after cord blood transplantation and in various type of myeloid malignancies, compared to the control group (p < 0.01). Continuous CD45RA expression and notable expansion of the CD34 + CD38 - CD45RA - population were exclusively observed in myelodysplastic syndrome-related diseases. The CD34 + CD38 - CD45RA + population displayed frequent expression of various markers in both leukemic and non-leukemic cells, in contrast to the CD34 + CD38 - CD45RA - population., Conclusions: The CD34 + CD38 - fraction should be carefully evaluated considering the nature of normal hematopoietic precursor cells, their cell frequency and immunophenotype, including CD45RA expression pattern, for improving the accuracy of myeloid malignancy diagnosis., (© 2023 International Clinical Cytometry Society.)

Seagrass is an important natural attribute of 28 World Heritage (WH) properties. These WH seagrass habitats provide a wide range of services to adjacent ecosystems and human communities, and are one of the largest natural carbon sinks on the planet. Climate change is considered the greatest and fastest-growing threat to natural WH properties and evidence of climate-related impacts on seagrass habitats has been growing. The main objective of this study was to assess the vulnerability of WH seagrass habitats to location-specific key climate stressors. Quantitative surveys of seagrass experts and site managers were used to assess exposure, sensitivity and adaptive capacity of WH seagrass habitats to climate stressors, following the Climate Vulnerability Index approach. Over half of WH seagrass habitats have high vulnerability to climate change, mainly from the long-term increase in sea-surface temperature and short-term marine heatwaves. Potential impacts from climate change and certainty scores associated with them were higher than reported by a similar survey-based study from 10 years prior, indicating a shift in stakeholder perspectives during the past decade. Additionally, seagrass experts' opinions on the cumulative impacts of climate and direct-anthropogenic stressors revealed that high temperature in combination with high suspended sediments, eutrophication and hypoxia is likely to provoke a synergistic cumulative (negative) impact (p < .05). A key component contributing to the high vulnerability assessments was the low adaptive capacity; however, discrepancies between adaptive capacity scores and qualitative responses suggest that managers of WH seagrass habitats might not be adequately equipped to respond to climate change impacts. This thematic assessment provides valuable information to help prioritize conservation actions, monitoring activities and research in WH seagrass habitats. It also demonstrates the utility of a systematic framework to evaluate the vulnerability of thematic groups of protected areas that share a specific attribute., (© 2023 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

In recent decades, microphysiological constructs and systems (MPCs and MPSs) have undergone significant development, ranging from self-organized organoids to high-throughput organ-on-a-chip platforms. Advances in biomaterials, bioinks, 3D bioprinting, micro/nanofabrication, and sensor technologies have contributed to diverse and innovative biofabrication tactics. MPCs and MPSs, particularly tissue chips relevant to absorption, distribution, metabolism, excretion, and toxicity, have demonstrated potential as precise, efficient, and economical alternatives to animal models for drug discovery and personalized medicine. However, current approaches mainly focus on the in vitro recapitulation of the human anatomical structure and physiological-biochemical indices at a single or a few simple levels. This review highlights the recent remarkable progress in MPC and MPS models and their applications. The challenges that must be addressed to assess the reliability, quantify the techniques, and utilize the fidelity of the models are also discussed., (© 2023 The Authors. Small Methods published by Wiley-VCH GmbH.)

Among the significant advances in the understanding of the organization of the neuronal networks that coordinate the body and brain, their complex nature is increasingly important, resulting from the interaction between the very large number of constituents strongly organized hierarchically and at the same time with "self-emerging." This awareness drives us to identify the measures that best quantify the "complexity" that accompanies the continuous evolutionary dynamics of the brain. In this chapter, after an introductory section (Sect. 15.1), we examine how the Higuchi fractal dimension is able to perceive physiological processes (15.2), neurological (15.3) and psychiatric (15.4) disorders, and neuromodulation effects (15.5), giving a mention of other methods of measuring neuronal electrical activity in addition to electroencephalography, such as magnetoencephalography and functional magnetic resonance. Conscious that further progress will support a deeper understanding of the temporal course of neuronal activity because of continuous interaction with the environment, we conclude confident that the fractal dimension has begun to uncover important features of the physiology of brain activity and its alterations., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Protein degradation is a general process to maintain cell homeostasis. The intracellular protein quality control system mainly includes the ubiquitin-proteasome system and the lysosome pathway. Inspired by the physiological process, strategies to degrade specific proteins have developed, which emerge as potent and effective tools in biological research and drug discovery. This review focuses on recent advances in targeted protein degradation techniques, summarizing the principles, advantages, and challenges. Moreover, the potential applications and future direction in biological science and clinics are also discussed., (© 2023 Wiley-VCH GmbH.)

Objectives: Age at menarche is a marker of pubertal timing that may influence adult height and body proportions. Previous studies have shown that socioeconomic status can affect age at menarche and growth patterns in different populations. This study aims to examine the associations between age at menarche, socioeconomic status, height, and leg length in a sample of Igbo ethnicity., Methods: The study used data from questionnaires and anthropometric measurements of 300 female students aged 18-25 years. Study tested the hypotheses that earlier menarche is associated with shorter stature and shorter leg length, and that these associations are modified by socioeconomic status using nonparametric analysis., Results: Mean age at menarche was fluctuating around 12.84 ± 1.40 and 13.59 ± 1.41 years with school girls and grew 3.0 cm taller per year birth cohort. The study also found that girls with earlier menarche were shorter adult height (162.51 ± 6.00) compared with girls who have menarche at a later age. The linear regression coefficients (bs) ranged from 0.37-0.49 in later year birth cohort and 0.37-0.44 in early year birth cohort for height. The effect of age at menarche on leg length was similar to the relation between age at menarche and birth cohort height., Conclusion: The study will contribute to the understanding of how pubertal timing and socioeconomic status interact to shape adult health outcomes in a transitioning population., (© 2023 Wiley Periodicals LLC.)

Background: We used data from a prospective cohort to explore 2-year trajectories of 'long COVID' (persistent symptoms after SARS-CoV-2 infection) and their association with illness perception., Methods: RECoVERED participants (adults; prospectively enrolled following laboratory-confirmed SARS-CoV-2 infection, May 2020-June 2021) completed symptom questionnaires at months 2-12, 18 and 24, and the Brief Illness Perception Questionnaire (B-IPQ) at months 1, 6 and 12. Using group-based trajectory models (GBTM), we modelled symptoms (mean total numbers and proportion with four specific complaints), including age, sex, BMI and timing of infection as covariates. In a multivariable linear mixed-effects model, we assessed the association between symptom trajectories and repeated B-IPQ scores., Results: Among 292 participants (42% female; median age 51 [IQR = 36-62]), four trajectories were identified, ranging from Trajectory 4 (8.9%; 6 + symptoms) to Trajectory 1 (24.8%; no symptoms). The occurrence of fatigue and myalgia increased among 23% and 12% of participants, respectively. Individuals in Trajectory 4 experienced more negative adjusted B-IPQ scores over time than those in Trajectories 1-3., Conclusions: We observed little fluctuation in the total number of symptoms, but individual symptoms may develop as others resolve. Reporting a greater number of symptoms was congruent with more negative illness perception over time., Competing Interests: The authors have no relevant conflicts of interests to declare., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Embryo implantation is a complex and highly coordinated process that involves an intricate network of factors establishing intimate contact at the maternal-fetal interface. Knowledge of the human implantation process is compromised by both ethical issues, which do not allow the study of this process in vivo, and by the accuracy and reproducibility of in vitro models of human endometrium. Effective and reliable embryo implantation models are, therefore, necessary to mimic the molecular event cascade that occurs in vivo. 3D models are considered a new step to foster precision medicine and an advanced tool for the study of endometrial biology, endometrium associated diseases and to understand the complex mechanisms surrounding endometrium-embryo crosstalk. In this review we explore the various methods by which 3D cultures of endometrium and trophoblast can be created, exploring targets and applications of these in vitro models., (©The Author(s) 2023. Open Access. This article is licensed under a Creative Commons CC-BY International License.)

Background and Rationale: Comprehensive care and service planning in home care is tailored to older people's individual needs and resources in order to support them living at home. However, little is known about how these individual resources and home-care-specific tasks are recognised in older people's care and service plans., Aims: To describe the content of care and service plans in older people's home care with special attention to their individual resources and home-care-specific tasks., Design: This was a document-based cross-sectional study with mixed-methods analysis, carried out in Eastern Finland during Spring 2018., Methods: A document analysis using the deductive Finnish Care Classification (FinCC), and an inductively developed framework of older people's care and service plans (n = 71). The data were analysed with descriptive statistical methods., Results: Altogether, 1718 notes were relevant to the FinCC main categories: 707 (41%) focused on older people's needs and 1011 (59%) on nursing interventions. We identified 1104 notes based on the 26 inductively developed main categories: the majority (n = 628, 57%) focused on individual resources and the remainder (n = 476, 43%) on home-care-specific tasks. Increasing age resulted in fewer notes on safety and sensory functions. There were fewer notes on resources related to sleeping and wakefulness after longer care and service periods. An increased number of home visits resulted in more documentation on tasks related to pharmaceutical issues, including repeat prescriptions., Discussion: Individual resources for older people were documented, to some extent, in their care and service plans. It is necessary to review these alongside home-care-specific tasks that support older people's independence and safety at home., Conclusion: Individual resources need to be recognised in order to enable home-care professionals to provide tailored, high-quality home care services. Home-care-specific tasks should be supported by documentation with updated, sensitive home care classifications., (© 2022 The Authors. Scandinavian Journal of Caring Sciences published by John Wiley & Sons Ltd on behalf of Nordic College of Caring Science.)

Adolescent motherhood has been linked with poor health outcomes at birth for children, including high neonatal mortality, low birthweight, and small-for-gestational-age rates. However, longer-term growth outcomes in the children of adolescent mothers in low-resource settings remain inadequately studied. We used longitudinal data from the India Human Development Surveys, 2004-2005 and 2011-2012 (n = 12,182) and employed regression and propensity score matching analysis to compare the following growth indicators of children born to adolescent mothers (ages 19 years or below) with those born to older mothers. Growth indicators included height and weight during ages 0-5 years and 6-12 years and change in height and weight between the two periods. In regression-based estimates, children born to adolescent mothers were 0.01 m shorter and weighed 0.2 kg less than children of older mothers at ages 0-5 years. At ages 6-12 years, those born to adolescent mothers were 0.02 m shorter and weighed 0.97 kg less. The height difference between the two groups increased by 0.01 m and the weight difference grew by 0.77 kg over time. Height and weight difference between the two groups worsened among boys over time, while for girls, only the weight gap worsened. The results were similar when using propensity score matching methods. Public policies for reducing child marriage, combined with targeted health, nutrition, and well-being programs for adolescent mothers, are essential for both preventing adolescent childbearing and reducing its impact on growth failure among children in India., (© 2023 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of New York Academy of Sciences.)

This study investigated the effect of butanol extract of AS (ASBUE) on atherosclerosis in apolipoprotein E-deficient (ApoE -/-) mice. The mice were administered ASBUE (390 or 130 mg/kg/day) or rosuvastatin (RSV) via oral gavage for eight weeks. In ApoE -/- mice, ASBUE suppressed the abnormal body weight gain and improved serum and liver biochemical indicators. ASBUE remarkably reduced the aortic plaque area, improved liver pathological conditions, and lipid metabolism abnormalities, and altered the intestinal microbiota structure in ApoE -/- mice. In the vascular tissue of ASBUE-treated mice, P-IKKβ, P-NFκB, and P-IκBα levels tended to decrease, while IκB-α increased in high fat-diet-fed atherosclerotic mice. These findings demonstrated the anti-atherosclerotic potential of ASBUE, which is mediated by the interaction between the gut microbiota and lipid metabolism and regulated via the Nuclear Factor-kappa B (NF-κB) pathway. This work paves the groundwork for subsequent studies to develop innovative drugs to treat atherosclerosis., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Background: Clinical trials have demonstrated the superior efficacy of immune checkpoint inhibitor (ICI)-based combination therapy over sunitinib, a multi-target tyrosine kinase inhibitor (TKI), in patients with advanced renal cell carcinoma. However, such benefits have not been elucidated in populations outside of clinical trials., Methods: We retrospectively evaluated data from 467 patients with advanced renal cell carcinoma who received ICI-based combination therapy or TKIs, as first-line therapy. Clinical outcome was compared between ICI-based combination therapy and TKIs in each population divided according to trial eligibility., Results: Among 152 patients treated with ICI-based combination therapy and 315 patients treated with TKIs, 76 (50.0%) and 156 (49.5%) were trial ineligible, respectively. Overall survival (p = 0.0072) and objective response rate (p < 0.0001) were significantly higher in ICI-based combination therapy than in TKIs, but progression-free survival was comparable (p = 0.681). In the trial-eligible population, overall survival was longer (p = 0.0906) and the objective response rate was significantly higher (p = 0.0124) in ICI-based combination therapy than in TKIs. In the trial-ineligible population, overall survival (p = 0.0208) and objective response rate (p = 0.0006) were significantly higher with ICI-based combination therapy than with TKIs. A multivariate analysis also showed that ICI-based combination therapy was independently associated with prolonged overall survival (hazard ratio, 0.47; p = 0.0016). Regardless of trial eligibility, progression-free survival did not differ between ICI-based combination therapy and TKIs (trial eligible: p = 0.287; trial ineligible: p = 0.0708)., Conclusions: The present study, using real-world data, provides evidence indicating the therapeutic benefit of ICI-based combination therapy over TKIs for advanced renal cell carcinoma was more statistically significant in the trial-ineligible population than in the trial-eligible population., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

As an integral part of autism spectrum symptoms, sensory processing issues including both hypo and hyper sensory sensitivities. These sensory specificities may result from an excitation/inhibition imbalance with a poorly understood of their level of convergence with genetic alterations in GABA-ergic and glutamatergic pathways. In our study, we aimed to characterize the hypo/hyper-sensory profile among autistic individuals. We then explored its link with the burden of deleterious mutations in a subset of individuals with available whole-genome sequencing data. To characterize the hypo/hyper-sensory profile, the differential Short Sensory Profile (dSSP) was defined as a normalized and centralized hypo/hypersensitivity ratio from the Short Sensory Profile (SSP). Including 1136 participants (533 autistic individuals, 210 first-degree relatives, and 267 controls) from two independent study samples (PARIS and LEAP), we observed a statistically significant dSSP mean difference between autistic individuals and controls, driven mostly by a high dSSP variability, with an intermediated profile represented by relatives. Our genetic analysis tended to associate the dSSP and the hyposensitivity with mutations of the GABAergic pathway. The major limitation was the dSSP difficulty to discriminate subjects with a similar quantum of hypo- and hyper-sensory symptoms to those with no such symptoms, resulting both in a similar ratio score of 0. However, the dSSP could be a relevant clinical score, and combined with additional sensory descriptions, genetics and endophenotypic substrates, will improve the exploration of the underlying neurobiological mechanisms of sensory processing differences in autism spectrum., (© 2022 International Society for Autism Research and Wiley Periodicals LLC.)

Higher access to medical care, advanced diagnostic tools, and overall public health improvements have favored increased humans lifespan. With a growing proportion of older adults, the associated costs to care for ageing-associated conditions will continue to grow. This chapter highlights recent cellular and clinical evidence of platelets at an older age, from the hyperreactive phenotype associated with thrombosis to the well-known hallmarks of ageing identifiable in platelets and their potential functional implications on platelets at an older age. Therefore, it is imperative to understand platelets' molecular and cellular mechanisms during ageing in health and disease. New knowledge will favor the development of new ways to prevent some of the age-associated complications where platelets are key players., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Cannabinoid receptor 1 (CB 1 R) and cannabinoid receptor 2 (CB 2 R) are G protein-coupled receptors (GPCRs) that activate a variety of pathways upon activation by (partial) agonists including the G protein pathway and the recruitment of β-arrestins. Differences in the activation level of these pathways lead to biased signaling. Here, we describe a detailed protocol to characterize the potency and efficacy of ligands to induce or inhibit β-arrestin recruitment to the human CB 1 R and CB 2 R using the PathHunter ® assay. This is a cellular assay that uses a β-galactosidase complementation system which has a chemiluminescent read-out and can be performed in 384-well plates. We have successfully used this assay to characterize a set of reference ligands (both agonists, antagonists, and an inverse agonist) on human CB 1 R and CB 2 R, of which some examples will be presented here., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Environmental variability poses a range of challenges to foraging animals trying to meet their energetic needs. Where food patches are unpredictable but shareable, animals can use social information to locate patches more efficiently or reliably. However, resource unpredictability can be heterogeneous and complex. The behavioural strategies animals employ to exploit such resources also vary, particularly if, when, and where animals use available social information. We reviewed the literature on social information use by foraging animals and developed a novel framework that integrates four elements - (1) food resource persistence; (2) the relative value of social information use; (3) behavioural context (opportunistic or coordinated); and (4) location of social information use - to predict and characterize four strategies of social information use - (1) local enhancement; (2) group facilitation; (3) following; and (4) recruitment. We validated our framework by systematically reviewing the growing empirical literature on social foraging in bats, an ideal model taxon because they exhibit extreme diversity in ecological niche and experience low predation risk while foraging but function at high energy expenditures, which selects for efficient foraging behaviours. Our framework's predictions agreed with the observed natural behaviour of bats and identified key knowledge gaps for future studies. Recent advancements in technology, methods, and analysis will facilitate additional studies in bats and other taxa to further test the framework and our conception of the ecological and evolutionary forces driving social information use. Understanding the links between food distribution, social information use, and foraging behaviour will help elucidate social interactions, group structure, and the evolution of sociality for species across the animal kingdom., (© 2022 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.)

Objectives: To present an empirical description of the association between height and lifetime fertility in women from low- and middle-income countries, allowing for flexible functional relationships., Methods: A pooled sample (N = 846 257) of women ages 35-49 in Demographic and Health Surveys (DHS) from 64 countries, with regional samples for Latin America, South Asia, and sub-Saharan Africa. Flexibly-estimated structured additive regression models estimate variations in the height-fertility relationship over the height distribution., Results: Across samples, height is shown to have nonlinear relationships with number of children ever born and age at first birth. Number of children increases with height until a maximum below average height, after which the number of children decreases. Age at first marriage decreases with height until a minimum below average height, and then increases. Except at the shortest heights, much of the variation in fertility is suggested to reflect socioeconomic differences across heights. At the shortest heights, variation is suggested to reflect later ages at first birth, except for women in sub-Saharan Africa., Conclusion: A nonlinear relationship is indicated between height and fertility. Much of the relationship is suggested to reflect height-variations in socioeconomic status and age at first birth., (© 2022 Wiley Periodicals LLC.)

Background: Currently, there is limited evidence about the long-term impact on physical, social and emotional functioning, i.e. health-related quality of life (HRQL) after mild or moderate COVID-19 not requiring hospitalization. We compared HRQL among persons with initial mild, moderate or severe/critical COVID-19 at 1 and 12 months following illness onset with Dutch population norms and investigated the impact of restrictive public health control measures on HRQL., Methods: RECoVERED, a prospective cohort study in Amsterdam, the Netherlands, enrolled adult participants after confirmed SARS-CoV-2 diagnosis. HRQL was assessed with the Medical Outcomes Study Short Form 36-item health survey (SF-36). SF-36 scores were converted to standard scores based on an age- and sex-matched representative reference sample of the Dutch population. Differences in HRQL over time were compared among persons with initial mild, moderate or severe/critical COVID-19 using mixed linear models adjusted for potential confounders., Results: By December 2021, 349 persons were enrolled of whom 269 completed at least one SF-36 form (77%). One month after illness onset, HRQL was significantly below population norms on all SF-36 domains except general health and bodily pain among persons with mild COVID-19. After 12 months, persons with mild COVID-19 had HRQL within population norms, whereas persons with moderate or severe/critical COVID-19 had HRQL below population norms on more than half of the SF-36 domains. Dutch-origin participants had significantly better HRQL than participants with a migration background. Participants with three or more COVID-19 high-risk comorbidities had worse HRQL than part participants with fewer comorbidities. Participants who completed the SF-36 when restrictive public health control measures applied reported less limitations in social and physical functioning and less impaired mental health than participants who completed the SF-36 when no restrictive measures applied., Conclusions: Twelve months after illness onset, persons with initial mild COVID-19 had HRQL within population norms, whereas persons with initial moderate or severe/critical COVID-19 still had impaired HRQL. Having a migration background and a higher number of COVID-19 high-risk comorbidities were associated with worse HRQL. Interestingly, HRQL was less impaired during periods when restrictive public health control measures were in place compared to periods without., (© 2022. The Author(s).)

Yeast mannoproteins are proposed as a paraprobiotics with antimicrobial and prebiotic properties. They can be used as biopreservatives in food and in diseases therapies. The knowledge about the specificity and/or capability of their influence on the growth of different microorganism is limited. The study determined the effect of mannoprotein preparations of Saccharomyces cerevisiae (S. cerevisiae) ATCC 7090 and nonconventional yeast origin [Metschnikowia reukaufii (M. reukaufii) WLP 4650 and Wickerhamomyces anomalus (W. anomalus) CCY 38-1-13] on the growth of selected bacteria of the genera: Lactobacilllus, Limosilatobacillus, Limosilatobacillus, Bifidobacterium, Staphylococcus, Enterococcus, Pseudomonas, Escherichia, Proteus and Salmonella. The degree of stimulation or growth inhibition of tested bacteria depended on the type and dose of the mannoprotein and the bacterial strain. The addition of the tested preparations in the entire range of applied concentrations had a positive effect especially on the growth of Lactobacillus arabinosus ATCC 8014 and Bifidobacterium animalis subsp. lactis B12. Mannoproteins isolated from S. cerevisiae limited the growth of the Escherichia coli (E. coli) ATCC 25922, Pseudomonas aureoginosa (P. aureoginosa) ATCC 27853, Proteus mirabilis ATCC 35659 and Salmonella Enteritidis ATCC 13076 to the greatest extent, while preparations of M. reukaufii and W. anomalus origin most effectively limited the growth of Staphylococcus aureus strains, E. coli and P. aureoginosa. The growth of Enterococcus faecalis was stimulated by the presence of all studied preparations in most of the concentrations used. Further research will determine how the purification process of studied mannoproteins or oligosaccharide fractions, its structure and composition influence on the growth of selected bacteria and what is the mechanism of its activity., (© 2022. The Author(s).)

This exploratory cross-sectional study aimed to examine the family quality of life (FQoL) among 51 Brazilian families who have children with Rubinstein-Taybi syndrome, a rare genetic disorder. Data were collected using sociodemographic and clinical data forms, as well as the Beach Center FQoL Scale, a 5-point Likert scale ranging from "very dissatisfied" (1) to "very satisfied" (5). The average score of the overall FQoL was 3.93 ± 0.64. Families' scores were higher for family interaction (4.17 ± 0.76), parenting (4.13 ± 0.61), and disability-related support (4.08 ± 0.76) domains, and lower for the family's emotional well-being (3.31 ± 0.96) and physical/material well-being (3.76 ± 0.82) domains. Family income, attendance at religious services, presence of ocular abnormalities, and aggressive behavior explained 46.2% of the variance in the overall FQoL. In summary, FQoL seems to be anchored in aspects such as family interaction and the care of parents, and be negatively affected by emotional issues, physical, and material limitations. In this context, psychological assistance should be provided to both parents and siblings whenever indicated, for improving emotional well-being and increasing family resilience. Additionally, investments in social policies, services, and human and material resources are needed to improve the physical and material conditions of families, promote better health care, and therefore reduce the family burden., (© 2022 Wiley Periodicals LLC.)

Zostera marina (seagrass) is a coastal marine angiosperm that sustains a diverse and productive ecosystem. Seagrass-associated microbiota support host health, yet the ecological processes that maintain biodiversity and stability of the seagrass leaf microbiota are poorly understood. We tested two hypotheses: (1) Microbes select seagrass leaves as habitat such that they consistently host distinct microbiota and/or core taxa in comparison to nearby substrates, and (2) seagrass leaf microbiota are stable once established and are resistant to change when transplanted to a novel environment. We reciprocally transplanted replicate seagrass shoots (natural and surface sterilized/dead tissue treatments) among four meadows with different environmental conditions and deployed artificial seagrass treatments in all four meadows. At the end of the 5-day experiment, the established microbiota on natural seagrass partially turned over to resemble microbial communities in the novel meadow, and all experimental treatments hosted distinct surface microbiota. We consistently found that natural and sterilized/dead seagrass hosted more methanol-utilizing bacteria compared to artificial seagrass and water, suggesting that seagrass core microbiota are shaped by taxa that metabolize seagrass exudates coupled with minor roles for host microbial defence and/or host-directed recruitment. We found evidence that the local environment strongly influenced the seagrass leaf microbiota in natural meadows and that transplant location explained more variation than experimental treatment. Transplanting resulted in high turnover and variability of the seagrass leaf microbiota, suggesting that it is flexibly assembled in a wide array of environmental conditions which may contribute to resilience of seagrass in future climate change scenarios., (© 2022 John Wiley & Sons Ltd.)

Hemorrhage events occur most frequently in anticoagulant therapy for non-valvular atrial fibrillation (NVAF). Rivaroxaban is used widely for routine anticoagulation care. Genetic polymorphisms are thought to contribute to the wide intraindividual variability seen in rivaroxaban metabolism and the anticoagulant response. The aim of this study was to evaluate the effect of drug transport related single-nucleotide polymorphisms (SNPs) on rivaroxaban metabolism and on the risk of a hemorrhage event. A total of 216 Chinese patients with NVAF were enrolled in the study. Rivaroxaban was used for anticoagulation therapy. Rivaroxaban plasma concentrations were detected using a validated ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Seven SNPs in four genes were genotyped using the Sanger dideoxy DNA sequencing method. Associations between genotype variants, the incidence of hemorrhage events, and the time of bleeding were analyzed. ABCB1 2677G (rs2032582) variation was highly associated with the dose-adjusted rivaroxaban peak concentration in plasma (C max /D) (p = 0.025, FDR = 0.042). The ABCB1 G allele carriers had a higher rivaroxaban C max /D than non-carriers. Logistic regression showed that rivaroxaban C max /D and ABCB1 genotype variants were associated with a higher incidence of hemorrhage events. No statistically significant difference was found between ABCB1 genotypes and the time of bleeding after anticoagulant therapy in 30 days. These results indicated that ABCB1 2677G (rs2032582) genetic variant affects the rivaroxaban C max /Dose and the incidence of hemorrhage events significantly., (© 2022 John Wiley & Sons Ltd.)

Background: The study aimed to evaluate the feasibility of using a comprehensive geriatric assessment (CGA) in a residential transition care setting to measure older adults' functional outcomes., Methods: A convenience sample of older adults (n = 10) and staff (n = 4) was recruited. The feasibility of using assessment tools that comprise a CGA to comprehensively measure function in physical, cognitive, social and emotional domains was evaluated pre- and post-rehabilitation., Results: 10 older adults (mean ± SD age = 78.9 ± 9.1, n = 6 male) completed a CGA performed using assessments across physical, cognitive, social and emotional domains. The CGA took 55.9 ± 7.3 min to complete. Staff found CGA using the selected assessment tools to be acceptable and suitable for the transition care population. Older adults found the procedure to be timely and 60% found the assessments easy to comprehend. Participating in CGA also assisted older adults in understanding their present state of health. The older adults demonstrated improvements across all assessed domains including functional mobility (de Morton Mobility Index; baseline 41.5 ± 23.0, discharge 55.0 ± 24.0, p = 0.01) and quality of life (EQ-5D-5L; baseline 59.0 ± 21.7, discharge 78.0 ± 16.0, p < 0.01)., Conclusions: Incorporating CGA to evaluate functional outcomes in transition care using a suite of assessment tools was feasible and enabled a holistic assessment., (© 2022. The Author(s).)

TRPM3 encodes a transient receptor potential cation channel of the melastatin family, expressed in the central nervous system and in peripheral sensory neurons of the dorsal root ganglia. The recurrent substitution in TRPM3: c.2509G>A, p.(Val837Met) has been associated with syndromic intellectual disability and seizures. In this report, we present the clinical and molecular features of seven previously unreported individuals, identified by exome sequencing, with the recurrent p.(Val837Met) variant and global developmental delay. Other shared clinical features included congenital hypotonia, dysmorphic facial features (broad forehead, deep-set eyes, and down turned mouth), exotropia, and musculoskeletal issues (hip dysplasia, hip dislocation, scoliosis). Seizures were observed in two of seven individuals (febrile seizure in one and generalized tonic-clonic seizures with atonic drops in another), and epileptiform activity was observed in an additional two individuals. This report extends the number of affected individuals to 16 who are heterozygous for the de novo recurrent substitution p.(Val837Met). In contrast with the initial report, epilepsy was not a mandatory feature observed in this series. TRPM3 pathogenic variation should be considered in individuals with global developmental delays, moderate-severe intellectual disability with, or without, childhood-onset epilepsy., (© 2022 Wiley Periodicals LLC.)

Background: Concerns have been raised regarding the risks of SARS-CoV-2 breakthrough infections in vaccinated patients with immune-mediated inflammatory diseases treated with immunosuppressants, but clinical data on breakthrough infections are still scarce. The primary objective of this study was to compare the incidence and severity of SARS-CoV-2 breakthrough infections between patients with immune-mediated inflammatory diseases using immunosuppressants, and controls (patients with immune-mediated inflammatory diseases not taking immunosuppressants and healthy controls) who had received full COVID-19 vaccinations. The secondary objective was to explore determinants of breakthrough infections of the delta (B.1.617.2) variant of SARS-CoV-2, including humoral immune responses after vaccination., Methods: In this substudy, we pooled data collected in two large ongoing prospective multicentre cohort studies conducted in the Netherlands (Target to-B! [T2B!] study and Amsterdam Rheumatology Center COVID [ARC-COVID] study). Both studies recruited adult patients (age ≥18 years) with immune-mediated inflammatory diseases and healthy controls. We sourced clinical data from standardised electronic case record forms, digital questionnaires, and medical files. We only included individuals who were vaccinated against SARS-CoV-2. For T2B!, participants were recruited between Feb 2 and Aug 1, 2021, and for ARC-COVID, participants were recruited between April 26, 2020, and March 1, 2021. In this study we assessed data on breakthrough infections collected between July 1 and Dec 15, 2021, a period in which the delta SARS-CoV-2 variant was the dominant variant in the Netherlands. We defined a SARS-CoV-2 breakthrough infection as a PCR-confirmed or antigen test-confirmed SARS-CoV-2 infection that occurred at least 14 days after vaccination. All breakthrough infections during this period were assumed to be due to the delta variant due to its dominance during the study period. We analysed post-vaccination serum samples for anti-receptor binding domain (RBD) antibodies to assess the humoral vaccination response (T2B! study only) and anti-nucleocapsid antibodies to identify asymptomatic breakthrough infections (ARC-COVID study only). We used multivariable logistic regression analyses to explore potential clinical and humoral determinants associated with the odds of breakthrough infections. The T2B! study is registered with the Dutch Trial Register, Trial ID NL8900, and the ARC-COVID study is registered with Dutch Trial Register, trial ID NL8513., Findings: We included 3207 patients with immune-mediated inflammatory diseases who receive immunosuppressants, and 1807 controls (985 patients with immune-mediated inflammatory disease not on immunosuppressants and 822 healthy controls). Among patients receiving immunosuppressants, mean age was 53 years (SD 14), 2042 (64%) of 3207 were female and 1165 (36%) were male; among patients not receiving immunosuppressants, mean age was 54 years (SD 14), 598 (61%) of 985 were female and 387 (39%) were male; and among healthy controls, mean age was 57 years (SD 13), 549 (67%) of 822 were female and 273 (33%) were male. The cumulative incidence of PCR-test or antigen-test confirmed SARS-CoV-2 breakthrough infections was similar in patients on immunosuppressants (148 of 3207; 4·6% [95% CI 3·9-5·4]), patients not on immunosuppressants (52 of 985; 5·3% [95% CI 4·0-6·9]), and healthy controls (33 of 822; 4·0% [95% CI 2·8-5·6]). There was no difference in the odds of breakthrough infection for patients with immune-mediate inflammatory disease on immunosuppressants versus combined controls (ie, patients not on immunosuppressants and healthy controls; adjusted odds ratio 0·88 [95% CI 0·66-1·18]). Seroconversion after vaccination (odds ratio 0·58 [95% CI 0·34-0·98]; T2B! cohort only) and SARS-CoV-2 infection before vaccination (0·34 [0·18-0·56]) were associated with a lower odds of breakthrough infections., Interpretation: The incidence and severity of SARS-CoV-2 breakthrough infections in patients with immune-mediated inflammatory diseases on immunosuppressants was similar to that in controls. However, caution might still be warranted for those on anti-CD20 therapy and those with traditional risk factors., Funding: ZonMw (the Netherlands Organization for Health Research and Development) and Reade foundation., Competing Interests: FE and TWK report (governmental) grants from ZonMw (the Netherlands Organization for Health Research and Development) to study immune responses after SARS-CoV-2 vaccination in autoimmune diseases. FE also reports grants from Prinses Beatrix Spierfonds, CSL Behring, Kedrion, Terumo BCT, Grifols, Takeda Pharmaceutical Company, and Guillain-Barré Syndrome-Chronic Inflammatory Demyelinating Polyneuropathy (GBS-CIDP) Foundation; consulting fees from UCB Pharma and CSl Behring; and honoraria from Grifols. AJvdK reports grants from CSL Behring and participation on an advisory board for Argen-X. MLö reports a grant from Galapagos NV not related to this study, and honoraria from Bristol Myers Squibb, Pfizer, Takeda, and Tillotts. PIS is involved in clinical trials with Regeneron, Sanofi, Leopharma, Lilly, AbbVie, Boerhinger, Celgene, Janssen, and UCB, which manufacture drugs used for the treatment of conditions, including psoriasis and atopic dermatitis, for which financial compensation is paid to their department or hospital, and is a chief investigator of the TREAT NL registry taskforce and SECURE-AD registry. MWB is a secretary for the Dutch Experimental Dermatology Board; head of the pigmentary disorders group within the Dutch Dermatology Board; and reports honoraria from Pfizer, Sanofi, Novartis, and Fondation René Touraine. JKi has consulting relationships with Merck Serono, Biogen Idec, Teva, Genzyme, Sanofi, Roche, and Novartis; Amsterdam UMC, location VUmc, MS Center Amsterdam has received financial support for research activities from Merck, Celgene, Biogen, GlaxoSmithKline, Immunic, Roche, Teva, Sanofi, Genzyme, and Novartis. BH reports unpaid positions as a medical adviser for several patient groups, a board position for European Reference Network for rare skin diseases (ERN-Skin), and associate editor for The British Journal of Dermatology; reports grants from AbbVIe, Akari Therapeutics, Celgene, and Novartis; consulting fees from UCB Pharma, Novartis, and Janssen; and honoraria from AbbVie. JJGMV reports consulting fees from Argen-X, Alexion, and NMD Pharma, and is a co-inventor on a patent applications based on MuSK-related research (patent number 9574015). DJH reports grants from AbbVie, AstraZeneca, Janssen, LEO Pharma, and UCB; honoraria from AbbVie, Galderma, Janssen, Lilly, Pfizer, Sanofi, and UCB; and a paid position on an advisory board for Biomarkers in Atopic Dermatitis and Psoriasis (BIOMAP IMI). PAvD has participated on an advisory board for Octapharma. PvP reports grants from Alexion Pharma and GSK, and participation on advisory boards for GSK and Vifor Pharma. GRAMD reports consulting fees from AbbVie, Agomab, AstraZeneca, AM Pharma, AMT, Arena Pharmaceuticals, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, Exeliom Biosciences, Exo Biologics, Galapagos, Index Pharmaceuticals, Kaleido, Roche, Gilead, GSK, Gossamerbio, Pfizer, Immunic, Johnson & Johnson, Origo, Polpharma, Procise Diagnostics, Prometheus Laboratories, Prometheus Biosciences, Progenity, and Protagonist; honoraria from AbbVie, Arena, Galapagos NV, Gilead, Pfizer, Bristol Myers Squibb, and Takeda; and participation on advisory boards for AbbVie, Seres Health, Galapagos NV, and AstraZeneca. RBT reports honoraria from Sobi and Norgine and participation on an advisory board for Norgine. HSG is a board member of the Dutch Society of Clinical Neurophysiology (unpaid), reports grants from Prinses Beatrix Spierfonds, and has received speaker fees from Shire/Takeda. KAHZ reports paid data safety monitoring board positions for Torrent and Foresee. All other authors declare no competing interests., (© 2022 Published by Elsevier Ltd.)

A forager's energy intake rate is usually constrained by a combination of handling time, encounter rate and digestion rate. On top of that, food intake may be constrained when a forager can only process a maximum amount of certain toxic compounds. The latter constraint is well described for herbivores with a limited tolerance to plant secondary metabolites. In sulfidic marine ecosystems, many animals host chemoautotrophic endosymbionts, which store sulfur compounds as an energy resource, potentially making their hosts toxic to predators. The red knot Calidris canutus canutus is a molluscivore shorebird that winters on the mudflats of Banc d'Arguin, where the most abundant bivalve prey Loripes orbiculatus hosts sulfide-oxidizing bacteria. In this system, we studied the potential effect of sulfur on the red knots' intake rates, by offering Loripes with various sulfur content to captive birds. To manipulate toxicity, we starved Loripes for 10 days by removing them from their symbiont's energy source sulfide. As predicted, we found lower sulfur concentrations in starved Loripes. We also included natural variation in sulfur concentrations by offering Loripes collected at two different locations. In both cases lower sulfur levels in Loripes resulted in higher consumption rates in red knots. Over time the red knots increased their intake rates on Loripes, showing their ability to adjust to a higher intake of sulfur., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Knowledge of changes in the outcome in patients with metastatic renal cell carcinoma from the molecular-targeted therapy era to the immune checkpoint inhibitor (ICI) era remains limited in the real-world setting., Objectives: We aimed to clarify outcome changes from the previous molecular-targeted therapy era to the current ICI era in patients with metastatic renal cell carcinoma using multi-institution real-world data., Methods: We retrospectively evaluated 415 patients with metastatic renal cell carcinoma who received first-line systemic therapy at five Japanese institutions between January 2008 and August 2021. We divided the patients into two groups based on the treatment era: molecular-targeted therapy era (January 2008-August 2018) and ICI era (September 2018-August 2021). According to the era, progression-free survival, overall survival, and objective response rate from first-line systemic therapy were compared., Results: Overall, 304 (73.3%) and 111 (26.7%) patients were categorized into the molecular-targeted therapy and ICI eras, respectively. The proportion of patients without prior nephrectomy (p = 0.0030) or those with low Karnofsky Performance Status scores [≤ 70] (p = 0.0258) were significantly higher in the ICI era group. The patients in the ICI era group had significantly longer overall survival (median: not reached vs 23.2 months, p = 0.0001) and a higher objective response rate (47.8% vs 24.7%, p < 0.0001) than those in the molecular-targeted therapy era group, and progression-free survival tended to be longer in the ICI era group (median: 13.3 vs 8.75 months, p = 0.0579). Multivariate analysis further showed that the treatment era (ICI vs molecular-targeted therapy) was an independent factor for overall survival and objective response (both, p < 0.0001)., Conclusions: The present multi-institution real-world data showed the improved outcome of previously untreated patients with metastatic renal cell carcinoma in the ICI era group compared with that in the molecular-targeted therapy era group. These findings strongly encourage the use of ICI-based treatment for patients with metastatic renal cell carcinoma in the real-world setting. Further studies with extended follow-up periods are needed to confirm our findings., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Severe fatigue can persist for months after coronavirus disease 2019 (COVID-19) onset. This longitudinal study describes fatigue severity and its determinants up to 12 months after illness onset across the full spectrum of COVID-19 severity., Methods: RECoVERED, a prospective cohort study in Amsterdam, the Netherlands, enrolled participants aged ≥16 years after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnosis. Fatigue was measured using the validated Short Fatigue Questionnaire (SFQ; range 4-28) at months 1, 3, 6, 9, and 12 of follow-up. Fatigue severity was modeled over time using mixed-effects linear regression. Determinants of severe fatigue (SFQ ≥18) at 6 months since illness onset (ie, persistent fatigue) were identified using logistic regression., Results: Between May 2020 and July 2021, 303 participants completed at least 1 fatigue questionnaire. Twelve months after illness onset, 17.4% (95% CI, 6.7% to 38.3%), 21.6% (95% CI, 11.2% to 37.7%), and 44.8% (95% CI, 28.0% to 62.9%) of participants with mild, moderate, and severe/critical COVID-19 (World Health Organization definition), respectively, experienced severe fatigue. When adjusting for age and sex, having ≥3 comorbidities ( P  = .007), severe/critical COVID-19 ( P  = .002), low mood ( P  < .001), and dyspnea in the first 2 weeks of illness ( P  = .001) were associated with more severe fatigue over time. Severe/critical COVID-19 (adjusted odds ratio [aOR], 3.37; 95% CI, 1.28 to 8.93) and low mood at enrollment (aOR, 2.43; 95% CI, 1.11 to 5.29) were associated with persistent fatigue. Recovery rarely occurred beyond 6 months after illness onset, regardless of COVID-19 severity., Conclusions: The occurrence of severe fatigue in our cohort was high, especially among those with initially severe/critical COVID-19, with little recovery beyond 6 months after illness onset. Our findings highlight an urgent need for improved understanding of persistent severe fatigue following COVID-19 to help inform prevention and intervention., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Cardiovascular disease, the leading cause of mortality worldwide, is primarily caused by atherosclerosis, which is characterized by lipid and inflammatory cell accumulation in blood vessels and carotid intima thickening. Although disease management has improved significantly, new therapeutic strategies focused on accelerating atherosclerosis regression must be developed. Atherosclerosis models mimicking in vivo-like conditions provide essential information for research and new advances toward clinical application. New nanotechnology-based therapeutic opportunities have emerged with apoA-I nanoparticles (recombinant/reconstituted high-density lipoproteins, rHDL) as ideal carriers to deliver molecules and the discovery that microRNAs participate in atherosclerosis establishment and progression. Here, a therapeutic strategy to improve cholesterol efflux is developed based on a two-step administration of rHDL consisting of a first dose of antagomiR-33a-loaded rHDLs to induce adenosine triphosphate-binding cassette transporters A1 overexpression, followed by a second dose of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine rHDLs, which efficiently remove cholesterol from foam cells. A triple-cell 2D-atheroma plaque model reflecting the cellular complexity of atherosclerosis is used to improve efficiency of the nanoparticles in promoting cholesterol efflux. The results show that sequential administration of rHDL potentiates cholesterol efflux indicating that this approach may be used in vivo to more efficiently target atherosclerotic lesions and improve prognosis of the disease., (© 2022 Wiley-VCH GmbH.)

Dietary lignans are phytoestrogens that are mostly found in plant-based foods, especially whole grains, seeds, nuts, legumes and vegetables. An accurate assessment of lignan exposure is crucial to evaluate their potential health benefits and to establish future recommendations and dietary guidelines. This narrative review aimed to (i) summarize the pros and the cons of the current main assessment methods for lignan exposure─i.e., dietary questionnaires, food composition tables and biomarkers, (ii) describe the individual lignans more consumed from a worldwide perspective, as well as their main food sources, (iii) determine the lignans concentrations in both urine and blood, and explore their heterogeneity among countries, and finally (iv) discuss the main determinants of lignan exposure., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Rubinstein-Taybi syndrome (RSTS) is characterized by dysmorphic facial features, broad thumbs, and intellectual disability. CREB-binding protein (CREBBP) or E1A-binding protein P300 (EP300) are causative genes. To elucidate the underlying genetic and genomic architecture related to the RSTS phenotype, we performed comprehensive genetic analysis targeting CREBBP and/or EP300 in 22 clinically diagnosed patients. During the 11-year study period, we used several analysis methods including high-resolution melting, array-based comparative genomic hybridization, panel-based exome sequencing, whole exome sequencing, and whole genome sequencing (WGS). We identified the causative variants in 19 patients (86.3%), but they were variable and complex, so we must combine multiple analysis methods. Notably, we found genetic alterations in the non-coding regions of two patients (10.5%, 2/19): scattered deletions including a partial 5'-untranslated region of CREBBP in one patient (all coding exons were intact), and a deep 229-bp intronic deletion in another patient, resulting in a splicing error. Furthermore, we identified rare clinical findings: two patients with an EP300 variant showed abnormal development of the neural tube, and one patient with a CREBBP variant had anorectal atresia with a cloaca. Our findings expand the allelic heterogeneity of RSTS, underscore the utility of comprehensive genetic analysis, and suggest that WGS may be a practical diagnostic strategy., (© 2021 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)