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A novel tick-borne orthonairovirus called the Yezo virus (YEZV), primarily transmitted by the Ixodes persulcatus tick, has been recently discovered and poses significant threats to human health. The YEZV is considered endemic in Japan and China. Clinical symptoms associated with this virus include thrombocytopenia, fatigue, headache, leukopenia, fever, depression, and neurological complications ranging from mild febrile illness to severe outcomes like meningitis and encephalitis. At present, there is no treatment or vaccine readily accessible for this pathogenic virus. Therefore, this research employed an immunoinformatics approach to pinpoint potential vaccine targets within the YEZV through an extensive examination of its structural proteins. Three structural proteins were chosen using specific criteria to pinpoint T-cell and B-cell epitopes, which were subsequently validated through interferon-gamma induction. Six overlapping epitopes for cytotoxic T-lymphocytes (CTL), helper T-lymphocytes (HTL), and linear B-lymphocytes (LBL) were selected to construct a multi-epitope vaccine, achieving a 92.29% coverage of the global population. These epitopes were then fused with the 50S ribosomal protein L7/L12 adjuvant to improve protection against international strains. The three-dimensional structure of the designed vaccine construct underwent an extensive evaluation through structural analysis. Following molecular docking studies, the YEZV vaccine construct emerged as a candidate for further investigation, showing the lowest binding energy (−78.7 kcal/mol) along with favorable physiochemical and immunological properties. Immune simulation and molecular dynamics studies demonstrated its stability and potential to induce a strong immune response within the host cells. This comprehensive analysis indicates that the designed vaccine construct could offer protection against the YEZV. It is crucial to conduct additional in vitro and in vivo experiments to verify its safety and effectiveness. [ABSTRACT FROM AUTHOR]

Freezing storage is the most common method of food preservation and the formation of ice crystals during freezing has an important impact on food quality. The water molecular structure, mechanism of ice crystal formation, and ice crystal structure are elaborated in the present review. Meanwhile the methods of ice crystal characterization are outlined. It is concluded that the distribution of the water molecule cluster structure during the crystallization process directly affects the formed ice crystals' structure, but the intrinsic relationship needs to be further investigated. The morphology and distribution of ice crystals can be observed by experimental methods while simulation methods provide the possibility to study the molecular structure changes in water and ice crystals. It is hoped that this review will provide more information about ice crystallization and promote the control of ice crystals in frozen foods. [ABSTRACT FROM AUTHOR]

Parasitic diseases, such as malaria, are an immense burden to many low- and middle-income countries. In 2022, 249 million cases and 608,000 deaths were reported by the World Health Organization for malaria alone. Climate change, conflict, humanitarian crises, resource constraints and diverse biological challenges threaten progress in the elimination of malaria. Undeniably, the lack of a commercialized vaccine and the spread of drug-resistant parasites beg the need for novel approaches to treat this infectious disease. Most approaches for the development of antimalarials to date take inspiration from tropical or sub-tropical environments; however, it is necessary to expand our search. In this review, we highlight the origin of antimalarial treatments and propose new insights in the search for developing novel antiparasitic treatments. Plants and microorganisms living in harsh and cold environments, such as those found in the largely unexploited Northern Canadian boreal forest, often demonstrate interesting properties that are not found in other environments. Most prominently, the essential oil of Rhododendron tomentosum spp. Subarcticum from Nunavik and mortiamides isolated from Mortierella species found in Nunavut have shown promising activity against Plasmodium falciparum. [ABSTRACT FROM AUTHOR]

Background: Tree ontogeny is the genetic trajectories of regenerative processes in trees, repeating in time and space, including both development and reproduction. Understanding the principles of tree ontogeny is a key priority in emulating natural ecological patterns and processes that fall within the calls for closer-to-nature forest management. By recognizing and respecting the growth and development of individual trees and forest stands, forest managers can implement strategies that align with the inherent dynamics of forest ecosystem. Therefore, this study aims to determine the ontogenetic characteristics of tree regeneration and growth in northern European hemiboreal forests. Methodology: We applied a three-step process to review i) the ontogenetic characteristics of forest trees, ii) ontogenetic strategies of trees for stand-forming species, and iii) summarise the review findings of points i and ii to propose a conceptual framework for transitioning towards closer-to-nature management of hemiboreal forest trees. To achieve this, we applied the super-organism approach to forest development as a holistic progression towards the establishment of natural stand forming ecosystems. Results: The review showed multiple aspects; first, there are unique growth and development characteristics of individual trees at the pre-generative and generative stages of ontogenesis under full and minimal light conditions. Second, there are four main modes of tree establishment, growth and development related to the light requirements of trees; they were described as ontogenetic strategies of stand-forming tree species: gap colonisers, gap successors, gap fillers and gap competitors. Third, the summary of our analysis of the ontogenetic characteristics of tree regeneration and growth in northern European hemiboreal forests shows that stand-forming species occupy multiple niche positions relative to forest dynamics modes. Conclusions: This study demonstrates the importance of understanding tree ontogeny under the pretext of closer-to-nature forest management, and its potential towards formulating sustainable forest management that emulates the natural dynamics of forest structure. We suggest that scientists and foresters can adapt closer-to-nature management strategies, such as assisted natural regeneration of trees, to improve the vitality of tree communities and overall forest health. The presented approach prioritizes ecological integrity and forest resilience, promoting assisted natural regeneration, and fostering adaptability and connectivity among plant populations in hemiboreal tree communities. [ABSTRACT FROM AUTHOR]

Spinophilin is an F-actin binding and protein phosphatase 1 (PP1) targeting protein that acts as a scaffold of PP1 to its substrates. Spinophilin knockout (Spino−/−) mice have decreased fat mass, increased lean mass, and improved glucose tolerance, with no difference in feeding behaviors. Although spinophilin is enriched in neurons, its roles in nonneuronal tissues, such as β cells of the pancreatic islets, are unclear. We have corroborated and expanded upon previous studies to determine that Spino−/− mice have decreased weight gain and improved glucose tolerance in two different models of obesity. We have identified multiple putative spinophilin-interacting proteins isolated from intact pancreas and observed increased interactions of spinophilin with exocrine, ribosomal, and cytoskeletal protein classes that normally act to mediate peptide hormone production, processing, and/or release in Leprdb/db and/or high-fat diet-fed (HFF) models of obesity. In addition, we have found that spinophilin interacts with proteins from similar classes in isolated islets, suggesting a role for spinophilin in the pancreatic islet. Consistent with a pancreatic β cell type-specific role for spinophilin, using our recently described conditional spinophilin knockout mice, we found that loss of spinophilin specifically in pancreatic β cells improved glucose tolerance without impacting body weight in chow-fed mice. Our data further support the role of spinophilin in mediating pathophysiological changes in body weight and whole body metabolism associated with obesity. Our data provide the first evidence that pancreatic spinophilin protein interactions are modulated by obesity and that loss of spinophilin specifically in pancreatic β cells impacts whole body glucose tolerance. NEW & NOTEWORTHY: To our knowledge, these data are the first to demonstrate that obesity impacts spinophilin protein interactions in the pancreas and identify spinophilin specifically in pancreatic β cells as a modulator of whole body glucose tolerance. [ABSTRACT FROM AUTHOR]

An accurate depiction of wildfire, harvesting, and insect outbreak disturbances is essential for sustainable ecosystem management of forests in Canada. Even though the advent of temporally consistent 30‐m resolution Landsat data has enabled the detailed mapping of forest disturbances in Canada from 1985 onward, the disturbance record prior to 1985 remains sparse. This study aimed to extend the existing pre‐1985 disturbance history record by mapping wildfire, harvest, and insect outbreaks in Canadian forests between 1965 and 1984. Our geospatial data processing methodology relied on multilayer perceptrons (MLP) trained on spectral recovery signatures to map and age these disturbances. Our model detected approximately 4.8, 7.3, and 3.8 million ha of burnt, harvested, and insect‐ravaged forest areas, respectively, that were absent from national and provincial disturbance databases and forest inventories. Results were validated using both internal and external validation datasets. Our disturbance detection methodology was highly effective, with an internal validation kappa score of 0.91 and an external score of 0.81. The fire and harvest age disturbance MLPs, whose predictions can also be used as a proxy of forest stand age, performed adequately on the internal (fire R2 = 0.675; root mean squared error [RMSE] = 4.42; harvest R2 = 0.723; RMSE = 3.17) and external validation datasets (fire R2 = 0.242; RMSE = 4.69; harvest R2 = 0.257; RMSE = 5.46), outperforming existing forest age disturbance products. Finally, we relied on several open data products, such as provincial forest inventories, to correct our disturbance type and year prediction whenever these more reliable, but incomplete, data sources were available. Specific years were not assigned to insect outbreaks due to the lack of dependable training and validation data. We also illustrate how extending the existing forest disturbance record by 20 years may provide a more in‐depth understanding of landscape‐disturbance dynamics with a case study of the 2023 Canadian wildfire season. [ABSTRACT FROM AUTHOR]

Our research investigates LXSWD's therapeutic effectiveness in rosacea treatment and delves into its underlying mechanisms. Methods: Network pharmacology was utilized to identify LXSWD's key components and their targets in rosacea management, which were then validated by molecular docking. An in vivo rosacea-like model in LL-37-induced mice was developed, subdividing them into control, model, and LXSWD groups. The LXSWD group received oral administration (25.0 g/kg/day) for six days before model induction. Post-treatment evaluations included skin tissue analyses to verify our network pharmacology predictions. Results: Key active ingredients in LXSWD, such as quercetin, kaempferol, and luteolin, were identified alongside central target proteins like TNF and MMPs. Our molecular docking study confirmed the interactions between these ingredients and targets. Analyses through GO and KEGG pathways indicated LXSWD's role in mitigating inflammation, particularly influencing the TNF and IL-17 pathways. LXSWD treatment in vivo markedly alleviated LL-37-induced symptoms in mice, showing a marked reduction in inflammatory cytokines (p < 0.05) and modulation of crucial genes (p < 0.05). These results, supported by immunofluorescence analysis and Western blot, underline the modulatory effects of LXSWD on MMPs, offering significant protection against rosacea's inflammation alterations (p < 0.05). Conclusion: Integrating network pharmacology, molecular docking, and in vivo experiments, this study elucidates LXSWD's potential mechanisms in rosacea treatment. It offers a novel theoretical framework for its clinical use in managing rosacea. [ABSTRACT FROM AUTHOR]

Adopting a multi-criteria approach in forest management is essential for preserving or improving specific benefits while minimizing negative environmental impacts. Determining the appropriate long-term management approach for a forest requires considering heterogeneous environmental and social factors, as well as changes in forest characteristics over time. Conducting a strategic assessment of forest use suitability (FUS), namely productive, protective, conservation-oriented, social and multifunctional, at the national level, taking into account the dynamics in the provision of forest ecosystem services and the trade-offs between FUS alternatives, can guide the development of customized management strategies and policies that align with the specific requirements and conditions of the forest. In this study, we evaluate the supply and simulation-based changes over time of diverse ecosystem services of Pinus sylvestris stands in Spain and utilize a decision model to determine the most suitable FUS alternative that enhances the provision of these services. The assignment of the most appropriate FUS alternative aims to help in decision-making processes and in the selection of the most adequate management strategies. To achieve this, we utilize the last version of ecosystem management decision support (EMDS) system, a spatially focused decision support tool capable of generating precise results for multi-criteria assessment. Participatory planning actions based on Delphi principles and Analytic Hierarchy Process (AHP) analysis were applied and combined with geospatial logic-based modelling. According to the results, the dominant FUS is protective, followed by productive alternative, exhibiting high levels of multifunctionality. [ABSTRACT FROM AUTHOR]

Background: Chronic pelvic pain is a common disease that affects approximately 4% of women of reproductive age in developed countries. This number is estimated to be higher in developing countries, with a significant negative personal and socioeconomic impact on women. The lack of data on this condition in several countries, particularly those in development and in socially and biologically vulnerable populations such as the indigenous, makes it difficult to guide public policies. Objectives: To evaluate the prevalence of chronic pelvic pain (dysmenorrhea, dyspareunia, non-cyclical pain) and identify which variables are independently associated with the presence of the condition in indigenous women from Otavalo-Ecuador. Design: A cross-sectional study was carried out including a sample of 2429 women of reproductive age between 14 and 49 years old, obtained from April 2022 to March 2023. A directed questionnaire was used, collected by bilingual interviewers (Kichwa and Spanish) belonging to the community itself; the number of patients was selected by random sampling proportional to the number of women estimated by sample calculation. Data are presented as case prevalence, odds ratio, and 95% confidence interval, with p < 0.05. Results: The prevalence of primary dysmenorrhea, non-cyclic pelvic pain, and dyspareunia was, respectively, 26.6%, 8.9%, and 3.9%.all forms of chronic pain were independently associated with each other. Additionally, dysmenorrhoea was independently associated with hypertension, intestinal symptoms, miscegenation, long cycles, previous pregnancy, use of contraceptives and pear body shape. Pain in other sites, late menarche, exercise, and pear body shape were associated with non-cyclic pelvic pain. And, urinary symptoms, previous pregnancy loss, miscegenation, and pear body shape were associated with dyspareunia. Conclusion: The prevalence of primary dysmenorrhea and non-cyclical chronic pelvic pain was notably high, in contrast with the frequency of reported dyspareunia. Briefly, our results suggest an association between dysmenorrhoea and conditions related to inflammatory and/or systemic metabolic disorders, including a potential causal relationship with other manifestations of pelvic pain, and between non-cyclical pelvic pain and signs/symptoms suggesting central sensitization. The report of dyspareunia may be influenced by local cultural values and beliefs. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a heavy metal element with a wide range of hazards and severe biotoxicity. Since Cd can be easily accumulated in the edible parts of plants, the exposure of humans to Cd is mainly through the intake of Cd-contaminated food. However, the intestinal responses to Cd exposure are not completely characterized. Herein, we simulated laboratory and environmental Cd exposure by feeding the piglets with CdCl2-added rice and Cd-contaminated rice (Cdcr) contained diet, as piglets show anatomical and physiological similarities to humans. Subsequent analysis of the metal element concentrations showed that exposure to the two types of Cd significantly increased Cd levels in piglets. After verifying the expression of major Cd transporters by Western blots, multi-omics further expanded the possible transporters of Cd and found Cd exposure causes wide alterations in the metabolism of piglets. Of significance, CdCl2 and Cdcr exhibited different body distribution and metabolic rewiring, and Cdcr had stronger carcinogenic and diabetes-inducing potential. Together, our results indicate that CdCl2 had a significant difference compared with Cdcr, which has important implications for a more intense study of Cd toxicity. [ABSTRACT FROM AUTHOR]

Zinc (Zn) is the second most abundant metal in the human body and is essential for the function of 10% of all proteins. As metals cannot be synthesized or degraded, they must be assimilated from the diet by specialized transport proteins, which unfortunately also provide an entry route for the toxic metal pollutant cadmium (Cd). The intestinal absorption of Zn depends on the composition of food that is consumed, firstly the amount of Zn itself and then the quantity of other food constituents such as phytate, protein, and calcium (Ca). In cells, Zn is involved in the regulation of intermediary metabolism, gene expression, cell growth, differentiation, apoptosis, and antioxidant defense mechanisms. The cellular influx, efflux, subcellular compartmentalization, and trafficking of Zn are coordinated by transporter proteins, solute-linked carriers 30A and 39A (SLC30A and SLC39A), known as the ZnT and Zrt/Irt-like protein (ZIP). Because of its chemical similarity with Zn and Ca, Cd disrupts the physiological functions of both. The concurrent induction of a Zn efflux transporter ZnT1 (SLC30A1) and metallothionein by Cd disrupts the homeostasis and reduces the bioavailability of Zn. The present review highlights the increased mortality and the severity of various diseases among Cd-exposed persons and the roles of Zn and other transport proteins in the manifestation of Cd cytotoxicity. Special emphasis is given to Zn intake levels that may lower the risk of vision loss and bone fracture associated with Cd exposure. The difficult challenge of determining a permissible intake level of Cd is discussed in relation to the recommended dietary Zn intake levels. [ABSTRACT FROM AUTHOR]

Plant-pollinator interactions play a vital role in the maintenance of biodiversity and ecosystem function. Geographical variation in environmental factors can influence the diversity of pollinators and thus, affect the structure of pollination networks. Given the current global climate change, understanding the variation of pollination network structure along environmental gradients is vital to predict how global change will affect the ecological interaction processes. Here, we used a global plant-pollinator interaction data collection by the same sampling method at the same period to explore the effects of elevation, latitude, and plant richness on the structure and robustness of pollination networks. We analyzed a total of 87 networks of plant-pollinator interactions on 47 sites from 14 countries. We conducted a piecewise structural equation model to examine the direct and indirect effects of elevation, latitude, and plant richness on the network robustness and analyzed the function of network structure in elucidating the relationship between robustness and these gradients. We found that plant richness had both positive effects on robustness under random and specialist-first scenarios. Elevation, latitude, and plant richness affected network connectance and modularity, and ultimately affected network robustness which were mediated by nestedness under specialist-first and random scenarios, and by connectance under the generalist-first scenario. This study reveals the indirect effects of elevation, latitude, and plant richness on pollination network robustness were mediated by nestedness or connectance depended on the order of species extinctions, implying that communities with different pollination network structures can resist different extinction scenarios. [ABSTRACT FROM AUTHOR]

This research investigates the intricate connection between indigenous knowledge and sustainable forest management, with two main objectives. It seeks to explore and outline indigenous knowledge, elements, and practices that support sustainable forest management (SFM). It aims to uncover the invaluable traditional insights and practices that have helped preserve and ensure the responsible use of forest ecosystems. Also, it investigated global environmental policies that support indigenous knowledge since the inception of the Convention on Biological Diversity (CBD). A narrative review method was employed to review and analyse peer-reviewed contents and reports to deduce ancestral or traditional wisdom, knowledge, practices, and beliefs from existing studies. The paper extracted data from existing literature from scholarly peer-reviewed journals. It aims to provide useful information for policy-makers, forest managers, and indigenous communities, to promote SFM and the sustainable development goals related to a sustainable environment. The study found that indigenous knowledge (IK) which includes ethnobotanical knowledge and plant selection, mixed land use, seed banks, and cultural beliefs such as sacred groves and taboos are some traditional practices, beliefs, and cultural knowledge that support SFM and can be integrated into international and national environmental management policies which the two-eyed seeing framework (TESF) seeks to promote. The framework highlights the potential of implementing IK into SFM. Also, the Akwé: Kon Guidelines, the United Nations Declaration on the Rights of Indigenous Peoples (UNDRIP), and the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES), are some global environment policies that recognise traditional people and indigenous knowledge since the commencement of the CBD in the nineties. The paper recommends, for a future study, investigating the applicability of the Akwé: Kon Guidelines in international and national projects and programs that impact traditional sacred lands, forests and rivers, and indigenous people. Also, the United Nations Framework Convention on Climate Change (UNFCCC) and the Paris Agreement need to fully acknowledge the supporting role of indigenous knowledge and people in climate change mitigation and adaptation solutions, especially in Africa, since the majority of the world's population constitutes indigenous people who inhabit healthy standing forests and ecosystems. [ABSTRACT FROM AUTHOR]

Introduction: Localized provoked vulvodynia (LPV) is a prevalent sexual health condition with significant negative impacts on quality of life. There is a lack of consensus regarding effective management. Methods: We used Arksey and O'Malley's five-step method to identify, collate, and evaluate literature published between 2010 and 2023. The scoping review investigated the efficacy or effectiveness of interventions in the management of LPV. The aim of this paper is to map the literature on the efficacy or effectiveness of physical interventions. Results: The review produced 19 primary studies of physical interventions for LPV. These include acupuncture, laser therapy, physiotherapy, transcutaneous electrical nerve stimulation, low-intensity shockwave therapy, transcranial direct current stimulation, and vestibulectomy. Conclusion: Published studies that investigated a range of physical treatments for LPV showed some positive effects, except for transcranial direct-current stimulation. The remaining modalities demonstrated improved sexual pain and treatment satisfaction, when measured. Findings were mixed for non-sexual pain. There was insufficient evidence to draw conclusions regarding other outcomes. Researchers are encouraged to conduct larger, high-quality studies that sample more diverse patient populations and use patient-oriented outcomes to assess effectiveness of physical modalities. [ABSTRACT FROM AUTHOR]

We present laboratory experiments on the growth of a tubular ice structure surrounding a plume of cold brine that descends under gravity into water with a higher freezing point. Brinicles are geological analogues of these structures found under sea ice in the polar regions on Earth. Brinicles are hypothesized to exist in the oceans of other celestial bodies, and being environments rich in minerals, serve a potentially analogous role as an ecosystem on icy-ocean worlds to that of submarine hydrothermal vents on Earth. [ABSTRACT FROM AUTHOR]

Silent mating type information regulation 2 homolog 1 (SIRT1) is a class III histone deacetylase (HDAC) that is NAD + dependent and essential for metabolism, senescence, and cell survival. SIRT1 is overexpressed in several cancers, including breast cancer. SIRT1 is a well-known target gene of the estrogen receptor alpha (ER alpha) and is closely related to ER alpha deacetylation. Transcription factor Estrogen-related receptors (ERRs) share sequence homology with ERs in the DNA-binding domain, therefore, the possibility of sharing target genes between them is high. Our current research aims to gain insight into the function of ERRβ in regulating the activity of SIRT1 during the progression of breast cancer. ER-positive (ER + ve) breast cancer cells and tissues had considerably enhanced SIRT1 expression. Six potential ERRE sites were identified by analysis of the 5' upstream region of SIRT1, and both in vitro and in vivo experiments supported their presence. We found SIRT1 to be up-regulated in ERRβ overexpressed ER + ve breast cancer cells. Furthermore, our findings suggested that ectopic production of ERR and PCAF would increase SIRT1 activity. Our findings also indicated that ectopic production of ERRβ and PCAF increased SIRT1 activity. With sufficient evidence demonstrating the substantial involvement of SIRT1 in cell proliferation, migration, and colony formation capability, we were also able to illustrate the tumorigenic role of SIRT1. Overall, our findings highlight SIRT1's tumorigenic influence on breast cancer and suggest that SIRT1 inhibitors might serve as potential therapeutic drugs for the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Tauopathies are neurodegenerative diseases that typically require postmortem examination for a definitive diagnosis. Detecting neurotoxic tau fragments in cerebrospinal fluid (CSF) and serum provides an opportunity for in vivo diagnosis and disease monitoring. Current assays primarily focus on total tau or phospho-tau, overlooking other post-translational modifications (PTMs). Caspase-cleaved tau is a significant component of AD neuropathological lesions, and experimental studies confirm the high neurotoxicity of these tau species. Recent evidence indicates that certain caspase-cleaved tau species, such as D13 and D402, are abundant in AD brain neurons and only show a modest degree of co-occurrence with phospho-tau, meaning caspase-truncated tau pathology is partially distinct and complementary to phospho-tau pathology. Furthermore, these caspase-cleaved tau species are nearly absent in 4-repeat tauopathies. In this review, we will discuss the significance of caspase-cleaved tau in the development of tauopathies, specifically emphasizing its role in AD. In addition, we will explore the potential of caspase-cleaved tau as a biomarker and the advantages for drug development targeting caspase-6. Developing specific and sensitive assays for caspase-cleaved tau in biofluids holds promise for improving the diagnosis and monitoring of tauopathies, providing valuable insights into disease progression and treatment efficacy. [ABSTRACT FROM AUTHOR]

CDK8 is an important member of the cyclin-dependent kinase family associated with transcription and acts as a key "molecular switch" in the Mediator complex. CDK8 regulates gene expression by phosphorylating transcription factors and can control the transcription process through Mediator complex. Previous studies confirmed that CDK8 is an important oncogenic factor, making it a potential tumor biomarker and a promising target for tumor therapy. However, CDK8 has also been confirmed to be a tumor suppressor, indicating that it not only promotes the development of tumors but may also be involved in tumor suppression. Therefore, the dual role of CDK8 in the process of tumor development is worth further exploration and summary. This comprehensive review delves into the intricate involvement of CDK8 in transcription-related processes, as well as its role in signaling pathways related to tumorigenesis, with a focus on its critical part in driving cancer progression. [ABSTRACT FROM AUTHOR]

Context: Large-scale natural disturbances are crucial drivers of ecosystem function and composition for many forested ecosystems. In the last century, the prevalence of anthropogenic disturbances has increased across Canada’s boreal forest. Habitat disturbance from timber harvest and wildfire is linked to declines of boreal species, including woodland caribou (Rangifer tarandus caribou). Objectives: We tested how disturbances influenced the recovery trajectory of ecological indicators of timber, biodiversity, and wildlife habitat through time following timber harvest and wildfire across the boreal forest of Alberta, Canada. Methods: During 2021 and 2022, we collected field data from 251 timber harvested and 264 burned stands (0–40 years since disturbance), as well as 256 older forest stands used by caribou (> 40 years since disturbance). Field data included metrics of stand attributes (e.g., basal area, stems per hectare), coarse woody debris (CWD), and abundance of forage for caribou, moose (Alces americanus), and bears (black bear: Ursus americanus, grizzly bear: Ursus arctos). Results: Basal area of trees and stems per hectare recovered more quickly in timber harvest sites when compared to wildfire sites, but as time since disturbance increased there were no differences in these attributes among timber harvest, wildfire, and caribou use sites. CWD was greatest in recently burned sites, but declined over time to be similar in quantity as in harvested stands and older forest stands. Terrestrial lichens, important forage for caribou, were most abundant in the older caribou use sites, whereas forage for moose and bears, including shrubs, was most abundant in younger timber harvest and wildfire sites. Conclusions: Our results demonstrate that timber harvesting may result in a quicker development of timber volume when compared to wildfire. However, this anthropogenic disturbance is less advantageous for the development of caribou habitat. [ABSTRACT FROM AUTHOR]

Over half of older adults experience polypharmacy, including medications that may be inappropriate or unnecessary. Deprescribing, which is the process of discontinuing or reducing inappropriate and/or unnecessary medications, is an effective way to reduce polypharmacy. This review summarizes (1) the process of deprescribing and conceptual models and tools that have been developed to facilitate deprescribing, (2) barriers, enablers, and factors associated with deprescribing, and (3) characteristics of deprescribing interventions in completed trials, as well as (4) implementation considerations for deprescribing in routine practice. In conceptual models of deprescribing, multilevel factors of the patient, clinician, and health‐care system are all related to the efficacy of deprescribing. Numerous tools have been developed for clinicians to facilitate deprescribing, yet most require substantial time and, thus, may be difficult to implement during routine health‐care encounters. Multiple deprescribing interventions have been evaluated, which mostly include one or more of the following components: patient education, medication review, identification of deprescribing targets, and patient and/or provider communication about high‐risk medications. Yet, there has been limited consideration of implementation factors in prior deprescribing interventions, especially with regard to the personnel and resources in existing health‐care systems and the feasibility of incorporating components of deprescribing interventions into the routine care processes of clinicians. Future trials require a more balanced consideration of both effectiveness and implementation when designing deprescribing interventions. [ABSTRACT FROM AUTHOR]

The mechanisms of neuronal cell death in neurodegenerative disease remain incompletely understood, although recent studies have made significant advances. Apoptosis was previously considered to be the only mechanism of neuronal cell death in neurodegenerative diseases. However, recent findings have challenged this dogma, identifying new subtypes of necrotic neuronal cell death. The present review provides an updated summary of necrosis subtypes and discusses their potential roles in neurodegenerative cell death. Among numerous necrosis subtypes, including necroptosis, paraptosis, ferroptosis, and pyroptosis, transcriptional repression-induced atypical cell death (TRIAD) has been identified as a potential mechanism of neuronal cell death. TRIAD is induced by functional deficiency of TEAD-YAP and self-amplifies via the release of HMGB1. TRIAD is a feasible potential mechanism of neuronal cell death in Alzheimer's disease and other neurodegenerative diseases. In addition to induction of cell death, HMGB1 released during TRIAD activates brain inflammatory responses, which is a potential link between neurodegeneration and neuroinflammation. [ABSTRACT FROM AUTHOR]

Aim: Food webs are essential for understanding how ecosystems function, but empirical data on the interactions that make up these ecological networks are lacking for most taxa in most ecosystems. Trait‐based models can fill these data gaps, but their ability to do so has not been widely tested. We test how well these models can extrapolate to new ecological communities both in terms of pairwise predator–prey interactions and higher level food web attributes (i.e. species position, food web‐level properties). Location: Canada, Europe, Tanzania. Time Period: Current. Major Taxa Studied: Terrestrial vertebrates. Methods: We train trait‐based models of pairwise trophic interactions on four independent vertebrate food webs (Canadian tundra, Serengeti, alpine south‐eastern Pyrenees and Europe) and evaluate how well these models predict pairwise interactions and network properties of each food web. Results: We find that, overall, trait‐based models predict most interactions and their absence correctly. Performance was best for training and testing on the same food web (AUC > 0.90) and declined with environmental and phylogenetic distances with the strongest loss of performance for the tundra‐Serengeti ecosystems (AUC > 0.75). Network metrics were less well‐predicted than single interactions by our models with predicted food webs being more connected, less modular, and with higher mean trophic levels than observed. Main Conclusions: Theory predicts that the variability observed in food webs can be explained by differences in trait distributions and trait‐matching relationships. Our finding that trait‐based models can predict many trophic interactions, even in contrasting environments, adds to the growing body of evidence that there are general constraints on interactions and that trait‐based methods can serve as a useful first approximation of food webs in unknown areas. However, food webs are more than the sum of their parts, and predicting network attributes will likely require models that simultaneously predict individual interactions and community constraints. [ABSTRACT FROM AUTHOR]

This study compares the clinical outcomes of Er,Cr:YSGG (2,780 nm) laser--assisted open-flap (OF) and flapless (FL) esthetic crown lengthening (ECL) for the treatment of altered passive eruption. Thirty-six healthy patients requiring ECL were randomly divided into two groups: OF and FL. Gingivectomy and ostectomy were performed with an Er,Cr:YSGG laser in both groups. The periodontal condition and gingival margin level (GML) were assessed at baseline, immediately postsurgery, and at 1, 3, and 9 months postsurgery. The effect of periodontal phenotype and tooth location on GML and supracrestal gingival tissue dimension were evaluated. A significant difference was detected in the mean of GML at all time points, except between 3 and 9 months. The main tissue rebound after 9 months was 0.25 ± 0.3 mm in the OF group and 0.26 ± 0.3 mm in the FL group (no significant difference) and was significantly higher in thick periodontal phenotypes. Er,Cr:YSGG laser--assisted ECL is a predictable technique that achieved similar outcomes using flap and flapless approaches, providing esthetic and restorative opportunities for clinicians. [ABSTRACT FROM AUTHOR]

Trichosanthis fruit (TF) is a classic medicinal material obtained from Shandong, China. The peel of this fruit (Trichosanthis pericarpium, TP) is known to exert antithrombotic effects. However, the anti-thrombotic active components and mechanisms of TP have yet to be fully elucidated. Combined with zebrafish models and high-performance liquid chromatography (HPLC), this study evaluated the endogenous anti-thrombotic effects with the combination of three compounds from TP. First, we used HPLC to investigate the components in the water extract of TP. Next, we used the zebrafish model to investigate the anti-thrombotic activity of the three compound combinations by evaluating a range of indicators. Finally, the expression of related genes was detected by real-time quantitative polymerase chain reaction (qPCR). HPLC detected a total of eight components in TP water extract, with high levels of paeonol (Pae), diosmetin-7-O-β-D-glucopyranoside (diosmetin-7- O-glucoside), and 5-hydroxymethylfurfural (5-HMF). The most significant antithrombotic activity was detected when the Pae: diosmetin-7-O-glucoside:5- HMF ratio was 4:3:3. qPCR analysis revealed that the abnormal expression levels of f2, fga, fgb, vwf, ptgs1, and tbxas1 induced by arachidonic acid (AA) were improved. The combination of Pae, diosmetin-7-O-glucoside, and 5-HMF may alleviate AA-induced thrombosis by inhibiting the inflammatory reaction, coagulation cascade reaction, and arachidonic acid metabolism pathways. [ABSTRACT FROM AUTHOR]

Cemeteries are among the most polluting sources of groundwater and surface water in the world. Necro-leachate, a liquid released during the putrefaction of corpses, is the main culprit of such pollution. Among the compounds in this liquid are the potentially toxic amines cadaverine and putrescine, which are still poorly understood in terms of the environmental health risks they pose. This study evaluated the acute toxicity of cadaverine and putrescine, using efficient contamination bioindicators of aquatic environments. Danio rerio and Daphnia magna were exposed to both amines individually or in a mixture. Acute toxicity (LC50) was then observed in both organisms after exposure to the amines individually. Cadaverine showed higher lethality for D. magna (LC50 – 9.5 mg. L−1) and D. rerio (LC50—335.5 mg. L−1) than did putrescine (LC50—36.7 mg. L−1 and LC50- 452.6 mg. L−1, respectively). In embryotoxicity tests with D. rerio (hatching rate and malformations), delayed hatching, vertebral column malformations, and pericardial edema were observed after exposure to an amine mixture. However, co-exposure to cadaverine and putrescine was not toxic to D. magna. The results of this study confirmed the efficiency of the bioindicators used to assess contaminants in cemeteries and raised awareness of the toxic potential of cadaveric decomposition by-products. [ABSTRACT FROM AUTHOR]

Aspirin (ASA) remains the most common antiplatelet agent used in children. VerifyNow Aspirin Test® (VN) assesses platelet response to ASA, with therapeutic effect defined by the manufacturer as ≤ 549 aspirin reaction units (ARU). Single-center, observational, analysis of 195 children (< 18 years-old) who underwent first VN between 2015 and 2020. Primary outcome was proportion of patients with ASA biochemical resistance (> 549 ARU). Secondary outcomes included incidence of new clinical thrombotic and bleeding events during ≤ 6 months from VN in those who received ASA monotherapy (n = 113). Median age was 1.8 years. Common indications for ASA included cardiac anomalies or dysfunction (74.8%) and ischemic stroke (22.6%). Median ASA dose before VN was 4.6 mg/kg/day. Mean VN was 471 ARU. ASA biochemical resistance was detected in 14.4% (n = 28). Of 113 patients receiving ASA monotherapy, 14 (12.4%) had a thrombotic event and 2 (1.8%) had a bleeding event. Mean VN was significantly higher at initial testing in patients experiencing thrombotic event compared to those without thrombosis (516 vs 465 ARU, [95% CI: 9.8, 92.2], p = 0.02). Multivariable analysis identified initial VN ASA result ≥ 500 ARU at initial testing as the only significant independent risk factor for thrombosis (p < 0.01). VN testing identifies ASA biochemical resistance in 14.4% of children. VN ASA ≥ 500 ARU rather than ≥ 550 ARU at initial testing was independently associated with increased odds of thrombosis. Designated cut-off of 550 ARU for detecting platelet dysfunction by ASA may need reconsideration in children. [ABSTRACT FROM AUTHOR]

Canopy structural complexity is a key emergent property of forest ecosystems that directly relates to their ability to store carbon, cycle water and nutrients, and provide habitat for biodiversity. However, we lack a general framework for quantifying the structural complexity of forest canopies, and it remains to be seen if there are simple rules that explain the huge variation in canopy structure that we observe across the world's forests.A leading candidate for characterizing differences in structural complexity among forest ecosystems are fractal scaling laws, or measures of statistical self‐similarity. If forest canopies were fractal in nature, their structural attributes could be distilled into a single coefficient—their fractal dimension—which could then be used to directly compare structural differences within and across biomes.To test this idea, we used airborne laser scanning (ALS) data acquired across nine landscapes in Australia that span a huge environmental gradient and include everything from dry shrublands, tropical savannas, dense rainforests, to 90 m tall Mountain Ash forests. Using the ALS data, we built high‐resolution 3D canopy height models of each landscape so that we could quantify how closely they followed fractal scaling laws, based on a comprehensive set of fractal dimension estimators.Across all ecosystem types, fractal scaling assumptions were consistently violated, with clear and systematic differences between real‐world forest canopies and simulated fractal surfaces. However, deviations from fractality did vary predictably among sites, with forests in less arid environments, dominated by tall trees with large crowns, exhibiting a higher degree of self‐similarity across scales.Synthesis: Our study conclusively shows that canopy surfaces are not fractal beyond the scale of individual tree crowns. Nevertheless, we still observed ecologically meaningful and generalisable patterns in forest structure across scales, which closely reflect biophysical and physiological constraints on tree size and architecture. These patterns point the way towards a more general framework for characterizing ecological complexity. [ABSTRACT FROM AUTHOR]

Simple Summary: Consuming unsafe food globally results in millions of illnesses and deaths. The safety of our food, from farm (pre-harvest) to table (postharvest), is paramount. In low- and middle-income countries (LMICs), ensuring food safety is challenging. This review explores current insights into pre-harvest critical issues related to food safety. At the farm level, critical food safety issues include animal health, antimicrobial resistance, and farmers' knowledge, attitudes, and practices. Globally, several pre-harvest interventions aim to mitigate risks from animal-origin food. Despite effectiveness at a small scale, these interventions often lack scalability. Many countries have established laws and regulations to shield consumers from unsafe food consumption. However, food safety regulations in several LMICs are weak, inconsistent, and inadequately enforced. Preventing foodborne diseases requires a One Health approach, uniting experts in animal, human, and environmental health. Despite its importance, the application of this approach to address food safety issues is limited in low- and middle-income countries. Food safety remains a significant global public health concern, with the risk of unsafe food varying worldwide. The economies of several low- and middle-income countries (LMICs) heavily rely on livestock, posing a challenge to ensuring the production of safe food. This review discusses our understanding of pre-harvest critical issues related to food safety in LMICs, specifically focusing on animal-derived food. In LMICs, food safety regulations are weak and inadequately enforced, primarily concentrating on the formal market despite a substantial portion of the food sector being dominated by informal markets. Key critical issues at the farm level include animal health, a low level of good agriculture practices, and the misuse of antimicrobials. Effectively addressing foodborne diseases requires a comprehensive One Health framework. Unfortunately, the application of the One Health approach to tackle food safety issues is notably limited in LMICs. In conclusion, considering that most animal-source foods from LMICs are marketed through informal channels, food safety legislation and policies need to account for this context. Interventions aimed at reducing foodborne bacterial pathogens at the farm level should be scalable, and there should be strong advocacy for the proper implementation of pre-harvest interventions through a One Health approach. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explores the impact of pre-slaughter stress on pigs, focusing on non-ambulatory, non-injured (NANI) pigs, and pigs showing no apparent anomalies (non-NANI). Pre-slaughter stress is known to affect animal welfare and meat quality. NANI pigs, often disabled or injured, exhibit higher body temperatures and significant blood count changes, indicating elevated stress levels. The study correlates these physiological markers with meat quality parameters, revealing that NANI pigs experience abnormalities in meat characteristics. The findings emphasize the potential use of blood biomarkers as predictive tools for evaluating pig welfare during handling, leading to improved practices and, consequently, better meat quality. This research aims to contribute to enhanced animal welfare and more efficient pork production practices. The study aimed to investigate the physiological and meat quality differences between Non-Ambulatory, Non-Injured (NANI), and without apparent abnormalities (non-NANI) pigs in a commercial slaughterhouse setting, focusing on the impact of stress and health conditions on the overall well-being and meat quality of the animals. A total of 241 surgically castrated crossbred male pigs from Southern Brazil were analyzed, with 131 non-NANI pigs and 110 NANI pigs. Infrared orbital temperature, rectal temperature, hematological parameters, and meat quality measurements were collected. Statistical analysis included ANOVA tests and principal component analysis (PCA). NANI pigs exhibited significantly higher infrared orbital temperatures and rectal temperature (p < 0.01). Hematological analysis revealed higher levels of hemoglobin, hematocrit, and red blood cells in NANI pigs (p < 0.05). White blood cell count and lactate dehydrogenase were significantly elevated in NANI pigs (p < 0.01), indicating potential infections or inflammatory responses. Meat quality parameters showed that NANI pigs had lower pH values, higher luminosity, and increased drip loss (p < 0.01), reflecting poorer water retention and potential muscle glycogen depletion. The study highlights the physiological and meat quality differences between NANI and non-NANI pigs, emphasizing the impact of stress, health conditions, and handling procedures on the animals. Blood biomarkers proved valuable in assessing physiological stress, immune response, and potential health issues in pigs, correlating with meat quality abnormalities. Utilizing these biomarkers as predictive tools can enhance animal welfare practices and contribute to improving meat quality in the swine industry. [ABSTRACT FROM AUTHOR]

As the permafrost region warms and permafrost soils thaw, vast stores of soil organic carbon (C) become vulnerable to enhanced microbial decomposition and lateral transport into aquatic ecosystems as dissolved organic carbon (DOC). The mobilization of permafrost soil C can drastically alter the net northern permafrost C budget. DOC entering aquatic ecosystems becomes biologically available for degradation as well as other types of aquatic processing. However, it currently remains unclear which landscape characteristics are most relevant to consider in terms of predicting DOC concentrations entering aquatic systems from permafrost regions. Here, we conducted a systematic review of 111 studies relating to, or including, concentrations of DOC in terrestrial permafrost ecosystems in the northern circumpolar region published between 2000 and 2022. We present a new permafrost DOC dataset consisting of 2845 DOC concentrations, collected from the top 3 m in permafrost soils across the northern circumpolar region. Concentrations of DOC ranged from 0.1 to 500 mg L -1 (median = 41 mg L -1) across all permafrost zones, ecoregions, soil types, and thermal horizons. Across the permafrost zones, the highest median DOC concentrations were in the sporadic permafrost zone (101 mg L -1), while lower concentrations were found in the discontinuous (60 mg L -1) and continuous (59 mg L -1) permafrost zones. However, median DOC concentrations varied in these zones across ecosystem type, with the highest median DOC concentrations in each ecosystem type of 66 and 63 mg L -1 found in coastal tundra and permafrost bog ecosystems, respectively. Coastal tundra (130 mg L -1), permafrost bogs (78 mg L -1), and permafrost wetlands (57 mg L -1) had the highest median DOC concentrations in the permafrost lens, representing a potentially long-term store of DOC. Other than in Yedoma ecosystems, DOC concentrations were found to increase following permafrost thaw and were highly constrained by total dissolved nitrogen concentrations. This systematic review highlights how DOC concentrations differ between organic- or mineral-rich deposits across the circumpolar permafrost region and identifies coastal tundra regions as areas of potentially important DOC mobilization. The quantity of permafrost-derived DOC exported laterally to aquatic ecosystems is an important step for predicting its vulnerability to decomposition. [ABSTRACT FROM AUTHOR]

Significant progress in permafrost carbon science made over the past decades include the identification of vast permafrost carbon stocks, the development of new pan‐Arctic permafrost maps, an increase in terrestrial measurement sites for CO2 and methane fluxes, and important factors affecting carbon cycling, including vegetation changes, periods of soil freezing and thawing, wildfire, and other disturbance events. Process‐based modeling studies now include key elements of permafrost carbon cycling and advances in statistical modeling and inverse modeling enhance understanding of permafrost region C budgets. By combining existing data syntheses and model outputs, the permafrost region is likely a wetland methane source and small terrestrial ecosystem CO2 sink with lower net CO2 uptake toward higher latitudes, excluding wildfire emissions. For 2002–2014, the strongest CO2 sink was located in western Canada (median: −52 g C m−2 y−1) and smallest sinks in Alaska, Canadian tundra, and Siberian tundra (medians: −5 to −9 g C m−2 y−1). Eurasian regions had the largest median wetland methane fluxes (16–18 g CH4 m−2 y−1). Quantifying the regional scale carbon balance remains challenging because of high spatial and temporal variability and relatively low density of observations. More accurate permafrost region carbon fluxes require: (a) the development of better maps characterizing wetlands and dynamics of vegetation and disturbances, including abrupt permafrost thaw; (b) the establishment of new year‐round CO2 and methane flux sites in underrepresented areas; and (c) improved models that better represent important permafrost carbon cycle dynamics, including non‐growing season emissions and disturbance effects. Plain Language Summary: Climate change and the consequent thawing of permafrost threatens to transform the permafrost region from a carbon sink into a carbon source, posing a challenge to global climate goals. Numerous studies over the past decades have identified important factors affecting carbon cycling, including vegetation changes, periods of soil freezing and thawing, wildfire, and other disturbance events. Overall, studies show high wetland methane emissions and a small net carbon dioxide sink strength over the terrestrial permafrost region but results differ among modeling and upscaling approaches. Continued and coordinated efforts among field, modeling, and remote sensing communities are needed to integrate new knowledge from observations to modeling and predictions and finally to policy. Key Points: Rapid warming of northern permafrost region threatens ecosystems, soil carbon stocks, and global climate targetsLong‐term observations show importance of disturbance and cold season periods but are unable to detect spatiotemporal trends in C fluxCombined modeling and syntheses show the permafrost region is a small terrestrial CO2 sink with large spatial variability and net CH4 source [ABSTRACT FROM AUTHOR]

The MEMS microphone is a representative device among the MEMS family, which has attracted substantial research interest, and those tailored for human voice have earned distinct success in commercialization. Although sustained development persists, challenges such as residual stress, environmental noise, and structural innovation are posed. To collect and summarize the recent advances in this subject, this paper presents a concise review concerning the transduction mechanism, diverse mechanical structure topologies, and effective methods of noise reduction for high-performance MEMS microphones with a dynamic range akin to the audible spectrum, aiming to provide a comprehensive and adequate analysis of this scope. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum (ER) luminal Ca2+ is vital for the function of the ER and regulates many cellular processes. Calreticulin is a highly conserved, ER‐resident Ca2+ binding protein and lectin‐like chaperone. Over four decades of studying calreticulin demonstrate that this protein plays a crucial role in maintaining Ca2+ supply under different physiological conditions, in managing access to Ca2+ and how Ca2+ is used depending on the environmental events and in making sure that Ca2+ is not misused. Calreticulin plays a role of ER luminal Ca2+ sensor to manage Ca2+‐dependent ER luminal events including maintaining interaction with its partners, Ca2+ handling molecules, substrates and stress sensors. The protein is strategically positioned in the lumen of the ER from where the protein manages access to and distribution of Ca2+ for many cellular Ca2+‐signalling events. The importance of calreticulin Ca2+ pool extends beyond the ER and includes influence of cellular processes involved in many aspects of cellular pathophysiology. Abnormal handling of the ER Ca2+ contributes to many pathologies from heart failure to neurodegeneration and metabolic diseases. [ABSTRACT FROM AUTHOR]

Reversing the negative impacts that anthropogenic habitat fragmentation has on animal movement is a key goal in the management of landscapes and conservation of species globally. Accurate assessment of measures to remediate habitat fragmentation, such as fish passage solutions in rivers, are imperative but are particularly challenging for territorial species, which are less likely to leave their existing home range, or populations composed of both migratory and resident individuals (i.e., partial migration). This investigation quantified the movements of translocated (captured upstream of the impediment and released downstream) and non‐translocated (captured and released downstream of the impediment) riverine brown trout (Salmo trutta L.), a species known to perform a homing movement, through a fish pass using passive integrated transponder (PIT) telemetry. A significantly higher proportion of translocated fish approached, entered, and passed (on a wider range of flows) compared to non‐translocated fish, consistent with the theory that motivation is a key driver in fish pass use. Translocated fish that entered the pass were significantly larger than those that approached but did not enter, presumably due to physiological capability. Translocated fish were a more reliable indicator of the fish passage solution effectiveness than non‐translocated fish. Our findings hence imply that many fish passage solutions globally, and potentially measures to remediate habitat fragmentation for other taxa, may have been mistakenly assessed for unmotivated animals. Studying both non‐translocated and translocated fish is recommended to provide more accurate and cost‐effective fish passage solution assessments. [ABSTRACT FROM AUTHOR]

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In this work, the sharp-interface immersed boundary (IB) method proposed by Mittal et al. (J Comput Phys 227(10):4825–4852, 2008) is extended to fluid-structure-interaction (FSI) simulation of parachute inflation by utilizing several open-source tools. The method employs a Cartesian-grid ghost-cell methodology to accurately represent the immersed boundary, and it is suitable for solving moving-boundary flows with arbitrarily complex geometries. The finite-element code CalculiX is employed to solve the structural dynamics of the parachute system. The IB flow solver is coupled with CalculiX in a minimally-invasive manner using the multi-physics coupling library preCICE. The implicit fluid-structure coupling together with the Aitken adaptive under-relaxation scheme is considered to improve the numerical accuracy and stability. The developed approach is validated by a benchmark FSI case. Numerical experiments on the inflation process of several typical parachutes are further conducted. The breathing process, flow structure, canopy displacement and drag coefficient are analyzed to demonstrate the applicability of the present approach for simulating parachute inflation. [ABSTRACT FROM AUTHOR]

Stability, thermal characterization, and identification of possible polymorphism are relevant in the development of novel therapeutic drugs. In this context, thirty new nonsteroidal anti-inflammatory drug (NSAID) derivatives containing selenium (Se) as selenoesters or diacyl diselenides with demonstrated anticancer activity were thermally characterized in order to establish thermal stability criteria and detect possible polymorphic forms. Compounds were analyzed by a combination of thermogravimetry, differential scanning calorimetry, and X-ray diffraction techniques, and five different calorimetric behaviors were identified. Two compounds based on naproxen (I.3d and I.3e) and an indomethacin-containing derivative (II.2) presented two crystalline forms. The stability under acid, alkaline and oxidative conditions of selected polymorphs was also assessed using high-performance liquid chromatography. In addition, the cytotoxic activity of Se-NSAID crystalline polymorphs was studied in several cancer cell lines in vitro. Remarkably, no significant differences were found among the polymorphic forms tested, thus proving that these compounds are thermally qualified for further drug development. [ABSTRACT FROM AUTHOR]

Simple Summary: Over the last two decades, there has been a major shift in cancer research models. What was once dominated by genetically engineered mice models and fast-growing immortalized cancer cell lines has given way to a number of patient-derived models of cancer (PDMCs) that may be more representative of human disease. However, the complexities of these patient-derived models, both in vitro and in vivo systems, influence both data interpretation and interoperability. To address these challenges, the PDMC Consortium within the National Cancer Institute undertook this review describing the past, present, and future use of PDMCs while providing example vignettes with practical recommendations from the collective experience of the consortium members. For over a century, early researchers sought to study biological organisms in a laboratory setting, leading to the generation of both in vitro and in vivo model systems. Patient-derived models of cancer (PDMCs) have more recently come to the forefront of preclinical cancer models and are even finding their way into clinical practice as part of functional precision medicine programs. The PDMC Consortium, supported by the Division of Cancer Biology in the National Cancer Institute of the National Institutes of Health, seeks to understand the biological principles that govern the various PDMC behaviors, particularly in response to perturbagens, such as cancer therapeutics. Based on collective experience from the consortium groups, we provide insight regarding PDMCs established both in vitro and in vivo, with a focus on practical matters related to developing and maintaining key cancer models through a series of vignettes. Although every model has the potential to offer valuable insights, the choice of the right model should be guided by the research question. However, recognizing the inherent constraints in each model is crucial. Our objective here is to delineate the strengths and limitations of each model as established by individual vignettes. Further advances in PDMCs and the development of novel model systems will enable us to better understand human biology and improve the study of human pathology in the lab. [ABSTRACT FROM AUTHOR]