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The rapid development of large language models (LLMs) has opened new avenues across various fields, including cybersecurity, which faces an evolving threat landscape and demand for innovative technologies. Despite initial explorations into the application of LLMs in cybersecurity, there is a lack of a comprehensive overview of this research area. This paper addresses this gap by providing a systematic literature review, covering the analysis of over 300 works, encompassing 25 LLMs and more than 10 downstream scenarios. Our comprehensive overview addresses three key research questions: the construction of cybersecurity-oriented LLMs, the application of LLMs to various cybersecurity tasks, the challenges and further research in this area. This study aims to shed light on the extensive potential of LLMs in enhancing cybersecurity practices and serve as a valuable resource for applying LLMs in this field. We also maintain and regularly update a list of practical guides on LLMs for cybersecurity at https://github.com/tmylla/Awesome-LLM4Cybersecurity. [ABSTRACT FROM AUTHOR]

Context: The vegetation composition of northeastern North American forests has significantly changed since pre-settlement times, with a marked reduction in conifer-dominated stands, taxonomic and functional diversity. These changes have been attributed to fire regime shifts, logging, and climate change. Methods: In this study, we disentangled the individual effects of these drivers on the forest composition in southwestern Quebec from 1830 to 2000 by conducting retrospective modelling using the LANDIS-II forest landscape model. The model was run based on pre-settlement forest composition and fire history reconstructions, historical timber harvest records, and climate reanalysis data. We compared counterfactual scenarios excluding individual factors to a baseline historical scenario. Results and Conclusions: Our results indicated that timber harvesting had the greatest impact on forest dynamics over the past centuries. In the absence of timber harvesting, pre-settlement species abundances were largely maintained, preserving key functional traits like fire and shade tolerance that contribute to ecosystem resilience. Increased fire activity during the settlement period contributed to the increase of early-successional aspen (Populus tremuloides), but timber harvesting played the dominant role. Fire exclusion had no influence on vegetation composition, suggesting mesophication unfolds over longer timescales than those captured in this study. Climate change, characterized by modest increases in temperature and precipitation, had a minor effect on vegetation shifts, as increased precipitation might have mitigated the adverse effects of rising temperatures. However, future climate change is projected to become a more significant driver of forest composition. These findings underscore the importance of forest restoration and continued research on past forest dynamics to better understand current and future changes. [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]

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]

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]

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]

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]

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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]

This review will discuss evidence that aspirin possesses anticancer activity. Long-term observational retrospective studies on nurses and health professionals demonstrated that regular aspirin users had a significantly lower incidence of colorectal cancer (RCT). Prospective studies on patients with a high risk of developing colorectal polyps/cancer confirmed that aspirin use significantly lowered colorectal dysplasia. Numerous observational studies focused on the use of aspirin in a broad range of cancers demonstrating a consistent 20–30% preventive effect on cancer incidence and mortality. Random Controlled Trials provided conflicting results on the benefit of aspirin in preventing CRC. Based on the age, weight/body size of the subjects for reasons still being explored. Studies on rats/mice further demonstrated that treatment of animals with aspirin where colon cancer was induced chemically or genetically (APCMin mice) reduced colonic dysplasia and polyp formation. Aspirin treatment was also effective at reducing the growth of cancer cells transplanted into normal/immunocompromised mice, suggesting that aspirin may be effective in treating different cancers. This possibility is also supported in clinical studies that aspirin use pre- and postcancer diagnosis significantly reduced the metastatic spread of cancer and increased patient survival. Lastly, the importance of the antiplatelet actions of aspirin in the drug's anticancer activity and specifically cancer metastatic spread is discussed and the current controversy related to the conflicting recommendations of the USPSTF over the past five years on the use of aspirin to prevent CRC. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The aim of our work was to determine the presence of GPx8, the latest discovered member of glutathione peroxidase family, in rat male genital organs. BACKGROUND: The oxidative stress is considered as one of the most important causalities of male infertility. To defend itself, the organism comprises many different antioxidants. METHODS: We assessed the GPx8 presence in tissues of genital organs from adult rat Sprague-Dawley males by mRNA expression, Western Blot analysis, and immunohistochemistry. RESULTS: The highest mRNA and protein levels were detected in the testis, followed by seminal vesicle. Within testis the enzyme was observed predominantly in the Leydig and Sertoli cells, residual and Hermes bodies. In other organs, such as epididymis, seminal vesicle and prostate gland, the GPx8 was seen in the cytoplasm of epithelial cells. The enzyme was also observed in the muscular layer of hollow organs, in blood plasma and extracellular matrix. CONCLUSIONS: The antioxidant enzyme GPx8 was detected in all examined male genital organs. The fact, that the enzyme was released into lumen of genital organs probably means, that GPx8 is also a component of the semen. To our knowledge, this is the first paper describing GPx8 presence in male genital organs of mammals (Fig. 8, Ref. 63). [ABSTRACT FROM AUTHOR]

Caspases are proteolytic enzymes that belong to the cysteine protease family and play a crucial role in homeostasis and programmed cell death. Caspases have been broadly classified by their known roles in apoptosis (caspase-3, caspase-6, caspase-7, caspase-8, and caspase-9 in mammals) and in inflammation (caspase-1, caspase-4, caspase-5, and caspase-12 in humans, and caspase-1, caspase-11, and caspase-12 in mice). Caspases involved in apoptosis have been subclassified by their mechanism of action as either initiator caspases (caspase-8 and caspase-9) or executioner caspases (caspase-3, caspase-6, and caspase-7). Caspases that participate in apoptosis are inhibited by proteins known as inhibitors of apoptosis (IAPs). In addition to apoptosis, caspases play a role in necroptosis, pyroptosis, and autophagy, which are non-apoptotic cell death processes. Dysregulation of caspases features prominently in many human diseases, including cancer, autoimmunity, and neurodegenerative disorders, and increasing evidence shows that altering caspase activity can confer therapeutic benefits. This review covers the different types of caspases, their functions, and their physiological and biological activities and roles in different organisms. [ABSTRACT FROM AUTHOR]

Urban streams are impacted by multiple anthropogenic environmental stressors that exert considerable pressure on resident fish populations. Species such as brook trout (Salvelinus fontinalis) are particularly vulnerable because urban environments typically limit the cold oxygenated water required by all life stages. To understand factors associated with native brook trout movement in urban streams, we monitored 20 radio-tagged individuals from late summer through the spawning season in autumn, and modelled how movement was influenced by body size and habitat. Tracking occurred in two adjacent streams that differed in forest cover and channelization. In both streams, brook trout mainly travelled upstream, particularly at the onset of the autumn spawning season. Larger individuals exhibited greater movements, and habitat complexity imposed stronger effects in larger individuals. Greater movements were made into locations of shallower depth and lower conductivity, although these factors were conflated with movement into upstream locations. This study addresses a fundamental knowledge gap in urban stream ecology by providing detailed information on the movement of a key indicator species of aquatic ecosystem health. [ABSTRACT FROM AUTHOR]

Introduction: Sexual health is fundamental in an individual's well-being. Genito-pelvic pain/penetration disorder, also known as dyspareunia, is one of the most common sexual disorders, and approaches from physiotherapy include multimodal options, being education, a recent resource often used. Social and economic factors might influence the effectiveness of educational therapies in patients suffering this affliction. The objective of this study was to determine if there is an existing correlation between the participant's socioeconomic status and the results of a therapeutic educational program. Methods: A randomized controlled trial was performed using therapeutic education as intervention in a sample of 69 women suffering from genito-pelvic pain/penetration disorder. Results over time were assessed regarding pain intensity, pain-related outcomes, and sexual functioning. Socioeconomic status measurements were obtained in February 2022, and these included age, educational level, household monthly income, or job rank. A correlation analysis was performed between these outcomes using Pearson's correlation index and Spearman's rho statistic. Results: Results from the correlation analysis show that there is no significant correlation between any of the outcomes found in the results of the intervention and the socioeconomic status measurements. Conclusion: A therapeutic educational program improves pain intensity, pain-related outcomes, and sexual functioning in patients with persistent pelvic pain, independently from their age, educational level, household monthly income, or job rank. Policy Implications: Education is a powerful resource that improves sexuality outcomes despite the patient's socioeconomical status in patients suffering from genito-pelvic pain/penetration disorder. [ABSTRACT FROM AUTHOR]

This article reports changes to virus taxonomy and taxon nomenclature that were approved and ratified by the International Committee on Taxonomy of Viruses (ICTV) in April 2023. The entire ICTV membership was invited to vote on 174 taxonomic proposals that had been approved by the ICTV Executive Committee in July 2022, as well as a proposed revision of the ICTV Statutes. All proposals and the revised ICTV Statutes were approved by a majority of the voting membership. Of note, the ICTV continued the process of renaming existing species in accordance with the recently mandated binomial format and included gene transfer agents (GTAs) in the classification framework by classifying them as viriforms. In total, one class, seven orders, 31 families, 214 genera, and 858 species were created. [ABSTRACT FROM AUTHOR]

Crossings between roads and streams can negatively affect fish, especially when culverts prevent free movement along the stream. Understanding this effect is essential to design structures that can mitigate the impact of roads on fishes. Here, we used a capture-recapture study and multi-state open population models to investigate the influence of a culvert on the movement probability of the armored catfish Rineloricaria aequalicuspis, a small benthic species (maximum total body length ca. 190 mm) endemic to streams in southern Brazil. Additionally, we tested whether environmental variables and body size affect movement probability through the culvert. Fish sampling and environmental data collection were carried out during 2016 and 2017, both in a stream section crossed by a road and in the adjacent free-flowing stream sections upstream and downstream. Movement probability was higher within free stream sections than through the culvert. Water depth in the culvert positively influenced movement probability, whereas body size was not related to movement through the road-stream crossing. Our results indicate that the culvert hinders free movement of R. aequalicuspis and that approximately 30 cm of water depth inside the culvert results in an eightfold increase in passage probability. These results extend the evidence that culverts affect fish movement in streams, even for non-migratory, relatively small species adapted to environments with natural obstacles. This indicates the need to design road-stream crossings that are more favorable to fish movement, especially in streams crossed by roads at multiple sites. [ABSTRACT FROM AUTHOR]

Context: Increasing fragmentation of rivers caused by barriers continues to impact watersheds, especially disruption of fish migration patterns and loss of access to spawning and nursery habitats. Infrastructure expansion and ageing installations exacerbate the problem, reducing effectiveness of management in addressing barriers. Reduction in watershed connectivity requires effective tools capable of guiding river managers in remediation actions. Objectives: Our objective was to develop a watershed dynamic connectivity assessment tool (D-CAT), a customizable geospatial tool capable of river analyses at varying watershed scales. The tool uses proven watershed connectivity modelling combined with an effective evaluation approach to provide measurable change model outcomes. Methods: Three different barrier encounter scenarios were examined using the D-CAT tool to study watershed connectivity. The tool was tested on a watershed area of the River Derwent, a major tributary of the River Trent system in the United Kingdom. Results: For each barrier scenario tested, the D-CAT tool indicated which barriers could be removed or modified to provide the greatest watershed connectivity improvement. The tool provided a prioritized list of barriers for each scenario under varying choices for the number of barriers to remove, demonstrating the utility of the D-CAT tool to planning and design. Conclusions: The D-CAT tool is built to handle geographical data and variable user input, allowing in-depth watershed connectivity analysis. The tool forecasts the cumulative effects of alternative change scenarios for watershed connectivity, providing prioritization and optimization of removal strategies. The D-CAT tool offers significant support for landscape management towards better barrier removal/remediation decisions. [ABSTRACT FROM AUTHOR]

In much of the world, currently employed upper limits of tolerable intake and acceptable excretion of cadmium (Cd) (ECd/Ecr) are 0.83 µg/kg body weight/day and 5.24 µg/g creatinine, respectively. These figures were derived from a risk assessment model that interpreted β2-microglobulin (β2MG) excretion > 300 μg/g creatinine as a "critical" endpoint. However, current evidence suggests that Cd accumulation reduces glomerular filtration rate at values of ECd/Ecr much lower than 5.24 µg/g creatinine. Low ECd/Ecr has also been associated with increased risks of kidney disease, type 2 diabetes, osteoporosis, cancer, and other disorders. These associations have cast considerable doubt on conventional guidelines. The goals of this paper are to evaluate whether these guidelines are low enough to minimize associated health risks reliably, and indeed whether permissible intake of a cumulative toxin like Cd is a valid concept. We highlight sources and levels of Cd in the human diet and review absorption, distribution, kidney accumulation, and excretion of the metal. We present evidence for the following propositions: excreted Cd emanates from injured tubular epithelial cells of the kidney; Cd excretion is a manifestation of current tissue injury; reduction of present and future exposure to environmental Cd cannot mitigate injury in progress; and Cd excretion is optimally expressed as a function of creatinine clearance rather than creatinine excretion. We comprehensively review the adverse health effects of Cd and urine and blood Cd levels at which adverse effects have been observed. The cumulative nature of Cd toxicity and the susceptibility of multiple organs to toxicity at low body burdens raise serious doubt that guidelines concerning permissible intake of Cd can be meaningful. [ABSTRACT FROM AUTHOR]

Platelets are formed from bone marrow megakaryocytes, circulate in blood for 7-10 days, and then are destroyed in the spleen and/or liver. Platelet production depends on the megakaryocyte population state in the bone marrow: number and size of the cells. The platelet turnover, i.e., the number of platelets passing through the bloodstream in a certain time, is determined by both the rate of their production and the rate of their destruction. The review considers laboratory markers, which are used to assess platelet production and turnover in the patients with hematologic and cardiovascular pathologies. These markers include some characteristics of platelets themselves: (i) content of reticulated (“young”) forms in the blood detected by their staining with RNA dyes; (ii) indicators of the platelet size determined in hematology analyzers (mean volume, percentage of large forms) and in flow cytometers (light scattering level). Alterations of platelet production and turnover lead to the changes in blood plasma concentrations of such molecules as thrombopoietin (TPO, main mediator of megakaryocyte maturation and platelet formation in the bone marrow) and glycocalicin (soluble fragment of the membrane glycoprotein Ib detached from the surface of platelets during their destruction). Specific changes in the markers of platelet production and turnover have been observed in: (i) hypoproductive thrombocytopenias caused by suppression of megakaryocytes in the bone marrow; (ii) immune thrombocytopenias caused by accelerated clearance of the autoantibody-sensitized platelets; and (iii) thrombocytosis (both primary and reactive). The paper presents the data indicating that in patients with cardiovascular diseases an increased platelet turnover and changes in the corresponding markers (platelet size indexes and content of reticulated forms) are associated with the decreased efficacy of antiplatelet drugs and increased risk of thrombotic events, myocardial infarction, and unstable angina (acute coronary syndrome). [ABSTRACT FROM AUTHOR]

Abstract—The climatic characteristics and morphometric indicators of the relief of habitats of forest communities described in the system of ecological and floristic classification on the Ufa plateau, as well as on the western macroslope and in the centrally elevated part of the Southern Urals were compared. It has been shown that syntaxonomic differences in forest vegetation in these areas are primarily caused by the differences in air temperature and summer precipitation. Existing climate change forecasts assume an increase in average annual and summer temperatures, as well as an increase in the amount of winter and a decrease in summer precipitation. This suggests that coniferous and mixed coniferous-broad-leaved forests will be enriched with species of the nemoral complex in the future in the Southern Urals, which in turn will lead to an increase in their similarity with modern forests of the Ufa plateau. [ABSTRACT FROM AUTHOR]

Effective planning animal transport is essential to safeguard animal welfare and reduce production losses. Environmental conditions, specifically extreme temperatures in combination with ranges of relative humidity are highlighted as one of the main risk factors for production losses during transport (e.g., fatalities). The majority of research evaluating both welfare and production impacts of pig transport have been primarily undertaken in Europe and North America, which cover a relatively limited range of distinct climates (e.g., temperate, sub-arctic, etc.). As a result, research on pig transport in semi-arid conditions is lacking. In this study, we evaluated the effects of both distance (short, 30 km; and long, 170 km) and transport daily periods (morning, (05:00-11:00); afternoon (12:00-17:00); and night, (23:00-04:00)) on the preslaughter losses and heat stress of pigs in commercial transport in a semiarid region. Across 19 journeys of standard slaughter-weight pig loads (124.0 ± 2.8 kg), 684 focal animals (36 per journey) were evaluated. For each journey, the load's thermal profile (THIadj and enthalpy) and physiological responses of individual pigs were recorded. On arrival at designated slaughterhouses, the percentage pig of non-ambulatory non-injured (NANI), non-ambulatory injured (NAI), death on arrival (DOA), and total losses were recorded. Short journeys in the afternoon were shown to be more detrimental to the thermal comfort of pigs, with higher rectal temperatures recorded. The highest percentage of total losses and DOA occurred in afternoon journeys, irrespective of distance, followed by the morning, with the lowest losses observed in pigs transported at night. Additionally, total losses and DOA were further exacerbated by journey distance, with higher rates observed in short journeys. Higher percentage averages of NANI and NAI were observed in shorter journeys, but daily periods effects were only observed for NANI. These results further demonstrate the welfare and production loss risks associated with journey distance and time of day (representing varying environmental conditions) during road transport of pigs, whilst providing novel data in semiarid conditions. Careful and effective planning for pig transportation is essential to minimize heat stress and production losses. Consideration of the thermal environment on the day of travel, as well as providing flexibility to adjust travel times (e.g., early morning or evening), should help to mitigate risks of heat stress and production losses during pig transport. [ABSTRACT FROM AUTHOR]

Tools to accurately predict and detect adverse drug reactions (ADR) in elderly patients have not been developed. We aimed to identify and evaluate reports on tools that predict and detect ADR in elderly patients (≥ 60 years). In this review, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Databases were searched until January 2022 using key terms "elderly," "adverse drug reaction," and "detection instruments." Eighteen studies met the inclusion criteria, and they examined assorted interventions: STOPP/START version 1/2 (n = 10), Beers Criteria 2012 or 2015 (n = 4), Systematic Tool to Reduce Inappropriate Prescribing (STRIP) (n = 2), Tool to Reduce Inappropriate Medications (TRIM) (n = 1), Medication Risk Score (MERIS) (n = 1), Computerized alert systems (n = 1), and Norwegian General Practice-Nursing Home criteria (n = 1). The interventions affected the number of potential prescription omissions (OR, 0.50 [0.37–0.69]; p < 0.0001; four studies). No apparent reduction in the number of drug interactions within 2 months (OR, 0.84 [0.70–1.02]; p = 0.08; two studies) and mortality (OR, 0.92 [0.76–1.12]; p = 0.41; three studies) was observed. In conclusion, there is no definitive and validated assessment tool for detecting and predicting ADR in elderly patients. Thus, more research on refining existing tools or developing new ones is warranted. [ABSTRACT FROM AUTHOR]

Culverts are very important hydraulic structures for stream crossing, and they come in various shapes and materials. There are generally two different types of culverts, i.e., closed bottom and open bottom structures. In the present study, two closed bottom culverts have been replaced by open bottom structures (arch culverts) during the summer of 2018. The objective of the present study was to analyze water temperature variability along the impacted sites, one year after the replacement, i.e., 2019 to assess potential impacts of the streamside vegetation removal on the thermal conditions of these streams. Results showed a significant (p < 0.05) change in mean summer temperatures at both sites. Changes in stream temperatures at Barnet Brook were attributed to the removal of an old sediment pond, whereas changes in stream temperatures at the tributary of the Nerepis River were likely due to the removal of the streamside vegetation. Increases in water temperatures (> 4 °C) were more pronounced during low flow periods compared to high flow conditions at both sites. [ABSTRACT FROM AUTHOR]

The placenta sustains embryonic development and is critical for a successful pregnancy outcome. It provides the site of exchange between the mother and the embryo, has immunological functions and is a vital endocrine organ. To perform these diverse roles, the placenta comprises highly specialized trophoblast cell types, including syncytiotrophoblast and extravillous trophoblast. The coordinated actions of transcription factors (TFs) regulate their emergence during development, subsequent specialization, and identity. These TFs integrate diverse signaling cues, form TF networks, associate with chromatin remodeling and modifying factors, and collectively determine the cell type-specific characteristics. Here, we summarize the general properties of TFs, provide an overview of TFs involved in the development and function of the human trophoblast, and address similarities and differences to their murine orthologs. In addition, we discuss how the recent establishment of human in vitro models combined with -omics approaches propel our knowledge and transform the human trophoblast field. [ABSTRACT FROM AUTHOR]

In neural tissue engineering, the use of electrical stimulation has been proposed to cure patients with damaged nervous systems. Electrical stimulation can promote nerve cell differentiation and regeneration. Due to certain properties of electrode materials, including thermal problems and corrosion, the wide application of electrical stimulation has been hindered. Here, we fabricated an electro-spun, nano-porous, membrane-based, electrode-embedded cell chip capable of electrical stimulation of cells. To provide conductivity on an electro-spun nano-porous membrane, a 1.0 µm-thick layer of Au was deposited by electron beam evaporation. The electrode had a length and height of 4 and 0.025 cm, respectively, and was fixed to the inner walls of transparent polydimethylsiloxane (PDMS) cell chip channels. For 5 days, when 1 kHz of electrical stimulation was given at 50 and 100 mVpp, the promotion of neurite outgrowth of neuroblastoma SH-SY5Y cells was significantly exhibited, while no thermal problems or corrosions were detected in the electrodes. Furthermore, at 100 mVpp of electrical stimulation, not only neurite outgrowth but also secondary branch induction was observed. We believe that the newly proposed cell chip can be applied to the study of neuronal differentiation and regeneration with stable and controllable electrical stimulation. [ABSTRACT FROM AUTHOR]

C-terminal cleaved tau at D421 (∆D421-tau) accumulates in the brains of Alzheimer's disease (AD) patients. However, it is unclear how tau truncation, an understudied tau post-translational modification, contributes to AD pathology and progression. Utilizing an adeno-associated virus (AAV) gene delivery-based approach, we overexpressed full-length tau (FL-tau) and ∆D421-tau in 4- and 12-month-old mice for 4 months to study the neuropathological impact of accumulation in young adult (8-month) and middle-aged (16-month) mice. Overall, we show that independent of the tau species, age was an important factor facilitating tau phosphorylation, oligomer formation, and deposition into silver-positive tangles. However, mice overexpressing ∆D421-tau exhibited a distinct phosphorylation profile to those overexpressing FL-tau and increased tau oligomerization in the middle-age group. Importantly, overexpression of ∆D421-tau, but not FL-tau in middle-aged mice, resulted in pronounced cognitive impairments and hippocampal long-term potentiation deficits. While both FL-tau and ∆D421-tau induced neuronal loss in mice with age, ∆D421-tau led to significant neuronal loss in the CA3 area of the hippocampus and medial entorhinal cortex compared to FL-tau. Based on our data, we conclude that age increases the susceptibility to neuronal degeneration associated with ΔD421-tau accumulation. Our findings suggest that ΔD421-tau accumulation contributes to synaptic plasticity and cognitive deficits, thus representing a potential target for tau-associated pathologies. [ABSTRACT FROM AUTHOR]

Estrogen-related receptor (ERR) is a member of the nuclear receptor (NR) superfamily and has three subtypes α, β, and γ. Despite their strong homology with estrogen receptor (ER) α, ERRs cannot accommodate endogenous hormones. However, they are able to regulate gene expression without ligand binding. ERRα and ERRγ orchestrate the expression of genes involved in bioenergetic pathways, while ERRβ controls placental development and stem cell maintenance. Evidence from recent studies, including clinical research, has also demonstrated close associations of ERRs with the pathophysiology of hormone-related cancers and metabolic disorders including type 2 diabetes mellitus. This review summarizes the basic knowledge and recent advances in ERRs and their associated proteins, focusing on the subcellular dynamics involved in transcriptional regulation. Fluorescent protein labeling enabled monitoring of ERRs in living cells and revealed previously unrecognized characteristics. Using this technique, we demonstrated a role of ERRβ in controlling estrogen signaling by regulating the subnuclear dynamics of ligand-activated ERα. Visualization of ERRs and related proteins and subsequent analyses also revealed a function of ERRγ in promoting liver lactate metabolism in association with LRPGC1, a recently identified lactic acid-responsive protein. These findings suggest that ERRs activate unique transregulation mechanisms in response to extracellular stimuli such as hormones and metabolic signals, implying an adaptive system behind the cellular homeostatic regulation by orphan NRs. Control of subcellular ERR dynamics will contribute toward the development of therapeutic approaches to treat various diseases including hormone-related cancers and metabolic disorders associated with abnormal ERR signaling pathways. [ABSTRACT FROM AUTHOR]

Estrogen-related receptor (ERR), a member of the nuclear receptor superfamily, consists of three subtypes (α, β, γ) and has strong homology with estrogen receptor. No endogenous ligands have been identified for ERRs, but they play key roles in metabolic, hormonal, and developmental processes as transcription factors without ligand binding. Although subnuclear dynamics are essential for nuclear events including nuclear receptor-mediated transcriptional regulation, the dynamics of ERRs are poorly understood. Here, we report that ERRs show subcellular kinetic changes in response to diethylstilbestrol (DES), a synthetic estrogen that represses the transactivity of all three ERR subtypes, using live-cell imaging with fluorescent protein labeling. Upon DES treatment, all ERR subtypes formed discrete clusters in the nucleus, with ERRγ also displaying nuclear export. Fluorescence recovery after photobleaching analyses revealed significant reductions in the intranuclear mobility of DES-bound ERRα and ERRβ, and a slight reduction in the intranuclear mobility of DES-bound ERRγ. After DES treatment, colocalization of all ERR subtypes with scaffold attachment factor B1 (SAFB1), a nuclear matrix-associated protein, was observed in dot-like subnuclear clusters, suggesting interactions of the ERRs with the nuclear matrix. Consistently, co-immunoprecipitation analyses confirmed enhanced interactions between ERRs and SAFB1 in the presence of DES. SAFB1 was clarified to repress the transactivity of all ERR subtypes through the ERR-response element. These results demonstrate ligand-dependent cluster formation of ERRs in the nucleus that is closely associated with SAFB1-mediated transrepression. Taken together, the present findings provide a new understanding of the pathophysiology regulated by ERR/SAFB1 signaling pathways and their subcellular dynamics. [ABSTRACT FROM AUTHOR]

Selective breaking of degenerate energy levels is a well-known tool for coherent manipulation of spin states. Though most simply achieved with magnetic fields, polarization-sensitive optical methods provide high-speed alternatives. Exploiting the optical selection rules of transition metal dichalcogenide monolayers, the optical Stark effect allows for ultrafast manipulation of valley-coherent excitons. Compared to excitons in these materials, microcavity exciton-polaritons offer a promising alternative for valley manipulation, with longer lifetimes, enhanced valley coherence, and operation across wider temperature ranges. Here, we show valley-selective control of polariton energies in WS2 using the optical Stark effect, extending coherent valley manipulation to the hybrid light-matter regime. Ultrafast pump-probe measurements reveal polariton spectra with strong polarization contrast originating from valley-selective energy shifts. This demonstration of valley degeneracy breaking at picosecond timescales establishes a method for coherent control of valley phenomena in exciton-polaritons. Microcavity exciton-polaritons in atomically thin semiconductors are a promising platform for valley manipulation. Here, the authors show valley-selective control of polariton energies in monolayer WS2 using the optical Stark effect, thereby extending coherent valley manipulation to a hybrid light-matter regime [ABSTRACT FROM AUTHOR]

Phospholipase D6 (PLD6) plays pivotal roles in mitochondrial dynamics and spermatogenesis, but the cellular and subcellular localization of endogenous PLD6 in testis germ cells is poorly defined. We examined the distribution and subcellular localization of PLD6 in mouse testes using validated specific anti-PLD6 antibodies. Ectopically expressed PLD6 protein was detected in the mitochondria of PLD6-transfected cells, but endogenous PLD6 expression in mouse testes was localized to the perinuclear region of pachytene spermatocytes, and more prominently, to the round (Golgi and cap phases) and elongating spermatids (acrosomal phase); these results suggest that PLD6 is localized to the Golgi apparatus. The distribution of PLD6 in the round spermatids partially overlapped with that of the cis-Golgi marker GM130, indicating that the PLD6 expression corresponded to the GM130-positive subdomains of the Golgi apparatus. Correlative light and electron microscopy revealed that PLD6 expression in developing spermatids was localized almost exclusively to several flattened cisternae, and these structures might correspond to the medial Golgi subcompartment; neither the trans-Golgi networks nor the developing acrosomal system expressed PLD6. Further, we observed that PLD6 interacted with tesmin, a testis-specific transcript necessary for successful spermatogenesis in mouse testes. To our knowledge, these results provide the first evidence of PLD6 as a Golgi-localized protein of pachytene spermatocytes and developing spermatids and suggest that its subcompartment-specific distribution within the Golgi apparatus may be related to the specific functions of this organelle during spermatogenesis. [ABSTRACT FROM AUTHOR]

Caspase-6 (Casp6) is implicated in Alzheimer disease (AD) cognitive impairment and pathology. Hippocampal atrophy is associated with cognitive impairment in AD. Here, a rare functional exonic missense CASP6 single nucleotide polymorphism (SNP), causing the substitution of asparagine with threonine at amino acid 73 in Casp6 (Casp6N73T), was associated with hippocampal subfield CA1 volume preservation. Compared to wild type Casp6 (Casp6WT), recombinant Casp6N73T altered Casp6 proteolysis of natural substrates Lamin A/C and α-Tubulin, but did not alter cleavage of the Ac-VEID-AFC Casp6 peptide substrate. Casp6N73T-transfected HEK293T cells showed elevated Casp6 mRNA levels similar to Casp6WT-transfected cells, but, in contrast to Casp6WT, did not accumulate active Casp6 subunits nor show increased Casp6 enzymatic activity. Electrophysiological and morphological assessments showed that Casp6N73T recombinant protein caused less neurofunctional damage and neurodegeneration in hippocampal CA1 pyramidal neurons than Casp6WT. Lastly, CASP6 mRNA levels were increased in several AD brain regions confirming the implication of Casp6 in AD. These studies suggest that the rare Casp6N73T variant may protect against hippocampal atrophy due to its altered catalysis of natural protein substrates and intracellular instability thus leading to less Casp6-mediated damage to neuronal structure and function. [ABSTRACT FROM AUTHOR]

Although the first successful numerical weather prediction (NWP) project led by Charney and von Neumann is widely known, little is known by the international community about the development of NWP during the 1950s in China. Here, a detailed historical perspective on the early NWP experiments in China is provided. The leadership in NWP of the late Professor Chen-Chao Koo, a protégé of C. G. Rossby at the University of Stockholm during the late 1940s and a key leader of modern meteorology (particularly of atmospheric dynamics and physics) in China during the 1950s–70s, is highlighted. The unique contributions to NWP by Koo and his students, such as the ideas of formulating NWP as an "evolution" problem, in which the past data over multiple time steps are utilized, rather than an initial-value problem, and on the cybernetic aspects of atmospheric processes, i.e., regarding the motion of the atmosphere at various time scales as an optimal control system, are also emphasized. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses the various topics within the issue like community-based participatory research, sex work, human sexuality, and chronic vulvar pain.

Provoked Vestibulodynia (PVD) is a type of localized vulvodynia (or pain in the vulva). The estimated prevalence of this condition is about 12% of the general population and approximately 20% of women under the age of 19. Many women who live with PVD suffer in silence for years before receiving a diagnosis. Whereas cognitive behavioral therapy (CBT) was already known to be effective for managing symptoms of PVD, there has recently been a published head-to-head comparison of CBT versus mindfulness-based therapy for the primary outcome of pain intensity with penetration. The trial revealed that both treatments were effective and led to statistically and clinically meaningful improvements in sexual function, quality of life, and reduced genital pain, with improvements retained at both 6- and 12-month follow-ups. We then undertook an end-of-grant knowledge translation (KT) campaign focused on the use of social media to disseminate an infographic video depicting the findings. Social media was strategically chosen as the primary mode of dissemination for the video as it has broad reach of audience, the public can access information on social media for free, and it presented an opportunity to provide social support to the population of women with PVD who are characterized as suffering in silence by starting a sensitive and empowering dialogue on a public platform. In this paper, we summarize the social media reach of our campaign, describe how and why we partnered with social media influencers, and share lessons learned that might steer future KT efforts in this field. [ABSTRACT FROM AUTHOR]

The absorption of high-power visible or near-IR laser radiation by free electrons is calculated using the modified resonance approximation. The probabilities Wexc of intraband transitions at which the electron energy changes by ℏ(ω ± ωl), where ω is the frequency of light and ωl is the frequency of longitudinal optical phonons involved in the process, are determined. It is shown that specific electron–phonon Rabi oscillations at a frequency of ΩR may take place, and that the light is absorbed only up to the moment of time at which the first maximum τ1 on the dependence Wexc(t) is reached, where t is the time elapsed from the beginning of the laser pulse. It is shown that, in the case of prebreakdown light intensities, processes of high orders in the field of the light wave affect substantially Wexc, τ1, and ΩR. [ABSTRACT FROM AUTHOR]

This study assessed the effects of season on health, behaviour, physiological stress parameters, and carcass and meat quality in a total of 480 slaughter pigs. The following health indicators were recorded: pneumonia, pleurisy, milk spots, and pericarditis. Behaviour was monitored during unloading (slipping, falling, turning back, reluctance to move, panting, shivering) and lairaging (panting, shivering, huddling). Blood lactate and glucose concentrations were determined at exsanguination. Performance indices (live weight, daily weight gain), carcass (carcass weight, backfat and loin thickness, lean meat content, carcass lesion score), and meat quality (pH, temperature, drip, thawing and cooking losses, colour, marbling) traits were measured postmortem. Pigs slaughtered in winter had the highest live weight, carcass weight, loin thickness, and carcass lesion score, while the lowest live weight, carcass weight, and backfat thickness were recorded in pigs slaughtered in summer. The highest lactate and glucose concentrations were recorded in pigs slaughtered in summer. The highest prevalence of red, soft, and exudative meat was recorded in pigs slaughtered in winter. Pigs slaughtered in summer had the lowest pH, the highest thawing loss, L* value, b* value, and occurrence of pale, soft, and exudative meat. Pigs slaughtered in autumn had the lowest drip loss, cooking loss, L* value, b* value, and the greatest percentage of red, firm, and nonexudative meat. In conclusion, the summer and winter temperatures compromised health and welfare and reduced carcass and meat quality in slaughter pigs, indicating that protection against heat and cold stress is not yet effective. [ABSTRACT FROM AUTHOR]

The predominance of Alzheimer's disease (AD) among the aged remains a global challenge. As such, the search for alternative and effective therapeutic options continuous unabated. Among the therapeutic targets explored over the years toward impeding the progression of AD is caspase-6 (Casp6), although selectively targeting Casp6 remains a challenge due to high homology with other members of the caspase family. Methyl 3-[(2,3-dihydro-1-benzofuran-2-yl formamido) methyl]-5-(furan-2-amido) benzoate (C13), a novel allosteric inhibitor, is reportedly shown to exhibit selective inhibition against mutant human Casp6 variants (E35K). However, structural and atomistic insights accounting for the reported inhibitory prowess of C13 remains unresolved. In this study, we seek to unravel the mechanistic selectivity of C13 coupled with the complementary effects of E35K single-nucleotide polymorphism (SNP) relative to Casp6 inhibition. Analyses of binding dynamics revealed that the variant Lysine-35 mediated consistent high-affinity interactions with C13 at the allosteric site, possibly forming the molecular basis of the selectivity of C13 as well as its high binding free energy as estimated. Analysis of residue interaction network around Glu35 and Lys35 revealed prominent residue network distortions in the mutant Casp6 conformation evidenced by a decrease in node degree, reduced number of edges and an increase short in path length relative to a more compact conformation in the wild system. The relatively higher binding free energy of C13 coupled with the stronger intermolecular interactions elicited in the mutant conformation further suggests that the mutation E35K probably favours the inhibitory activity of C13. Further analysis of atomistic changes showed increased C-α atom deviations consistent with structural disorientations in the mutant Casp6. Structural Insights provided could open up a novel paradigm of structure-based design of selective allosteric inhibition of Casp6 towards the treatment of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

We used bioproxies from paleosoils buried within two aeolian dunes to test hypotheses concerning the origin of dry sandy boreal forests in Canada. These forests are dominated today by Pinus banksiana Lamb. One hypothesis is that too frequent Holocene stand-replacing fires would have transformed the original vegetation through extirpation of susceptible species to fire in water stress habitat. Alternatively, the ecosystem would have not changed since the dunes stabilized enough to support forest establishment. The vegetation composition and richness were determined by identification of charcoal and macroremains and radiocarbon dating for the chronology. Both sites revealed a similar history covering 6400 years. Half of the charcoal layers were less than 2500 years old in both sites, indicating that they had been subjected to the same fire history. Data indicated a stable plant composition and richness, although the percentage of Pinus decreased slightly over 4000 years (decreasing rate 1% per century). The fungus Cenococcum geophilum was consistently present, with a stochastic abundance. The vegetation grew under natural fire conditions and soil dryness since 6000 years. The ecosystem was probably not stressed by late-Holocene fires or climate changes, as the multi-millennial steady state reveals a resistant and resilient ecosystem. [ABSTRACT FROM AUTHOR]

Soil is a complex and dynamic network of different biological processes linked in an intricate manner to facilitate effective ecosystem functioning. Microbial diversity and its functioning are crucial to effective ecosystem working and its sustenance. Metagenomic studies undertaken to-date have illustrated the tremendous diversity of both culturable and unculturable microbiome in specific ecosystems, but their exact role in ecosystem functioning needs to be addressed. This can be undertaken by studying the protein repertoire in the ecosystem, which are the direct and undeviating key players in the ongoing metabolic processes. Metaproteomics, an emerging science, tries to snapshot the entire proteins present in a specific environment at a particular time interval. It links the phylogeny and functionality of soil microorganisms, describing not only at the level of the individual dominant organism, but also at the community level, therefore, profiling microbial enzymes may be a sensitive indicator of the soil ecosystem. With the emergence of high-performance mass spectrometry, the approach to mine these functional complex soil microbiomes became feasible; however, it is hindered by the presence of innumerable interfering molecules present in the soil samples. This review focuses on recent developments in soil metaproteomics, particularly, in terms of protein extraction methodologies and mass spectrometry-based measurements, as well as their applications in soil based approaches to decipher the underlying processes responsible for differential functioning in diverse environments. [ABSTRACT FROM AUTHOR]