bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fluorescence confocal microscopy for margin assessment in prostatectomy: IP8‐FLUORESCE study protocol
Authors: Mayor Nikhil , Light Alexander , Silvanto Anna , Cullen Emma , Ng Peng Yun , Badreldin Almostafa , Khoubehi Bijan , Hellawell Giles , Fiorentino Francesca , Connor Martin J. , Shah Taimur T. , Ahmed Hashim U. , Winkler Mathias 
Published: November 2024

BackgroundRadical prostatectomy (RP) represents the cornerstone of surgical treatment for prostate cancer. Assessing surgical margin status intraoperatively with current techniques remains challenging due to high costs in the context of an already stretched pathology workforce. Fluorescence confocal microscopy (FCM) is a promising technique to detect margins in prostate cancer surgery not bound by such limitations.Study DesignThe Imperial Prostate 8 – Fluorescence Confocal Microscopy for Rapid Evaluation of Surgical Cancer Excision (IP8‐FLUORESCE) study is a multicentre, prospective, ex vivo, ‘blinded’, comparative cohort study. It aims to assess the accuracy of digital FCM for detection of prostate cancer at surgical margins compared to traditional histopathology.EndpointsThe primary endpoint is the accuracy of digital FCM for detection of prostate cancer at surgical margins on a per‐patient level, reported with sensitivity, specificity, positive and negative predictive values.Patients and MethodsA total of 153 patients with localised prostate cancer undergoing robot‐assisted RP across three UK National Health Service tertiary referral centres will be recruited. Following RP, prostate specimens will undergo immediate immersion in Acridine Orange solution, scanning ‘en face’ with FCM using the Histolog® Scanner, and subsequent formalin fixation and paraffin embedding. Two independent, ‘blinded’ uro‐pathologists will report both the FCM images and the histopathology slides. Recruitment commenced on 17 August 2023.
Genetic, Clinical, and Biochemical Characterization of a Large Cohort of Palestinian Patients With Fanconi‐Bickel Syndrome
Authors: Hodrob Tamer , Abusalameh Alaaeddin , Ismail Ibrahim , Dweikat Imad , Rmeilah Sarah Abu , Sultan Mutaz , Libdeh Bassam Abu , Libdeh Abd‐Al‐Salam Abu , Shweiki Shaher , Damseh Nadirah 
Published: November 2024

ABSTRACTThis study aims to investigate the clinical, biochemical, and genetic characteristics of Fanconi‐Bickel syndrome (FBS) in a cohort of 20 individuals from Palestine and to identify novel pathogenic variants. A retrospective analysis was conducted on medical records from Al‐Makassed Hospital's pediatric department spanning 2015 to 2023. Individuals diagnosed with FBS via molecular genetic testing were included in the study. Among the 20 genetically confirmed FBS patients, hepatomegaly was prevalent in 95%, whereas 70% exhibited both developmental delay and hypophosphatemic rickets, and 68.4% experienced growth retardation. Hypertriglyceridemia (HTG) was universal. Elevated liver enzymes and alkaline phosphatase were common, along with hypophosphatemia (95%) and urinary abnormalities. Genetic analysis revealed five distinct SLC2A2 pathogenic variants, including three previously unreported variants: p.Gln23Arg (c.68A > G), p.Thr353Arg (c.1058_1059delinsGG), and an exon 7 deletion. This study presents the largest single‐center cohort of FBS patients, expanding our understanding of the disorder's phenotypic and genotypic spectrum. Despite FBS generally carrying a favorable prognosis, timely diagnosis remains crucial to prevent severe complications.
Endothelial Dysfunctions in Blood–Brain Barrier Breakdown in Alzheimer's Disease: From Mechanisms to Potential Therapies
Authors: Yue Qian , Leng Xinyue , Xie Ningqing , Zhang Zaijun , Yang Deguang , Hoi Maggie Pui Man 
Published: November 2024

ABSTRACTRecent research has shown the presence of blood–brain barrier (BBB) breakdown in Alzheimer's disease (AD). BBB is a dynamic interface consisting of a continuous monolayer of brain endothelial cells (BECs) enveloped by pericytes and astrocytes. The restricted permeability of BBB strictly controls the exchange of substances between blood and brain parenchyma, which is crucial for brain homeostasis by excluding blood‐derived detrimental factors and pumping out brain‐derived toxic molecules. BBB breakdown in AD is featured as a series of BEC pathologies such as increased paracellular permeability, abnormal levels and functions of transporters, and inflammatory or oxidative profile, which may disturb the substance transportation across BBB, thereafter induce CNS disorders such as hypometabolism, Aβ accumulation, and neuroinflammation, eventually aggravate cognitive decline. Therefore, it seems important to protect BEC properties for BBB maintenance and neuroprotection. In this review, we thoroughly summarized the pathological alterations of BEC properties reported in AD patients and numerous AD models, including paracellular permeability, influx and efflux transporters, and inflammatory and oxidative profiles, and probably associated underlying mechanisms. Then we reviewed current therapeutic agents that are effective in ameliorating a series of BEC pathologies, and ultimately protecting BBB integrity and cognitive functions. Regarding the current drug development for AD proceeds extremely hard, this review aims to discuss the therapeutic potentials of targeting BEC pathologies and BBB maintenance for AD treatment, therefore expecting to shed a light on the future AD drug development by targeting BEC pathologies and BBB protection.
Phospholipase D Family Member 4 Regulates Microglial Phagocytosis and Remyelination via the AKT Pathway in a Cuprizone‐Induced Multiple Sclerosis Mouse Model
Authors: Sun Ran , Ma Tengyun , Zhao Zheng , Gao Yan , Feng Juan , Yang Xue 
Published: November 2024

ABSTRACTAimsRemyelination is an endogenous repair process that is often deficient in multiple sclerosis (MS). Stimulation of remyelination is thought to help limit the progression of MS. This study aimed to investigate the expression pattern and function of a microglial phagocytosis‐related gene, phospholipase D family member 4 (PLD4), in a cuprizone (CPZ)‐induced MS mouse model.MethodsThe extent of remyelination was assessed using LFB staining. Myelin phagocytosis assay was used to investigate the effect of Pld4 on microglial phagocytic activity.ResultsPld4 was upregulated in the corpus callosum during demyelination and remyelination. AAV9‐mediated Pld4 deficiency impaired remyelination and reduced the number of Olig2‐positive cells. In the corpus callosum of Pld4‐deficient mice, the microglial phagocytosis marker MAC2 was reduced, accompanied by inhibition of TrkA/AKT signaling. Similarly, the phagocytosis assay showed that Pld4 knockdown significantly inhibited myelin debris phagocytosis by BV2 cells. The AKT activator SC79 reversed the Pld4 deficiency‐induced inhibition of microglial phagocytic activity and rescued the impaired remyelination in Pld4‐deficient mice.ConclusionPLD4 is upregulated in CPZ‐induced MS and modulates microglial phagocytosis and remyelination via the AKT pathway. Our findings provide experimental evidence for a better understanding of the molecular mechanism of MS.
One ring does not fit all: Evaluation of banding‐related injuries in tricolored bats
Authors: Perea Santiago , Ferrall Emily A. , Morris Katrina M. , Pattavina Pete E. , Castleberry Steven B. 
Published: November 2024

AbstractThe potential harm inflicted by forearm bands on bats has been debated for decades. To aid in decision‐making regarding bat marking, we conducted a comprehensive assessment of banding injuries using recapture data from a long‐term overwintering study in Georgia, USA, involving 776 banded tricolored bats (Perimyotis subflavus) with 284 recaptures. Most recaptured bats showed no visible injuries (77.8%); however, 22.2% of bats presented varying degrees of band‐related injuries. Although <25% of tricolored bats exhibited banding‐related injuries, sublethal effects of injuries are unknown and could add additional stressors to bat populations already facing multiple threats, including mortality from white‐nose syndrome. Thus, we recommend that banding bats, especially species that have experienced white‐nose syndrome‐related population declines, be appropriately justified and their use carefully considered. Our study contributes valuable knowledge to aid in informed decision‐making on the use of capture‐mark‐recapture methods in the research and management of bat communities.
Cost–benefit analysis as a decision tool for effective conservation planning—The case of the Nyerere Selous‐Udzungwa wildlife corridor in Tanzania
Authors: Hilton Tom , Smit Josephine B. , Jones Trevor , Mwalugelo Joseph , Lim Kim , Seidl Andrew , Jones Kelly W. , Bruyere Brett , Salerno Jonathan 
Published: November 2024

AbstractCost benefit analysis (CBA) is used in many fields to ensure efficient allocation of scarce resources but is rarely applied in conservation. By using a common metric to evaluate projects in complex social‐ecological systems, CBA can help to maximize the impact of conservation funding. It can also help to interrogate issues of distributional equity, plan for effective community‐based conservation, and inform future research and strategic priorities. We demonstrate this using the example of the Nyerere Selous‐Udzungwa Wildlife Corridor in Tanzania, a wildlife corridor aiming to restore connectivity between two protected areas to enhance African elephant (Loxodonta africana) conservation outcomes and mitigate human–elephant conflict. We combine novel data on elephant crop depredation with crop price and productivity data, elephant valuation methods, and ecosystem service values to analyze corridor costs and benefits from contrasting global and local community perspectives. From the global perspective, we find benefits to outweigh costs by at least 4.6:1. From the communities' perspective, we find that while substantial benefits should secure buy‐in to the project, continued subsidy will be required to cover the costs. Our findings support generalized recommendations for application of CBA across diverse systems and conservation priorities.
Prevalence and risk factors for impaired awareness of hypoglycaemia: A registry‐based study of 10,202 adults with type 1 diabetes in Norway
Authors: Hernar Ingvild , Strandberg Ragnhild B. , Nilsen Roy M. , Cooper John G. , Skinner Timothy C. , Iversen Marjolein M. , Richards David A. , Lie Silje S. , Løvaas Karianne F. , Madsen Tone Vonheim , Ueland Grethe Å. , Haugstvedt Anne 
Published: November 2024

AbstractAimsThe aim of this study is to determine the prevalence of impaired awareness of hypoglycaemia (IAH) and examine risk factors for IAH in adults with type 1 diabetes.MethodsWe conducted a population‐based registry study of 10,202 adults (≥18 years) with type 1 diabetes using data from the Norwegian Diabetes Register for Adults. The registry used the 1‐item Gold scale, measuring hypoglycaemia symptom awareness. We calculated the overall prevalence of IAH (Gold score ≥4) (95% CI) and prevalence for subgroups based on demographic and clinical variables. We estimated IAH prevalence based on continuous scales of age, diabetes duration and HbA1c using predicted probabilities from generalised additive logistic regression models. Finally, we quantified the associations of selected variables on IAH prevalence using log‐binomial regression models.ResultsOverall, 18.0% reported IAH (95% CI 17.2, 18.7). The prevalence increased linearly with the participants' age, whereas the associations of diabetes duration and HbA1c with IAH were non‐linear with higher prevalence in both lower and higher tails of their distributions. Multiple severe hypoglycaemic events, female sex, age ≥ 65 years, diabetes duration ≤4 years or ≥ 30 years, multiple DKA events and CGM use were associated with higher risk for IAH. HbA1c 65–74 mmol/mol (8.1–8.9%) was associated with lower risk for IAH.ConclusionsIn this nationwide study, the IAH prevalence was 18.0%. Multiple hypoglycaemic events, female sex and diabetes duration were identified as important risk factors for IAH. Study findings highlight the complexity of self‐reported hypoglycaemia symptom awareness and emphasise the importance of routinely addressing symptom awareness in diabetes follow‐up.
Blood CD45+/CD3+ lymphocyte‐released extracellular vesicles and mortality in hospitalized patients with coronavirus disease 2019
Authors: Suades Rosa , Greco Maria F. , Padró Teresa , de Santisteban Victoria , Domingo Pere , Benincasa Giuditta , Napoli Claudio , Greco Simona , Madè Alisia , Ranucci Marco , Devaux Yvan , Martelli Fabio , Badimon Lina 
Published: November 2024

AbstractBackgroundThe global pandemic of coronavirus disease 2019 (COVID‐19) represented a major public health concern. Growing evidence shows that plasma of COVID‐19 patients contains large numbers of circulating extracellular vesicles (cEVs) that correlate with disease severity and recovery. In this study, we sought to characterize the longitudinal cEV signature in critically ill COVID‐19 patients during hospitalization and its relation to mortality risk.MethodscEVs were quantitatively and phenotypically analysed in hospitalized non‐surviving COVID‐19 patients at baseline (n = 42) and before exitus (n = 40) and in 40 healthy volunteers as a reference group by high sensitivity nano flow cytometry using specific markers for parental cell sources and activation.ResultsLevels of cEV subtypes differed between patients with severe COVID‐19 and healthy subjects, specifically those from platelets and endothelial, inflammatory and viral infected cells, which associate to high mortality risk. In the longitudinal analysis from baseline to the time point immediately preceding death, no changes were found for platelet, pan‐leukocyte, and lung epithelial cell‐shed cEVs, while endothelial cell releases of EVs (eEVs) significantly differed. Vascular endothelial growth factor receptor 2‐positive eEVs were significantly increased before death compared to admission whereas endoglin and E‐selectin‐containing eEVs did not change. Conversely, lymphocyte (ℓEV), monocyte, macrophage, pericyte and progenitor cell‐derived cEVs displayed significant reductions before exitus. Noteworthy, levels of CD45+/CD3+‐ℓEVs were significantly associated to the patient's survival time.ConclusionsAn evolving cEV profile able to discriminate prompt risk of death during hospitalization has been defined suggesting a role for circulating and vascular cell‐derived EVs in COVID‐19 pathogenesis.
Cereal aphid species: their natural enemies and efficiency of Lysiphlebus testaceipes (Cresson, 1880) to control Rhopalosiphum maidis (Fitch, 1856)
Authors: Haouas Dalila , Mdellel Lassaad , Zgolli Mayssa , Manai Mohamed Habib , Sarthou Jean Pierre 
Published: November 2024

AbstractCereal grains both for human consumption and animal feed are an essential component of global food systems. However, during production they are often targeted by various pest insects, including aphids. A survey was carried out from 2017 to 2021 in six cereal production sites in Tunisia to evaluate aphid diversity and identify natural enemies on Triticum turgidum subsp. durum (durum wheat), Hordeum vulgare (barley), Avena sativa (oat) and Triticum secale (triticale). Six aphid species belonging to four genera were recorded: Diuraphis noxia, Rhopalosiphum maidis, R. padi, Schizaphis graminum, Sitobion avenae and Sitobion fragariae. Among these, S. avenae and R. padi emerged as the most prevalent species across the majority of sites, infesting durum wheat, barley and triticale. Sc. graminum, R. maidis and D. noxia were less frequent, while S. fragariae was exclusively found on oat plants. Common aphid predators observed included Coccinella algerica, Hippodamia variegata and C. undecimpunctata, as well as syrphid flies such as Episyrphus balteatus and Sphaerophoria rueppellii. Lysiphlebus testaceipes was the sole parasitoid species detected, emerging exclusively from R. padi and R. maidis mummies. Furthermore, the study on the efficacy of L. testaceipes against R. maidis indicated that parasitism levels increased with the number of introduced parasitoid pairs. Aphid and natural enemy diversity were also evaluated.
Feed‐induced hypersalivation in horses from Austria, Germany and Switzerland
Authors: Böswald Linda Franziska , Gottschalk Christoph , Kaltner Florian , Merk Joana , Schwaiger Karin , Kienzle Ellen 
Published: November 2024

AbstractBackgroundWhile previous reports come mostly from the southern Americas, several outbreaks of hypersalivation in horses were observed in Middle Europe from 2016 to 2018.ObjectiveTo describe feed‐induced hypersalivation in European horses.Study designAnalysis of feedstuffs.MethodsVeterinarians and horse or stable owners were encouraged to submit feedstuffs from case outbreaks of hypersalivation in which, infectious diseases or other systemic causes of the syndrome were ruled out and intoxication was suspected. Feedstuff analysis was performed, including gross examination, microscopic analysis of fine particles, and for hay and forage mycological culturing and mycotoxin testing.ResultsEleven case outbreaks were investigated. Typical clinical findings in the horses were either foamy saliva around the mouth or serous salivation with puddles forming on the ground. Some horses also showed lesions of the gingival mucosa and/or the tongue. Foamy hypersalivation, sometimes combined with lesions of tongue and/or gingiva, was associated with finding of ergot sclerotia and ergot alkaloids in hay or pasture plants (ergocornin and ergocorninin having the highest concentrations). Serous hypersalivation with massive loss of fluid was associated with the fungus Rhizoctonia spp. As indicated by the detection of traces of swainsonine, mycotoxin production on the forage was seen as likely cause. The cessation of clinical signs took days to weeks after diet change, probably depending on the duration, type and amount of toxin intake.Main limitationsSmall number of case outbreaks, records of clinical findings and horses' management were incomplete and were reported by horse owners.ConclusionHypersalivation due to mycotoxins in the feed has become an emerging problem for horses in middle Europe.
A new player in the game: identification of C1ql1 as a novel factor driving OPC differentiation
Authors: Van Broeckhoven Jana , Mussen Femke , Schepers Melissa , Vanmierlo Tim , Hellings Niels 
Published: November 2024

Oligodendrocytes (OLGs) are the myelin‐producing cells in the central nervous system (CNS). Following injury, these cells are prone to death, leading to demyelination and, eventually, axonal loss and neurodegeneration. Upon injury, the damaged CNS repopulates the lesion with oligodendrocyte precursor cells (OPCs) that consequently mature into OLGs to repair the myelin damage and prevent further axonal loss. In this issue, Altunay et al. identified that complement component 1, q subcomponent‐like‐1 (C1ql1), a factor known to play a role in neuron–neuron synapses, is also expressed by OPCs and drives their differentiation into OLGs. These data suggest that C1ql1 or other downstream factors could be therapeutic targets in the context of demyelinating disorders in which remyelination fails, such as in multiple sclerosis (MS).
Near‐Term Forecasting of Terrestrial Mobile Species Distributions for Adaptive Management Under Extreme Weather Events
Authors: Dobson Rachel , Willis Stephen G. , Jennings Stewart , Cheke Robert A. , Challinor Andrew J. , Dallimer Martin 
Published: November 2024

ABSTRACTAcross the globe, mobile species are key components of ecosystems. Migratory birds and nomadic antelope can have considerable conservation, economic or societal value, while irruptive insects can be major pests and threaten food security. Extreme weather events, which are increasing in frequency and intensity under ongoing climate change, are driving rapid and unforeseen shifts in mobile species distributions. This challenges their management, potentially leading to population declines, or exacerbating the adverse impacts of pests. Near‐term, within‐year forecasting may have the potential to anticipate mobile species distribution changes during extreme weather events, thus informing adaptive management strategies. Here, for the first time, we assess the robustness of near‐term forecasting of the distribution of a terrestrial species under extreme weather. For this, we generated near‐term (2 weeks to 7 months ahead) distribution forecasts for a crop pest that is a threat to food security in southern Africa, the red‐billed quelea Quelea quelea. To assess performance, we generated hindcasts of the species distribution across 13 years (2004–2016) that encompassed two major droughts. We show that, using dynamic species distribution models (D‐SDMs), environmental suitability for quelea can be accurately forecast with seasonal lead times (up to 7 months ahead), at high resolution, and across a large spatial scale, including in extreme drought conditions. D‐SDM predictive accuracy and near‐term hindcast reliability were primarily driven by the availability of training data rather than overarching weather conditions. We discuss how a forecasting system could be used to inform adaptive management of mobile species and mitigate impacts of extreme weather, including by anticipating sites and times for transient management and proactively mobilising resources for prepared responses. Our results suggest that such techniques could be widely applied to inform more resilient, adaptive management of mobile species worldwide.
Managing the Global Wetland Methane‐Climate Feedback: A Review of Potential Options
Authors: Ury Emily A. , Hinckley Eve‐Lyn S. , Visioni Daniele , Buma Brian 
Published: November 2024

ABSTRACTMethane emissions by global wetlands are anticipated to increase due to climate warming. The increase in methane represents a sizable emissions source (32–68 Tg CH4 year−1 greater in 2099 than 2010, for RCP2.6–4.5) that threatens long‐term climate stability and poses a significant positive feedback that magnifies climate warming. However, management of this feedback, which is ultimately driven by human‐caused warming and thus “indirectly” anthropogenic, has been largely unexplored. Here, we review the known range of options for direct management of rising wetland methane emissions, outline contexts for their application, and explore a global scale thought experiment to gauge their potential impact. Among potential management options for methane emissions from wetlands, substrate amendments, particularly sulfate, are the most well studied, although the majority have only been tested in laboratory settings and without considering potential environmental externalities. Using published models, we find that the bulk (64%–80%) of additional wetland methane will arise from hotspots making up only about 8% of global wetland extent, primarily occurring in the tropics and subtropics. If applied to these hotspots, sulfate might suppress 10%–21% of the total additional wetland methane emissions, but this treatment comes with considerable negative consequences for the environment. This thought experiment leverages results from experimental simulations of sulfate from acid rain, as there is essentially no research on the use of sulfate for intentional suppression of additional wetland methane emissions. Given the magnitude of the potential climate forcing feedback of methane from wetlands, it is critical to explore management options and their impacts to ensure that decisions made to directly manage—or not manage—this process be made with the best available science.