bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microglial AKAP8L: a key mediator in diabetes-associated cognitive impairment via autophagy inhibition and neuroinflammation triggering
Authors: Zhang Wen-yuan , Wei Qian-qian , Zhang Tao , Wang Chang-shui , Chen Jing , Wang Jian-hua , Xie Xin , Jiang Pei 
Published: July 2024

Abstract
Background
Diabetes-associated cognitive impairment (DACI) poses a significant challenge to the self-management of diabetes, markedly elevating the risk of adverse complications. A burgeoning body of evidence implicates microglia as a central player in the pathogenesis of DACI.

Methods
We utilized proteomics to identify potential biomarkers in high glucose (HG)-treated microglia, followed by gene knockdown techniques for mechanistic validation in vitro and in vivo.

Results
Our proteomic analysis identified a significant upregulation of AKAP8L in HG-treated microglia, with concurrent dysregulation of autophagy and inflammation markers, making AKAP8L a novel biomarker of interest. Notably, the accumulation of AKAP8L was specific to HG-treated microglia, with no observed changes in co-cultured astrocytes or neurons, a pattern that was mirrored in streptozotocin (STZ)-induced diabetic mice. Further studies through co-immunoprecipitation and proximity ligation assay indicated that the elevated AKAP8L in HG-treated microglial cells interacts with the mTORC1. In the STZ mouse model, we demonstrated that both AKAP8L knockdown and rapamycin treatment significantly enhanced cognitive function, as evidenced by improved performance in the Morris water maze, and reduced microglial activation. Moreover, these interventions effectively suppressed mTORC1 signaling, normalized autophagic flux, mitigated neuroinflammation, and decreased pyroptosis.

Conclusions
Our findings highlight the critical role of AKAP8L in the development of DACI. By interacting with mTORC1, AKAP8L appears to obstruct autophagic processes and initiate a cascade of neuroinflammatory responses. The identification of AKAP8L as a key mediator in DACI opens up new avenues for potential therapeutic interventions.
Advanced screening methods for assessing motility and hatching in plant-parasitic nematodes
Authors: Kadlecová Alena , Hendrychová Romana , Jirsa Tomáš , Čermák Václav , Huang Mengmeng , Grundler Florian M.W. , Schleker A. Sylvia S. 
Published: July 2024

Abstract
Background
Plant-parasitic nematodes are economically important pests responsible for substantial losses in agriculture. Researchers focusing on plant-parasitic nematodes, especially on finding new ways of their control, often need to assess basic parameters such as their motility, viability, and reproduction. Traditionally, these assays involve visually counting juveniles and eggs under a dissecting microscope, making this investigation time-consuming and laborious.

Results
In this study, we established a procedure to efficiently determine the motility of two plant-parasitic nematode species, Heterodera schachtii and Ditylenchus destructor, using the WMicrotracker ONE platform. Additionally, we demonstrated that hatching of the cyst nematode H. schachtii can be evaluated using both the WMicrotracker ONE and by assessing the enzymatic activity of chitinase produced during hatching.

Conclusions
We present fast and straightforward protocols for studying nematode motility and hatching that allow us to draw conclusions about viability and survival. Thus, these methods are useful tools for facilitating fast and efficient evaluation in various fields of research focused on plant-parasitic nematodes.
Feasibility of epicardial implantation of medtronic 3830 lead in a pediatric patient : case report
Authors: Yuan Dou , Lin Ke , Xu Yuanning 
Published: July 2024

Abstract
Background
High-grade atrioventricular block is the primary reason for epicardial permanent pacemaker implantation during the perioperative period in patients with congenital heart disease. Due to the smaller diameter of venous vessels in children, epicardial permanent pacemaker implantation is usually a preferred choice, we report one pediatric patient who received epicardial permanent pacemaker implantation using a new approach.

Case presentation
We present the case of a 2-year-old girl who underwent the modified Konno procedure and Pulmonary valvuloplasty surgery and presented after surgery with a High-grade atrioventricular block. At over 20 days after the patient underwent a redo-sternotomy which epicardial permanent pacemaker implantation. Medtronic Model 4965 Capsure Epi ® steroid-eluting unipolar epicardial pacing lead was immobilized on the surface of the right ear. The Medtronic 3830 pacing lead was screwed obliquely and clockwise under direct view from the surface of the right ventricle to the endocardium near the interventricular septum. The patient’s recovery was uneventful.

Conclusion
In this case report, we demonstrate the feasibility and potential benefits of using the Medtronic 3830 lead for epicardial pacing in a pediatric patient with severe cardiac complications following surgery for congenital heart disease. This approach offers a viable alternative to traditional epicardial pacing methods, particularly in complex cases where conventional leads fail to provide stable pacing thresholds.
Early treatment for children with mental health problems and genetic conditions through a parenting intervention (The GAP): study protocol for a pragmatic randomized controlled trial
Authors: Serrano Mercedes , Elias Maria , Llorens Marta , Bolasell Mercè , Vall-Roqué Helena , Villalta Laia 
Published: July 2024

Abstract
Background
Children with genetic conditions are at increased risk for mental health and neurodevelopmental problems, often accompanied by significant parental distress. Genetic and family factors can impact children and parents’ mental health. Early parenting interventions, like the Incredible Years® programs, have demonstrated to improve parental distress and children’s mental health. The recent version for young children with language delays or autism spectrum disorder (IY-ASLD®) has shown to be feasible and effective to support parents in their children’s developmental trajectories. The effectiveness of treatments for children with genetic conditions and neurodevelopmental problems is largely unexplored, leaving significant gaps in evidence-based options. Clinicians lack guidance, especially when patients exhibit language or social communication impairments but do not meet diagnostic criteria for a full-blown autism spectrum disorder (ASD). We aim to fill this gap, providing evidence on the feasibility and effectiveness of the IY-ASLD® intervention for such patients.

Methods
We designed a prospective multicenter pragmatic randomized controlled trial including approximately 68 children aged 3 to 7 years, recruited from three tertiary care reference hospitals. Inclusion criteria will necessitate genetic confirmation of a neurodevelopmental disorder along with language, communication, or socialization difficulties. Individuals with an ASD diagnosis will be excluded. All subjects are included in a territorial register for rare conditions (ReMin, Registre de Malalties Minoritàries de Catalunya). Families will randomly be assigned to the intervention or the control group. The intervention will be held online by clinical psychologists and child and adolescent psychiatrists.

Discussion
Our group has recently piloted the online implementation of the IY-ASLD® intervention for the first time in Spain, for parents of children with language delays, socialization difficulties, or ASD, but not genetically determined. Our multicenter research consortium is well-positioned to recruit patients with rare conditions and implement efficient treatment pathways within the National Health System. Given the geographical dispersion of families affected by rare conditions, the online format offers logistical advantages and improved therapy access, enhancing homogeneity across all patients. The results of this study will inform clinicians and policymakers about evidence-based treatment options for this vulnerable and overlooked group of young children.

Trial registration
ClinicalTrials.gov NCT06125093. Date of registration: first submitted 2023–10-23; first posted 2023–11-09. URL of trial registry record.
Protocol update for a multi-centre randomised controlled trial of exercise rehabilitation for people with pulmonary hypertension: the SPHERe trial
Authors: Ennis Stuart , Bruce Julie , Sandhu Harbinder , Ratna Mariam , Lall Ranjit , Ji Chen , Mason James , Kandiyali Rebecca , Seers Kate , Banerjee Prithwish , Taylor Stephanie J. C. , Robertson Elizabeth , Underwood Martin , McGregor Gordon 
Published: July 2024

Abstract
Background
The SPHERe (Supervised Pulmonary Hypertension Exercise Rehabilitation) trial is a multi-centre, pragmatic, randomised controlled trial assessing the clinical and cost-effectiveness of supervised exercise rehabilitation with psychosocial and motivational support compared to best-practice usual care for people with pulmonary hypertension (PH). The original protocol was published in BMC Pulmonary Medicine (accessible online). We randomised our first participant in January 2020. In response to the COVID-19 pandemic, the trial was stopped in March 2020. In person delivery of the SPHERe intervention to a vulnerable population was not possible during the COVID-19 pandemic. We describe here how trial procedures and intervention delivery were adapted in response to the COVID-19 pandemic.

Methods
Restrictions imposed by the COVID-19 pandemic on the clinically vulnerable PH population meant that trial delivery was changed from a centre-based rehabilitation programme to remotely delivered group online sessions. This led to minor alterations to the eligibility criteria. These changes followed a consultation process with stakeholders and people with PH and were approved by the funder and independent trial committees.

Conclusions
We describe the modified SPHERe trial protocol in response to restrictions imposed by the COVID-19 pandemic. SPHERe is the first randomised controlled trial to assess the clinical and cost-effectiveness of an online group rehabilitation programme for people with PH compared to usual care.

Trial registration
ISRCTN no. 10608766. Prospectively registered on 18th March 2019, updated 16th August 2023.
CUT&Tag applied to zebrafish adult tail fins reveals a return of embryonic H3K4me3 patterns during regeneration
Authors: Duong Phu , Rodriguez-Parks Anjelica , Kang Junsu , Murphy Patrick J. 
Published: July 2024

AbstractRegenerative potential is governed by a complex process of transcriptional reprogramming, involving chromatin reorganization and dynamics in transcription factor binding patterns throughout the genome. The degree to which chromatin and epigenetic changes contribute to this process remains only partially understood. Here we provide a modified CUT&Tag protocol suitable for improved characterization and interrogation of changes in chromatin modifications during adult fin regeneration in zebrafish. Our protocol generates data that recapitulates results from previously published ChIP-Seq methods, requires far fewer cells as input, and significantly improves signal to noise ratios. We deliver high-resolution enrichment maps for H3K4me3 of uninjured and regenerating fin tissues. During regeneration, we find that H3K4me3 levels increase over gene promoters which become transcriptionally active and genes which lose H3K4me3 become silenced. Interestingly, these reprogramming events recapitulate the H3K4me3 patterns observed in developing fin folds of 24-h old zebrafish embryos. Our results indicate that changes in genomic H3K4me3 patterns during fin regeneration occur in a manner consistent with reactivation of developmental programs, demonstrating CUT&Tag to be an effective tool for profiling chromatin landscapes in regenerating tissues.
Anticandidal activity of a wild Bacillus subtilis NAM against clinical isolates of pathogenic Candida albicans
Authors: Gharieb Mohamed M. , Rizk Aya , Elfeky Nora 
Published: July 2024

Abstract
Background
Resistance to antifungal medications poses a significant obstacle in combating fungal infections. The development of novel therapeutics for Candida albicans is necessary due to the increasing resistance of candidiasis to the existing medications. The utilization of biological control is seen as a more advantageous and less hazardous strategy therefore the objective of this study is to identify the antifungal properties of Bacillus subtilis against pathogenic C. albicans.

Results
We conducted a study to evaluate the antifungal properties of three bacterial isolates against the human pathogen Candida albicans. One of the bacterial isolates exhibited a potent antifungal activity against this fungal pathogen. This bacterium was identified as Bacillus subtilis based on the 16Sr RNA gene sequence. It exhibited inhibitory efficacy ranging from 33.5 to 44.4% against 15 Candida isolates. The optimal incubation duration for achieving the maximum antifungal activity was determined to be 48 h, resulting in a mean inhibition zone diameter of 29 ± 0.39 mm. The Potato Dextrose agar (PDA) medium was the best medium for the most effective antifungal activity. Incubation temperature of 25oC and medium pH value of 8.0 were the most favorable conditions for maximum antagonistic activity that resulted fungal growth inhibition of 40 ± 0.16 and 36 ± 0.94 mm respectively. Furthermore, the addition of 10.5 mg/ml of bacterial filtrate to C. albicans colonies resulted in 86.51%. decrease in the number of germinated cells. The fungal cell ultrastructural responses due to exposure to B. subtilis filtrate after 48 h were investigated using transmission electron microscopy (TEM). It revealed primary a drastic abnormality that lead to cellular disintegration including folding and lysis of the cell wall, total collapse of the yeast cells, and malformed germ tube following the exposure to the filtrate. However, the control culture treatment had a characteristic morphology of the normal fungal cells featuring a consistently dense central region, a well-organized nucleus, and a cytoplasm containing several components of the endomembrane system. The cells were surrounded by a uniform and intact cell wall.

Conclusion
The current study demonstrates a notable antifungal properties of B. subtilis against C. albicans as a result of production of bioactive components of the bacterial exudate. This finding could be a promising natural antifungal agent that could be utilized to combat C. albicans.
Radiotherapy for subependymal giant cell astrocytoma: time to challenge a historical ban? A case report and review of the literature
Authors: Kamel Randa , Van den Berge Dirk 
Published: July 2024

Abstract
Background
Subependymal giant cell astrocytoma is a benign brain tumor that occurs in patients with tuberous sclerosis complex. Surgical removal is the traditional treatment, and expert opinion is strongly against the use of radiotherapy. Recently, success has been reported with the mTor inhibitor everolimus in reducing tumor volume, but regrowth has been observed after dose reduction or cessation.

Case report
We present the case of a 40-year-old Asian female patient treated successfully for growing bilateral subependymal giant cell astrocytoma with fractionated stereotactic radiotherapy before everolimus became available. After a follow-up of 8 years, everolimus was administered for renal angiomyolipoma and the patient was followed up until 13 years after radiotherapy. Successive magnetic resonance imaging demonstrated an 80% volume reduction after radiotherapy that increased to 90% with everolimus. A review of the literature was done leveraging Medline via PubMed, and we assembled a database of 1298 article references and 780 full-text articles in search of evidence for contraindicating radiotherapy in subependymal giant cell astrocytoma. Varying results of single-fraction radiosurgery were described in a total of 13 cases. Only in two published cases was the radiation dose of fractionated radiotherapy mentioned. One single publication mentions an induced secondary brain tumor 8 years after whole-brain radiotherapy.

Conclusion
There is no evidence of contraindication and exclusion of fractionated radiotherapy in treating subependymal giant cell astrocytoma. Our experience demonstrates that subependymal giant cell astrocytoma, as other benign intracranial tumors, responds slowly but progressively to radiotherapy and suggests that fractionated stereotactic radiotherapy holds promise to consolidate responses obtained with mTor inhibitors avoiding regrowth after cessation.
The influence of vesicularity on grain morphology in basaltic pyroclasts from Mauna Loa and Kīlauea volcanoes
Authors: van Helden Kira M. , Schmith Johanne , Downs Drew T. 
Published: July 2024

AbstractVesicularity of individual pyroclasts from airfall tephra deposits is an important parameter that is commonly measured at basaltic volcanoes. Conventional methods used to determine pyroclast vesicularity on a large number of clasts has the potential to be time consuming, particularly when rapid analysis is required. Here we propose dynamic image analysis on two-dimensional (2D) projection shapes of crushed pyroclasts from tephra deposits as a new method to estimate vesicularity. This method relies on the influence of vesicles and uses grain morphology as a proxy for vesicle size and abundance. Pyroclasts from a variety of basaltic tephra deposits from the volcanoes of Mauna Loa and Kīlauea were analyzed. Vesicularities between 52–98% were measured via nitrogen-gas pycnometry. The same pyroclasts were then crushed and sieved, and their grain shapes measured using dynamic image analysis on a CAMSIZER®. This yields values for the mean sphericity, elongation, compactness, and Krumbein roundness of the grains. Our data show that grains become increasingly irregular with increasing vesicularity, with the degree of correlation between shape parameters and vesicularity depending on the size of measured grains. Shape irregularities in small grains (60–250 µm) are mostly area-based, with elongation being the best vesicularity indicator, whereas shape irregularities in large grains (250–700 µm) are mostly perimeter-based, with Krumbein roundness as the best vesicularity indicator. Using mean shape parameter values with all grain sizes included, grain elongation is the most well-correlated shape parameter with vesicularity, with the best fitted model explaining 76% of variation in the observations. Microscope images of thin sections of intact pyroclasts, as well as from crushed pyroclasts, were analyzed using CSDCorrections 1.6 software in ImageJ to find local vesicularity, vesicle size, grain size, grain elongation, and vesicle spatial distribution by stereological conversion. Observed correlation between grain shape and vesicularity can be explained by the local effect of vesicles on the shape of the solid structure in between those vesicles. Grain shape depends not only on vesicularity, but also on vesicle to grain size ratio and the spatial distribution of vesicles. The influence of vesicles on grain shape is best captured by grains with the size of the solid structure in between vesicles, which generally increases with decreasing vesicularity. Dynamic image analysis is a useful tool to quickly gauge vesicularity, which could be used in near-real-time during an eruption response. However, this method is best suited for highly vesicular (> 80%) basaltic pyroclasts from tephra deposits with few microlites and phenocrysts. Further research on crushing techniques, optimum grain size for shape measurements, and Krumbein roundness measurements for the grain size range of 250–700 µm might enable application of this method to lower vesicularity pyroclasts.
Time-series metagenomics reveals changing protistan ecology of a temperate dimictic lake
Authors: Krinos Arianna I. , Bowers Robert M. , Rohwer Robin R. , McMahon Katherine D. , Woyke Tanja , Schulz Frederik 
Published: July 2024

Abstract
Background
Protists, single-celled eukaryotic organisms, are critical to food web ecology, contributing to primary productivity and connecting small bacteria and archaea to higher trophic levels. Lake Mendota is a large, eutrophic natural lake that is a Long-Term Ecological Research site and among the world’s best-studied freshwater systems. Metagenomic samples have been collected and shotgun sequenced from Lake Mendota for the last 20 years. Here, we analyze this comprehensive time series to infer changes to the structure and function of the protistan community and to hypothesize about their interactions with bacteria.

Results
Based on small subunit rRNA genes extracted from the metagenomes and metagenome-assembled genomes of microeukaryotes, we identify shifts in the eukaryotic phytoplankton community over time, which we predict to be a consequence of reduced zooplankton grazing pressures after the invasion of a invasive predator (the spiny water flea) to the lake. The metagenomic data also reveal the presence of the spiny water flea and the zebra mussel, a second invasive species to Lake Mendota, prior to their visual identification during routine monitoring. Furthermore, we use species co-occurrence and co-abundance analysis to connect the protistan community with bacterial taxa. Correlation analysis suggests that protists and bacteria may interact or respond similarly to environmental conditions. Cryptophytes declined in the second decade of the timeseries, while many alveolate groups (e.g., ciliates and dinoflagellates) and diatoms increased in abundance, changes that have implications for food web efficiency in Lake Mendota.

Conclusions
We demonstrate that metagenomic sequence-based community analysis can complement existing efforts to monitor protists in Lake Mendota based on microscopy-based count surveys. We observed patterns of seasonal abundance in microeukaryotes in Lake Mendota that corroborated expectations from other systems, including high abundance of cryptophytes in winter and diatoms in fall and spring, but with much higher resolution than previous surveys. Our study identified long-term changes in the abundance of eukaryotic microbes and provided context for the known establishment of an invasive species that catalyzes a trophic cascade involving protists. Our findings are important for decoding potential long-term consequences of human interventions, including invasive species introduction.