bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimal Systolic Blood pressure control after thrombectomy in acute ischemic stroke-a systematic review and meta-analysis
Authors: Panigrahi Baikuntha , Bhatia Rohit , Haldar Partha , Sarkar Risha , Longkumer Imnameren 
Published: April 2024

AbstractBackground and ObjectivesAlthough endovascular thrombectomy(EVT) is the standard of care for acute large vessel occlusions(LVO), optimal systolic blood pressure (SBP) control post procedure has remained elusive. Our study aimed to address the question of whether in adult patients of acute ischemic stroke(AIS) who undergo EVT does an intensive SBP control as compared to a less intensive SBP control/conventional control up to 24 hours post procedure lead to a good functional outcomes defined by modified Rankin score(mRS) of 0-2 at 90days.MethodsThis PRISMA guidelines were followed for this review. Databases(PubMed, SCOPUS, EMBASE, Google Scholar and Web of Science) were searched for English language articles using predefined search terms till Sep 15 2023. The inclusion criteria consisted of randomized controlled trials (RCTs) and observational studies(at least total 20patients) analysing intensive vs conventional SBP control in AIS due to LVO post-EVT up to 24hours. Studies without a separate comparison primary outcome data, comparing SBP control in AIS due to LVO treated only with IV thrombolysis (IVT) without EVT, case series and case reports were excluded. The primary outcome was the rate of functional independence defined by mRS 0-2 at 90days. Risk of bias was assessed using the New Castle Ottawa scale(NOS) for observational studies, and the revised Cochrane risk-of-bias 2 (ROB2) tool for RCTs.ResultsTwelve studies(n=5439 patients-eight observational and four RCTs) were included in the final analysis. The primary outcome was not significantly different between both the arms(RR:1.16;95%CI-0.98-1.37;p=0.08).There were no significant differences in the mortality at 90days(RR:0.83;95%CI-0.68-1.02;p=0.08) and the risk of symptomatic intracranial haemorrhage(RR:0.84;95%CI-0.61-1.16;p=0.29). Fewer patients required decompressive surgery in the intensive arm(RR-0.40; 95%CI-0.25-0.66; p=0.0003). A separate analysis for the primary outcome from pooled observational data favoured intensive control(RR-1.34;95%CI-1.20-1.48; p<0.00001) and data from RCTs favoured conventional control(RR-0.82;95%CI-0.72-0.93;p=0.003).ConclusionNeither intensive nor conventional SBP control resulted in better functional outcome in the combined analysis of all studies. Although, observational studies favoured intensive control, data from RCTs suggested conventional management as the preferred approach which could currently be a pragmatic strategy. Further ongoing RCTs using homogenous SBP cut-offs will provide more clarity on the ideal SBP target after EVT.
Incidence and Risk of Post-COVID-19 Thromboembolic Disease and the Impact of Aspirin Prescription; Nationwide Observational Cohort at the US Department of Veteran Affairs
Authors: Ware Anna D , Veigulis Zachary P , Hoover Peter J , Blumke Terri L , Ioannou George N , Boyko Edward J , Osborne Thomas F 
Published: April 2024

AbstractIntroductionCOVID-19 triggers prothrombotic and proinflammatory changes, with thrombotic disease prevalent in up to 30% SARS-CoV-2 infected patients. Early work suggests that aspirin could prevent COVID-19 related thromboembolic disorders in some studies but not others. This study leverages data from the largest integrated healthcare system in the United States to better understand this association. Our objective was to evaluate the incidence and risk of COVID-19 associated acute thromboembolic disorders and the potential impact of aspirin.MethodsThis retrospective, observational study utilized national electronic health record data from the Veterans Health Administration. 334,374 Veterans who tested positive for COVID-19 from March 2, 2020, to June 13, 2022, were included, 81,830 of whom had preexisting aspirin prescription prior to their COVID-19 diagnosis. Patients with and without aspirin prescriptions were matched and the odds of post-COVID acute thromboembolic disorders were assessed.Results10.1% of Veterans had a documented thromboembolic disorder within 12 months following their COVID-19 diagnosis. Those with specific comorbidities were at greatest risk. Preexisting aspirin prescription was associated with a significant decrease risk of post-COVID-19 thromboembolic disorders, including pulmonary embolism (OR [95% CI]: 0.69 [0.65, 0.74]) and deep vein thrombosis (OR [95% CI]: 0.76 [0.69, 0.83], but an increased risk of acute arterial diseases, including ischemic stroke (OR [95% CI]: 1.54 [1.46, 1.60]) and acute ischemic heart disease (1.33 [1.26, 1.39]).ConclusionsFindings demonstrated that preexisting aspirin prescription prior to COVID-19 diagnosis was associated with significantly decreased risk of venous thromboembolism and pulmonary embolism but increased risk of acute arterial disease. The risk of arterial disease may be associated with increased COVID-19 prothrombotic effects superimposed on preexisting chronic cardiovascular disease for which aspirin was already prescribed. Prospective clinical trials may help to further assess the efficacy of aspirin use prior to COVID-19 diagnosis for the prevention of post-COVID-19 thromboembolic disorders.
The Immobilization of Hyaluronic Acid in 3D Hydrogel Scaffolds Modulates Macrophage Polarization
Authors: Oates Tiah CL , Boyd Jasmin , Dolan Louise , Kergariou C de , Toye Ash , Perriman Adam W , Boussahel Asme 
Published: April 2024

AbstractMacrophages are key modulators of immunity, tissue homeostasis and disease development. As our understanding of macrophage biology and their tissue specific behaviors grow the necessity to model macrophages within a 3D biomimetic environment becomes increasingly apparent. Numerous hydrogels have been developed and explored for this purpose, extracellular matrix (ECM) mimicking hydrogels gaining a special interest. In this study, we present the use of such a hydrogel composed of collagen and hyaluronic acid (HA), two of the major ECM components, for the 3D culture of macrophages to model their role in different tissues and diseases. We demonstrate the ability to tailor the mechanical properties of the hydrogel through formulation modulation. Human macrophages retain morphology, viability, and expression of key cell surface markers when 3D cultured within the hydrogel. Interestingly, we demonstrate in this work, that independent of mechanical properties, by adjusting the composition of the hydrogel, specifically HA molecular weight, we can steer macrophage polarization towards either a pro-inflammatory or anti-inflammatory phenotype. This HA-dependent modulation of macrophage behavior is nullified if the HA is chemically crosslinked, shedding light on the impact of one of the most commonly used preparation methods for collagen-HA hydrogels on macrophage behavior.Graphical abstractHyaluronic acid (HA) is an extracellular matrix component, which can modulate the polarization of macrophages. The chemical crosslinking of HA to hydrogel scaffolds counteracts the cell signaling role of this molecule, preventing HA from modulating the immune polarization of macrophages within the model.Key pointsCollagen-HA hydrogels form suitable biomimetic niches for the 3D culture of human macrophages in which hydrogel composition modulates macrophage phenotype, specifically the presence and molecular weight of HA.Polarization of macrophage phenotype by HA is nullified if HA is chemically cross-linked within the hydrogel.
Loading of extracellular vesicles with nucleic acids via hybridization with sponge-like lipid nanoparticles
Authors: Bader Johannes , Rüedi Pascal , Mantella Valeria , Geisshüsler Silvana , Brigger Finn , Qureshi Bilal M. , Arroyo Jaime Ortega , Montanari Elita , Leroux Jean-Christophe 
Published: April 2024

AbstractThe translation of cell-derived extracellular vesicles (EVs) into biogenic gene delivery systems is limited by relatively inefficient loading strategies. In this work, we describe the loading of various nucleic acids into small EVsviatheir spontaneous hybridization with preloaded non-lamellar liquid crystalline lipid nanoparticles (LCNPs) under physiological conditions, forming hybrid EVs (HEVs). We correlate LCNPs’ topological characteristics with their propensity to fuse/aggregate with EVs and found that sponge (L3) phases at pH 7.4 were particularly suitable to induce a controlled hybridization process. State-of-the-art single-particle analysis techniques revealed that L3-based LCNPs interact with various EV subpopulations and that around 40% of HEVs were loaded with the genetic cargo. Importantly, this study demonstrates that EV membrane proteins remain accessible on HEV surfaces, with their intrinsic enzymatic activity unaffected after the hybridization process. Finally, HEVs showedin vitroimproved transfection efficiencies compared to unhybridized LCNPs. In summary, this versatile platform holds potential for loading various nucleic acid molecules into native EVs and may help developing EV-based therapeutics.TeaserTopology of lipid nanoparticles influences their hybridization behavior with extracellular vesicles and produces novel biogenic gene delivery systems.
Unexpectedly dense colonization of soil pore space by microbes
Authors: Schmidt Hannes , Schlüter Steffen , Raynaud Xavier , Felde Vincent J.M.N.L. , Zeller-Plumhoff Berit , Richter Andreas , Nunan Naoise 
Published: April 2024

AbstractPore surfaces in soil are considered to be sparsely colonised, dispersed only with isolated cells or colonies of bacteria and archaea. Here, we question this ‘empty space’-concept by combining microstructure analysis with molecular biology and provide a data-driven update on habitable surface areas (HSA) in soil. Our unique approach allowed us to provide 1) evidence that microbial densities in soil have been underestimated for decades and 2) two-dimensional simulations of their potential distribution within the soil pore space. Our results demonstrate the need for a new perspective on how densely soil is colonised, with implications for how we think of basic ecological processes such as microbial motility or predation, and how microbial processes, including organic matter dynamics, are ultimately modelled.
The role of FraI in cell-cell communication and differentiation in the hormogonia-forming cyanobacterium Nostoc punctiforme
Authors: Janović Ana , Maldener Iris , Menzel Claudia , Parrett Gabriel A. , Risser Douglas D. 
Published: April 2024

AbstractMulticellular cyanobacteria, likeNostoc punctiforme, rely on septal junctions for cell-cell communication, which is crucial for coordinating various physiological processes including differentiation of N2-fixing heterocysts, spore-like akinetes and hormogonia - short, motile filaments important for dispersal. In this study we functionally characterize a protein, encoded by geneNpF4142, which in a random mutagenesis approach, initially showed a motility-related function. The reconstructedNpF4142knockout mutant exhibits further distinct phenotypic traits, including altered hormogonia formation with significant reduced motility, inability to differentiate heterocysts and filament fragmentation. For that reason, we named the protein FraI (fragmentation phenotype). The mutant displays severely impaired cell-cell communication, due to almost complete absence of the nanopore array in the septal cell wall, which is an essential part of the septal junctions. Despite lack of communication, hormogonia in the ΔfraImutant maintain motility and phototactic behaviour, even though less pronounced than the wild type. This suggests an alternative mechanism for coordinated movement beyond septal junctions. Our study underscores the significance of FraI in nanopore formation and cell differentiation and provides additional evidence for the importance of septal junction formation and communication in various differentiation traits of cyanobacteria. The findings contribute to a deeper understanding of the regulatory networks governing multicellular cyanobacterial behaviour, with implications for broader insights into microbial multicellularity.ImportanceThe filament-forming cyanobacteriumNostoc punctiformeserves as a valuable model for studying cell differentiation, including the formation of nitrogen-fixing heterocysts and hormogonia. Hormogonia filaments play a crucial role in dispersal and plant colonization, providing a nitrogen source through atmospheric nitrogen fixation, thus holding promise for fertilizer-free agriculture. The coordination among the hormogonia cells enabling uniform movement towards the positive signal remains poorly understood. This study investigates the role of septal junction-mediated communication in hormogonia differentiation and motility, by studying a ΔfraImutant with significantly impaired communication. Surprisingly, impaired communication does not abolish synchronized filament movement, suggesting an alternative coordination mechanism. These findings deepen our understanding of cyanobacterial biology and have broader implications for multicellular behavior in prokaryotes.
Mechanically Sheared Axially Swept Light-Sheet Microscopy
Authors: Lin Jinlong , Mehra Dushyant , Marin Zach , Wang Xiaoding , Borges Hazel M. , Shen Qionghua , Gałecki Seweryn , Haug John , Dean Kevin M. 
Published: April 2024

AbstractWe present a mechanically sheared image acquisition format for upright and open-top light-sheet microscopes that automatically places data in its proper spatial context. This approach, which reduces computational post-processing and eliminates unnecessary interpolation or duplication of the data, is demonstrated on an upright variant of Axially Swept Light-Sheet Microscopy (ASLM) that achieves a field of view, measuring 774 x 435 microns, that is 3.2-fold larger than previous models and a raw and isotropic resolution of ∼420 nm. Combined, we demonstrate the power of this approach by imaging sub-diffraction beads, cleared biological tissues, and expanded specimens.
Diffusion tractography predicts Deep Brain Stimulation evoked potential amplitude and delay
Authors: Abe Sumiko , Vidmark Jessica , Hernandez-Martin Estefania , Kasiri Maral , Sorouhmojdehi Rahil , Seyyed Mousavi S. Alireza , Sanger Terence D. 
Published: April 2024

AbstractObjectiveThis study investigated the relationship between DBS evoked potentials (EPs) and diffusion tensor imaging (DTI) in a group of patients with dystonia who underwent DBS treatment. EPs and DTI are both useful methods for studying neural connectivity in the brain but measure different aspects of brain function. EPs provide information on electrical connectivity, while DTI provides information on anatomical pathways connecting regions.MethodsThis study focused on the pallidum and motor thalamus nuclei, which are common targets for DBS in dystonia. Prior to DBS implantation, DTI images were acquired for each patient, and were processed to obtain DTI coefficients such as length (L), volume (V), and fractional anisotropy (FA) of the fiber tracts. The relationship between the fiber tracts and electrophysiology was examined using a generalized linear model (GLM).ResultsWe showed that the amplitude of EPs correlated with FA and tract volume, while delay correlated with tract length. These findings suggest that DBS signals travel across tracts to affect both local and distant brain regions, and the magnitude of the effect of DBS is determined by the integrity of the white matter tract, while DBS signal delay is affected by the tract length. Our results further suggest that the magnitude and delay of the spread of the DBS signal may be predicted by the DTI connectivity. This provides strong supporting evidence for other studies that have assumed, but have been unable to test, such a relationship.ConclusionOverall, this study suggests that the electrical effects of DBS can be at least partially predicted by noninvasive DTI imaging in patients with dystonia. By combining EPs with DTI, we could investigate the propagation of stimulation pulses through brain regions. While this relationship has been previously hypothesized by the neuroscience community, this is the first study in humans to demonstrate this relationship between DBS EPs and DTI, thereby advancing the field of human brain mapping and enhancing the precision of neurosurgical targeting.
Understanding emotional and health indicators underlying the burnout risk of healthcare workers
Authors: Güveyi Elçin , Elvin Garry , Kennedy Angela , Kurt Zeyneb , Sice Petia , Patel Paras , Dubruel Antoinette , Heckels Drummond 
Published: April 2024

AbstractBackgroundBurnout of healthcare workers is of increasing concern as workload pressures mount. Burnout is usually conceptualised as resulting from external pressures rather than internal resilience and although is not a diagnosable condition, it is related to help seeking for its psychological sequelae.ObjectiveTo understand how staff support services can intervene with staff heading for burnout, it is important to understand what other intrapsychic factors that are related to it.MethodsA diary tool was used by staff in a region of England to self monitor their wellbeing over time. The tool explores many areas of mental health and wellbeing and enabled regression analysis to predict which of the various factors predicted scores on the burnout item.FindingsBurnout can be best explained with independent variables includingdepression, receptiveness, mental wellbeing, andconnectedness(p<0.05) using a multiple linear regression model. It was also shown that 71% of the variance present in the response variable, i.e. burnout, explained by independent variables. There is no evidence found for multicollinearity in our regression models confirmed by both the Spearman Rank Correlation and the Variance Inflation Factor methods.ConclusionWe showed how burnout can be explained using a handful number of factors including emotional and mental health indicators.Clinical implicationsThe findings suggest a simple set of items can predict burnout and could be used for screening. The data suggests attention to four factors around social safeness, grounding and care in the self, hope and meaning and having sufficient energy could form the basis of attention in weelbeing programs.
Differences in sleep spindle wave density between patients with diabetes mellitus and matched controls: implications for sensing and regulation of peripheral blood glucose
Authors: Yeung Deryck , Talukder Amlan , Shi Min , Umbach David M. , Li Yuanyuan , Motsinger-Reif Alison , Fan Zheng , Li Leping 
Published: April 2024

ABSTRACTBackgroundBrain waves during sleep are involved in sensing and regulating peripheral glucose level. Whether brain waves in patients with diabetes differ from those of healthy subjects is unknown. We examined the hypothesis that patients with diabetes have reduced sleep spindle waves, a form of brain wave implicated in periphery glucose regulation during sleep.MethodsFrom a retrospective analysis of polysomnography (PSG) studies on patients who underwent sleep apnea evaluation, we identified 1,214 studies of patients with diabetes mellitus (>66% type 2) and included a sex- and age-matched control subject for each within the scope of our analysis. We similarly identified 376 patients with prediabetes and their matched controls. We extracted spindle characteristics from artifact-removed PSG electroencephalograms and other patient data from records. We used rank-based statistical methods to test hypotheses. We validated our finding on an external PSG dataset.ResultsPatients with diabetes mellitus exhibited on average about half the spindle density (median=0.38 spindles/min) during sleep as their matched control subjects (median=0.70 spindles/min) (P<2.2e-16). Compared to controls, spindle loss was more pronounced in female patients than in male patients in the frontal regions of the brain (P=0.04). Patients with prediabetes also exhibited signs of lower spindle density compared to matched controls (P=0.01-0.04).ConclusionsPatients with diabetes have fewer spindle waves that are implicated in glucose regulation than matched controls during sleep. Besides offering a possible explanation for neurological complications from diabetes, our findings open the possibility that reversing/reducing spindle loss could improve the overall health of patients with diabetes mellitus.FundingThis research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (ZIA ES101765).
Differential Serum Levels of CACNA1C, Circadian Rhythm and Stress Response Molecules in Subjects with Bipolar Disorder: Associations with Genetic and Clinical Factors
Authors: Allen Obie , Coombes Brandon J. , Pazdernik Vanessa , Gisabella Barbara , Hartley Joshua , Biernacka Joanna M. , Frye Mark A. , Markota Matej , Pantazopoulos Harry 
Published: April 2024

AbstractBackgroundMany patients with bipolar disorder (BD) do not respond to or have difficulties tolerating lithium and/or other mood stabilizing agents. There is a need for personalized treatments based on biomarkers in guiding treatment options. The calcium voltage-gated channel CACNA1C is a promising candidate for developing personalized treatments. CACNA1C is implicated in BD by genome-wide association studies and several lines of evidence suggest that targeting L-type calcium channels could be an effective treatment strategy. However, before such individualized treatments can be pursued, biomarkers predicting treatment response need to be developed.MethodsAs a first step in testing the hypothesis that CACNA1C genotype is associated with serum levels of CACNA1C, we conducted ELISA measures on serum samples from 100 subjects with BD and 100 control subjects.ResultsWe observed significantly higher CACNA1C (p<0.01) protein levels in subjects with BD. The risk SNP (rs11062170) showed functional significance as subjects homozygous for the risk allele (CC) had significantly greater CACNA1C protein levels compared to subjects with one (p=0.013) or no copies (p=0.009). We observed higher somatostatin (SST) (p<0.003) protein levels and lower levels of the clock protein ARTNL (p<0.03) and stress signaling factor corticotrophin releasing hormone (CRH) (p<0.001) in BD. SST and PER2 protein levels were associated with both alcohol dependence and lithium response.ConclusionsOur findings represent the first evidence for increased serum levels of CACNA1C in BD. Along with altered levels of SST, ARNTL, and CRH our findings suggest CACNA1C is associated with circadian rhythm and stress response disturbances in BD.