bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Microbubble Size, Composition and Multiple Sonication Points on Sterile Inflammatory Response in Focused Ultrasound-Mediated Blood-Brain Barrier Opening
Authors: Martinez Payton J. , Song Jane J. , Castillo Jair , DeSisto John , Song Kang-Ho , Green Adam L. , Borden Mark 
Published: May 2024

ABSTRACTBlood-brain barrier opening (BBBO) using focused ultrasound (FUS) and microbubble (MBs) has emerged as a promising technique for delivering therapeutics to the brain. However, the influence of various FUS and MB parameters on BBBO and subsequent sterile inflammatory response (SIR) remains unclear. In this study, we investigated the effects of MB size and composition, as well as the number of FUS sonication points, on BBBO and SIR in an immunocompetent mouse model. Using MRI-guided MB+FUS, we targeted the striatum and assessed extravasation of an MRI contrast agent to assess BBBO and RNAseq to assess SIR. Our results revealed distinct effects of these parameters on BBBO and SIR. Specifically, at a matched microbubble volume dose (MVD), MB size did not affect the extent of BBBO, but smaller (1 µm diameter) MBs exhibited a lower classification of SIR than larger (3 or 5 µm diameter) MBs. Lipid-shelled microbubbles exhibited greater BBBO and a more pronounced SIR compared to albumin-shelled microbubbles, likely owing to the latter’s poorin vivostability. As expected, increasing the number of sonication points resulted in greater BBBO and SIR. Furthermore, correlation analysis revealed strong associations between passive cavitation detection measurements of harmonic and inertial MB echoes, BBBO and the expression of SIR gene sets. Our findings highlight the critical role of MB and FUS parameters in modulating BBBO and subsequent SIR in the brain. These insights inform the development of targeted drug delivery strategies and the mitigation of adverse inflammatory reactions in neurological disorders.
A Tip Optofluidic Immunoassay System for COVID-19 Immuno-protection Evaluation Using Fingertip Blood
Authors: Li Ruihan , Zhang Binmao , Li Hao , An Lixiang , Zhu Tianen , Hu Shi , Yang Fan , Wu Weishu , Fan Xudong , Chai Yujuan , Yang Hui , Tan Xiaotian 
Published: May 2024

AbstractInfectious diseases such as COVID-19 continue posing significant global health challenges, with recurrent re-infections contributing to long-term symptoms such as cardiac issues and anosmia. Effective management of re-infections relies heavily on maintaining high levels of circulating binding and neutralizing antibodies. Traditional methods for antibody quantification, such as ELISA, face significant challenges, including narrow dynamic ranges and complex sample preparation procedures, which hinder their applications in rapid and routine diagnosis. This study introduces a novel optofluidic biosensing technology, tip optofluidic immunoassay (TOI), that addresses these limitations by enabling the quantitative analysis of binding IgG against multiple SARS-CoV-2 strains from only 1 μL of fingertip blood. The proposed TOI system, featuring industrial-grade micro-fabricated immuno-reactors and a portable chemiluminescent imaging station, can provide test results within 12 minutes. For IgG binding assays, TOI possesses a lower limit of detection of 0.1 ng/mL, a dynamic range of 3-4 orders of magnitude, along with a high signal-to-noise ratio (approximately 10,000). This technology not only simplifies the antibody quantification process but also enhances patient compliance and facilitates decentralized testing, which is crucial for infectious disease management. By enabling precise and rapid antibody assessment, this system can support the optimization of vaccination strategies and broader public health responses to COVID-19 and other infectious diseases.
Diagnostic utility of plasma ptau217, ptau181, GFAP for Alzheimer disease in a heterogeneous younger onset dementia clinical cohort
Authors: Eratne Dhamidhu , Li Qiao-Xin , Lewis Courtney , Dang Christa , Kang Matthew JY , Grewal Jasleen , Loi Samantha , Walterfang Mark , Evans Andrew H , Malpas Charles B , Pedrini Steve , Martins Ralph , Chatterjee Pratishtha , Zetterberg Henrik , Blennow Kaj , Berkovic Samuel F , Santillo Alexander F , Collins Steven , Masters Colin L , Velakoulis Dennis ,   The MiND Study Group
Published: May 2024

ABSTRACTObjectiveWe investigated diagnostic utility of phosphorylated tau 217 and 181 (ptau217, ptau181), glial fibrillary acidic protein (GFAP), amyloid beta 42 and 40 (Aβ42, Aβ40), neurofilament light (NfL) to distinguish AD from non-AD conditions, in a heterogenous clinical cohort of younger people.MethodsPlasma biomarkers were analysed using ultrasensitive technology, and compared in patients with CSF Alzheimer disease profiles (A+T+) to other profiles (OtherAT).ResultsSeventy-nine patients were included, median age 60.8 years: 16 A+T+, 63 OtherAT. Ptau217, ptau181, GFAP were significantly elevated in A+T+ compared to OtherAT (3.67 vs 1.12pg/mL, 3.87 vs 1.79pg/mL, 189 vs 80pg/mL, respectively). ptau217 distinguished AD from OtherAT with 90% accuracy (88% specificity, 100% sensitivity)ConclusionsPlasma ptau217 has strong diagnostic utility to diagnose AD in a clinically relevant, younger cohort of people with symptoms, adding further weight for a simple diagnostic blood test for AD as a cause of a patient’s symptoms.
Auricular Vagus Nerve Stimulation Mitigates Inflammation and Vasospasm in Subarachnoid Hemorrhage: A Randomized Trial
Authors: Huguenard Anna L , Tan Gansheng , Rivet Dennis J , Gao Feng , Johnson Gabrielle W , Adamek Markus , Coxon Andrew T , Kummer Terrance T , Osbun Joshua W , Vellimana Ananth K , Limbrick David D , Zipfel Gregory J , Brunner Peter , Leuthardt Eric C 
Published: May 2024

AbstractBackgroundInflammation contributes to morbidity following subarachnoid hemorrhage (SAH). Transauricular vagus nerve stimulation (taVNS) offers a noninvasive approach to target the inflammatory response following SAH.MethodsIn this prospective, triple-blinded, randomized, controlled trial, twenty-seven patients were randomized to taVNS or sham stimulation. Blood and cerebrospinal fluid (CSF) were collected to quantify inflammatory markers. Cerebral vasospasm severity and functional outcomes (modified Rankin Scale, mRS) were analyzed.ResultsNo adverse events occurred. Radiographic vasospasm was significantly reduced (p = 0.018), with serial vessel caliber measurements demonstrating a more rapid return to normal than sham (p < 0.001). In the taVNS group, TNF-α was significantly reduced in both plasma (days 7 and 10) and CSF (day 13); IL-6 was also significantly reduced in plasma (day 4) and CSF (day 13) (p < 0.05). Patients receiving taVNS had higher rates of favorable outcomes at discharge (38.4% vs 21.4%) and first follow-up (76.9% vs 57.1%), with significant improvement from admission to first follow-up (p = 0.014), unlike the sham group (p = 0.18). The taVNS group had a significantly lower rate of discharge to skilled nursing facility or hospice (p = 0.04).ConclusiontaVNS is a non-invasive method of neuro- and systemic immunomodulation. This trial supports that taVNS following SAH can mitigate the inflammatory response, reduce radiographic vasospasm, and potentially improve functional and neurological outcomes.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT04557618
Dopaminergic inhibition of the inwardly rectifying potassium current in direct pathway medium spiny neurons in normal and parkinsonian striatum
Authors: Wang Qian , Wang Yuhan , Liao Francesca-Fang , Zhou Fu-Ming 
Published: May 2024

AbstractDespite the profound behavioral effects of the striatal dopamine (DA) activity and the inwardly rectifying potassium channel (Kir) being a key determinant of striatal medium spiny neuron (MSN) activity that also profoundly affects behavior, previously reported DA regulations of Kir are conflicting and incompatible with MSN function in behavior. Here we show that in normal mice with an intact striatal DA system, the predominant effect of DA activation of D1Rs in D1-MSNs is to cause a modest depolarization and increase in input resistance by inhibiting Kir, thus moderately increasing the spike outputs from behavior-promoting D1-MSNs. In parkinsonian (DA-depleted) striatum, DA increases D1-MSN intrinsic excitability more strongly than in normal striatum, consequently strongly increasing D1-MSN spike firing that is behavior-promoting; this DA excitation of D1-MSNs is stronger when the DA depletion is more severe. The DA inhibition of Kir is occluded by the Kir blocker barium chloride (BaCl2). In behaving parkinsonian mice, BaCl2microinjection into the dorsal striatum stimulates movement but occludes the motor stimulation of D1R agonism. Taken together, our results resolve the long-standing question about what D1R agonism does to D1-MSN excitability in normal and parkinsonian striatum and strongly indicate that D1R inhibition of Kir is a key ion channel mechanism that mediates D1R agonistic behavioral stimulation in normal and parkinsonian animals.
Solutions of ferrous salts protect liposomes from UV damage: implications for Life Origin
Authors: Turner Ben , Fiksel Gennady , Subbotin Vladimir 
Published: May 2024

AbstractPreviously, we presented a hypothesis on the Darwinian evolution of liposomes that relies only on natural and ever-present phenomena: solar UV radiation, day/night cycle, gravity, and the formation of amphiphiles, e.g., fatty acids and phospholipids, in aqueous media. The hypothesis further suggests that liposomes, formed at the air-water interface, will be inevitably destroyed by Sun UV unless they are submerged and shielded by primordial water. The hypothesis makes two testable predictions. First, certain ingredients of the Archean waters, e.g., ferric salts, can completely attenuate UV; and second, such ferric salts solution can protect the submerged liposomes from the solar UV damage. In our previous experiments (Subbotin and Fiksel 2023a), we tested the prediction of UV attenuation by ferrous salt solutions. We have demonstrated that out of several tested iron salt solutions, two salts demonstrated very strong UV attenuation: at a concentration of 2.5 g/L of (NH4)5[Fe(C6H4O7)2] and FeCl3, the UV intensity drops by a factor of 1000 at a submersion depth of 7.4 mm and 6.3 mm, respectively. In the present study, we tested the second prediction: we investigated whether the above ferrous salt solutions can protect UV-sensitive liposomes from UV damage. The results demonstrated that 10 mm of solutions, the ferric ammonium citrate or iron trichoride, completely protected UV-sensitive liposomes from UV damage. These results supplement and reinforce the proposed hypothesis.
Segmental regulation of intestinal motility by colitis and the adaptive immune system in the ileum and colon
Authors: Bris Raquel Gómez , Rodríguez-Rodríguez Pilar , Zapero Marina Ortega , Ruvira Santiago , Saez Angela , Arribas Silvia Magdalena , Granado Jose Maria Gonzalez 
Published: May 2024

AbstractGastrointestinal motility disturbances are common in inflammatory bowel disease (IBD); however, their exact causes remain elusive.This study explores the motility of various intestinal segments in both healthy and IBD states, focusing on the role of the adaptive immune system. Using a dextran sulfate sodium (DSS)-induced colitis model in mice lacking B and T lymphocytes, we evaluated motility in the ileum and colon using an organ bath system.In healthy mice, absence of adaptive lymphocytes in the ileum reduces muscarinic receptor sensitivity or increase cholinesterase activity. Colitis increases motility, intensifying the intensity and frequency of spontaneous contractions while decreasing responsiveness to cholinergic stimuli.In the proximal colon, healthy mice lacking adaptive immune system exhibit increased contractile capacity and frequency, along with reduced muscarinic receptor sensitivity or increased cholinesterase activity. Conversely, colitis diminishes contractile capacity regardless of genotype, while recovery increases frequency of spontaneous contractions.In the mid-colon during colitis, healthy mice lacking adaptive immune system exhibit reduced muscarinic receptor sensitivity or increased cholinesterase activity, while the absence of adaptive lymphocytes during colitis exacerbates both spontaneous and stimuli-induced contractions. Finally, in the distal colon, the adaptive immune system enhances stimuli-induced contractility in health and reduces contractility and enhances muscarinic responses during colitis.Overall, intestinal motility in both the ileum and colon is finely regulated, with the adaptive immune system playing a crucial role. These findings contribute to our understanding of IBD pathology, emphasizing the importance of investigating gastrointestinal motility in IBD research.
Fast feature- and category-related parafoveal previewing support natural visual exploration
Authors: Fakche Camille , Hickey Clayton , Jensen Ole 
Published: May 2024

AbstractStudies on vision tend to prevent or control eye movements, while humans naturally saccade every ∼250 ms. As the oculomotor system takes ∼100 ms to initiate and execute a saccade, this leaves only ∼150 ms to identify the fixated object and select the next saccade goal. This is very little time, suggesting that vision relies on parafoveal processing before and after the eye movement. However, evidence of high-level parafoveal access is sparse. The purpose of our study was to use magnetoencephalography (MEG) combined with eye-tracking and multivariate pattern analysis to identify the neuronal dynamics of parafoveal processing which support natural visual exploration. We demonstrated that future saccade goals in the parafovea could be decoded at the feature and category level peaking at ∼90 ms and ∼160 ms respectively. Simultaneously, decoding of fixated objects at the feature and category level peaked at ∼70 ms and ∼145 ms respectively. Also decoding feature and category specific neuronal information related to past parafoveal objects were sustained for ∼230 ms after saccading away from them. The feature and category of objects in the parafovea could only be decoded if they were in the saccade goal. In sum, we provide insight on the neuronal mechanism of pre-saccadic attention by demonstrating that feature and category specific information of foveal and parafoveal objects can be extracted in succession within a ∼150 ms time-interval and may serve to plan the next saccade. This information is maintained also after fixations and may support integration across the full visual scene. Our study provides novel insight on the temporal dynamics of foveal and parafoveal processing at the feature and semantic levels during natural visual exploration.
Generalization in motor learning: learning bimanual coordination with one hand
Authors: Wang Yiyu , Weinrich Madison M. , Lei Yuming , Wright David L. , Sandhu Milap , Buchanan John J. , Kennedy Deanna M. 
Published: May 2024

ABSTRACTThe ability to coordinate movements between the hands is crucial for many daily tasks. However, the precise mechanisms governing the storage and utilization of bimanual movement and the distinct contributions of each limb in this process are currently not fully understood. Two key questions persist: 1) How is the neural representation of bimanual coordination stored in the brain, and 2) How is the information governing bimanual coordination shared between hemispheres? In this investigation, we used a virtual partner (VP) to systematically address these issues by allowing the same coordination pattern (CP) to be acquired with unimanual and bimanual movements. More specifically, we used four experimental groups: unimanual (left, right) VP, bimanual, and control conditions. For each condition, retention and transfer tests were administered immediately and 6 hours after the initial practice. The control condition employed the same protocol as unimanual conditions without practice. As anticipated, performance after practice and during retention sessions indicated that all groups learned to perform the target CP. Furthermore, generalization from unimanual to bimanual occurred when the same type of visual feedback (VF) was provided. Interestingly, the absence of VF impaired motor generalization from unimanual to bimanual condition unless the participants initially practiced the task bimanually. Taken together, our results demonstrated that both limbs could access the memory representation of the CP. However, this globally shared representation appeared to be encoded in the visual-spatial domain. The conditions without VF underscored the importance of proprioception in forming a motor representation in intrinsic coordinates.NEW & NOTEWORTHYConventional views on acquiring bimanual skills stress the need for simultaneous engagement of both hands. However, our study challenges this notion by demonstrating that the coordination pattern learned in unimanual conditions significantly boosts subsequent bimanual coordination—a novel approach to skill acquisition. Yet, this advantage diminishes without visual feedback, resulting in a breakdown of the intended bimanual coordination, highlighting the limitations of relying solely on unimanual practice.
Copy number variations ofPlasmodium vivax DBP1,EBP/DBP2, andRBP2bin Duffy-positive and Duffy-negative Ethiopians
Authors: Pestana Kareen , Ford Anthony , Rama Rei , Abagero Beka , Kepple Daniel , Tomida Junya , Popovici Jean , Yewhalaw Delenasaw , Lo Eugenia 
Published: May 2024

AbstractRecent evidence challenges the belief that Duffy-negative individuals are resistant toPlasmodium vivaxdue to lacking Duffy Antigen Receptor for Chemokines (DARC). Erythrocyte Binding Protein (EBP/DBP2) has shown moderate binding to Duffy-negative erythrocytesin vitro. Reticulocyte Binding Protein 2b (RBP2b) interactions with Transferrin Receptor 1 (TfR1) suggest involvement in Duffy-negative infections. Gene copy number variations inPvDBP1,PvEBP/DBP2, andPvRBP2bwere investigated in Duffy-positive and Duffy-negativeP. vivax-infected individuals from Ethiopia. Among Duffy-positive samples, 34% displayedPvDBP1duplications (Cambodian-type). In Duffy-negative infections, 30% showed duplications, mostly Cambodian-type. ForPvEBP/DBP2andPvRBP2b, Duffy-positive samples exhibited higher duplication rates (1-8 copies forPvEBP/DBP2, 1-5 copies forPvRBP2b46% and 43% respectively) compared to Duffy-negatives (20.8% and 26% respectively). The range of copy number variations was lower in Duffy-negative infections. Demographic and clinical factors associated with gene multiplications in both Duffy types were explored, enhancing understanding ofP. vivaxevolution in Duffy-negative Africans.
Dynamic mechanisms for membrane skeleton transitions
Authors: Bonilla-Quintana M. , Ghisleni A. , Gauthier N. , Rangamani P. 
Published: May 2024

AbstractThe plasma membrane and the underlying skeleton form a protective barrier for eukaryotic cells. The molecules forming this complex composite material constantly rearrange under mechanical stress to confer this protective capacity. One of those molecules, spectrin, is ubiquitous in the membrane skeleton and primarily located proximal to the inner leaflet of the plasma membrane and engages in protein-lipid interactions via a set of membrane-anchoring domains. Spectrin is linked by short actin filaments and its conformation varies in different types of cells. In this work, we developed a generalized network model for the membrane skeleton integrated with myosin contractility and membrane mechanics to investigate the response of the spectrin meshwork to mechanical loading. We observed that the force generated by membrane bending is important to maintain a smooth skeletal structure. This suggests that the membrane is not just supported by the skeleton, but has an active contribution to the stability of the cell structure. We found that spectrin and myosin turnover are necessary for the transition between stress and rest states in the skeleton. Our model reveals that the actin-spectrin meshwork dynamics are balanced by the membrane forces with area constraint and volume restriction promoting the stability of the membrane skeleton. Furthermore, we showed that cell attachment to the substrate promotes shape stabilization. Thus, our proposed model gives insight into the shared mechanisms of the membrane skeleton associated with myosin and membrane that can be tested in different types of cells.Significance StatementSpectrin was first observed in red blood cells, as a result of which, many theoretical models focused on understanding its function in this cell type. However, recently, experiments have shown that spectrin is an important skeletal component for many different cell types and that it can form different configurations with actin. In this work, we proposed a model to study the shared mechanisms behind the function of the actin-spectrin meshwork in different types of cells. We found that membrane dynamics in addition to spectrin and myosin turnover are necessary to achieve conformational changes when stresses are applied and to guarantee shape stability when the stresses are removed. We observed that membrane bending is important to support skeletal structure. Furthermore, our model gives insight into how cell shape is maintained despite constant spectrin turnover and myosin contraction.
Alleviation of allergic rhinoconjunctivitis symptoms in participants treated with a 0.005% tacrolimus eye drop solution
Authors: Sladek S. , Unger-Manhart N. , Siegl C. , Dellago H. , Zieglmayer P. , Lemell P. , Savli M. , Zieglmayer R. , Geitzenauer W. , Laengauer M. , Prieschl-Grassauer E. 
Published: May 2024

AbstractPurposeThis randomized, placebo-controlled, crossover, double-blind, single site trial was aimed to evaluate efficacy and safety of Tacrosolv, a novel eye drop solution containing solubilized tacrolimus, in adult participants with grass pollen induced allergic conjunctivitis.Methods64 adult participants with proven grass pollen allergy were randomized to either 2.5 µg or 5 µg tacrolimus/eye/day or placebo treatment for 8 days. Allergic symptoms were induced by 4h grass pollen exposure on day 1 and day 8. After a 2-week wash-out period, placebo participants crossed over to high or low dose and vice versa, and repeated treatment and exposure. During exposure, participants recorded ocular, nasal and respiratory allergy symptoms every 15 minutes. The primary endpoint was the mean ‘Total Ocular Symptom Score’ (TOSS) on Day 8. Objective ocular safety parameters were assessed before, during and after exposure. Adverse events (AEs) were recorded throughout the study.ResultsOn Day 8, TOSS was reduced towards the end of exposure in participants receiving Tacrosolv high dose compared to placebo (p<0.05 at timepoints 3h45min and 4h). Accordingly, intensity of the single ocular symptoms like redness and watery eyes was reduced versus placebo by end of exposure on Day 8. A 26% reduction of baseline adjusted TOSS from day 1 to day 8 was observed in participants treated with high dose Tacrosolv, whereas placebo treated participants showed no difference in TOSS between day 1 and day 8. Interestingly, a significant reduction of total nasal symptoms, mainly itching and sneezing, was seen both on day 1 and day 8 in participants treated with high dose Tacrosolv (p<0.05). No safety concerns were raised upon ocular assessments by the investigator like redness of the eye, corneal and conjunctival staining. All AEs were resolved within the study period.ConclusionTreatment with Tacrosolv at the dose and frequency studied is safe and alleviates symptoms in participants suffering from allergic rhinoconjunctivitis.Trial registrationNCT04532710; EudraCT No. 2019-002847-62