bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlating nanoscale motion and ATP production in healthy and favism erythrocytes: a real-time nanomotion sensor study
Authors: Girasole Marco , Dinarelli Simone , Longo Giovanni 
Published: June 2023

IntroductionRed blood cells (RBCs) are among the simplest, yet physiologically relevant biological specimens, due to their peculiarities, such as their lack of nucleus and simplified metabolism. Indeed, erythrocytes can be seen as biochemical machines, capable of performing a limited number of metabolic pathways. Along the aging path, the cells’ characteristics change as they accumulate oxidative and non-oxidative damages, and their structural and functional properties degrade.MethodsIn this work, we have studied RBCs and the activation of their ATP-producing metabolism using a real-time nanomotion sensor. This device allowed time-resolved analyses of the activation of this biochemical pathway, measuring the characteristics and the timing of the response at different points of their aging and the differences observed in favism erythrocytes in terms of the cellular reactivity and resilience to aging. Favism is a genetic defect of erythrocytes, which affects their ability to respond to oxidative stresses but that also determines differences in the metabolic and structural characteristic of the cells.ResultsOur work shows that RBCs from favism patients exhibit a different response to the forced activation of the ATP synthesis compared to healthy cells. In particular, the favism cells, compared to healthy erythrocytes, show a greater resilience to the aging-related insults which was in good accord with the collected biochemical data on ATP consumption and reload.ConclusionThis surprisingly higher endurance against cell aging can be addressed to a special mechanism of metabolic regulation that permits lower energy consumption in environmental stress conditions.
Novel gold(III)-dithiocarbamate complex targeting bacterial thioredoxin reductase: antimicrobial activity, synergy, toxicity, and mechanistic insights
Authors: Ratia Carlos , Ballén Victoria , Gabasa Yaiza , Soengas Raquel G. , Velasco-de Andrés María , Iglesias María José , Cheng Qing , Lozano Francisco , Arnér Elias S. J. , López-Ortiz Fernando , Soto Sara M. 
Published: June 2023

IntroductionAntimicrobial resistance is a pressing global concern that has led to the search for new antibacterial agents with novel targets or non-traditional approaches. Recently, organogold compounds have emerged as a promising class of antibacterial agents. In this study, we present and characterize a (C^S)-cyclometallated Au(III) dithiocarbamate complex as a potential drug candidate.Methods and resultsThe Au(III) complex was found to be stable in the presence of effective biological reductants, and showed potent antibacterial and antibiofilm activity against a wide range of multidrug-resistant strains, particularly gram-positive strains, and gram-negative strains when used in combination with a permeabilizing antibiotic. No resistant mutants were detected after exposing bacterial cultures to strong selective pressure, indicating that the complex may have a low propensity for resistance development. Mechanistic studies indicate that the Au(III) complex exerts its antibacterial activity through a multimodal mechanism of action. Ultrastructural membrane damage and rapid bacterial uptake suggest direct interactions with the bacterial membrane, while transcriptomic analysis identified altered pathways related to energy metabolism and membrane stability including enzymes of the TCA cycle and fatty acid biosynthesis. Enzymatic studies further revealed a strong reversible inhibition of the bacterial thioredoxin reductase. Importantly, the Au(III) complex demonstrated low cytotoxicity at therapeutic concentrations in mammalian cell lines, and showed no acute in vivo toxicity in mice at the doses tested, with no signs of organ toxicity.DiscussionOverall, these findings highlight the potential of the Au(III)-dithiocarbamate scaffold as a basis for developing novel antimicrobial agents, given its potent antibacterial activity, synergy, redox stability, inability to produce resistant mutants, low toxicity to mammalian cells both in vitro and in vivo, and non-conventional mechanism of action.
Identification of novel candidate targets for suppressing ovarian cancer progression through IL-33/ST2 axis components using the system biology approach
Authors: Reivan Ortiz Geovanny Genaro , Ciongradi Carmen Iulia , Chaitanya M. V. N. L. , Narayanan Jayasankar , Mohany Mohamed , Al-Rejaie Salim S. , Arias-Gonzáles José Luis , Sârbu Ioan , Assefi Marjan , Akram Shaik Vaseem , Döğüş Yusuf , Bahrami Abolfazl , Akhavan-Sigari Reza 
Published: June 2023

Background: Cancer-associated fibroblasts (CAFs) of ovarian cancer (OvC) are the most prevalent element of the tumor microenvironment (TM). By promoting angiogenesis, immunological suppression, and invasion, CAFs speed up the growth of tumors by changing the extracellular matrix’s structure and composition and/or initiating the epithelial cells (EPT). IL-33/ST2 signaling has drawn a lot of attention since it acts as a pro-tumor alarmin and encourages spread by altering TM.Methods: Differentially expressed genes (DEGs) of the OvC tumor microenvironment were found in the GEO database, qRT-PCR, western blotting, and immunohistochemistry, and their presence and changes in healthy and tumor tissue content were examined. Primary cultures of healthy fibroblasts and CAFs obtained from healthy and tumor tissues retrieved from OvC samples were used for in vitro and in vivo investigations. Cultured primary human CAFs were utilized to investigate the regulation and the IL-33/ST2 axis role in the inflammation reactions.Results: Although ST2 and IL-33 expression was detected in both epithelial (EPT) and fibroblast cells of ovarian cancer, they are more abundant in CAFs. Lipopolysaccharides, serum amyloid A1, and IL-1β, the inflammatory mediators, could all induce IL-33 expression through NF-κB activation in human CAFs. In turn, via the ST2 receptor, IL-33 affected the production of IL-6, IL-1β, and PTGS2 in human CAFs via the MAPKs-NF-κB pathway.Conclusion: Our findings suggest that IL-33/ST2 is affected by the interaction of CAFs and epithelial cells inside the tumor microenvironment. Activation of this axis leads to increased expression of inflammatory factors in tumor CAFs and EPT cells. Therefore, targeting the IL-33/ST2 axis could have potential value in the prevention of OvC progression.
Wall enhancement predictive of abnormal hemodynamics and ischemia in vertebrobasilar non-saccular aneurysms: a pilot study
Authors: Jiang Yeqing , Ge Liang , Lu Gang , Wan Hailin , Chen Qi , Zou Rong , Leng Xiaochang , Xiang Jianping , Zhang Xiaolong 
Published: June 2023

ObjectiveTo analyze how wall enhancement affects hemodynamics and cerebral ischemic risk factors in vertebrobasilar non-saccular intracranial aneurysms (VBNIAs).Materials and methodsTen consecutive non-saccular aneurysms were collected, including three transitional vertebrobasilar dolichoectasia (TVBD). A wall enhancement model was quantitatively constructed to analyze how wall enhancement interacts with hemodynamics and cerebral ischemic factors.ResultsEnhanced area revealed low wall shear stress (WSS) and wall shear stress gradient (WSSG), with high oscillatory shear index (OSI), relative residence time (RRT), and gradient oscillatory number (GON) while the vortex and slow flow region in fusiform aneurysms are similar to TVBD fusiform aneurysms. With low OSI, high RRT and similar GON in the dilated segment, the enhanced area still manifests low WSS and WSSG in the slow flow area with no vortex. In fusiform aneurysms, wall enhancement was negatively correlated with WSS (except for case 71, all p values  &lt; 0.05, r = −0.52 ~ −0.95), while wall enhancement was positively correlated with OSI (except for case 5, all p values &lt; 0.05, r = 0.50 ~ 0.83). For the 10 fusiform aneurysms, wall enhancement is significantly positively correlated with OSI (p = 0.0002, r = 0.75) and slightly negatively correlated with WSS (p = 0.196, r = −0.30) throughout the dataset. Aneurysm length, width, low wall shear stress area (LSA), high OSI, low flow volume (LFV), RRT, and high aneurysm-to-pituitary stalk contrast ratio (CRstalk) area plus proportion may be predictive of cerebral ischemia.ConclusionA wall enhancement quantitative model was established for vertebrobasilar non-saccular aneurysms. Low WSS was negatively correlated with wall enhancement, while high OSI was positively correlated with wall enhancement. Fusiform aneurysm hemodynamics in TVBD are similar to simple fusiform aneurysms. Cerebral ischemia risk appears to be correlated with large size, high OSI, LSA, and RRT, LFV, and wall enhancement.
Neuroprotection after cardiac arrest with 2-iminobiotin: a single center phase IIa study on safety, tolerability, and pharmacokinetics
Authors: Admiraal M. M. , Velseboer D. C. , Tjabbes H. , Vis P. , Peeters-Scholte C. , Horn J. 
Published: June 2023

BackgroundBrain injury is a serious problem in patients who survive out-of-hospital cardiac arrest (OHCA). Neuroprotective drugs could reduce hypoxic–ischemic reperfusion injury. The aim of this study was to investigate the safety, tolerability, and pharmacokinetics (PK) of 2-iminobiotin (2-IB), a selective inhibitor of neuronal nitric oxide synthase.MethodsSingle-center, open-label dose-escalation study in adult OHCA patients, investigating three 2-IB dosing schedules (targeting an AUC0-24h of 600–1,200 ng*h/m in cohort A, of 2,100–3,300 ng*h/mL in cohort B, and 7,200–8,400 of ng*h/mL in cohort C). Safety was investigated by monitoring vital signs until 15 min after study drug administration and adverse events up to 30 days after admission. Blood sampling for PK analysis was performed. Brain biomarkers and patient outcomes were collected 30 days after OHCA.ResultsA total of 21 patients was included, eight in cohort A and B and five in cohort C. No changes in vital signs were observed, and no adverse events related to 2-IB were reported. A two-compartment PK model described data the best. Exposure in group A (dosed on bodyweight) was three times higher than targeted (median AUC0-24h 2,398 ng*h/mL). Renal function was an important covariate; therefore, in cohort B, dosing was performed on eGFR on admission. In cohort B and C, the targeted exposure was met (median AUC0-24h 2,917 and 7,323 ng*h/mL, respectively).ConclusionThe administration of 2-IB to adults after OHCA is feasible and safe. PK can be well predicted with correction for renal function on admission. Efficacy studies with 2-IB after OHCA are needed.
Prognostic changes after sudden deafness in patients with inner ear malformations characterized by LSCC: a retrospective study
Authors: Chen Lei , Dai Qinglei , Gao Xin , Hu Na , Sun Xiao , Wang Haibo , Wang Mingming 
Published: June 2023

IntroductionThis study aimed to investigate the clinical features and prognosis of sudden sensorineural hearing loss in patients with lateral semicircular canal (LSCC) malformation.MethodsThis study enrolled patients with LSCC malformation and sudden sensorineural hearing loss (SSNHL) who were admitted to Shandong ENT Hospital between 2020 and 2022. We collected and analyzed data on examinations of audiology, vestibular function, and imaging records of patients and summarized the clinical characteristics and prognosis of these patients.ResultsFourteen patients were enrolled. Patients with LSCC malformation was noted in 0.42% of all SSNHL cases during the same period. One patients had bilateral SSNHL and the rest had unilateral SSNHL. Of them, eight and six patients had unilateral and bilateral LSCC malformations, respectively. Flat hearing loss was noted in 12 ears (80.0%) and severe or profound hearing loss was noted in 10 ears (66.7%). After treatment, the total efficacy rate of SSNHL with LSCC malformation was 40.0%. Vestibular function was abnormal in all patients, but only five patients (35.7%) had dizziness. There were statistically significant differences in the vestibular functions between patients with LSCC malformation and matched patients without the malformation hospitalized during the same period (p &lt; 0.05).ConclusionPatients with SSNHL and LSCC malformation had flat-type and severe hearing loss and worse disease prognosis compared to those with SSNHL without LSCC malformation. Vestibular function is more likely to be abnormal; however, there was no significant difference in vestibular symptoms between patients with and without LSCC malformation. LSCC is a risk factor for the prognosis of SSNHL.
Tau expression and phosphorylation in enteroendocrine cells
Authors: Chapelet Guillaume , Béguin Nora , Castellano Blandine , Grit Isabelle , de Coppet Pierre , Oullier Thibauld , Neunlist Michel , Blottière Hervé , Rolli-Derkinderen Malvyne , Le Dréan Gwenola , Derkinderen Pascal 
Published: June 2023

Background and objectiveThere is mounting evidence to suggest that the gut-brain axis is involved in the development of Parkinson’s disease (PD). In this regard, the enteroendocrine cells (EEC), which faces the gut lumen and are connected with both enteric neurons and glial cells have received growing attention. The recent observation showing that these cells express alpha-synuclein, a presynaptic neuronal protein genetically and neuropathologically linked to PD came to reinforce the assumption that EEC might be a key component of the neural circuit between the gut lumen and the brain for the bottom-up propagation of PD pathology. Besides alpha-synuclein, tau is another key protein involved in neurodegeneration and converging evidences indicate that there is an interplay between these two proteins at both molecular and pathological levels. There are no existing studies on tau in EEC and therefore we set out to examine the isoform profile and phosphorylation state of tau in these cells.MethodsSurgical specimens of human colon from control subjects were analyzed by immunohistochemistry using a panel of anti-tau antibodies together with chromogranin A and Glucagon-like peptide-1 (two EEC markers) antibodies. To investigate tau expression further, two EEC lines, namely GLUTag and NCI-H716 were analyzed by Western blot with pan-tau and tau isoform specific antibodies and by RT-PCR. Lambda phosphatase treatment was used to study tau phosphorylation in both cell lines. Eventually, GLUTag were treated with propionate and butyrate, two short chain fatty acids known to sense EEC, and analyzed at different time points by Western blot with an antibody specific for tau phosphorylated at Thr205.ResultsWe found that tau is expressed and phosphorylated in EEC in adult human colon and that both EEC lines mainly express two tau isoforms that are phosphorylated under basal condition. Both propionate and butyrate regulated tau phosphorylation state by decreasing its phosphorylation at Thr205.Conclusion and inferenceOur study is the first to characterize tau in human EEC and in EEC lines. As a whole, our findings provide a basis to unravel the functions of tau in EEC and to further investigate the possibility of pathological changes in tauopathies and synucleinopathies.
Neural correlates of perceptual texture change during active touch
Authors: Henderson Jessica , Mari Tyler , Hopkinson Andrew , Hewitt Danielle , Newton-Fenner Alice , Giesbrecht Timo , Marshall Alan , Stancak Andrej , Fallon Nicholas 
Published: June 2023

IntroductionTexture changes occur frequently during real-world haptic explorations, but the neural processes that encode perceptual texture change remain relatively unknown. The present study examines cortical oscillatory changes during transitions between different surface textures during active touch.MethodsParticipants explored two differing textures whilst oscillatory brain activity and finger position data were recorded using 129-channel electroencephalography and a purpose-built touch sensor. These data streams were fused to calculate epochs relative to the time when the moving finger crossed the textural boundary on a 3D-printed sample. Changes in oscillatory band power in alpha (8–12 Hz), beta (16–24 Hz) and theta (4–7 Hz) frequency bands were investigated.ResultsAlpha-band power reduced over bilateral sensorimotor areas during the transition period relative to ongoing texture processing, indicating that alpha-band activity is modulated by perceptual texture change during complex ongoing tactile exploration. Further, reduced beta-band power was observed in central sensorimotor areas when participants transitioned from rough to smooth relative to transitioning from smooth to rough textures, supporting previous research that beta-band activity is mediated by high-frequency vibrotactile cues.DiscussionThe present findings suggest that perceptual texture change is encoded in the brain in alpha-band oscillatory activity whilst completing continuous naturalistic movements across textures.
Gut microbiota-derived metabolite trimethylamine-N-oxide and stroke outcome: a systematic review
Authors: Zhang Peng , Wang Rui , Qu Yang , Guo Zhen-Ni , Yang Yi 
Published: June 2023

IntroductionThe relationship between baseline trimethylamine N-oxide (TMAO) levels and stroke outcomes remains unclear. Therefore, this systematic review aimed to summarize the existing relevant research.MethodsWe searched for studies on the association between baseline plasma levels of TMAO and stroke outcomes in the PubMed, EMBASE, Web of Science, and Scopus databases from their inception to 12 October 2022. Two researchers independently reviewed the studies for inclusion and extracted the relevant data.ResultsSeven studies were included in the qualitative analysis. Among them, six studies reported the outcome of acute ischemic stroke (AIS) and one study of intracerebral hemorrhage (ICH), respectively. Furthermore, no study reported the outcome of subarachnoid hemorrhage. Among patients with AIS, high baseline TMAO levels were associated with unfavorable functional outcomes or mortality at 3 months, as well as a high hazard ratio of mortality, recurrence, or major adverse cardiac event. Moreover, TMAO levels showed predictive utility for unfavorable functional outcomes or mortality at 3 months. Among patients with ICH, high TMAO levels were associated with unfavorable functional outcomes at 3 months, regardless of whether the TMAO value was considered a continuous or a categorical variable.ConclusionLimited evidence indicates that high baseline plasma levels of TMAO may be associated with poor stroke outcomes. Further studies are warranted to confirm the relationship between TMAO and stroke outcomes.
Risk factors for the development of macular edema in children with uveitis
Authors: Friling Ronit , Berliner Ori , Eiger-Moscovich Maya , Chen Yi-Hsing , Tomkins-Netzer Oren , Kramer Michal 
Published: June 2023

AimTo determine the risk factors for macular edema (ME) in children with uveitis.MethodsA retrospective study was conducted of 150 pediatric patients (264 eyes) with uveitis attending 2 tertiary medical centers. Data were collected from the medical files on demographics, type of uveitis, etiology, clinical findings, treatment, and time to development of ME. Risk factors for the development of ME were identified.ResultsME developed in 63 eyes (23.9%) over a mean period of 15.3 ± 2.95 months from diagnosis of uveitis, at a rate of 0.08 eyes per eye-year. On univariate analysis, risk factors for the development of ME were the non-anterior location of the inflammation (p=0.002), band keratopathy (p &lt;0.0001), posterior synechiae (p=0.003), cataract (p=0.002), and vision impairment at presentation (p &lt;0.0001). On multivariate analysis, non-anterior uveitis, which includes intermediate, pan, and posterior-uveitis, and vision impairment retained significance as independent risk factors of ME.ConclusionWithin the pediatric population with uveitis, non-anterior location is associated with the highest risk of ME, followed by the presence of complications, such as band keratopathy and posterior synechiae. These findings indicate a need for close follow-up in children with uveitis for early detection of ME.
Use of perennial plants in the fight against gastrointestinal nematodes of sheep
Authors: Bosco Antonio , Prigioniero Antonello , Falzarano Alessandra , Maurelli Maria Paola , Rinaldi Laura , Cringoli Giuseppe , Quaranta Giovanni , Claps Salvatore , Sciarrillo Rosaria , Guarino Carmine , Scarano Pierpaolo 
Published: June 2023

BackgroundGastrointestinal nematodes (GINs) are a serious problem in ruminant pastures worldwide. They generate production losses, from the point of view of both the food chain and animal mortality. This study provides preliminary results concerning the use of pasture plants in the Campania region (of southern Italy) to control GINs in sheep.MethodsSixteen species of wild and cultivated perennial plants present in seminatural pastures were sampled. All species were extracted with the conventional maceration technique, using three different solvents (i.e., H2O, EtOH, and an EtOH:H2O (8:2) mixture) in order to extract different bioactive compounds. The total phenolic content (TPC; assessed via the Folin–Ciocȃlteu assay) of all extract samples was preliminarily characterized. Each sample was aliquoted across six different concentrations and an in vitro egg hatching test (EHT) was conducted to evaluate the ovicidal effect on sheep GINs.ResultsThe results indicated that Cichorium intybus L. and Foeniculum vulgare Mill. extracts greatly inhibited egg hatching within 48 hours of exposure, showing efficacy (≥ 62.6%) at the three higher concentrations when compared with the other plants.ConclusionThe use of extracts of wild and cultivated perennial plant species in pastures can be a valid alternative to the use of synthetic anthelmintic drugs, which can generate problems, such as anthelmintic resistance, in the long term. Looking forward, further in vitro studies that evaluate the in vitro effect of these extracts on ruminant cell cultures, and field application through in vivo studies, would likely confirm the results obtained from preliminary in vitro EHTs. All these studies should be aimed at evaluating the therapeutic potential and future applicability of specific plant cultures in pastures to achieve sustainable pest control.
An evaluation of the association between lockdown during the SARS-CoV-2 pandemic and prematurity at the Nice University Hospital
Authors: Lorenzi Marine , Mayerus Mathilde , Eleni Dit Trolli Sergio , Hue-Bigé Amandine , Legueult Kévin , Guellec-Renne Isabelle , François-Garret Bérengère 
Published: June 2023

AimTo study the association between lockdown in France due to the SARS-CoV-2 pandemic and premature births at the Nice University Hospital.MethodsData concerning neonates born at the level III maternity of the Nice University Hospital and immediately hospitalised in the neonatal reanimation unit or the neonatology department of the hospital with their mothers between the 1st of January 2017 and the 31st of December 2020, included.ResultsWe did not find a significant decrease in the global number of premature births &lt;37 weeks of gestation, in low weight at birth or a significant increase in stillbirths during lockdown compared to a period with no lockdown. The profiles of the mothers and their newborns were compared when birth occurred during lockdown vs. no lockdown.ConclusionWe did not find any evidence of an association between lockdown and prematurity at the Nice University Hospital. This result is in agreement with meta-analyses published in the medical literature. The possible decrease in factors of risk of prematurity during lockdown is controversial.