bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intrinsic and synaptic determinants of receptive field plasticity in Purkinje cells of the mouse cerebellum
Authors: Lin Ting-Feng , Busch Silas E. , Hansel Christian 
Published: July 2023

AbstractNon-synaptic (‘intrinsic’) plasticity of membrane excitability contributes to aspects of memory formation, but it remains unclear whether it merely facilitates synaptic long-term potentiation (LTP), or whether it plays a permissive role in determining the impact of synaptic weight increase. We use tactile stimulation and electrical activation of parallel fibers to probe intrinsic and synaptic contributions to receptive field (RF) plasticity in awake mice during two-photon calcium imaging of cerebellar Purkinje cells. Repetitive activation of both stimuli induced response potentiation that is impaired in mice with selective deficits in either intrinsic plasticity (SK2 KO) or LTP (CaMKII TT305/6VA). Intrinsic, but not synaptic, plasticity expands the local, dendritic RF representation. Simultaneous dendrite and axon initial segment recordings confirm that these dendritic events affect axonal output. Our findings support the hypothesis that intrinsic plasticity provides an amplification mechanism that exerts a permissive control over the impact of LTP on neuronal responsiveness.
MERTK Coordinates Efferocytosis by Regulating Integrin Localization and Activation
Authors: Dickson Brandon H , Tasnim Tarannum , Lam Austin L , Vreize Angela , Blythe Eoin N , Dekaban Gregory A , Heit Bryan 
Published: July 2023

AbstractEfferocytosis – the phagocytic removal of apoptotic cells – is a central component of tissue homeostasis, and in many tissues is mediated by the efferocytic receptor MERTK expressed by macrophages. Although MERTK is critical for efferocytosis, the mechanism by which it directs the engulfment of apoptotic cells is largely unknown. Using immunoprecipitation, mass spectrometry, and super-resolution microscopy, we have identified a pre-formed receptor complex on the macrophage plasma membrane comprised of ∼180 nm clusters of MERTK, β2integrins, and multiple signaling molecules including Src-family kinases, PI3-kinases, and the integrin regulatory proteins ILK and FAK. MERTK is unable to mediate efferocytosis in the absence of β2integrins or their opsonins, while β2integrins require activation via MERTK signaling to induce the engulfment of apoptotic cells. Using FRET microscopy, we determined that MERTK directly induces the conformational change of β2integrins from the low to high-affinity form via a PI3-kinase-dependent signaling pathway. MERTK and β2integrins then form a highly structured synapse in which MERTK is retained by ligand-induced clustering in the synapse centre, while β2integrins and actin form a Src family kinase-, ILK- and FAK-dependent expanding ring which defines the leading edge of the synapse that ultimately engulfs the apoptotic cell. The identification of the MERTK membrane-proximal signaling pathway and the role of β2integrins in this pathway provides new insights into the function of this critical homeostatic receptor and provides new insights into how MERTK mutations and signaling defects may contribute to inflammatory and autoimmune diseases.
Associations between COVID-19 and putative markers of neuroinflammation: A diffusion basis spectrum imaging study
Authors: Zhang Wei , Gorelik Aaron J , Wang Qing , Norton Sara A , Hershey Tamara , Agrawal Arpana , Bijsterbosch Janine D , Bogdan Ryan 
Published: July 2023

AbstractCOVID-19 remains a significant international public health concern. Yet, the mechanisms through which symptomatology emerges remain poorly understood. While SARS-CoV-2 infection may induce prolonged inflammation within the central nervous system, the evidence primarily stems from limited small-scale case investigations. To address this gap, our study capitalized on longitudinal UK Biobank neuroimaging data acquired prior to and following COVID-19 testing (N=416 including n=224 COVID-19 cases; Mage=58.6). Putative neuroinflammation was assessed in gray matter structures and white matter tracts using non-invasive Diffusion Basis Spectrum Imaging (DBSI), which estimates inflammation-related cellularity (DBSI-restricted fraction; DBSI-RF) and vasogenic edema (DBSI-hindered fraction; DBSI-HF).We hypothesized that COVID-19 case status would be associated with increases in DBSI markers after accounting for potential confound (age, sex, race, body mass index, smoking frequency, and data acquisition interval) and multiple testing.COVID-19 case status was not significantly associated with DBSI-RF (|β|’s<0.28, pFDR>0.05), but with greater DBSI-HF in left pre- and post-central gyri and right middle frontal gyrus (β’s>0.3, all pFDR=0.03). Intriguingly, the brain areas exhibiting increased putative vasogenic edema had previously been linked to COVID-19-related functional and structural alterations, whereas brain regions displaying subtle differences in cellularity between COVID-19 cases and controls included regions within or functionally connected to the olfactory network, which has been implicated in COVID-19 psychopathology.Nevertheless, our study might not have captured acute and transitory neuroinflammatory effects linked to SARS-CoV-2 infection, possibly due to symptom resolution before the imaging scan. Future research is warranted to explore the potential time- and symptom-dependent neuroinflammatory relationship with COVID-19.
Coenzyme Q4is a functional substitute for coenzyme Q10and can be targeted to the mitochondria
Authors: Steenberge Laura H. , Sung Andrew Y. , Fan Jing , Pagliarini David J. 
Published: July 2023

ABSTRACTCoenzyme Q10(CoQ10) is an important cofactor and antioxidant for numerous cellular processes, and its deficiency has been linked to human disorders including mitochondrial disease, heart failure, Parkinson’s disease, and hypertension. Unfortunately, treatment with exogenous oral CoQ10is often ineffective, likely due to the extreme hydrophobicity and high molecular weight of CoQ10. Here, we show that less hydrophobic CoQ species with shorter isoprenoid tails can serve as viable substitutes for CoQ10in human cells. We demonstrate that CoQ4can perform multiple functions of CoQ10in CoQ-deficient cells at markedly lower treatment concentrations, motivating further investigation of CoQ4as a supplement for CoQ10deficiencies. In addition, we describe the synthesis and evaluation of an initial set of compounds designed to target CoQ4selectively to mitochondria using triphenylphosphonium (TPP). Our results indicate that select versions of these compounds can successfully be delivered to mitochondria in a cell model and be cleaved to produce CoQ4, laying the groundwork for further development.
Besting Monarchy: The Anti‐Classism Argument
Authors: Benn Alex 
Published: July 2023

AbstractFollowing the death of a monarch and the crowning of another, this article considers monarchy as a topic in political theory. It seeks to revitalise the topic, which has been given limited attention by political theorists in recent years. It identifies traditional objections to monarchy, alongside newer objections that attack it (particularly the British institution) for being racist and imperialist. However, those objections—though increasingly common—are not fatal to monarchy as an idea. This article develops an argument against monarchy based on the concept of classism: discrimination based on a person's class. Reframing familiar criticisms of monarchy for being elitist and snobbish, the anti‐classism argument draws on discrimination theory to outline the best objection to monarchy at the conceptual level.
Personalized cancer avatars for patients with thymic malignancies: A pilot study with circulating tumor cell‐derived organoids
Authors: Wu Yuan‐Hung , Chao Heng‐sheng , Chiang Chi‐Lu , Luo Yung‐Hung , Chiu Chao‐Hua , Yen Sang‐Hue , Liu Chun‐Yu , Chiou Jeng‐Fong , Burnouf Thierry , Chen Yin‐Ju , Wang Peng‐Yuan , Chao Tsu‐Yi , Hsu Shih‐Ming , Lu Long‐Sheng 
Published: July 2023

AbstractBackgroundSystemic therapy is the primary treatment for advanced thymic malignancies. However, there is an urgent need to improve clinical outcome. Personalized treatment based on predictive biomarkers is a potential approach to address this requirement. In this study, we aimed to show the correlation between drug sensitivity tests on CTCs‐derived organoids and clinical response in patients with thymic malignancies. This approach carries the potential to create personalized cancer avatars and improve treatment outcome for patients.MethodsWe previously reported potential treatment outcome prediction with patient‐derived organoids (cancer avatars) in patients with pancreatic ductal adenocarcinoma. To further investigate the feasibility of this approach in advanced thymic malignancies, we conducted a study in which 12 patients were enrolled and 21 liquid biopsies were performed.ResultsCancer avatars were successfully derived in 16 out of 21 samples (success rate 76.2%). We found a sensitivity of 1.0 and specificity of 0.6 for drug sensitivity tests on the cancer avatars, and a two‐tailed Fisher's exact test revealed a significant correlation between drug sensitivity tests and clinical responses (p = 0.0275).ConclusionThis study supports the potential of circulating tumor cell‐derived organoids to inform personalized treatment for advanced thymic malignancies. Further validation of this proof of concept finding is ongoing.
Pressure‐controlled versus manual facemask ventilation for anaesthetic induction in adults: A randomised controlled non‐inferiority trial
Authors: Edmark Lennart , Englund Emma‐Karin , Jonsson Alexandra Schöttle , Zilic Almira Teskeredzic , Cajander Per , Östberg Erland 
Published: July 2023

AbstractBackgroundPressure‐controlled face mask ventilation (PC‐FMV) with positive end‐expiratory pressure (PEEP) after apnoea following induction of general anaesthesia prolongs safe apnoea time and reduces atelectasis formation. However, depending on the set inspiratory pressure, a delayed confirmation of a patent airway might occur. We hypothesised that by lowering the peak inspiratory pressure (PIP) when using PC‐FMV with PEEP, confirmation of a patent airway would not be delayed as studied by the first return of CO2, compared with manual face mask ventilation (Manual FMV).MethodsThis was a single‐centre, randomised controlled non‐inferiority trial. Seventy adult patients scheduled for elective day‐case surgery under general anaesthesia with body mass index between 18.5 and 29.9 kg m−2, American Society of Anesthesiologists (ASA) classes I–III, and without anticipated difficult FMV, were included. Before the start of pre‐oxygenation and induction of general anaesthesia, participants were randomly allocated to receive ventilation with either PC‐FMV with PEEP, at a PIP of 11 and a PEEP of 6 cmH2O or Manual FMV, with the adjustable pressure‐limiting valve set at 11 cmH2O. The primary outcome variable was the number of ventilatory attempts needed until confirmation of a patent airway, defined as the return of at least 1.3 kPa CO2.ResultsThe return of ≥1.3 kPa CO2 on the capnography curve was observed after mean ± SD, 3.6 ± 4.2 and 2.5 ± 1.9 ventilatory attempts/breaths with PC‐FMV with PEEP and Manual FMV, respectively. The difference in means (1.1 ventilatory attempts/breaths) had a 99% CI of −1.0 to 3.1, within the accepted upper margin of four breaths for non‐inferiority.ConclusionFollowing induction of general anaesthesia, PC‐FMV with PEEP was used without delaying a patent airway as confirmed with capnography, if moderate pressures were used.
Dismantling the diorama: A case study in “unknowable” human remains
Authors: Lans Aja M. , Boza Cuadros Maria Fernanda 
Published: July 2023

AbstractBlack Americans have long been disproportionately represented among the victims of state‐sanctioned violence. In response, the Black community has mobilized around movements like Black Lives Matter and Say Her Name. However, the exploitation, objectification, and anonymization of Black bodies persists. In many academic disciplines, Black death and suffering are regularly presented as acceptable research findings. Here, we consider the role objectified Black bodies have played in upholding white supremacy within the context of the museum by piecing together the suspect itinerary of the individual whose skull is contained within Lion Attacking a Dromedary. This diorama, currently housed at the Carnegie Museum of Natural History in Pittsburgh, exemplifies how scientific institutions have perpetuated imperial scientific ideologies in their ongoing exhibitions. By engaging with Black feminism and decolonial frameworks, we present a path forward for such artifacts and consider how museums can truly support the Movement for Black Lives.
Cognitive phenotype of juvenile absence epilepsy: An investigation of patients and unaffected siblings
Authors: Caciagli Lorenzo , Ratcliffe Corey , Xiao Fenglai , van Graan Louis A. , Trimmel Karin , Vollmar Christian , Centeno Maria , Duncan John S. , Thompson Pamela J. , Baxendale Sallie , Koepp Matthias J. , Wandschneider Britta 
Published: July 2023

AbstractObjectiveThe cognitive profile of juvenile absence epilepsy (JAE) remains largely uncharacterized. This study aimed to: (1) elucidate the neuropsychological profile of JAE; (2) identify familial cognitive traits by investigating unaffected JAE siblings; (3) establish the clinical meaningfulness of JAE‐associated cognitive traits; (4) determine whether cognitive traits across the idiopathic generalized epilepsy (IGE) spectrum are shared or syndrome‐specific, by comparing JAE to juvenile myoclonic epilepsy (JME); and (5) identify relationships between cognitive abilities and clinical characteristics.MethodsWe investigated 123 participants—23 patients with JAE, 16 unaffected siblings of JAE patients, 45 healthy controls, and 39 patients with JME—who underwent a comprehensive neuropsychological test battery including measures within four cognitive domains: attention/psychomotor speed, language, memory, and executive function. We correlated clinical measures with cognitive performance data to decode effects of age at onset and duration of epilepsy.ResultsCognitive performance in individuals with JAE was reduced compared to controls across attention/psychomotor speed, language, and executive function domains; those with ongoing seizures additionally showed lower memory scores. Patients with JAE and their unaffected siblings had similar language impairment compared to controls. Individuals with JME had worse response inhibition than those with JAE. Across all patients, those with older age at onset had better attention/psychomotor speed performance.SignificanceJAE is associated with wide‐ranging cognitive difficulties that encompass domains reliant on frontal lobe processing, including language, attention, and executive function. JAE siblings share impairment with patients on linguistic measures, indicative of a familial trait. Executive function subdomains may be differentially affected across the IGE spectrum. Cognitive abilities are detrimentally modulated by an early age at seizure onset.
Biogeographic pattern of living vegetation carbon turnover time in mature forests across continents
Authors: Yu Kailiang , Ciais Philippe , Bloom Anthony A. , Wang Jinsong , Liu Zhihua , Chen Han Y. H. , Wang Yilong , Chen Yizhao , Ballantyne Ashley P. 
Published: July 2023

AbstractAimTheoretically, woody biomass turnover time () quantified using outflux (i.e. tree mortality) predicts biomass dynamics better than using influx (i.e. productivity). This study aims at using forest inventory data to empirically test the outflux approach and generate a spatially explicit understanding of woody in mature forests. We further compared woody estimates with dynamic global vegetation models (DGVMs) and with a data assimilation product of C stocks and fluxes—CARDAMOM.LocationContinents.Time PeriodHistoric from 1951 to 2018.Major Taxa StudiedTrees and forests.MethodsWe compared the approaches of using outflux versus influx for estimating woody and predicting biomass accumulation rates. We investigated abiotic and biotic drivers of spatial woody and generated a spatially explicit map of woody at a 0.25‐degree resolution across continents using machine learning. We further examined whether six DGVMs and CARDAMOM generally captured the observational pattern of woody .ResultsWoody quantified by the outflux approach better (with R2 0.4–0.5) predicted the biomass accumulation rates than the influx approach (with R2 0.1–0.4) across continents. We found large spatial variations of woody for mature forests, with highest values in temperate forests (98.8 ± 2.6 y) followed by boreal forests (73.9 ± 3.6 y) and tropical forests. The map of woody extrapolated from plot data showed higher values in wetter eastern and pacific coast USA, Africa and eastern Amazon. Climate (temperature and aridity index) and vegetation structure (tree density and forest age) were the dominant drivers of woody across continents. The highest woody in temperate forests was not captured by either DGVMs or CARDAMOM.Main ConclusionsOur study empirically demonstrated the preference of using outflux over influx to estimate woody for predicting biomass accumulation rates. The spatially explicit map of woody and the underlying drivers provide valuable information to improve the representation of forest demography and carbon turnover processes in DGVMs.
Exploring the perceived influence of social media use on disordered eating in nutrition and dietetics students
Authors: Law Rebecca , Jevons Emily F. P. 
Published: July 2023

AbstractBackgroundSocial media use (SMU) is increasingly widespread. More recently, SMU has been associated with increases in disordered eating; however, few qualitative studies have explored this issue in nutrition and dietetics students specifically, where susceptibility to disordered eating may be particularly high. The present study therefore aimed to investigate the perceived impact of SMU on disordered eating in nutrition and dietetics students.MethodsOne‐to‐one, in‐depth, semi‐structured interviews were conducted with nutrition and dietetics students from universities across the UK. Interviews explored students’ views on the potential influence of SMU on their eating‐related thoughts, feelings and behaviours. Data were thematically analysed to identify key themes.ResultsThe findings suggested that SMU may provide students with a useful tool for the exploration of new recipes, ingredients and health‐related information, thus enabling them to improve their eating behaviour and diet quality. However, students also showed high levels of objective awareness regarding the problems associated with SMU, including the presence of misinformation, body image dissatisfaction, social pressures and disordered eating. Interestingly, despite enabling them to detect sources of misinformation, students also discussed the negative impact that their course had on their eating habits, suggesting course content may be an additional risk factor for the development of disordered eating for this particular group.ConclusionsFuture research should investigate ways to mitigate the negative impact of SMU and course content on disordered eating in nutrition and dietetics students.
Physiological and pathophysiological roles of the KCNK3 potassium channel in the pulmonary circulation and the heart
Authors: Saint‐Martin Willer Anaïs , Santos‐Gomes Joana , Adão Rui , Brás‐Silva Carmen , Eyries Mélanie , Pérez‐Vizcaino Francisco , Capuano Véronique , Montani David , Antigny Fabrice 
Published: July 2023

AbstractPotassium channel subfamily K member 3 (KCNK3), encoded by the KCNK3 gene, is part of the two‐pore domain potassium channel family, constitutively active at resting membrane potentials in excitable cells, including smooth muscle and cardiac cells. Several physiological and pharmacological mediators, such as intracellular signalling pathways, extracellular pH, hypoxia and anaesthetics, regulate KCNK3 channel function. Recent studies show that modulation of KCNK3 channel expression and function strongly influences pulmonary vascular cell and cardiomyocyte function. The altered activity of KCNK3 in pathological situations such as atrial fibrillation, pulmonary arterial hypertension and right ventricular dysfunction demonstrates the crucial role of KCNK3 in cardiovascular homeostasis. Furthermore, loss of function variants of KCNK3 have been identified in patients suffering from pulmonary arterial hypertension and atrial fibrillation. This review focuses on current knowledge of the role of the KCNK3 channel in pulmonary circulation and the heart, in healthy and pathological conditions.
image
Is vaccine response to SARS-CoV-2 preserved after switching to anti-CD20 therapies in patients with multiple sclerosis or related disorders?
Authors: Jeantin Lina , Abdi Basma , Soulié Cathia , Sterlin Delphine , Maillart Elisabeth , Beigneux Ysoline , Hippolyte Amandine , Belin Lisa , Marcelin Anne-Geneviève , Pourcher Valérie , Louapre Céline 
Published: July 2023

BackgroundAlthough vaccination against SARS-CoV-2 is recommended prior to introducing anti-CD20 therapies, limited data are available regarding the evolution of post-vaccinal immunity.MethodsThis retrospective study compared anti-Spike antibody titres at 6 and 12 months from SARS-CoV-2 vaccination between patients vaccinated before switching to anti-CD20 (‘Switch’) and two control groups: (1) patients vaccinated under disease-modifying therapies (DMTs) other than fingolimod and anti-CD20 (‘Other DMTs’); (2) patients vaccinated on anti-CD20 (‘Anti-CD20’). Anti-Spike-specific T-cell responses were compared between ‘Switch’ and ‘Anti-CD20’ groups.ResultsFifty-three patients were included in the ‘Switch’ group, 54 in the ‘Other DMTs’ group and 141 in the ‘Anti-CD20’ group. At 6 months, in the subset of patients who received a booster dose, the ‘Switch’ group had lower anti-Spike titres compared with the ‘Other DMTs’ group (median 241.0 IQR (88.0; 504.0) BAU/mL vs 2034 (1155; 4634) BAU/mL, p<0.001), and less patients in the ‘Switch’ group reached the protective threshold of 264 BAU/mL. The ‘Switch’ group had higher anti-Spike titres than the ‘Anti-CD20’ group (7.5 (0.0; 62.1) BAU/mL, p=0.001). Anti-Spike titres were not different between the ‘Switch’ and ‘Other DMTs’ groups before booster administration. These results were similar at 12 months. Spike-specific T-cell positivity was similar between the ‘Switch’ and ‘Anti-CD20’ groups at 6 and 12 months (60.4% vs 61.0%, p=0.53, and 79.4% vs 87.5%, p=0.31, respectively).ConclusionsDespite a primary vaccination performed before the first anti-CD20 cycle, our results suggest weaker immune responses at 6 and 12 months and decreased booster efficacy after introducing anti-CD20. Patients vaccinated prior to anti-CD20 introduction might falsely be considered as fully protected by vaccination.