bluuebunny/crossref_metadata_2025_split huggingface dataset:
Individualized genetic makeup that controls natural killer cell function influences the efficacy of isatuximab immunotherapy in patients with multiple myeloma
Authors: Sun Haibo , Martin Thomas G , Marra John , Kong Denice , Keats Jonathon , Macé Sandrine , Chiron Marielle , Wolf Jeffrey L , Venstrom Jeffrey M , Rajalingam Raja 
Published: July 2021

BackgroundPhase IIb clinical trial with isatuximab (Isa)-lenalidomide (Len)-dexamethasone (Dex) showed an improved progression-free survival (PFS) in patients with relapsed or refractory multiple myeloma (RRMM), but the efficacy varied by patient. Antibody-dependent cell-mediated cytotoxicity (ADCC) by natural killer (NK) cells plays a crucial role in arbitrating antitumor activities of therapeutic-antibodies. We tested if patient-specific genetic makeup known to set NK cell functional threshold influence response to Isa-Len-Dex therapy.MethodsWe characterized 57 patients with RRMM receiving Isa-Len-Dex for polymorphisms of killer-cell immunoglobulin-like receptors (KIR), human leukocyte antigen (HLA) class I, and FCGR3A loci. In vitro ADCC assay, coincubating primary NK cells expressing specific KIR repertoire with multiple myeloma cell lines (MM cells) expressing selected HLA class I ligands, was used to confirm the identified genetic correlatives of clinical response.ResultsPatients with KIR3DL2+ and its cognate-ligand HLA-A3/11+ had superior PFS than patients missing this combination (HR=0.43; p=0.02), while patients carrying KIR2DL1+ and HLA-C2C2+ compared with to patients missing this pair showed short PFS (HR=3.54; p=0.05). Patients with KIR3DL2+ and HLA-A3/11+ plus high-affinity FCGR3A-158V allele showed the most prolonged PFS (HR=0.35; p=0.007). Consistent with these clinical data, mechanistic experiments demonstrated that NK cells expressing KIR3DL2 trigger greater ADCC when MM cells express HLA-A3/11. Inversely, NK cells expressing KIR2DL1 do not kill if MM cells express the HLA-C2C2 ligand. NK cells expressing high-affinity FCGR3A-158VV-induced greater ADCC compared with those with low-affinity FCGR3A-158FF.ConclusionsOur results suggest that KIR3DL2+ and HLA-A3/11+ with FCGR3A-158V markers lead to enhanced Isa-dependent NK-mediated cytolysis against MM cells and results in improved PFS in patients with RRMM treated by Isa-Len-Dex. Moreover, the presence of KIR2DL1+ and HLA-C2C2+ identifies patients who may have a lower response to Isa-Len-Dex therapy linked to a reduced NK-mediated ADCC. These biomarkers could potentially identify, via precision medicine, patients more likely to respond to Isa-Len-Dex immunotherapy.Trial registration numberNCT01749969.
#3083 Fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): an interoceptive predictive coding model of pain and fatigue expression
Authors: Sharp Harriet , Themelis Kristy , Amato Marisa , Barritt Andrew , Davies Kevin , Harrison Neil , Garfinkel Sarah , Critchley Hugo , Eccles Jessica 
Published: July 2021

IntroductionThe aetiology and pathophysiology of fibromyalgia and ME/CFS are poorly characterised but altered inflammatory, autonomic and interoceptive processes have been implicated. Interoception has been conceptualised as a predictive coding process; where top-down prediction signals compare to bottom-up afferents, resulting in prediction error signals indicating mismatch between expected and actual bodily states. Chronic dyshomeostasis and elevated interoceptive prediction error signals have been theorised to contribute to the expression of pain and fatigue in fibromyalgia and ME/CFS.Objectives/AimsTo investigate how altered interoception and prediction error relates to baseline expression of pain and fatigue in fibromyalgia and ME/CFS and in response to an inflammatory challenge.MethodsSixty-five patients with fibromyalgia and/or ME/CFS diagnosis and 26 matched controls underwent baseline assessment: self-report questionnaires assessing subjective pain and fatigue and objective measurements of pressure-pain thresholds. Participants received injections of typhoid (inflammatory challenge) or saline (placebo) in a randomised, double-blind, crossover design, then completed heartbeat tracking task (assessing interoceptive accuracy). Porges Body Questionnaire assessed interoceptive sensibility. Interoceptive prediction error (IPE) was calculated as discrepancy between objective accuracy and subjective sensibility.ResultsPatients with fibromyalgia and ME/CFS had significantly higher IPE (suggesting tendency to over-estimate interoceptive ability) and interoceptive sensibility, despite no differences in interoceptive accuracy. IPE and sensibility correlated positively with all self-report fatigue and pain measures, and negatively with pain thresholds. Following inflammatory challenge, IPE correlated negatively with the mismatch between subjective and objective measures of pain induced by inflammation.ConclusionsThis is the first study to reveal altered interoception processes in patients with fibromyalgia and ME/CFS, who are known to have dysregulated autonomic function. Notably, we found elevated IPE in patients, correlating with their subjective experiences of pain and fatigue. We hypothesise a predictive coding model, where mismatch between expected and actual internal bodily states (linked to autonomic dysregulation) results in prediction error signalling which could be metacognitively interpreted as chronic pain and fatigue. Our results demonstrate potential for further exploration of interoceptive processing in patients with fibromyalgia and ME/CFS, aiding understanding of these poorly defined conditions and providing potential new targets for diagnostic and therapeutic intervention.
Thrombectomy for secondary distal, medium vessel occlusions of the posterior circulation: seeking complete reperfusion
Authors: Meyer Lukas , Stracke Christian Paul , Wallocha Marta , Broocks Gabriel , Sporns Peter B , Piechowiak Eike I , Kaesmacher Johannes , Maegerlein Christian , Dorn Franziska , Zimmermann Hanna , Naziri Weis , Abdullayev Nuran , Kabbasch Christoph , Behme Daniel , Jamous Ala , Maus Volker , Fischer Sebastian , Möhlenbruch Markus , Weyland Charlotte Sabine , Langner Soenke , Meila Dan , Miszczuk Milena , Siebert Eberhard , Lowens Stephan , Krause Lars Udo , Yeo Leonard LL , Tan Benjamin YQ , Gopinathan Anil , Gory Benjamin , Arenillas Juan F , Navia Pedro , Raz Eytan , Shapiro Maksim , Arnberg Fabian , Zeleňák Kamil , Martínez-Galdámez Mario , Kastrup Andreas , Papanagiotou Panagiotis , Kemmling Andre , Psychogios Marios N , Andersson Tommy , Chapot René , Fiehler Jens , Hanning Uta 
Published: July 2021

BackgroundWhether to approach distal occlusions endovascularly or not in medium-sized vessels secondary to proximal large vessel occlusion stroke remains unanswered.ObjectiveTo investigates the technical feasibility and safety of thrombectomy for secondary posterior circulation distal, medium vessel occlusions (DMVO).MethodsTOPMOST (Treatment fOr Primary Medium vessel Occlusion STroke) is an international, retrospective, multicenter, observational registry of patients treated for distal cerebral artery occlusions. This study subanalysis endovascularly treated occlusions of the posterior cerebral artery in the P2 and P3 segment secondary preprocedural or periprocedural thrombus migration between January 2014 and June 2020. Technical feasibility was evaluated with the modified Thrombolysis in Cerebral Infarction (mTICI) scale. Procedural safety was assessed by the occurrence of symptomatic intracranial hemorrhage (sICH) and intervention-related serious adverse events.ResultsAmong 71 patients with secondary posterior circulation DMVO who met the inclusion criteria, occlusions were present in 80.3% (57/71) located in the P2 segment and in 19.7% (14/71) in the P3 segment. Periprocedural migration occurred in 54.9% (39/71) and preprocedural migration in 45.1% (32/71) of cases. The first reperfusion attempt led in 38% (27/71) of all cases to mTICI 3. On multivariable logistic regression analysis, increased numbers of reperfusion attempts (adjusted odds ratio (aOR)=0.39, 95% CI 0.29 to 0.88, p=0.009) and preprocedural migration (aOR=4.70, 95% CI,1.35 to 16.35, p=0.015) were significantly associated with mTICI 3. sICH occurred in 2.8% (2/71).ConclusionThrombectomy for secondary posterior circulation DMVO seems to be safe and technically feasible. Even though thrombi that have migrated preprocedurally may be easier to retract, successful reperfusion can be achieved in the majority of patients with secondary DMVO of the P2 and P3 segment.
Effect of quitting smoking on health outcomes during treatment for tuberculosis: secondary analysis of the TB & Tobacco Trial
Authors: Siddiqi Kamran , Keding Ada , Marshall Anna-Marie , Dogar Omara , Li Jinshuo , Huque Rumana , Fatima Razia , Khan Amina , Elsey Helen , Gabe Rhian , Kotz Daniel , Sheikh Aziz 
Published: July 2021

BackgroundDespite treatment, patients with tuberculosis (TB) who smoke have poorer outcomes compared with non-smokers. It is unknown, however, if quitting smoking during the 6 months of TB treatment improves TB outcomes.MethodsThe TB & Tobacco Trial was a double-blind, placebo-controlled randomised trial of cytisine for smoking cessation in 2472 patients with pulmonary TB in Bangladesh and Pakistan. In a secondary analysis, we investigated the hypothesis that smoking cessation improves health outcomes in patients during the TB treatment course. The outcomes included an eight-point TB clinical score, sputum conversion rates, chest X-ray grades, quality of life (EQ-5D-5L), TB cure plus treatment completion rates and relapse rates. These were compared between those who stopped smoking and those who did not, using regression analysis.ResultsWe analysed the data of 2273 (92%) trial participants. Overall, 25% (577/2273) of participants stopped smoking. Compared with non-quitters, those who quit had better TB cure plus treatment completion rates (91% vs 80%, p<0.001) and lower TB relapse rates (6% vs 14%, p<0.001). Among quitters, a higher sputum conversion rate at week 9 (91% vs 87%, p=0.036), lower mean TB clinical scores (−0.20 points, 95% CI −0.31 to −0.08, p=0.001) and slightly better quality of life (mean EQ-5D-5L 0.86 vs 0.85, p=0.015) at 6 months were also observed. These differences, except quality of life, remained statistically significant after adjusting for baseline values, trial arm and TB treatment adherence rates.ConclusionPatients with TB who stop smoking may have better outcomes than those who don’t. Health professionals should support patients in stopping smoking.
Does pay-for-performance improve patient outcomes in acute exacerbation of COPD admissions?
Authors: Stone Philip W , Adamson Alexander , Hurst John R , Roberts C Michael , Quint Jennifer K 
Published: July 2021

BackgroundThe COPD Best Practice Tariff (BPT) is a pay-for-performance scheme in England that incentivises review by a respiratory specialist within 24 hours of admission and completion of a list of key care components prior to discharge, known as a discharge bundle, for patients admitted with acute exacerbation of COPD (AECOPD). We investigated whether the two components of the COPD BPT were associated with lower 30-day mortality and readmission in people discharged following AECOPD.MethodsLongitudinal study of national audit data containing details of AECOPD admissions in England and Wales between 01 February 2017 and 13 September 2017. Data were linked with national admissions and mortality data. Mixed-effects logistic regression, using a random intercept for hospital to adjust for clustering of patients, was used to determine the relationship between the COPD BPT criteria (combined and separately) and 30-day mortality and readmission. Models were adjusted for age, sex, socioeconomic status, length of stay, smoking status, Charlson comorbidity index, mental illness and requirement for oxygen or noninvasive ventilation during admission.Results28 345 patients discharged from hospital following AECOPD were included. 37% of admissions conformed to the two COPD BPT criteria. No relationship was observed between BPT conforming admissions and 30-day mortality (OR: 1.09 (95% CI 0.92 to 1.29)) or readmissions (OR: 0.96 (95% CI 0.90 to 1.02)). No relationship was observed between either of the individual COPD BPT components and 30-day mortality or readmissions. However, a specialist review at any time during admission was associated with lower inpatient mortality (OR: 0.69 (95% CI 0.58 to 0.81)).ConclusionCompletion of the combined COPD BPT criteria does not appear associated with a reduction in 30-day mortality or readmission. However, specialist review was associated with reduced inpatient mortality. While it is difficult to argue that discharge bundles do not improve care, this analysis questions whether the pay-for-performance model improves mortality or readmissions.
Impact of standardised packaging in the UK on warning salience, appeal, harm perceptions and cessation-related behaviours: a longitudinal online survey
Authors: Moodie Crawford , Best Catherine , Hitchman Sara C , Critchlow Nathan , MacKintosh Anne-Marie , McNeill Ann , Stead Martine 
Published: July 2021

IntroductionIn the UK, since 20 May 2017, tobacco companies must sell cigarettes and rolling tobacco in standardised packs.MethodsThree waves of a longitudinal online survey with smokers (≥16) before standardised packaging (wave 1 (W1): April to May 2016) and after standardised packaging (wave 2 (W2): September to November 2017; wave 3 (W3): May to July 2019). Of the 6233 smokers at W1, 4293 responded at W2 and 3175 at W3. We explored smokers’ response to warning salience, appeal (appeal, quality, value, satisfaction and taste compared with a year ago), harm (harmfulness compared with a year ago, harm compared with other brands and whether some brands have more harmful substances), and quit plans, attempts and quitting.ResultsCompared with W1, the proportions noticing warnings first on packs, and rating cigarettes/rolling tobacco less appealing and worse value than a year ago, were higher at W2 and W3. Disagreeing that some brands contain more harmful substances was higher at W2. Interactions between social grade and survey wave for warning salience, and each appeal and harm outcome, were non-significant. Smokers switching from not noticing warnings first at W1 to noticing warnings first at W2, or who had a lower composite appeal score at W2, were more likely to plan to quit and to have made a quit attempt at W2. Smokers who switched to disagreeing that some brands contain more harmful substances at W2, after giving a different response at W1, were more likely to quit at W3.ConclusionsStandardised packaging appears to be having the intended impacts.
FAST CAT
Authors: Fafalios Pavlos , Petrakis Kostas , Samaritakis Georgios , Doerr Korina , Kritsotaki Athina , Tzitzikas Yannis , Doerr Martin 
Published: July 2021

Descriptive and empirical sciences, such as History, are the sciences that collect, observe and describe phenomena to explain them and draw interpretative conclusions about influences, driving forces and impacts under given circumstances. Spreadsheet software and relational database management systems are still the dominant tools for quantitative analysis and overall data management in these these sciences, allowing researchers to directly analyse the gathered data and perform scholarly interpretation. However, this current practice has a set of limitations, including the high dependency of the collected data on the initial research hypothesis, usually useless for other research, the lack of representation of the details from which the registered relations are inferred, and the difficulty to revisit the original data sources for verification, corrections or improvements. To cope with these problems, in this article we present FAST CAT, a collaborative system for assistive data entry and curation in Digital Humanities and similar forms of empirical research. We describe the related challenges, the overall methodology we follow for supporting semantic interoperability, and discuss the use of FAST CAT in the context of a European (ERC) project of Maritime History, called
SeaLiT
, which examines economic, social and demographic impacts of the introduction of steamboats in the Mediterranean area between the 1850s and the 1920s.
(Invited) Nanodiamonds and Bioapplications
Authors: Arnault Jean-Charles 
Published: July 2021

Like other nanocarbons, nanodiamond (ND) is the object of a rising interest from researchers, engineers and companies. Indeed, its outstanding properties, partly inhered from bulk diamond, are completed by new ones conferred at the nanoscale. Moreover, ND can host photostable luminescent color centers (NV, SiV, GeV,...) that can possess spin properties [1]. Combining these uncommon assets, ND are actively investigated for nanomedicine and bioapplications, quantum technologies, catalysis and energy applications, advanced composites and lubricants.
After set the scene of ND and nanomedicine, this talk will focus on the recent developments of our research group towards bioapplications using ND differing by their origin (HPHT, detonation) and their surface chemistry. These studies are based on an extended characterization of ND. Toxicity issues will be discussed with investigations of the in vitro genotoxicity of HPHT ND and a comparative ecotoxicology study involving other nanocarbons. We will illustrate that ND can act as an efficient vector for biological species of interest, either grafted at its surface thanks to the versatile carbon chemistry or loaded by electrostatic interactions. Surprisingly, we have also demonstrated that detonation ND can behave as an active nanoparticle under gamma irradiation with a radiosensitization effect [2]. More recently, tritium labelled detonation ND allowed to explore the distribution throughout mouse organs and their excretion in urine and feces [3].

References

[1] O. A. Shenderova, A. I. Shames, N. A. Nunn, M. D. Torelli, I. Vlasov, A. Zaitsev, Review Article: Synthesis, properties, and applications of fluorescent diamond particles, J. Vac. Sci. Technol. B 37 (2019) 030802. doi.org/10.1116/1.5089898
[2] R. Grall, H. A. Girard, L. Saad, T. Petit, C. Gesset, M. Combis-Schlumberger, V. Paget, J. Delic, J. C. Arnault, S. Chevillard, Impairing the radioresistance of cancer cells by hydrogenated nanodiamonds. Biomaterials 61 (2015) 290–298. doi.org/10.1016/j.biomaterials.2015.05.034
[3] S. Claveau, E. Nehlig, S. Garcia-Argote, S. Feuillastre, G. Pieters, H. A. Girard, J. C. Arnault, F. Treussart, J. R. Bertrand, Delivery of siRNA to Ewing sarcoma tumor xenografted on mice, using hydrogenated detonation nanodiamond: treatment efficacy and tissue distribution Nanomaterials 10 (2020) 553. doi:10.3390/nano10030553
(Invited) Multifunctional Carbon Nanodots for Theranostic Applications
Authors: Bianco Alberto 
Published: July 2021

Carbon nanodots are a form of carbon that is attracting a lot of attention, as they are considered promising nanomaterials for future clinical translation. Carbon nanodots combine numerous characteristics including high photostability, low cytotoxicity, and superior biocompatibility. We have conceived and synthesised multifunctional carbon nanodots with deep-red emission properties through their controlled chemical modification using folic acid ligand (Figure). These carbon nanodots, endowed of a high colloidal stability and an enhanced luminescence, are suitable for targeted intracellular production of reactive oxygen species by laser irradiation leading to efficient cancer cell death [1]. In addition, we have modified carbon nanodots with a chelating agent for gadolinium. These nanodots showed a better magnetic resonance relaxivity than commercial MRI agents, resulting potential clinical tools as MRI/fluorescence dually functional imaging probes.
[1] Ji, D.-K.; Reina,G.; Guo,S.; Eredia,M.; Samorì, P.; Ménard-Moyon, C.; BiancoA. Controlled Functionalization of Red-emissive Carbon Nanodots for Targeted Intracellular Production of Reactive Oxygen Species. Nanoscale Horizons
2020, 5, 1240-1249. DOI:10.1039/D0NH00300J

Figure 1
(Invited) Photoluminescence Study of Carbon Nanomaterial Interactions with the Immune System
Authors: Star Alexander 
Published: July 2021

Carbon nanomaterials such as graphene and carbon nanotubes have attracted tremendous attention for various applications in science and technology. However, increasing use of carbon nanomaterials also necessitates careful scrutiny of their impact on human health. Understanding their interactions with different components of the innate immune system is of particular importance.
Myeloperoxidase (MPO), a key enzyme released by neutrophils during inflammation, has been shown to catalyze the biodegradation of carbon nanomaterials. We investigated the changes in photoluminescence (PL) properties of graphene oxide (GO) and single-walled carbon nanotubes (SWCNT) during MPO degradation. Increased fluorescence emission was observed with the progression of enzymatic oxidation of GO as a result of the formation of graphene quantum dots (GQDs). In contrast, the fluorescence of surfactant-coated SWCNT was either quenched or remained almost unchanged (depending on the surfactant used) during 5-day degradation. The two different PL systems were combined as SWCNT/GO nanoscrolls into ratiometric fluorescence sensors to monitor MPO activity.
Lipid metabolites play an important role in the immune response. We demonstrated a photo-induced cycloaddition reaction between oxygenated lipid metabolites containing enone functional group and SWCNTs. By creating covalent and tunable sp3 defects in the sp2 carbon lattice of SWCNTs, this photochemical reaction results in the gradual appearance of the bright red-shifted near-IR photoluminescence in SWCNTs.
What Can We Learn from Carbon Nanotube Diffusion Trajectories Recorded in the Live Brain?
Authors: Lee Antony , Danne Noemie , Paviolo Chiara , Soria Federico , Ferreira Joana , Bezard Erwan , Groc Laurent , Cognet Laurent 
Published: July 2021

Luminescent single wall carbon nanotubes are now well established, as unique nanoreporters to probe the brain extracellular space[1]. On the imaging side, this comes from their rich near-infrared optical properties, which also eventually be improved by sp3-chemical functionalization[2]. In addition, their uncommon 1D morphology is an important asset for tissue penetration, yet understanding their diffusion behavior in the complex brain extracellular network is challenging and necessitates dedicated analysis tools. To this aim, we have developed two novel approaches (i) based on the local analysis of trajectory contours to locally measure the nanoscale dimensions of the brain network [3] and (ii) based on the transient evaluation of anomalous carbon nanotube diffusion to delineate the ECS molecular diffusion landscape [4]. The application of these analytical tools to extract relevant biological parameters in physiological and pathological brain models will be presented [5].

References

[1] Godin et al Nat. Nanotechnol. 12 (2017) 238-243 ; Gao, et al, Nanomaterials 7, 11, (2017) 393 ; Danné et al ACS Photonics, 5, 2, (2018) 359-364
[2] Mandal et al. Scientific Reports, 10 (2020) 5286
[3] Paviolo et al Methods 174 (2020) 91-99
[4] Lee et al, in preparation
[5] Soria et al Nat. Commun., 11 (2020) 3440