bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of potential transthyretin amyloid cardiomyopathy cases in the Brazilian public health system using a Machine Learning Model
Authors: Zuppo Laper Isabella , Camacho-Hubner Cecilia , Vansan Ferreira Rafaela , Leite Bertoli de Souza Claudenice , Simões Marcus Vinícius , Fernandes Fabio , de Barros Correia Edileide , de Jesus Lopes de Abreu Ariane , Silva Julian Guilherme 
Published: November 2022

AbstractObjectivesTo identify and describe the profile of potential transthyretin cardiac amyloidosis (ATTR-CM) cases in the Brazilian public health system (SUS), using a predictive machine learning (ML) model.MethodsThis was a retrospective descriptive database study that aimed to estimate the frequency of potential ATTR-CM cases in the Brazilian public health system using a supervised ML model, from January 2015 to December 2021. To build the model, a list of ICD-10 codes and procedures potentially related with ATTR-CM was created based on literature review and validated by experts.ResultsFrom 2015 to 2021, the ML model classified 262 hereditary ATTR-CM (hATTR-CM) and 1,581 wild-type ATTR-CM (wtATTR-CM) potential cases. Overall, the median age of hATTR-CM and wtATTR-CM patients was 66.8 and 59.9 years, respectively. The ICD-10 codes most presented as hATTR-CM and wtATTR-CM were related to heart failure and arrythmias. Regarding the therapeutic itinerary, 13% and 5% of hATTR-CM and wtATTR-CM received treatment with tafamidis meglumine, respectively, while 0% and 29% of hATTR-CM and wtATTR-CM were referred to heart transplant.ConclusionOur findings may be useful to support the development of health guidelines and policies to improve diagnosis, treatment, and to cover unmet medical needs of patients with ATTR-CM in Brazil.
A life-history perspective on the evolutionary interplay of sex ratios and parental sex roles
Authors: Long Xiaoyan , Székely Tamas , Komdeur Jan , Weissing Franz J. 
Published: November 2022

AbstractParental care is one of the most diverse social behaviours, and caring by the male, female or both parents is essential for successful reproduction of many organisms. Theoretical and empirical studies suggest that parental sex roles are associated with biased sex ratios. However, there is considerable debate on the causal relationship between parental sex roles and sex ratio biases and on the relative importance of the operational sex ratio (OSR), the adult sex ratio (ASR), and the maturation sex ratio (MSR). Here we use individual-based evolutionary simulations to investigate the joint evolution of sex-specific parental behaviour and the various sex ratios in several life history scenarios. We show that sex differences in maturation time or mortality rates at various life-history stages predict the evolution of parental sex roles relatively well: typically, but not always, parental care is biased toward the sex with the lower mortality or the faster maturation. The association of parental sex roles with the various sex ratios is more intricate. In our simulations, the operational sex ratio at evolutionary equilibrium was typically biased toward the less-caring sex. However, the direction and strength of OSR biases often changed drastically in the course of evolution, implying that, rather than being a driver of parental sex roles, OSR biases emerge as a consequence of sex-biases in parental care. When the MSR or the ASR is biased, this bias is generally associated with a bias in parental care: the overrepresented sex does most of the caring. However, the opposite pattern (that the underrepresented sex did most of the caring) also occurs in some scenarios. Moreover, pronounced parental sex roles may also evolve in the absence of an MSR or ASR bias. Taken together, we conclude that none of the sex ratios can be viewed as drivers of a parental care bias; they rather co-evolve with parental care bias in a subtle manner.
Large depth differences between target and flankers can increase crowding: Evidence from a multi-depth plane display
Authors: Smithers Samuel P. , Shao Yulong , Altham James , Bex Peter J. 
Published: November 2022

AbstractCrowding occurs when the presence of nearby features causes highly visible objects to become unrecognizable. Although crowding has implications for many everyday tasks and the tremendous amounts of research reflect its importance, surprisingly little is known about how depth affects crowding. Most available studies show that stereoscopic disparity reduces crowding, indicating that crowding may be relatively unimportant in three-dimensional environments. However, most previous studies tested only small stereoscopic differences in depth in which disparity, defocus blur, and accommodation are inconsistent with the real world. Using a novel multi-depth plane display, this study investigated how large (0.54 - 2.25 diopters), real differences in target-flanker depth, representative of those experienced between many objects in the real world, affect crowding. Our findings show that large differences in target-flanker depth increased crowding in the majority of observers, contrary to previous work showing reduced crowding in the presence of small depth differences. Furthermore, when the target was at fixation depth, crowding was generally more pronounced when the flankers were behind the target as opposed to in front of it. However, when the flankers were at fixation depth, crowding was generally more pronounced when the target was behind the flankers. These findings suggest that crowding from clutter outside the limits of binocular fusion can still have a significant impact on object recognition and visual perception in the peripheral field.
Signatures of electrical stimulation driven network interactions in the human limbic system
Authors: Valencia Gabriela Ojeda , Gregg Nicholas M. , Worrell Gregory A. , Huang Harvey , Lundstrom Brian N. , Brinkmann Benjamin H. , Attia Tal Pal , Van Gompel Jamie J. , Bernstein Matt A. , In Myung-Ho , Huston John III , Miller Kai J. , Hermes Dora 
Published: November 2022

AbstractStimulation-evoked signals are starting to be used as biomarkers to indicate the state and health of brain networks. The human limbic network, often targeted for brain stimulation therapy, is involved in emotion and memory processing. Previous anatomical, neurophysiological and functional studies suggest distinct subsystems within the limbic network (Rolls, 2015). Previous studies using intracranial electrical stimulation, however, have emphasized the similarities of the evoked waveforms across the limbic network. We test whether these subsystems have distinct stimulation-driven signatures. In seven patients with drug-resistant epilepsy we stimulated the limbic system with single pulse electrical stimulation (SPES). Reliable cortico-cortical evoked potentials (CCEPs) were measured between hippocampus and the posterior cingulate cortex (PCC) and between the amygdala and the anterior cingulate cortex (ACC). However, the CCEP waveform in the PCC after hippocampal stimulation showed a unique and reliable morphology, which we term the limbic H-wave. This limbic H-wave was visually distinct and separately decoded from the amygdala to ACC waveform. Diffusion MRI data show that the measured endpoints in the PCC overlap with the endpoints of the parolfactory cingulum bundle rather than the parahippocampal cingulum, suggesting that the limbic H-wave may travel through fornix, mammillary bodies and the anterior nucleus of the thalamus (ANT). This was further confirmed by stimulating the ANT, which evoked the same limbic H-wave but with a shorter latency. Limbic subsystems have unique stimulation evoked signatures that may be used in the future to help develop stimulation therapies.Significance StatementThe limbic system is often compromised in diverse clinical conditions, such as epilepsy or Alzheimer’s disease, and it is important to characterize its typical circuit responses. Stimulation evoked waveforms have been used in the motor system to diagnose circuit pathology. We translate this framework to limbic subsystems using human intracranial stereo EEG (sEEG) recordings that measure deeper brain areas. Our sEEG recordings describe a stimulation evoked waveform characteristic to the memory and spatial subsystem of the limbic network that we term the limbic H-wave. The limbic H-wave follows anatomical white matter pathways from hippocampus to thalamus to the posterior cingulum and shows promise as a distinct biomarker of signaling in the human brain memory and spatial limbic network.
Auditory deprivation during development alters efferent neural feedback and perception
Authors: Mishra Srikanta K , Moore David R. 
Published: November 2022

AbstractAuditory experience plays a critical role in hearing development. Developmental auditory deprivation due to otitis media, a common childhood disease, produces long-standing changes in the central auditory nervous system, even after the middle ear pathology is resolved. The effects of sound deprivation due to otitis media have been mostly studied in the ascending neural system but remain to be examined in the descending pathway that runs from the auditory cortex to the cochlea via the brainstem. Alterations in the efferent neural system could be important because the descending olivocochlear pathway influences the neural representation of transient sounds in noise in the afferent auditory system and is thought to be involved in auditory relearning following injury. The main objectives of the present study were to (1) investigate whether degraded auditory input due to otitis media during childhood is associated with weakened medial olivocochlear efferent neural responses, even after the resolution of the middle ear pathology, and (2) to examine the involvement of the efferent neural feedback in perceptual masking deficits associated with auditory deprivation due to otitis media.We measured contralateral inhibition of otoacoustic emissions—a biomarker for medial efferent activity—and speech-in-noise recognition in children with a medical history of otitis media (N=76) and age-matched controls (N=99). All children had normal auditory function at the time of experimentation.We found that the inhibitory strength of the medial olivocochlear efferents is weaker in children with a documented history of otitis media relative to controls. In addition, children with otitis media history required a more advantageous signal-to-noise ratio than controls to achieve the same criterion performance level. Importantly, the deficits in perceptual masking were related to efferent inhibition, and these effects could not be attributed to the middle ear or cochlear mechanics.These findings raise the possibility that perceptual masking deficits—a hallmark of impaired (central) auditory processing—resulting from otitis media can arise from the altered brainstem efferent feedback. To date, it was known that degraded auditory experience reorganizes the ascending neural pathways; here, we show that the lack of optimal auditory input to the afferent system during development could have a long-standing impact on the functioning of the descending neural pathways.
Comparative effectiveness of heterologous booster schedules with AZD1222, BNT162b2, or mRNA-1273 vaccines against COVID-19 during omicron predominance in the Nordic countries
Authors: Andersson Niklas Worm , Thiesson Emilia Myrup , Baum Ulrike , Pihlström Nicklas , Starrfelt Jostein , Faksová Kristýna , Poukka Eero , Lund Lars Christian , Hansen Christian Holm , Aakjær Mia , Kjær Jesper , Cohet Catherine , Goossens Mathijs , Andersen Morten , Hallas Jesper , Meijerink Hinta , Ljung Rickard , Hviid Anders 
Published: November 2022

ABSTRACTObjectiveTo investigate the effectiveness of heterologous booster schedules with AZD1222 (Oxford-AstraZeneca, referred to as AZD), BNT162b2 (Pfizer-BioNTech, BNT), and mRNA-1273 (Moderna, MOD) vaccines compared with primary schedules and with homologous mRNA-vaccine booster schedules during a period of omicron predominance.DesignPopulation-based cohort analyses.SettingDenmark, Finland, Norway, and Sweden, 27 December 2020 to 28 February 2022.ParticipantsAdults that had received at least a primary vaccination schedule (ie, two doses) of the AZD, BNT, and/or MOD vaccines during the study period.Main outcome measuresUsing the Kaplan-Meier estimator, we compared country-specific risks of SARS-CoV-2 infection and severe COVID-19 outcomes in heterologous booster vaccinated with primary schedule vaccinated (matched analyses) and homologous booster vaccinated (weighted analyses) since emergence of omicron.ResultsHeterologous booster schedules improved protection against all outcomes compared with primary schedules, with the largest and most robust effects observed for severe COVID-19. Risk differences for documented infection ranged from -22.4% to -3.1% (comparative vaccine effectiveness [CVE] 9.7% to 60.9%; >63.2% for COVID-19 hospitalisation) across countries for AZD1BNT2BNT3 (AZD as primary dose followed by two doses of BNT) vs AZD1BNT2 and -22.2% to -3.2% (CVE 37.4% to 67.8%; >34.6% for hospitalisation) for BNT1BNT2MOD3 vs BNT1BNT2, the two most common heterologous booster schedules. Heterologous- and homologous booster schedules had comparable effectiveness. Risk differences of documented infection ranged from -0.4% to 4.4% (CVE -20.0% to 2.4%) for AZD1BNT2BNT3 vs BNT1BNT2BNT3 and -19.8% to 1.7% (CVE -14.6% to 53.8%) for BNT1BNT2MOD3 vs BNT1BNT2BNT3; for most comparisons, risk differences for severe COVID-19 outcomes were smaller than 1 per 1000 vaccinated. Previous infection followed by a booster dose conferred the greatest protection.ConclusionHeterologous booster vaccine schedules are associated with an increased protection against omicron-related COVID-19 outcomes that is comparable to that afforded by homologous booster schedules.
Interpretable Detection of Epiretinal Membrane from Optical Coherence Tomography with Deep Neural Networks
Authors: Ayhan Murat Seçkin , Neubauer Jonas , Uzel Mehmet Murat , Gelisken Faik , Berens Philipp 
Published: November 2022

AbstractPurposeTo automatically detect epiretinal membranes (ERMs) of different sizes in various OCT scans of the central and paracentral macula region and classify them by size using deep neural networks (DNNs).Methods11,061 OCT-images of 624 volume OCT scans (624 eyes of 461 patients) were included and graded according to the presence of an ERM and its size (small 100-1000µm, large >1000 µm). The data set was divided into training, validation and test sets (comprising of 75%, 10%, 15% of the data, respectively). An ensemble of DNNs was trained and saliency maps were generated using Guided Backprob. OCT-scans were also transformed into a one-dimensional value using t-SNE analysis.ResultsThe DNNs’ receiver-operating-characteristics on the test set showed a high performance for no ERM, small ERM and large ERM cases (AUC: 0.99, 0.92, 0.99, respectively; 3-way accuracy: 89%), with small ERMs being the most difficult ones to detect. t-SNE analysis sorted cases by size and, in particular, revealed increased classification uncertainty at the transitions between groups. Saliency maps reliably highlighted ERMs, regardless of the presence of other OCT features (i.e. retinal thickening, intraretinal pseudocysts, epiretinal proliferation) and entities such as ERM-retinoschisis, macular pseudohole and lamellar macular hole.ConclusionDNNs can reliably detect and grade ERMs according to their size not only in the fovea but also in the paracentral region. This is also achieved in cases of hard-to-detect, small ERMs. In addition, the generated saliency maps can be used effectively to highlight small ERMs that might otherwise be missed. The proposed model could be used for screening programs or decision support systems in the future.
Human neutralizing antibodies to cold linear epitopes and to subdomain 1 of SARS-CoV-2
Authors: Bianchini Filippo , Crivelli Virginia , Abernathy Morgan E. , Guerra Concetta , Palus Martin , Muri Jonathan , Marcotte Harold , Piralla Antonio , Pedotti Mattia , Gasparo Raoul De , Simonelli Luca , Matkovic Milos , Toscano Chiara , Biggiogero Maira , Calvaruso Veronica , Svoboda Pavel , Rincón Tomás Cervantes , Fava Tommaso , Podešvová Lucie , Shanbhag Akanksha A. , Celoria Andrea , Sgrignani Jacopo , Stefanik Michal , Hönig Vaclav , Pranclova Veronika , Michalcikova Tereza , Prochazka Jan , Guerrini Giuditta , Mehn Dora , Ciabattini Annalisa , Abolhassani Hassan , Jarrossay David , Uguccioni Mariagrazia , Medaglini Donata , Pan-Hammarström Qiang , Calzolai Luigi , Fernandez Daniel , Baldanti Fausto , Franzetti-Pellanda Alessandra , Garzoni Christian , Sedlacek Radislav , Ruzek Daniel , Varani Luca , Cavalli Andrea , Barnes Christopher O. , Robbiani Davide F. 
Published: November 2022

Emergence of SARS-CoV-2 variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes. Antibody fp.006 binds the fusion peptide and cross-reacts against coronaviruses of the fourgenera, including the nine human coronaviruses, through recognition of a conserved motif that includes the S2’ site of proteolytic cleavage. Antibody hr2.016 targets the stem helix and neutralizes SARS-CoV-2 variants. Antibody sd1.040 binds to subdomain 1, synergizes with antibody rbd.042 for neutralization and, like fp.006 and hr2.016, protects mice when present as bispecific antibody. Thus, coldspot-guided antibody discovery reveals donor-derived neutralizing antibodies that are cross-reactive withOrthocoronavirinae, including SARS-CoV-2 variants.One sentence summaryBroadly cross-reactive antibodies that protect from SARS-CoV-2 variants are revealed by virus coldspot-driven discovery.
Polyethylene glycol (PEG)-associated immune responses triggered by clinically relevant lipid nanoparticles in rats
Authors: Wang Haiyang , Wang Yisha , Yuan Changzheng , Xu Xiao , Zhou Wenbin , Huang Yuhui , Lu Huan , Zheng Yue , Luo Gan , Shang Jia , Sui Meihua 
Published: November 2022

AbstractWith the large-scale vaccination of lipid nanoparticles (LNP)-based COVID-19 mRNA vaccines, elucidating the potential polyethylene glycol (PEG)-associated immune responses triggered by clinically relevant LNP has become imminent. However, inconsistent findings were observed across very limited population-based studies. Herein we initiated a study using LNP carrier of Comirnaty®as a representative, and simulated real-world clinical practice covering a series of time points and various doses correlated with approved LNP-delivered drugs in a rat model. We demonstrated the time- and dose-dependency of LNP-induced anti-PEG antibodies in rats. As a thymus-independent antigen, LNP unexpectedly induced isotype switch and immune memory, leading to rapid enhancement and longer lasting time of anti-PEG IgM and IgG upon re-injection in rats. Importantly, initial LNP injection accelerated the blood clearance of subsequent dosing in rats. These findings refine our understandings on LNP and possibly other PEG derivatives, and may promote optimization of related premarket guidelines and clinical protocols.
A single-dose MCMV-based vaccine elicits long-lasting immune protection in mice against distinct SARS-CoV-2 variants
Authors: Metzdorf Kristin , Jacobsen Henning , Kim Yeonsu , Teixeira Alves Luiz Gustavo , Kulkarni Upasana , Eschke Kathrin , Chaudhry M. Zeeshan , Hoffmann Markus , Bertoglio Federico , Ruschig Maximilian , Hust Michael , Brdovčak Maja Cokarić , Materljan Jelena , Šustić Marko , Krmpotić Astrid , Jonjić Stipan , Widera Marek , Ciesek Sandra , Pöhlmann Stefan , Landthaler Markus , Čičin-Šain Luka 
Published: November 2022

AbstractCurrent vaccines against COVID-19 elicit immune responses that are overall strong but wane rapidly. As a consequence, the necessary booster shots have led to vaccine fatigue. Hence, vaccines that would provide lasting protection against COVID-19 are needed, but are still unavailable. Cytomegaloviruses (CMV) elicit lasting and uniquely strong immune responses. Used as vaccine vectors, they may be attractive tools that obviate the need for boosters. Therefore, we tested the murine CMV (MCMV) as a vaccine vector against COVID-19 in relevant preclinical models of immunization and challenge. We have previously developed a recombinant murine CMV (MCMV) vaccine vector expressing the spike protein of the ancestral SARS-CoV-2 (MCMVS). In this study, we show that the MCMVSelicits a robust and lasting protection in young and aged mice. Notably, S-specific humoral and cellular immunity was not only maintained but even increased over a period of at least 6 months. During that time, antibody avidity continuously increased and expanded in breadth, resulting in neutralization of genetically distant variants, like Omicron BA.1. A single dose of MCMVSconferred rapid virus clearance upon challenge. Moreover, MCMVSvaccination controlled two immune-evading variants of concern (VoCs), the Beta (B.1.135) and the Omicron (BA.1) variants. Thus, CMV vectors provide unique advantages over other vaccine technologies, eliciting broadly reactive and long-lasting immune responses against COVID-19.Authors SummaryWhile widespread vaccination has substantially reduced risks of severe COVID presentations and morbidity, immune waning and continuous immune escape of novel SARS-CoV-2 variants have resulted in a need for numerous vaccine boosters and a continuous adaptation of vaccines to new SARS-CoV-2 variants. We show in proof of principle experiments with a recombinant murine cytomegalovirus expressing the SARS-CoV-2 spike protein (MCMVS) that one immunization with a CMV vaccine vector drives enduring protection in both young and aged mice, with long-term maturation of immune responses that broaden the antiviral effects over time. Hence, this approach resolves issues of immune waning and mitigates the effects of COVID-19 evolution and immune escape, reducing the need for additional immunizations and potentially improving vaccine compliance.
Plasma after both SARS-CoV-2 boosted vaccination and COVID-19 potently neutralizes BQ.1.1 and XBB.1
Authors: Sullivan David J , Franchini Massimo , Senefeld Jonathon W. , Joyner Michael J. , Casadevall Arturo , Focosi Daniele 
Published: November 2022

AbstractObjectivesRecent 2022 SARS-CoV-2 Omicron variants, have acquired resistance to most neutralizing anti-Spike monoclonal antibodies authorized, and the BQ.1.* sublineages are notably resistant to all authorized monoclonal antibodies. Polyclonal antibodies from individuals both vaccinated and recently recovered from Omicron COVID-19 (VaxCCP) could retain new Omicron neutralizing activity.MethodsHere we reviewed BQ.1.* virus neutralization data from 920 individual patient samples from 43 separate cohorts defined by boosted vaccinations with or without recent Omicron COVID-19, as well as infection without vaccination.ResultsMore than 90% of the plasma samples from individuals in the recently (within 6 months) boosted VaxCCP study cohorts neutralized BQ.1.1, and BF.7 with 100% neutralization of WA-1, BA.4/5, BA.4.6 and BA.2.75. The geometric mean of the geometric mean 50% neutralizing titers (GM (GMT50) were 314, 78 and 204 for BQ.1.1, XBB.1 and BF.7, respectively. Compared to VaxCCP, plasma sampled from COVID-19 naïve subjects who also recently within 6 months received at least a third vaccine dose had about half of the GM (GMT50) for all viral variants.ConclusionsBoosted VaxCCP characterized by either recent vaccine dose or infection event within 6 months represents a robust, variant-resilient, passive immunotherapy against the new Omicron BQ.1.1, XBB.1 and BF.7 variants.