bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 antibody changes in patients receiving COVID-19 convalescent plasma from normal and vaccinated donors
Authors: Leon Judith , Merrill Anna E. , Rogers Kai , Kurt Julie , Dempewolf Spencer , Ehlers Alexandra , Jackson J. Brooks , Knudson C. Michael 
Published: August 2021

ABSTRACTBackground and ObjectivesVaccination has been shown to stimulate remarkably high antibody levels in donors who have recovered from COVID-19. Our objective was to examine patient antibody responses following COVID-19 Convalescent Plasma (CCP) transfusion and compare responses to CCP from vaccinated and nonvaccinated donors.Materials and methodsPlasma samples were obtained from 25 recipients of CCP and COVID-19 antibody levels measured before and after CCP treatment. Factors that effect antibody levels were examined.ResultsIn the 21 patients who received CCP from nonvaccinated donors, only modest increases in antibody levels were observed. Patients who received two units were more likely to seroconvert than those receiving just one unit. The strongest predictor of changes in patient antibody level was the CCP dose. Using patient plasma volume and donor antibody level, the post-transfusion antibody level could be predicted with remarkable accuracy. In contrast, the 4 patients who received CCP from vaccinated donors all had dramatic increases in antibody levels following transfusion of a single unit. In this subset of recipients, antibody levels observed after transfusion of CCP were comparable to those seen in donors who had fully recovered from COVID-19.ConclusionIf available, CCP from vaccinated donors with very high antibody levels should be used. CCP from vaccinated donors increases patient antibody levels much more than 1 or 2 units of CCP from unvaccinated donors.
Salivary proteome of aphthous stomatitis reveals the participation of vitamin metabolism, nutrients, and bacteria
Authors: Hernández-Olivos Romina , Muñoz Mariagrazia , Núñez Esteban , Camargo-Ayala Paola Andrea , Garcia-Huidobro Jenaro , Pereira Alfredo , Nachtigall Fabiane M. , Santos Leonardo S. , Rivera César 
Published: August 2021

ABSTRACTThere are currently no preventative options for recurrent aphthous stomatitis, and the only available treatments are palliative. This is partly due to a poor understanding of its etiopathogenesis. In this case-control study, we characterized the salivary proteome of patients with recurrent aphthous stomatitis in the presence and absence of lesions. Through mass spectrometry-based proteomics and bioinformatics tools, we identified that the presence of oral ulcers is associated with several specific biological processes, including the metabolic pathways of vitamin B9, B12, nitrogen, selenium, and the bacterium Neisseria meningitidis. These changes occurred only in the presence of clinically visible lesions, and there were no relevant differences between patients in anatomical regions unaffected by ulcers. Additionally, using western blot and ELISA assays, we verified that carbonic anhydrase 1 (CA1, UniProtKB - P00915, CAH1_HUMAN) and hemoglobin subunit beta (HBB, UniProtKB - P68871, HBB_HUMAN) proteins are highly expressed during the ulcerative and remission phases of recurrent aphthous stomatitis. Our results cumulatively support saliva as an indicator of the pathophysiological changes, which occur during the clinical course of lesions. From a clinical perspective, we suggest that recurrent aphthous stomatitis is a condition triggered by temporary biological changes in people with lesions.
Novel Driver Strength Index highlights important cancer genes in TCGA PanCanAtlas patients
Authors: Belikov Aleksey V. , Otnyukov Danila V. , Vyatkin Alexey D. , Leonov Sergey V. 
Published: August 2021

AbstractElucidating crucial driver genes is paramount for understanding the cancer origins and mechanisms of progression, as well as selecting targets for molecular therapy. Cancer genes are usually ranked by the frequency of mutation, which, however, does not necessarily reflect their driver strength. Here we hypothesize that driver strength is higher for genes that are preferentially mutated in patients with few driver mutations overall, because these few mutations should be strong enough to initiate cancer. We propose a formula to calculate the corresponding Driver Strength Index (DSI), as well as the Normalized Driver Strength Index (NDSI), the latter completely independent of the overall gene mutation frequency. We validate these indices using the largest database of human cancer mutations – TCGA PanCanAtlas, multiple established algorithms for cancer driver prediction (2020plus, CHASMplus, CompositeDriver, dNdScv, HotMAPS, OncodriveCLUSTL, OncodriveFML) and four custom computational pipelines that integrate driver contributions from SNA, CNA and aneuploidy at the patient-level resolution. We demonstrate that DSI and especially NDSI provide substantially different rankings of genes as compared to frequency approach. For example, NDSI prioritized members of specific protein families, including G proteins GNAQ, GNA11 and GNAS, isocitrate dehydrogenases IDH1 and IDH2, and fibroblast growth factor receptors FGFR2 and FGFR3. KEGG analysis shows that top NDSI-ranked genes comprise EGFR/FGFR2/GNAQ/GNA11 – NRAS/HRAS/KRAS – BRAF pathway, AKT1 – MTOR pathway, and TCEB1 – VHL – HIF1A pathway. NDSI does not seem to correlate with the number of protein-protein interactions. We share our software to enable calculation of DSI and NDSI for outputs of any third-party driver prediction algorithms or their combinations.
Development of Goal Management Training+ (GMT+) for Methamphetamine Use Disorder Through Collaborative Design: A Process Description
Authors: Anderson Alexandra C. , Robinson Alex H. , Potter Eden , Kerley Bronte , Flynn Daphne , Lubman Dan I. , Verdejo-García Antonio 
Published: August 2021

AbstractBackgroundMethamphetamine use disorder (MUD) is associated with executive dysfunctions, which are linked with poorer treatment outcomes including earlier drop out and relapse. However, current treatments for MUD do not address executive functions. Goal Management Training (GMT) is an evidence-based cognitive remediation program for executive dysfunction but required modifications to enhance its relevance and application within addiction treatment settings. This study aimed to 1) tailor GMT to the key cognitive deficits and typical treatment duration of MUD; 2) explore consumers’ (people with MUD) engagement with the revised program; 3) implement a protocol of the program with consumers; and 4) present the manualised standard administration to clinical service providers.MethodsWe followed the Medical Research Council Complex Interventions Framework and employed an evidence- and person-based intervention development process. We used a four-phased approach and collaborated with neuropsychology experts, design researchers in healthcare, consumers with MUD, and clinical service providers. Each aim was addressed in a separate study phase; including content refinement and review with neuropsychology experts (phase 1), intervention design and collaboration with consumers (phase 2), prototype development and review with consumers (phase 3), and final program modifications and review with clinical stakeholders (phase 4).ResultsFindings from phase 1 indicated support for targeting four cognitive processes (attention, impulse control, goal setting, and decision-making). Key feedback included the need to help habitualise program strategies and guide consumers in applying them in emotionally salient situations. Findings from phases 2 and 3 indicated consumer support for the program strategies and materials but highlighted the need to further enhance the personal relevance of specific content and journal activities. Findings from phase 4 provided overall clinical support for the revised program but indicated an opportunity to minimise unintended effects. We present the intervention materials for the revised program, Goal Management Training+ (GMT+), in line with TIDieR guidelines.ConclusionsGMT+ targets tailored cognitive processes, includes reimagined materials and activities, and is sensitive to the clinical needs of people with MUD. Our intervention development process was important for informing the training components, design and intervention materials, and indicating initial acceptability prior to conducting a clinical trial.
Exploring the Relationship of Rush Hour Period and Fatal and Non-Fatal Crash Injuries in The U.S.: A Systematic Review and Meta-Analysis
Authors: Adeyemi Oluwaseun John , Arif Ahmed , Paul Rajib 
Published: August 2021

AbstractRoad crashes are preventable causes of morbidity and mortality. In the U.S., substantial crashes occur during the rush hour period. The rush hour represents the period of the day during which the density of humans and vehicles in the road environment is highest. In the U.S., the rush hour period is bi-modal, occurring in the morning and the afternoon, at times that vary by state and urban-rural status. This systematic review and meta-analysis aimed to evaluate the association between the rush hour period and fatal and non-fatal crash injuries. Selected articles were limited to peer-reviewed full-text articles that measured crash injury as an outcome and rush hour as either a predictor, covariate, stratification, or a control variable. A total of 13 articles were identified for systematic review and seven articles were included in the meta-analysis. Across the selected studies, the rush-hour period signified the period of “peak traffic flow.” During the rush hour period, aggressive driving behavior, truck driving, bicycle riding, and precipitation were associated with increased crash events or crash injuries. Across the seven studies included in the meta-analysis, the effective sample size was 220,471. The rush-hour period was associated with a 41% increased risk of fatal crash injury (Pooled RR: 1.41; 95% CI: 1.35 - 1.48). The morning and afternoon rush hour periods were associated with 40% (Pooled RR: 1.40; 95% CI: 1.13-1.67) and 27% (Pooled RR:1.27; 95% CI: 1.10-1.44) increased crash injury risk, respectively. The rush hour period, though less commonly studied as a predictor of fatal and non-fatal crash injuries, represents an important domain in need of crash injury prevention attention. The knowledge of the pattern of crash injuries, as it varies across countries, states, regions, and county can inform policy and intervention, in the presence of competing public health needs.
Learning the mutational landscape of the cancer genome
Authors: Sherman Maxwell A. , Yaari Adam , Priebe Oliver , Dietlein Felix , Loh Po-Ru , Berger Bonnie 
Published: August 2021

AbstractAn ongoing challenge to better understand and treat cancer is to distinguish neutral mutations, which do not affect tumor fitness, from those that provide a proliferative advantage. However, the variability of mutation rates has limited our ability to model patterns of neutral mutations and therefore identify cancer driver mutations. Here, we predict cancer-specific mutation rates genome-wide by leveraging deep neural networks to learn mutation rates within kilobase-scale regions and then refining these estimates to test for evidence of selection on combinations of mutations by comparing observed to expected mutation counts. We mapped mutation rates for 37 cancer types and used these maps to identify new putative drivers in understudied regions of the genome including cryptic alternative-splice sites, 5’ untranslated regions and infrequently mutated genes. These results, available for exploration via web interface, indicate the potential for high-resolution neutral mutation models to empower further driver discovery as cancer sequencing cohorts grow.
TAS-Seq: a robust and sensitive amplification method for bead-based scRNA-seq
Authors: Shichino Shigeyuki , Ueha Satoshi , Hashimoto Shinichi , Ogawa Tatsuro , Aoki Hiroyasu , Wu Bin , Chen Chang-Yu , Kitabatake Masahiro , Ouji-Sageshima Noriko , Sawabata Noriyoshi , Kawaguchi Takeshi , Okayama Toshitugu , Sugihara Eiji , Hontsu Shigeto , Ito Toshihiro , Iwata Yasunori , Wada Takashi , Ikeo Kazuho , Sato Taka-aki , Matsushima Kouji 
Published: August 2021

AbstractSingle-cell RNA-sequencing (scRNA-seq) is valuable for analyzing cellular heterogeneity. Cell composition accuracy is critical for analyzing cell–cell interaction networks from scRNA-seq data. We developed terminator-assisted solid-phase cDNA amplification and sequencing (TAS-Seq) for scRNA-seq based on a terminator, terminal transferase, and nanowell/bead-based scRNA-seq platform; TAS-Seq showed high tolerance to variations in the terminal transferase reaction, which complicate the handling of existing terminal transferase-based scRNA-seq methods. In murine and human lung samples, TAS-Seq yielded scRNA-seq data that were highly correlated with flow-cytometric data, showing higher gene-detection sensitivity and more robust detection of important cell–cell interactions and expression of growth factors/interleukins in cell subsets than 10X Chromium v2 and Smart-seq2. Expanding TAS-Seq application will improve understanding and atlas construction of lung biology at the single-cell level.
IMPDH1 retinal variants control filament architecture to tune allosteric regulation
Authors: Burrell Anika L , Nie Chuankai , Said Meerit , Simonet Jacqueline C , Fernández-Justel David , Johnson Matthew C , Quispe Joel , Buey Rubén M , Peterson Jeffrey R , Kollman Justin M 
Published: August 2021

ABSTRACTIMP dehydrogenase (IMPDH), a key regulatory enzyme in purine nucleotide biosynthesis, dynamically assembles filaments in response to changes in metabolic demand. Humans have two isoforms: IMPDH2 filaments reduce sensitivity to feedback inhibition by the downstream product GTP, while IMPDH1 assembly remains uncharacterized. IMPDH1 plays a unique role in retinal metabolism, and point mutants cause blindness and disrupt GTP regulation. Here, in a series of cryo-EM structures we show that IMPDH1 assembles polymorphic filaments with different assembly interfaces in active and inhibited states. Retina-specific splice variants introduce structural elements that reduce sensitivity to GTP inhibition, including stabilization of the active filament form. Finally, we show that IMPDH1 disease mutations fall into two classes: one disrupts GTP regulation and the other has no in vitro phenotype. These findings provide a foundation for understanding the role of IMPDH1 in retinal function and disease and demonstrate the diverse mechanisms by which metabolic enzyme filaments are allosterically regulated.
Altered low frequency brain rhythms precede changes in gamma power during tauopathy
Authors: Rodrigues Fabio R. , Papanikolaou Amalia , Holeniewska Joanna , Phillips Keith G. , Saleem Aman B. , Solomon Samuel G. 
Published: August 2021

AbstractAlzheimer’s disease and other dementias are associated with disruptions of electrophysiological brain activity, including low frequency and gamma rhythms. Many of these dementias are also associated with the malfunction of the membrane associated protein tau. Tauopathy disrupts neuronal function and the stability of synapses and is a key driver of neurodegeneration. Here we ask how brain rhythms are affected by tauopathy, at different stages of its progression. We performed local field potential recordings from visual cortex of rTg4510 and control animals at early stages of neurodegeneration (5 months) and at a more advanced stage where pathology is evident (8 months). We measured brain activity in the presence or absence of external visual stimulation, and while monitoring pupil diameter and locomotion to establish animal behavioural states. At 5 months, before substantial pathology, we found an increase in low frequency rhythms during resting state in tauopathic animals. This was because tauopathic animals entered intermittent periods of increased neural synchronisation, where activity across a wide band of low frequencies was strongly correlated. At 8 months, when the degeneration was more advanced, the increased synchronisation and low frequency power was accompanied by a reduction in power in the gamma range, with diverse effects across different components of the gamma rhythm. Our results indicate that slower rhythms are impaired earlier than gamma rhythms in tauopathy, suggesting that electrophysiological measurements can indicate both the presence and progression of tauopathic degeneration.
Redox state and cellular uptake of copper is regulated by N-terminus of human Copper Transporter-1
Authors: Kar Sumanta , Sen Samarpita , Maji Saptarshi , Ruturaj  , Paul Rupam , Dutt Sohini , Mondal Basudeb , Rodriguez-Boulan Enrique , Schreiner Ryan , Sengupta Durba , Gupta Arnab 
Published: August 2021

AbstractCopper(I) is essential for all life forms. Though Cu(II) is most abundant state in environment, its reduction to Cu(I) is prerequisite for bio-utilization, by a mechanism that is uncharacterized. We show that in human Copper Transporter-1, two amino-terminal methionine-histidine clusters and neighbouring aspartates distinctly binds Cu(II) and Cu(I) preceding its import. The endocytosis of hCTR1 from basolateral membrane of polarized epithelia to Common-Recycling-Endosomes is dependent on copper reduction and Cu(I) coordination by methionines. The transient binding of both Cu(II) and Cu(I) during the reduction process facilitated by aspartates acts as another crucial determinant of hCTR1 endocytosis. Mutating7Met-Gly-Met9and Asp13abrogates copper uptake and endocytosis that is correctable by reduced and non-reoxidizable Cu(I). Histidines clusters are crucial for hCTR1 functioning at limiting copper. Finally, we show that two N-terminal His-Met-Asp clusters exhibit functional complementarity in regulating Cu(I)-induced hCTR1 endocytosis. We propose a mechanistic model where His-Met-Asp residues of amino-terminal hCTR1 coordinates copper and maintains its reduced state crucial for uptake.
Contribution of arm movements to balance recovery after tripping in older adults
Authors: Bruijn Sjoerd M. , Sloot Lizeth H. , Kingma Idsart , Pijnappels Mirjam 
Published: August 2021

AbstractFalls are common in daily life, often caused by trips and slips and, particularly in older adults, with serious consequences. Although arm movements play an important role in balance control, there is limited research into the role of arm movements during balance recovery after tripping in older adults. We investigated how older adults use their arms to recover from a trip and the difference in the effects of arm movements between fallers (n=5) and non-fallers (n=11).Sixteen older males and females (69.7±2.3 years) walked along a walkway and were occasionally tripped over suddenly appearing obstacles. We analysed the first trip using a biomechanical model based on full-body kinematics and force-plate data to calculate whole body orientation during the trip and recovery phase. With this model, we simulated the effects of arm movements at foot-obstacle impact and during trip recovery on body orientation.Apart from an increase in sagittal plane forward body rotation at touchdown in fallers, we found no significant differences between fallers and non-fallers in the effects of arm movements on trip recovery. Like earlier studies in young adults, we found that arm movements during the recovery phase had most favourable effects in the transverse plane: by delaying the transfer of angular momentum of the arms to the body, older adults rotated the tripped side more forward thereby allowing for a larger recovery step. Older adults that are prone to falling might improve their balance recovery after tripping by learning to prolong ongoing arm movements.
St18 specifies globus pallidus projection neuron identity in MGE lineage
Authors: Nunnelly Luke F. , Campbell Melissa , Lee Dylan I. , Gu Guoqiang , Menon Vilas , Au Edmund 
Published: August 2021

AbstractThe medial ganglionic eminence (MGE) is a progenitor domain in the subpallium that produces both locally-projecting interneurons which undergo tangential migration in structures such as the cortex as well as long-range projection neurons that occupy subcortical nuclei. Very little is known about the transcriptional mechanisms specifying the migratory behavior and axonal projection patterns of these two broad classes of MGE-derived neurons. In this study, we identify St18 as a novel transcriptional determinant specifying projection neuron fate in the MGE lineage. St18 is transiently expressed in the MGE subventricular zone (SVZ) and mantle, and we assessed its function using an ES cell-based model of MGE development. Induction of St18 is sufficient to direct ES-derived MGE neurons to adopt a projection neuron-like identity as defined by migration and morphology. Using genetic loss-of-function in mice, we find that St18 is required for the production of globus pallidus pars externa (GPe) prototypic projection neurons. Single cell RNA sequencing revealed that St18 regulates MGE output of specific neuronal populations: in the absence of St18, we observe a large expansion of cortical interneurons at the expense of putative GPe neurons. Through gene expression analysis we identified a downstream effector of St18, Cbx7, which is a component of Polycomb repressor complex 1. We find that Cbx7 is essential for projection neuron-like migration and is not involved in St18-mediated projection neuron-like morphology. Our results characterize a novel transcriptional determinant that directs GPe prototypic projection neuron identity. Further, we identified a downstream target of St18, Cbx7, which regulates only the migratory behavior of long-range projection neurons, suggesting that specific features of MGE projection neuron identity may be governed in a compartmentalized fashion by distinct transcriptional modules downstream of St18.
The control and training of single motor units in isometric tasks are constrained by a common synaptic input signal
Authors: Bräcklein Mario , Ibáñez Jaime , Barsakcioglu Deren Y , Eden Jonathan , Burdet Etienne , Mehring Carsten , Farina Dario 
Published: August 2021

AbstractRecent developments in neural interfaces enable the real-time and non-invasive tracking of motor neuron spiking activity. Such novel interfaces provide a promising basis for human motor augmentation by extracting potential high-dimensional control signals directly from the human nervous system. However, it is unclear how flexibly humans can control the activity of individual motor neurones to effectively increase the number of degrees-of-freedom available to coordinate multiple effectors simultaneously. Here, we provided human subjects (N=7) with real-time feedback on the discharge patterns of pairs of motor units (MUs) innervating a single muscle (tibialis anterior) and encouraged them to independently control the MUs by tracking targets in a 2D space. Subjects learned control strategies to achieve the target-tracking task for various combinations of MUs. These strategies rarely corresponded to a volitional control of independent input signals to individual MUs. Conversely, MU activation was consistent with a common input to the MU pair, while individual activation of the MUs in the pair was predominantly achieved by alterations in de-recruitment order that could be explained with history-dependent changes in motor neuron excitability. These results suggest that flexible MU control based on independent synaptic inputs to single MUs is not a simple to learn control strategy.