bluuebunny/crossref_metadata_2025_split huggingface dataset:
CAR Density Influences Antitumoral Efficacy of BCMA CAR T cells and Correlates with Clinical Outcome
Authors: Rodriguez-Marquez Paula , Calleja-Cervantes Maria E. , Serrano Guillermo , Oliver-Caldes Aina , Palacios-Berraquero Maria L. , Martin-Mallo Angel , Calviño Cristina , Español-Rego Marta , Ceballos Candela , Lozano Teresa , Martin-Uriz Patxi San , Vilas-Zornoza Amaia , Rodriguez-Diaz Saray , Martinez-Turrillas Rebeca , Jauregui Patricia , Alignani Diego , Viguria Maria C. , Redondo Margarita , Pascal Mariona , Juan Manel , Urbano-Ispizua Alvaro , Rodriguez-Otero Paula , Alfonso-Pierola Ana , Paiva Bruno , Lasarte Juan Jose , Inoges Susana , de Cerio Ascension Lopez-Diaz , San-Miguel Jesus , de Larrea Carlos Fernandez , Hernaez Mikel , Rodriguez-Madoz Juan R. , Prosper Felipe 
Published: January 2022

ABSTRACTIdentification of new markers associated with long-term efficacy in patients treated with CAR T cells is a current medical need, particularly in diseases such as multiple myeloma. In this study we address the impact of CAR density on the functionality of BCMA-CAR T cells. Functional and transcriptional studies demonstrate that CAR T cells with high expression of the CAR construct show an increased tonic signaling with upregulation of exhaustion markers, increased in vitro cytotoxicity but a decrease in in vivo BM infiltration. Characterization of Gene Regulatory Networks using scRNA-seq identified regulons associated to activation and exhaustion upregulated in CARHigh T cells, providing mechanistic insights behind differential functionality of these cells. Finally, we demonstrate that patients treated with CAR T cell products enriched in CARHigh T cells show a significantly worse clinical response in several hematological malignancies. In summary, our work demonstrates that CAR density plays an important role in CAR T activity with significant impact on clinical response.TeaserHigh CAR molecule density affects CAR T cell activity and associates with impaired clinical response.
Gaseous micro-embolism (GME) is associated with systemic inflammatory response syndrome (SIRS) after open heart surgery. A missing piece of a complex puzzle?
Authors: Demertzis Stefanos , Puthettu Mira , Nafi Matteo , Bagnato Pietro , Cassina Tiziano , Vandenberghe Stijn 
Published: January 2022

AbstractBackgroundGaseous micro-embolism (GME) occurring during contemporary open heart surgery is poorly studied. Current understanding of the biological impact of cardiac surgery focuses on the surgical aggression itself together with contact activation of inflammatory cascades by the extracorporeal circulation (ECC), both promoting various degrees of a systemic inflammatory response syndrome (SIRS).Methods and FindingsWe prospectively collected data on GME in the ECC circuit according to a quality control protocol during a 12-month period at our institution. Bubbles were measured means of a last generation multi-channel ultrasound measuring unit (BCC300, Gampt GmbH, Meerseburg, Germany) upstream of the arterial line filter. For analysis, bubbles were separated in three size categories: small (S) (10-40 µm), medium (M) (41-200 µm) and large (L) (201-2000 µm). Small bubbles were considered as noise and excluded. A total of 58 out of 70 open heart procedures were included in the final evaluation performed on 58 patients (45 males, 13 females, mean age 66 ± 9 years). Patient baseline data, type of procedure and perfusion data were retrieved. Preoperative treatment with beta-blockers, ACE-inhibitors, calcium-antagonists and statins was considered. Postoperative SIRS was identified according to modified SIRS and qSOFA criteria.A variably high amount of GME was detected (mean count 847 ± 2560), we focused on M-sized GME (mean count 820 ± 2546, mean volume 233 ± 730 nL). A total of 22 patients (38%) developed SIRS. To account for differences between patient groups (SIRS-/ SIRS+) propensity score (PS) matching was performed on the presence of M-bubbles at or above the 75thpercentile (count and volume). The impact of such GME on the development of SIRS was statistically highly significant, as shown by the corresponding average treatment effects (ATE).ConclusionsSignificant GME was associated with postoperative SIRS after cardiac surgery in our setting. This novel finding warrants further confirmation.
Comparison between mid-nasal swabs and buccal swabs for SARS-CoV-2 detection in mild COVID-19 patients
Authors: Blanco Ignacio , Violán Concepción , Suñer Clara , Garcia-Prieto Julio , Argerich Maria José , Rodriguez-Illana Meritxell , Moreno Nemesio , Cardona Pere-Joan , Blanco Anna , Torán-Monserrat Pere , Clotet Bonaventura , Bonet Josep Ma , Prat Nuria 
Published: January 2022

ABSTRACTBackgroundThe use of rapid antigen diagnostics tests (Ag-RDT) has gained widespread acceptance as an alternative method for diagnosis of COVID-19 outside of health care settings. Various authors have reported that saliva is a reliable specimen, alternative to nasopharyngeal and mid-nasal swabs, to detect SARS-CoV-2 infections by RT-PCR. We assessed the performance of buccal swabs containing saliva for SARS-CoV-2 detection by Ag-RDT, using mid-nasal specimens as a reference in the northern area of Barcelona (Catalonia, Spain)MethodsIn the context of routine clinical diagnosis of mild COVID-19 patients, we enrolled 300 adults in a study to directly compare mid-nasal swabs and saliva specimens for SARS-CoV-2 detection by Ag-RDT.. When mid-nasal and buccal Ag-RDTs showed discordant results, a third mid-nasal swab was collected and analysed by RT-PCR.ResultsPaired samples were successfully obtained in 300 suspected cases of SARS-CoV-2 infection. Of the 300 paired samples, Ag-RDT with the mid-nasal swab detected 139 (46.3%) positive COVID-19 cases. In comparison, buccal swabs showed a sensitivity and specificity of 31.7% (44/139) and 98.8% (159/161), respectively. 65 discordant results with positive mid-nasal swabs and negative buccal swabs were tested by RT-qPCR. All samples tested by Rt-PCR resulted positive, with a mean cycle threshold (Ct) of 28.3 (SD 7.3).ConclusionOur findings show that mid-nasal swabs have better performance than buccal swabs for detecting SARS-CoV-2 with Ag-RDT tests. Of note, the sensitivity of buccal samples was affected in samples with high viral loads (Ct<33), suggesting that buccal swabs might not be sensitive enough to detect individuals at risk of transmission. Taken together, the existing literature and the results provided in our analysis we advise against the use of buccal specimens for SARS-CoV-2 diagnostics with Ag-RDT.
Broad Spectrum Antimicrobial Potential of Crassula ovata
Authors: Puga Troy , Schafer Josh , Buffalo Alexander , Agbedanu Prince N. 
Published: January 2022

AbstractThis study investigates the antimicrobial properties of Crassula ovata (C. ovata) against both gram-positive and gram-negative bacteria. About 1-3g samples of C. Ovata leaf samples were extracted with 95 % ethanol and the extract infused into paper discs by soaking and drying. The dried discs were screened against various strains of bacteria and the antimicrobial effects of the infused agents determined by measuring zones of inhibition due to the agents infused into the discs. By the zones of inhibition, C. ovata showed antimicrobial activity against the following gram-negative bacteria: E. coli (14 mm mean zone of clearing), P. vulgaris (13 mm mean zone of clearing), E. cloacae (16 mm mean zone of clearing), and K. pneumoniae (13 mm mean zone of clearing). C. ovata showed antimicrobial activity against the following gram-positive bacteria: S. aureus (22 mm mean zone of clearing) and S. agalactiae (8 mm mean zone of clearing). C. ovata did not show antimicrobial activity against S. pyogenes. By its antimicrobial activity against gram-positive and gram-negative bacteria, C. ovata displayed broad spectrum antimicrobial activity against E. coli, S. aureus, S. agalactiae, P. vulgaris, E. cloacae, and K. pneumoniae. C. ovata may have the potential to serve as a broad-spectrum antimicrobial in the future. Further testing should be done to investigate the toxicities and side effects of C. ovata. Further testing must also be done with C. ovata against drug-resistant strains of bacteria.
Assessing responsiveness to direct verbal suggestions in depersonalization-derealization disorder
Authors: Millman L. S. Merritt , Hunter Elaine C. M. , David Anthony S. , Orgs Guido , Terhune Devin B. 
Published: January 2022

AbstractThe dissociative disorders and germane conditions are reliably characterized by elevated responsiveness to direct verbal suggestions. However, it remains unclear whether atypical responsiveness to suggestion is similarly present in depersonalization-derealization disorder (DDD). 55 DDD patients and 36 healthy controls completed a standardised behavioural measure of direct verbal suggestibility that includes a correction for compliant responding (BSS-C), and psychometric measures of depersonalization-derealization (CDS), mindfulness (FFMQ), imagery vividness (VVIQ), and anxiety (GAD-7). Patients displayed nonsignificantly lower suggestibility than controls, (g= 0.26) but significantly lower mindfulness (g= 1.38), and imagery vividness (g= 0.63), and significantly greater anxiety (g= 1.39). Although suggestibility did not correlate with severity of depersonalization-derealization symptoms in controls,r=-.03 [95% CI: -.36, .30], there was a weak tendency for a positive association in patients,r=.25, [95% CI: -.03, .48]. Exploratory analyses revealed that patients with more severe anomalous bodily experiences were also more responsive to suggestion, an effect not seen in controls. This study demonstrates that DDD is not characterized by elevated responsiveness to direct verbal suggestions. These results have implications for the aetiology and treatment of this condition, as well as its classification as a dissociative disorder in psychiatric nosology.
Genetic control of neuronal activity enhances axonal growth only on permissive substrates
Authors: Mesquida-Veny Francina , Martinez-Torres Sara , Del Río José Antonio , Hervera Arnau 
Published: January 2022

AbstractNeural tissue has limited regenerative ability, to cope with that, in the recent years a diverse set of novel tools have been used to tailor neurostimulation therapies and promote functional regeneration after axonal injuries. In this report, we explore cell-specific methods to modulate neuronal activity, including opto- and chemogenetics to assess the effect of specific neuronal stimulation in the promotion of axonal regeneration after injury. We found that opto- or chemogenetic modulations of neuronal activity on both dorsal root ganglia and corticospinal motor neurons increase their axonal growth capacity only on permissive substrates.
Multivalent binding proteins can drive collapse and reswelling of chromatin in confinement
Authors: Guha Sougata , Mitra Mithun K. 
Published: January 2022

AbstractCollapsed conformations of chromatin have been long suspected of being mediated by interactions with multivalent binding proteins, such as CTCF, which can bring together distant sections of the chromatin fiber. In this study, we use Langevin dynamics simulation of coarse grained chromatin polymer to show that the role of binding proteins can be more nuanced than previously suspected. In particular, for chromatin polymer in confinement, entropic forces can drive reswelling of collapsed chromatin with increasing binder concentrations. The reswelling transition happens at physiologically relevant binder concentrations and the extent of reswelling is mediated both by the concentration of binding proteins as well as the strength of confinement. We also study the kinetics of collapse and reswelling and show that both processes occur in similar timescales. We characterise this reswelling of chromatin in biologically relevant regimes and discuss implications for the spatial organisation of the genome.
Trichomes on female reproductive tract: rapid diversification and underlying gene regulatory network in Drosophila suzukii and its related species
Authors: Tanaka Kentaro M. , Takahashi Kanoko , Rice Gavin , Rebeiz Mark , Kamimura Yoshitaka , Takahashi Aya 
Published: January 2022

AbstractBackgroundThe ovipositors of some insects are external female genitalia, which have their primary function to deliver eggs. Drosophila suzukii and its sibling species D. subpulchrella are known to have acquired highly sclerotized and enlarged ovipositors upon their shifts in oviposition sites from rotting to ripening fruits. Inside the ovipositor plates, there are scale-like polarized protrusions termed “oviprovector scales” that are likely to aid the mechanical movement of the eggs. The size and spatial distribution of the scales need to be rearranged following the divergence of the ovipositors. In this study, we examined the features of the oviprovector scales in D. suzukii and its closely related species. We also investigated whether the scales are single-cell protrusions comprised of F-actin under the same conserved gene regulatory network as the well-characterized trichomes on the larval cuticular surface.ResultsThe oviprovector scales of D. suzukii and D. subpulchrella were distinct in size and spatial arrangement compared to those of a closely related species D. biarmipes and D. melanogaster. The comparisons of the size of the scales suggested that the apical cell area of the oviprovector has expanded upon the elongation of the ovipositor plates in these species. Our transcriptome analysis revealed that 43 out of the 46 genes known to be involved in the trichome gene regulatory network are expressed in the developing female genitalia of D. suzukii and D. subpulchrella. An antibody staining depicted the presence of Shavenbaby (Svb) in the inner cavity of the developing ovipositors of D. melanogaster at 44–48 h after puparium formation (APF). Also, shavenoid (sha) was expressed in the corresponding patterns in the developing ovipositors and showed differential expression levels between D. suzukii and D. subpulchrella at 48 h APF.ConclusionsThe oviprovector scales have divergent size and spatial arrangements among species. Therefore, these scales may represent a rapidly diversifying morphological trait of the female reproductive tract reflecting ecological contexts. Furthermore, our results showed that the gene regulatory network underlying trichome formation is adopted to develop the rapidly evolving trichomes on the oviprovectors of these flies.
Neuro-toxicogenomic mapping of TMT induced neurotoxicity using human minibrain reveals associated adverse outcome events
Authors: Subashika Govindan , Daniel Alpern , Stoppini Luc , Deplancke Bart , Adrien Roux 
Published: January 2022

AbstractGenome-wide transcriptomic interrogation of organoids and 3D tissue models are increasingly used for characterizing drug, toxicity responses and neurodevelopmental disorders. We established here a neuro-toxicogenomic assay by utilizing “minibrain”, a humanin vitro3D brain model system and a low-cost, highly multiplexable RNA-seq methodology (BRB-seq) for screening the effect of trimethyltin chloride (TMT) induced neurotoxicity. We demonstrate that transcriptomic profiling is insightful to the cellular composition and regional identity of the minibrain. Further, we characterize the transcriptomic changes associated with the dose-time neurotoxic response of minibrain upon exposure to TMT. The distinct gene expression changes and molecular candidates identified with our pipeline provides insight to map the key events involved in the adverse outcome pathway of TMT associated neurotoxicity. We identify processes such as endoplasmic reticulum stress, dysregulation of synaptic genes and downregulation of neuron-morphology associated genes upon exposure to TMT. In response to TMT, we identify activation of an early response homeostatic mechanism in minibrain and an interplay of STAT pathways correlating with the dose severity. In this study, we present a neuro-toxicogenomic assay that demonstrates the power of a low-cost transcriptomic screening to study chemical induced neurotoxicity.
A unified Method for assessing the Observability of Dynamic Complex Systems
Authors: Diaz Ochoa Juan G. 
Published: January 2022

AbstractProblemSystems theory applied to biology and medicine assumes that the complexity of a system can be described by quasi-generic models to predict the behavior of many other similar systems. To this end, the aim of various research works in systems theory is to developinductive modeling(based on data-intensive analysis) ordeductive modeling(based on the deduction of mechanistic principles) to discover patterns and identify plausible correlations between past and present events, or to connect different causal relationships of interacting elements at different scales and compute mathematical predictions. Mathematical principles assume that there are constant and observable universal causal principles that apply to all biological systems. Nowadays, there are no suitable tools to assess the soundness of these universal causal principles, especially considering that organisms not only respond to environmental stimuli (and inherent processes) across multiple scales but also integrate information about and within these scales. This implies an uncontrollable degree of uncertainty.MethodologyA method has been developed to detect the stability of causal processes by evaluating the information contained in the trajectories identified in a phase space. Time series patterns are analyzed using concepts from geometric information theory and persistent homology. In essence, recognizing these patterns in different time periods and evaluating their geometrically integrated information leads to the assessment of causal relationships. With this method, and together with the evaluation of persistent entropy in trajectories in relation to different individual systems, we have developed a method calledΦ-S diagramas a complexity measure to recognize when organisms follow causal pathways leading to mechanistic responses.ResultsWe calculated the Φ-S diagram of a deterministic dataset available in the ICU repository to test the method’s interpretability. We also calculated the Φ-S diagram of time series from health data available in the same repository. This includes patients’ physiological response to sport measured with wearables outside laboratory conditions. We confirmed the mechanistic nature of both datasets in both calculations. In addition, there is evidence that some individuals show a high degree of autonomous response and variability. Therefore, persistent individual variability may limit the ability to observe the cardiac response. In this study, we present the first demonstration of the concept of developing a more robust framework for representing complex biological systems.
PERSISTENT RELIEF OF MOTOR SYMPTOMS IN A PARKINSONIAN MOUSE MODEL AFTER INDUCTION OF LTD AT CORTICAL INPUTS TO INDIRECT PATHWAY STRIATAL NEURONS
Authors: Abburi Chandrika , Thome Jason , Rodriguez Braeden , Zhaung Xiaoxi , McGehee Daniel S 
Published: January 2022

SummaryIn Parkinson’s disease (PD) patients, dopamine replacement therapy requires days to reach maximal effects, and the return of symptoms without treatment is similarly delayed. We previously postulated that these phenomena are mediated by plasticity of coritcostriatal synapses. As dopamine depletion is expected to promote aberrant potentiation of the cortical inputs onto indirect pathway neurons, we reasoned that induction of LTD here could reduce motor deficits in a PD model. Optogenetic cortical stimulation combined with a D2 receptor agonist, quinpirole, induces robust optical LTD (oLTD) in brain slices from 6-OHDA lesioned mice. When lesioned mice were subjected to corticostriatal oLTD treatment over 5 days, motor performance was improved for >3 weeks. Consistent with LTD induction, oLTD-treated mice had reduced VGLUT1 expression in striatum and greater excitability of D2 neurons. These findings suggest that reversing aberrant corticostriatal synaptic plasticity in the indirect pathway may lead to persistent relief of PD motor symptoms.
Becoming metrics literate: An analysis of brief videos that teach about the h-index
Authors: Maggio Lauren A. , Jeffrey Alyssa , Haustein Stefanie , Samuel Anita 
Published: January 2022

AbstractIntroductionAcademia uses scholarly metrics, such as the h-index, to make hiring, promotion, and funding decisions. These high-stakes decisions require that those using scholarly metrics be able to recognize, interpret, critically assess and effectively and ethically use them. This study aimed to characterize educational videos about the h-index to understand available resources and provide recommendations for future educational initiatives.MethodsThe authors analyzed videos on the h-index posted to YouTube. Videos were identified by searching YouTube and were screened by two authors. To code the videos the authors created a coding sheet, which assessed content and presentation style with a focus on the videos’ educational quality based on Cognitive Load Theory. Two authors coded each video independently with discrepancies resolved by group consensus.ResultsThirty-one videos met inclusion criteria. Twenty-one videos (68%) were screencasts and seven used a “talking head” approach. Twenty-six videos defined the h-index (83%) and provided examples of how to calculate and find it. The importance of the h-index in high-stakes decisions was raised in 14 (45%) videos. Sixteen videos (52%) described caveats about using the h-index, with potential disadvantages to early researchers the most prevalent (n=7; 23%). All videos incorporated various educational approaches with potential impact on viewer cognitive load. Most videos (n=21; 68%) displayed amateurish production quality.DiscussionThe videos featured content with potential to enhance viewers’ metrics literacies such that many defined the h-index and described its calculation, providing viewers with skills to recognize and interpret the metric. However, less than half described the h-index as an author quality indicator, which has been contested, and caveats about h-index use were inconsistently presented, suggesting room for improvement. While most videos integrated practices to facilitate balancing viewers’ cognitive load, few (32%) were of professional production quality. Some videos missed opportunities to adopt particular practices that could benefit learning.