bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicenter phase II trial of Camrelizumab combined with Apatinib and Eribulin in heavily pretreated patients with advanced triple-negative breast cancer
Authors: Liu Jieqiong , Wang Ying , Tian Zhenluan , Lin Ying , Li Hengyu , Zhu Zhaowen , Liu Qiang , Su Shicheng , Zeng Yinduo , Jia Weijuan , Yang Yaping , Xu Shengqiang , Yao Herui , Jiang Wen , Song Erwei 
Published: May 2022

AbstractIn the later-line setting or for patients with PD-L1-negative tumors, immunotherapy-based regimens remain ineffective against advanced triple-negative breast cancer (TNBC). In this multicentered phase II trial (NCT04303741), 46 patients with pretreated advanced TNBC were enrolled to receive camrelizumab 200 mg (day 1), and apatinib 250 mg daily, plus eribulin 1.4 mg/m2 (day 1 and 8) on a 21-day cycle until progression, or unacceptable toxicity. Primary endpoint was objective response rate (ORR) according to RECIST 1.1. Secondary endpoints included toxicities, disease control rate (DCR), clinical benefit rate, progression-free survival (PFS), and 1-year overall survival. With a median of 3 lines of prior chemotherapy in the advanced setting, 17.4% had received PD-1/PD-L1 blockade plus chemotherapy for advanced disease. The ORR was 37.0% (17/46, 95% CI 23.2–52.5). The DCR was 87.0% (40/46, 95% CI 73.7–95.1). Median PFS was 8.1 (95% CI 4.6–10.3) months. Tertiary lymphoid structure was associated with higher ORR. Patients with lower tumor PML or PLOD3 expression had favorable ORR and PFS. PD-L1 status was not associated with ORR/PFS. Grade 3/4 treatment-related adverse events occurred in 19 (41.3%) of 46 patients. Camrelizumab plus apatinib and eribulin shows promising efficacy with a measurable safety profile in patients with heavily pretreated advanced TNBC.
Non-selective distribution of infectious disease prevention may outperform risk-based targeting
Authors: Steinegger Benjamin , Iacopini Iacopo , Teixeira Andreia Sofia , Bracci Alberto , Casanova-Ferrer Pau , Antonioni Alberto , Valdano Eugenio 
Published: May 2022

AbstractEpidemic control often requires optimal distribution of available vaccines and prophylactic tools, to protect from infection those susceptible. Well-established theory recommends prioritizing those at the highest risk of exposure. But the risk is hard to estimate, especially for diseases involving stigma and marginalization. We address this conundrum by proving that one should target those at high risk only if the infection-averting efficacy of prevention is above a critical value, which we derive analytically. We apply this to the distribution of pre-exposure prophylaxis (PrEP) of the Human Immunodeficiency Virus (HIV) among men-having-sex-with-men (MSM), a population particularly vulnerable to HIV. PrEP is effective in averting infections, but its global scale-up has been slow, showing the need to revisit distribution strategies, currently risk-based. Using data from MSM communities in 58 countries, we find that non-selective PrEP distribution often outperforms risk-based, showing that a logistically simpler strategy is also more effective. Our theory may help design more feasible and successful prevention.
P-selectin mobility undergoes a sol-gel transition as it diffuses from exocytosis sites into the cell membrane
Authors: Hellen Nicola , Mashanov Gregory I. , Conte Ianina L. , le Trionnaire Sophie , Babich Victor , Knipe Laura , Mohammed Alamin , Ogmen Kazim , Martin-Almedina Silvia , Török Katalin , Hannah Matthew J. , Molloy Justin E. , Carter Tom 
Published: May 2022

AbstractIn response to vascular damage, P-selectin molecules are secreted onto the surface of cells that line our blood vessels. They then serve as mechanical anchors to capture leucocytes from the blood stream. Here, we track individual P-selectin molecules released at the surface of live endothelial cells following stimulated secretion. We find P-selectin initially shows fast, unrestricted diffusion but within a few minutes, movement becomes increasingly restricted and ~50% of the molecules become completely immobile; a process similar to a sol-gel transition. We find removal of the extracellular C-type lectin domain (ΔCTLD) and/or intracellular cytoplasmic tail domain (ΔCT) has additive effects on diffusive motion while disruption of the adapter complex, AP2, or removal of cell-surface heparan sulphate restores mobility of full-length P-selectin close to that of ΔCT and ΔCTLD respectively. We have found P-selectin spreads rapidly from sites of exocytosis and evenly decorates the cell surface, but then becomes less mobile and better-suited to its mechanical anchoring function.
Structural variant-based pangenome construction has low sensitivity to variability of haplotype-resolved bovine assemblies
Authors: Leonard Alexander S. , Crysnanto Danang , Fang Zih-Hua , Heaton Michael P. , Vander Ley Brian L. , Herrera Carolina , Bollwein Heinrich , Bickhart Derek M. , Kuhn Kristen L. , Smith Timothy P. L. , Rosen Benjamin D. , Pausch Hubert 
Published: May 2022

AbstractAdvantages of pangenomes over linear reference assemblies for genome research have recently been established. However, potential effects of sequence platform and assembly approach, or of combining assemblies created by different approaches, on pangenome construction have not been investigated. Here we generate haplotype-resolved assemblies from the offspring of three bovine trios representing increasing levels of heterozygosity that each demonstrate a substantial improvement in contiguity, completeness, and accuracy over the currentBos taurusreference genome. Diploid coverage as low as 20x for HiFi or 60x for ONT is sufficient to produce two haplotype-resolved assemblies meeting standards set by the Vertebrate Genomes Project. Structural variant-based pangenomes created from the haplotype-resolved assemblies demonstrate significant consensus regardless of sequence platform, assembler algorithm, or coverage. Inspecting pangenome topologies identifies 90 thousand structural variants including 931 overlapping with coding sequences; this approach reveals variants affectingQRICH2,PRDM9,HSPA1A,TAS2R46, andGCthat have potential to affect phenotype.
Dosage-sensitive miRNAs trigger modulation of gene expression during genomic imbalance in maize
Authors: Shi Xiaowen , Yang Hua , Chen Chen , Hou Jie , Ji Tieming , Cheng Jianlin , Birchler James A. 
Published: May 2022

AbstractThe genomic imbalance caused by varying the dosage of individual chromosomes or chromosomal segments (aneuploidy) has more detrimental effects than altering the dosage of complete chromosome sets (ploidy). Previous analysis of maize (Zea mays) aneuploids revealed global modulation of gene expression both on the varied chromosome (cis) and the remainder of the genome (trans). However, little is known regarding the role of microRNAs (miRNAs) under genomic imbalance. Here, we report the impact of aneuploidy and polyploidy on the expression of miRNAs. In general, cis miRNAs in aneuploids present a predominant gene-dosage effect, whereas trans miRNAs trend toward the inverse level, although other types of responses including dosage compensation, increased effect, and decreased effect also occur. By contrast, polyploids show less differential miRNA expression than aneuploids. Significant correlations between expression levels of miRNAs and their targets are identified in aneuploids, indicating the regulatory role of miRNAs on gene expression triggered by genomic imbalance.
Acute threat enhances perceptual sensitivity without affecting the decision criterion
Authors: de Voogd Lycia D. , Hagenberg Eline , Zhou Ying Joey , de Lange Floris P. , Roelofs Karin 
Published: May 2022

AbstractThreatening situations ask for rapid and accurate perceptual decisions to optimize coping. Theoretical models have stated that psychophysiological states, such as bradycardia during threat-anticipatory freezing, may facilitate perception. However, it’s unclear if this occurs via enhanced bottom-up sensory processing or by relying more on prior expectations. To test this, 52 (26 female) participants completed a visual target-detection paradigm under threat-of-shock (15% reinforcement rate) with a manipulation of prior expectations. Participants judged the presence of a backward-masked grating (target presence rate 50%) after systematically manipulating their decision criterion with a rare (20%) or frequent (80%) target presence rate procedure. Threat-of-shock induced stronger heart rate deceleration compared to safe, indicative of threat-anticipatory freezing. Importantly, threat-of-shock enhanced perceptual sensitivity but we did not find evidence of an altered influence of the effect of prior expectations on current decisions. Correct target detection (hits) was furthermore accompanied by an increase in the magnitude of this heart rate deceleration compared to a missed target. While this was independent of threat-of-shock manipulation, only under threat-of-shock this increase was accompanied by more hits and increased sensitivity. Together, these findings suggest that under acute threat participants may rely more on bottom-up sensory processing versus prior expectations in perceptual decision-making. Critically, bradycardia may underlie such enhanced perceptual sensitivity.
High-resolution analysis of long-term serum antibodies in humans following convalescence of SARS-CoV-2 infection
Authors: Facciuolo Antonio , Scruten Erin , Lipsit Sean , Lang Amanda , Parker Cates Zoë , Lew Jocelyne M. , Falzarano Darryl , Gerdts Volker , Kusalik Anthony J. , Napper Scott 
Published: May 2022

AbstractLong-term antibody responses to SARS-CoV-2 have focused on responses to full-length spike protein, specific domains within spike, or nucleoprotein. In this study, we used high-density peptide microarrays representing the complete proteome of SARS-CoV-2 to identify binding sites (epitopes) targeted by antibodies present in the blood of COVID-19 resolved cases at 5 months post-diagnosis. Compared to previous studies that evaluated epitope-specific responses early post-diagnosis (< 60 days), we found that epitope-specific responses to nucleoprotein and spike protein have contracted, and that responses to membrane protein have expanded. Although antibody titers to full-length spike and nucleoprotein remain steady over months, taken together our data suggest that the population of epitope-specific antibodies that contribute to this reactivity is dynamic and evolves over time. Further, the spike epitopes bound by polyclonal antibodies in COVID-19 convalescent serum samples aligned with known target sites that can neutralize viral activity suggesting that the maintenance of these antibodies might provide rapid serological immunity. Finally, the most dominant epitopes for membrane protein and spike showed high diagnostic accuracy providing novel biomarkers to refine blood-based antibody tests. This study provides new insights into the specific regions of SARS-CoV-2 targeted by serum antibodies long after infection.
On the remarkable nonlinear optical properties of natural tomato lycopene
Authors: Numan N. , Jeyaram S. , Kaviyarasu K. , Neethling P. , Sackey J. , Kotsedi C. L. , Akbari M. , Morad R. , Mthunzi-Kufa P. , Sahraoui B. , Maaza M. 
Published: May 2022

AbstractIn line with the renewed interest in developing novel Non Linear Optical (NLO) materials, natural Lycopene’s NLO Properties are reported for the first time within the scientific literature. Correlated to its 1-D conjugated π-electrons linear conformation, it is shown that natural Lycopene exhibits a significantly elevated 3rd order nonlinearity χ(3) as high as 2.65 10−6 esu, the largest value of any investigated natural phyto-compound so far, including β-carotene. In addition to a saturable absorption, the corresponding observed self-defocusing effect in Lycopene seems to be the result of a thermal nonlinearity. The nonlinear response coupled to the observed fluorescence in the Visible spectral range points to a potential photodynamic therapy application as well as the possibility of engineering of novel hybrid Lycopene based NLO nano-materials.
Sociality of future outcomes moderates the effects of warmth and competence on social optimism bias
Authors: Dricu Mihai , Jossen Sina Ladina , Aue Tatjana 
Published: May 2022

AbstractPeople are overoptimistic about the future of those they like or admire (social optimism bias), expecting significantly more desirable than undesirable outcomes. By contrast, they are pessimistic about those they don’t like. To operationalize the (dis)like of social targets, warmth and competence are used as two universal dimensions of social perception. In this pre-registered study, we replicate previous findings while adding two new levels of complexity. First, we make the distinction between the sociality of future outcomes: “alone” outcomes (e.g., enjoying a quiet afternoon by oneself) and “social” outcomes (e.g., enjoying a vacation with the significant other). Second, we investigate the effect of attachment styles on one’s expectations for alone and social outcomes toward the social targets. In line with our hypotheses, the sociality of outcomes moderates both the additive and the multiplicative effects of the perceived warmth and competence of social targets on social optimism bias. Diverging from our hypotheses, we find that attachment anxiety and avoidance do not influence the effects of warmth and competence on social optimism bias. However, exploratory analyses reveal that attachment dimensions buffer the magnitude of social optimism bias for highly self-relevant social targets but do not impact social pessimism bias for irrelevant targets.
Synthesizing controlled microstructures of porous media using generative adversarial networks and reinforcement learning
Authors: Nguyen Phong C. H. , Vlassis Nikolaos N. , Bahmani Bahador , Sun WaiChing , Udaykumar H. S. , Baek Stephen S. 
Published: May 2022

AbstractFor material modeling and discovery, synthetic microstructures play a critical role as digital twins. They provide stochastic samples upon which direct numerical simulations can be conducted to populate material databases. A large ensemble of simulation data on synthetic microstructures may provide supplemental data to inform and refine macroscopic material models, which might not be feasible from physical experiments alone. However, synthesizing realistic microstructures with realistic microstructural attributes is highly challenging. Thus, it is often oversimplified via rough approximations that may yield an inaccurate representation of the physical world. Here, we propose a novel deep learning method that can synthesize realistic three-dimensional microstructures with controlled structural properties using the combination of generative adversarial networks (GAN) and actor-critic (AC) reinforcement learning. The GAN-AC combination enables the generation of microstructures that not only resemble the appearances of real specimens but also yield user-defined physical quantities of interest (QoI). Our validation experiments confirm that the properties of synthetic microstructures generated by the GAN-AC framework are within a 5% error margin with respect to the target values. The scientific contribution of this paper resides in the novel design of the GAN-AC microstructure generator and the mathematical and algorithmic foundations therein. The proposed method will have a broad and substantive impact on the materials community by providing lenses for analyzing structure-property-performance linkages and for implementing the notion of ‘materials-by-design’.
Epigenetic regulation of BAF60A determines efficiency of miniature swine iPSC generation
Authors: Jiao Hongli , Lee Ming-Song , Sivapatham Athillesh , Leiferman Ellen M. , Li Wan-Ju 
Published: May 2022

AbstractMiniature pigs are an ideal animal model for translational research to evaluate stem cell therapies and regenerative applications. While the derivation of induced pluripotent stem cells (iPSCs) from miniature pigs has been demonstrated, there is still a lack of a reliable method to generate and maintain miniature pig iPSCs. In this study, we derived iPSCs from fibroblasts of Wisconsin miniature swine (WMS), Yucatan miniature swine (YMS), and Göttingen minipigs (GM) using our culture medium. By comparing cells of the different pig breeds, we found that YMS fibroblasts were more efficiently reprogrammed into iPSCs, forming colonies with well-defined borders, than WMS and GM fibroblasts. We also demonstrated that YMS iPSC lines with a normal pig karyotype gave rise to cells of the three germ layers in vitro and in vivo. Mesenchymal stromal cells expressing phenotypic characteristics were derived from established iPSC lines as an example of potential applications. In addition, we found that the expression level of the switch/sucrose nonfermentable component BAF60A regulated by STAT3 signaling determined the efficiency of pig iPSC generation. The findings of this study provide insight into the underlying mechanism controlling the reprogramming efficiency of miniature pig cells to develop a viable strategy to enhance the generation of iPSCs for biomedical research.
Prevalence of left ventricular thrombus formation after mitral valve edge-to-edge repair
Authors: Tichelbäcker Tobias , Körber Maria Isabel , Mauri Victor , Iliadis Christos , Metze Clemens , Adler Christoph , Baldus Stephan , Rudolph Volker , Halbach Marcel , Pfister Roman , ten Freyhaus Henrik 
Published: May 2022

AbstractThe prevalence of left ventricular (LV) thrombus formation following percutaneous mitral valve edge-to-edge repair (TMVR) with the MitraClip system is unclear. Decreased total stroke volume and perfusion of the LV apex after mitral valve repair may facilitate thrombus formation especially in the context of reduced LV function. LV thrombus may cause disabling stroke or other thromboembolic events in this elderly and multimorbid patient cohort. Analyses of the prevalence of and risk factors for left ventricular thrombus formation in patients treated with the MitraClip system due to severe mitral valve regurgitation. All discharge and follow-up transthoracic echocardiographic examinations up to 6 months of 453 consecutive patients treated with the MitraClip system were screened for the presence of LV thrombus. Prevalence of LV thrombus formation was 1.1% (5/453). Importantly, LV thrombi were exclusively found in patients with severely depressed left ventricular systolic function (LV-EF < 30%), comprising a prevalence of 4.4% in this subgroup (5/113). Importantly, two of these patients were under active DOAC therapy with Rivaroxaban and Apixaban, respectively. Apart from LV-EF, we did not identify other factors that might have facilitated LV thrombus formation. LV thrombus formation following percutaneous mitral valve repair occurred exclusively in patients with severely depressed LV-EF. As two patients developed LV thrombus despite of DOAC therapy, anticoagulation with a Vitamin K antagonist should be considered in patients with an indication for oral anticoagulation following TMVR.
Population collapse of a Gondwanan conifer follows the loss of Indigenous fire regimes in a northern Australian savanna
Authors: Bowman David M. J. S. , Williamson Grant J. , Johnston Fay H. , Bowman Clarence J. W. , Murphy Brett P. , Roos Christopher I. , Trauernicht Clay , Rostron Joshua , Prior Lynda D. 
Published: May 2022

AbstractColonialism has disrupted Indigenous socioecological systems around the globe, including those supported by intentional landscape burning. Because most disruptions happened centuries ago, our understanding of Indigenous fire management is largely inferential and open to debate. Here, we investigate the ecological consequences of the loss of traditional Aboriginal fire management on fire-exposed savannas on the Arnhem Plateau, northern Australia, using the fire-sensitive conifer Callitris intratropica as a bio-indicator. We contrast Kakadu National Park, where traditional Aboriginal fire management was severely disrupted during the early twentieth century following Aboriginal relocation to surrounding settlements, and an adjacent Aboriginal estate where traditional Aboriginal fire management endures. Since 2006, traditional Aboriginal fire management at this site has been overlaid by a program of broad-scale institutionalized burning in the early dry season, designed to reduce greenhouse emissions. Using remote sensing, field survey, and dendrochronology, we show that on the Aboriginal estate, C. intratropica populations depend on the creation of a shifting patch mosaic of long unburned areas necessary for the recruitment of C. intratropica. However, the imposition of broad-scale fire management is disrupting this population patch dynamic. In Kakadu, there have been extreme declines of C. intratropica associated with widespread fires since the mid twentieth century and consequent proliferation of grass fuels. Fire management in Kakadu since 2007, designed to increase the size and abundance of patches of unburned vegetation, has not been able to reverse the population collapse of C. intratropica. Our study demonstrates that colonial processes including relocation of Indigenous people and institutional fire management can have deleterious consequences that are nearly irreversible because of hysteresis in C. intratropica population dynamics.
Epidural anesthesia needle guidance by forward-view endoscopic optical coherence tomography and deep learning
Authors: Wang Chen , Calle Paul , Reynolds Justin C. , Ton Sam , Yan Feng , Donaldson Anthony M. , Ladymon Avery D. , Roberts Pamela R. , de Armendi Alberto J. , Fung Kar-ming , Shettar Shashank S. , Pan Chongle , Tang Qinggong 
Published: May 2022

AbstractEpidural anesthesia requires injection of anesthetic into the epidural space in the spine. Accurate placement of the epidural needle is a major challenge. To address this, we developed a forward-view endoscopic optical coherence tomography (OCT) system for real-time imaging of the tissue in front of the needle tip during the puncture. We tested this OCT system in porcine backbones and developed a set of deep learning models to automatically process the imaging data for needle localization. A series of binary classification models were developed to recognize the five layers of the backbone, including fat, interspinous ligament, ligamentum flavum, epidural space, and spinal cord. The classification models provided an average classification accuracy of 96.65%. During puncture, it is important to maintain a safe distance between the needle tip and the dura mater. Regression models were developed to estimate that distance based on the OCT imaging data. Based on the Inception architecture, our models achieved a mean absolute percentage error of 3.05% ± 0.55%. Overall, our results validated the technical feasibility of using this novel imaging strategy to automatically recognize different tissue structures and measure the distances ahead of the needle tip during the epidural needle placement.