bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determination of HLA-DR level in cytotoxic T lymphocytes: a new validated tool to predict breast cancer response to treatment
Authors: Saraiva D.P. , Azeredo-Lopes S. , Antunes A. , Salvador R. , Borralho P. , Assis B. , Pereira I. , Seabra Z. , Negreiros I. , Jacinto A. , Braga S. , Cabral M. G. 
Published: May 2021

AbstractBackgroundNeoadjuvant chemotherapy (NACT) is the usual treatment for locally-advanced breast cancer (BC). However, more than half of the patients lack an effective response to this treatment. Thus, it’s urgent to find predictive biomarkers. Recently, we proposed the HLA-DR expression level in cytotoxic T lymphocytes (CTLs) as a robust biomarker to select, in advance, patients that will actually benefit from NACT.Patients and MethodsA total of 202 BC patients, 102 of which submitted to NACT, were enrolled in this study. 61 biopsies and 41 blood samples collected pre-NACT and 100 non-NACT tumor samples were immunophenotyped by flow cytometry. Both NACT and non-NACT patients were followed up for 34 months. Blood-isolated immune cells were cultured with BC cell lines in a 3D system.ResultsHere we confirmed that HLA-DR level in CTLs is a highly sensitive and specific biomarker to predict BC response to NACT, reflected in circulation and independent of the patients’ age, BC subtype and other tumor-immunological features. Therefore, we developed a predictive probability model, based on the determination of HLA-DR level in tumor-infiltrating CTLs, that could be used to guide therapeutic decisions. Interestingly, this biomarker was also associated with progression-free survival, regardless the treatment. Contrary to HLA-DRnegative CTLs, HLA-DR+ CTLs were able to reduce the viability of tumor cells, in culture, in agreement with their higher expression of activation, proliferation and cytotoxicity-related molecules. Tissue-residency and memory markers were also increased in HLA-DR+ CTLs. These anti-tumor features of HLA-DR+ CTLs may justify the clinical observations.ConclusionHLA-DR level in CTLs is a validated and independent biomarker to predict response to NACT which allow the establishment of a clinical meaningful tool to select in advance patients that will truly benefit from this treatment. Intriguingly, it may be further used as a biomarker of BC patients’ general prognosis.Highlights- HLA-DR level in cytotoxic T cells is an independent predictive factor of breast cancer response to NACT- A predictive probability model based on this biomarker was developed as a new tool to improve treatment decisions- HLA-DR level in cytotoxic T cells is also reflected systemically- HLA-DR level in cytotoxic T cells is also a prognostic factor, associated with progression-free survival- HLA-DR+ cytotoxic T cells exhibit several phenotypic and functional anti-tumor characteristics
Admixture mapping reveals loci for carcass mass in red deer x sika hybrids in Kintyre, Scotland
Authors: McFarlane S. Eryn , Pemberton Josephine M. 
Published: May 2021

AbstractWe deployed admixture mapping on a sample of 386 deer from a hybrid swarm between native red deer (Cervus elaphus) and introduced Japanese sika (Cervus nippon) sampled in Kintyre, Scotland to search for Quantitative Trait Loci (QTL) underpinning phenotypic differences between the species. These two species are highly diverged genetically (Fstbetween pure species, based on 50K SNPs, = 0.532) and phenotypically: pure red have on average twice the carcass mass of pure sika in our sample (38.7kg vs 19.1 kg). After controlling for sex, age and population genetic structure we found ten autosomal genomic locations with QTL for carcass mass. Effect sizes ranged from 0.191 to 1.839 Kg and as expected, in all cases the allele derived from sika conferred lower carcass mass. The sika population was fixed for all small carcass mass alleles, whereas the red deer population was typically polymorphic. GO term analysis of genes lying in the QTL regions are associated with oxygen transport. Although body mass is a likely target of selection, none of the SNPs marking QTL are introgressing faster or slower than expected in either direction.
A Method for Cost-Effective and Rapid Characterization of Genetic Parts
Authors: McManus John B. , Bernhards Casey B. , Sharpes Caitlin E. , Garcia David C. , Cole Stephanie D. , Murray Richard M. , Emanuel Peter A. , Lux Matthew W. 
Published: May 2021

ABSTRACTCharacterizing and cataloging genetic parts are critical to the design of useful genetic circuits. Having well-characterized parts allows for the fine-tuning of genetic circuits, such that their function results in predictable outcomes. With the growth of synthetic biology as a field, there has been an explosion of genetic circuits that have been implemented in microbes to execute functions pertaining to sensing, metabolic alteration, and cellular computing. Here, we show a cost-effective and rapid method for characterizing genetic parts. Our method utilizes cell-free lysate, prepared in-house, as a medium to evaluate parts via the expression of a reporter protein. Template DNA is prepared by PCR-amplification using inexpensive primers to add variant parts to the reporter gene, and the template is added to the reaction as linear DNA without cloning. Parts that can be added in this way include promoters, operators, ribosome binding sites, insulators, and terminators. This approach, combined with the incorporation of an acoustic liquid handler and 384-well plates, allows the user to carry out high-throughput evaluations of genetic parts in a single day. By comparison, cell-based screening approaches require time-consuming cloning and have longer testing times due to overnight culture and culture density normalization steps. Further, working in cell-free lysate allows the user to exact tighter control over the expression conditions through the addition of exogenous components, or by titrating DNA concentrations rather than relying on limited plasmid copy numbers. Because this method retains a cell-like environment, the function of the genetic part will typically mimic its function in whole cells.SUMMARYWell-characterized genetic parts are necessary for the design of novel genetic circuits. Here we describe a cost-effective, high-throughput method for rapidly characterizing genetic parts. Our method reduces cost and time by combining cell-free lysates, linear DNA to avoid cloning, and acoustic liquid handling to increase throughput and reduce reaction volumes.
Neutralization of B.1.1.28 P2 variant with sera of natural SARS-CoV-2 infection and recipients of BBV152 vaccine
Authors: Sapkal Gajanan , Yadav Pragya D. , Ella Raches , Abraham Priya , Patil Deepak Y. , Gupta Nivedita , Panda Samiran , Mohan V. Krishna , Bhargava Balram 
Published: May 2021

AbstractThe emergence of new SARS-CoV-2 variants has been a serious threat to the public health system and vaccination program. The variant of concerns have been the under investigation for their neutralizing potential against the currently available COVID-19 vaccines. Here, we have determined the neutralization efficacy of B.1.1.28.2 variant with the convalescent sera of individuals with natural infection and BBV152 vaccination. The two-dose vaccine regimen significantly boosted the IgG titer and neutralizing efficacy against both B.1.1.28.2 and D614G variants compared to that seen with natural infection. The study demonstrated 1.92 and 1.09 fold reductions in the neutralizing titer against B.1.1.28.2 variant in comparison with prototype D614G variant with sera of vaccine recipients and natural infection respectively.
Neural dynamics between anterior insular cortex and right supramarginal gyrus dissociate genuine affect sharing from automatic responses to pretended pain
Authors: Zhao Yili , Zhang Lei , Rütgen Markus , Sladky Ronald , Lamm Claus 
Published: May 2021

AbstractEmpathy for pain engages both shared affective responses and self-other distinction. In this study, we addressed the highly debated question of whether neural responses previously linked to affect sharing could result from the perception of salient affective displays. Moreover, we investigated how affect sharing and self-other distinction interact to determine our response to a pain that is either perceived as genuine or pretended (while in fact both were acted for reasons of experimental control). We found stronger activations in regions associated with affect sharing (anterior insula, aIns, and anterior mid-cingulate cortex, aMCC) as well as with affective self-other distinction (right supramarginal gyrus, rSMG), in participants watching video clips of genuine vs. pretended facial expressions of pain. Using dynamic causal modeling (DCM), we then assessed the neural dynamics between the right aIns and rSMG in these two conditions. This revealed a reduced inhibitory effect on the aIns to rSMG connection for genuine compared to pretended pain. For genuine pain only, brain-to-behavior regression analyses highlighted a linkage between this inhibitory effect on the one hand, and pain ratings as well as empathic traits on the other. These findings imply that if the pain of others is genuine and thus calls for an appropriate empathic response, neural responses in the aIns indeed seem related to affect sharing and self-other distinction is engaged to avoid empathic over-arousal. In contrast, if others merely pretend to be in pain, the perceptual salience of their painful expression results in neural responses that are down-regulated to avoid inappropriate affect sharing and social support.
Influenza viral particles harboring the SARS-CoV-2 spike RBD as a combination respiratory disease vaccine
Authors: Chaparian Ryan R. , Harding Alfred T. , Riebe Kristina , Karlsson Amelia , Sempowski Gregory D. , Heaton Nicholas S. , Heaton Brook E. 
Published: May 2021

AbstractVaccines targeting SARS-CoV-2 have gained emergency FDA approval, however the breadth against emerging variants and the longevity of protection remains unknown. Post-immunization boosting may be required, perhaps on an annual basis if the virus becomes an endemic pathogen. Seasonal influenza virus vaccines are already developed every year, an undertaking made possible by a robust global vaccine production and distribution infrastructure. To create a seasonal combination vaccine targeting influenza viruses and SARS-CoV-2 that is also amenable to frequent reformulation, we have developed a recombinant influenza A virus (IAV) genetic platform that “reprograms” the virus to package an immunogenic domain of the SARS-CoV-2 spike (S) protein onto IAV particles. Vaccination with this combination vaccine elicits neutralizing antibodies and provides protection from lethal challenge with both pathogens. This technology may allow for leveraging of established influenza vaccine infrastructure to generate a cost-effective and scalable seasonal vaccine solution for both influenza and coronaviruses.
The effects of epistasis and linkage on the invasion of locally beneficial mutations and the evolution of genomic islands
Authors: Pontz Martin , Bürger Reinhard 
Published: May 2021

AbstractWe study local adaptation of a peripheral population by investigating the fate of new mutations using a haploid two-locus two-allele continent-island migration model. We explore how linkage, epistasis, and maladaptive gene flow affect the invasion probability of weakly beneficial de-novo mutations that arise on the island at an arbitrary physical distance to a locus that already maintains a stable migration-selection polymorphism. By assuming a slightly supercritical branching process, we deduce explicit conditions on the parameters that permit a positive invasion probability and we derive approximations for it. They show how the invasion probability depends on the additive and epistatic effects of the mutant, on its linkage to the polymorphism, and on the migration rate. We use these approximations together with empirically motivated distributions of epistatic effects to analyze the influence of epistasis on the expected invasion probability if mutants are drawn randomly from such a distribution and occur at a random physical distance to the existing polymorphism. We find that the invasion probability generally increases as the epistasis parameter increases or the migration rate decreases, but not necessarily as the recombination rate decreases. Finally, we shed light on the size of emerging genomic islands of divergence by exploring the size of the chromosomal neighborhood of the already established polymorphism in which 50% or 90% of the successfully invading mutations become established. These ‘window sizes’ always decrease in a reverse sigmoidal way with stronger migration and typically increase with increasing epistatic effect.
JNK activity modulates postsynaptic scaffold protein SAP102 and kainate receptor dynamics in dendritic spines
Authors: Kunde Stella-Amrei , Schmerl Bettina , Ahmadyar Elham , Rademacher Nils , Zieger Hanna L. , Shoichet Sarah A. 
Published: May 2021

AbstractWe show here that the dynamics of the synaptic scaffold molecule SAP102 are negatively regulated by JNK inhibition, that SAP102 is a direct phosphorylation target of JNK3, and that SAP102 regulation by JNK is restricted to neurons that harbour mature synapses. We further demonstrate that SAP102 and JNK3 cooperate in the regulated trafficking of kainate receptors to the cell membrane. Specifically, we observe that SAP102, JNK3, and the kainate receptor subunit GluK2 exhibit overlapping expression at synaptic sites, and that modulating JNK activity influences the surface expression of the kainate receptor subunit GluK2 in a neuronal context. We also show that SAP102 participates in this process in a JNK-dependent fashion. In summary, our data support a model in which JNK-mediated regulation of SAP102 influences the dynamic trafficking of kainate receptors to postsynaptic sites, and thus shed light on common pathophysiological mechanisms underlying the cognitive developmental defects associated with diverse mutations.
HyMM: Hybrid method for disease-gene prediction by integrating multiscale module structures
Authors: Xiang Ju , Meng Xiangmao , Wu Fang-Xiang , Li Min 
Published: May 2021

AbstractMotivationIdentifying disease-related genes is important for the study of human complex diseases. Module structures or community structures are ubiquitous in biological networks. Although the modular nature of human diseases can provide useful insights, the mining of information hidden in multiscale module structures has received less attention in disease-gene prediction.ResultsWe propose a hybrid method, HyMM, to predict disease-related genes more effectively by integrating the information from multiscale module structures. HyMM consists of three key steps: extraction of multiscale modules, gene rankings based on multiscale modules and integration of multiple gene rankings. The statistical analysis of multiscale modules extracted by three multiscale-module-decomposition algorithms (MO, AS and HC) shows that the functional consistency of the modules gradually improves as the resolution increases. This suggests the existence of different levels of functional relationships in the multiscale modules, which may help reveal disease-gene associations. We display the effectiveness of multiscale module information in the disease-gene prediction and confirm the excellent performance of HyMM by 5-fold cross-validation and independent test. Specifically, HyMM with MO can more effectively enhance the ability of disease-gene prediction; HyMM (MO, RWR) and HyMM (MO, RWRH) are especially preferred due to their excellent comprehensive performance, and HyMM (AS, RWRH) is also good choice due to its local performance. We anticipate that this work could provide useful insights for disease-module analysis and disease-gene prediction based on multi-scale module structures.Availabilityhttps://github.com/xiangiu0208/HvMMContactlimin@mail.csu.edu.cnSupplementary informationSupplementary data are available atBioinformaticsonline.
Action at a distance: Defects in division plane positioning in the root meristematic zone affect cell organization in the differentiation zone
Authors: Mills Alison M. , Rasmussen Carolyn G 
Published: May 2021

AbstractCell division plane orientation is critical for plant and animal development and growth. TANGLED1 (TAN1) and AUXIN-INDUCED-IN-ROOT-CULTURES9 (AIR9) are division-site localized microtubule-binding proteins required for division plane positioning.tan1andair9 Arabidopsis thalianasingle mutants have minor or no noticeable phenotypes but thetan1 air9double mutant has synthetic phenotypes including stunted growth, misoriented divisions, and aberrant cell-file rotation in the root differentiation zone. These data suggest that TAN1 plays a role in nondividing cells. To determine whether TAN1 is required in elongating and differentiating cells in thetan1 air9double mutant, we limited its expression to actively dividing cells using the G2/M-specific promoter of the syntaxinKNOLLE(pKN:TAN1-YFP). Unexpectedly, in addition to rescuing division plane defects,pKN:TAN1-YFPrescued root growth and the root differentiation zone cell file rotation defects in thetan1 air9double mutant. This suggests that defects that occur in the meristematic zone later affect the organization of elongating and differentiating cells.Summary StatementExpression ofTAN1in the root meristematic zone rescues cell file rotation defects intan1 air9mutants, suggesting defects that occur in mitosis may influence organization of nondividing cells.
Burdwan University Thalassemia Severity (BUTS) Scoring System: A numerical Method For Defining the Clinicopathological status of Thalassaemia Patient
Authors: Basu Anupam , Chowdhury Prosanto Kumar , Chowdhuy Tamoghna , Sadhukhan Sukhendu , Chakrabarti Pabitra Kumar , Saha Dipankar , Pal Debashis 
Published: May 2021

ABSTRACTBackgroundβ-haemoglobinopathies are the most common monogenic disorders worldwide. They present with extreme clinical heterogeneity, which makes generalized therapeutic approaches often ineffective. Currently available risk stratification approaches are either too complicated to be deployed at a primary healthcare level or are limited in their applicability across the spectrum of haemoglobinopathies. All current systems also classify patients into the three categories of mild, moderate and severe, where the moderate category is not well-characterized in terms of their expected prognosis.MethodsThe current study proposes a severity scoring scheme, utilizing five clinical parameters, viz., steady-state average pre-transfusion haemoglobin, age at presentation, transfusion interval, palpable splenomegaly and growth retardation to classify patients of various β-haemoglobinopathies into severe and non-severe categories. The study then proceeds to validate this scoring scheme on a clinically heterogeneous cohort of 224 Eastern Indian β-thalassaemia and β-haemoglobinopathy patients, and evaluate the predictive performance of the proposed scheme against a clinical standard.ResultsAll of the chosen parameters except steady-state haemoglobin display strong individual contribution to the final determination of severity, though steady-state haemoglobin conferred increased discriminatory power to the overall scheme. The proposed system achieved an accuracy of 94% against the clinical standard.ConclusionsThe proposed risk stratification strategy, being almost entirely empirically-determined, should possess wider applicability across the spectrum of β-haemoglobinopathies than currently existing systems, and should also be more suitable than said systems for studying genotype-phenotype correlations especially within the Eastern Indian β-haemoglobinopathy population.
Raabin-WBC: a large free access dataset of white blood cells from normal peripheral blood
Authors: Kouzehkanan Zahra Mousavi , Saghari Sepehr , Tavakoli Eslam , Rostami Peyman , Abaszadeh Mohammadjavad , Mirzadeh Farzaneh , Satlsar Esmaeil Shahabi , Gheidishahran Maryam , Gorgi Fatemeh , Mohammadi Saeed , Hosseini Reshad 
Published: May 2021

AbstractAccurate and early detection of peripheral white blood cell anomalies plays a crucial role in the evaluation of an individual’s well-being. The emergence of new technologies such as artificial intelligence can be very effective in achieving this. In this regard, most of the state-of-the-art methods use deep neural networks. Data can significantly influence the performance and generalization power of machine learning approaches, especially deep neural networks. To that end, we collected a large free available dataset of white blood cells from normal peripheral blood samples called Raabin-WBC. Our dataset contains about 40000 white blood cells and artifacts (color spots). To reassure correct data, a significant number of cells were labeled by two experts, and the ground truth of nucleus and cytoplasm were extracted by experts for some cells (about 1145), as well. To provide the necessary diversity, various smears have been imaged. Hence, two different cameras and two different microscopes were used. The Raabin-WBC dataset can be used for different machine learning tasks such as classification, detection, segmentation, and localization. We also did some primary deep learning experiments on Raabin-WBC, and we showed how the generalization power of machine learning methods, especially deep neural networks, was affected by the mentioned diversity.
Considerations for using reproduction data in toxicokinetic-toxicodynamic modelling
Authors: Jager Tjalling , Trijau Marie , Sherborne Neil , Goussen Benoit , Ashauer Roman 
Published: May 2021

ABSTRACTToxicokinetic-toxicodynamic (TKTD) modelling is essential to make sense of the time dependence of toxic effects, and to interpret and predict consequences of time-varying exposure. These advantages have been recognised in the regulatory arena, especially for environmental risk assessment (ERA) of pesticides, where time-varying exposure is the norm. We critically evaluate the link between the modelled variables in TKTD models and the observations from laboratory ecotoxicity tests. For the endpoint reproduction, this link is far from trivial. The relevant TKTD models for sub-lethal effects are based on Dynamic-Energy Budget (DEB) theory, which specifies a continuous investment flux into reproduction. In contrast, experimental tests score egg or offspring release by the mother. The link between model and data is particularly troublesome when a species reproduces in discrete clutches, and even more so when eggs are incubated in the mother’s brood pouch (and release of neonates is scored in the test). This situation is quite common among aquatic invertebrates (e.g., cladocerans, amphipods, mysids), including many popular test species. We discuss these and other issues with reproduction data, reflect on their potential impact on DEB-TKTD analysis, and provide preliminary recommendations to correct them. Both modellers and users of model results need to be aware of these complications, as ignoring them could easily lead to unnecessary failure of DEB-TKTD models during calibration, or when validating them against independent data for other exposure scenarios.