bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical implementation and initial experience with a 1.5 Tesla MR-linac for MR-guided radiotherapy for gynecologic cancer: An R-IDEAL stage 1/2a first in humans/feasibility study of new technology implementation
Authors: Lakomy David S. , Yang Jinzhong , Vedam Sastry , Wang Jihong , Lee Belinda , Sobremonte Angela , Castillo Pamela , Hughes Neil , Mohammadsaid Mustefa , Jhingran Anuja , Klopp Ann H. , Choi Seungtaek , Fuller C. David , Lin Lilie L. 
Published: December 2021

ABSTRACTPurposeMagnetic resonance imaging–guided linear accelerator systems (MR-linacs) can facilitate the daily adaptation of radiotherapy plans. Here, we report our early clinical experience using an MR-linac for adaptive radiotherapy of gynecologic malignancies.Methods and MaterialsTreatments were planned with an Elekta Monaco v5.4.01 and delivered by a 1.5 Tesla Elekta Unity MR-linac. The system offers a choice of daily adaptation based on either position (ATP) or shape (ATS) of the tumor and surrounding normal structures. The ATS approach has the option of manually editing the contours of tumors and surrounding normal structures before the plan is adapted. Here we documented the duration of each treatment fraction; set-up variability (assessed by isocenter shifts in each plan) between fractions; and, for quality assurance, calculated the percentage of plans meeting the y-criterion of 3%/3-mm distance to agreement. Deformable accumulated dose calculations were used to compare ATP plans with reference dose plans.ResultsOf the 10 patients treated with 90 fractions on the MR-linac, most received boost doses to recurrence in nodes or isolated tumors. Each treatment fraction lasted a median 32 minutes; fractions were shorter with ATP than with ATS (30 min vs 42 min, P<0.0001). The y criterion for all fraction plans exceeded >90% (median 99.9%, range 92.4%–100%), i.e., all plans passed quality assurance testing. The average extent of isocenter shift was <0.5 cm in each axis. The accumulated dose to the gross tumor volume was within 10% of the reference plan for all ATP cases. Accumulated doses for lesions in the pelvic periphery were within 1% of the reference plan as opposed to –5.8% to –9.6% for central tumors.ConclusionsThe MR-linac is a reliable and clinically feasible tool for treating patients with gynecologic cancer.
Genome, proteome, and immunome data explain why 6 month controlled human malaria infection with sporozoites of the Pf7G8 clone of Plasmodium falciparum is a rigorous predictor of the efficacy of the PfNF54-based PfSPZ Vaccine in Africa
Authors: Silva Joana C. , Dwivedi Ankit , Moser Kara A. , Sissoko Mahamadou S. , Epstein Judith E. , Healy Sara A. , Lyke Kirsten E. , Mordmüller Benjamin , Kremsner Peter G. , Duffy Patrick E. , Murshedkar Tooba , Lee Sim B. Kim , Richie Thomas L. , Hoffman Stephen L. 
Published: December 2021

ABSTRACTControlled human malaria infection (CHMI) has supported Plasmodium falciparum (Pf) malaria vaccine development by providing preliminary estimates of vaccine efficacy (VE). Because CHMIs generally use Pf strains similar to vaccine strains, VE against antigenically heterogeneous Pf in the field has been required to establish VE. We increased the stringency of CHMI by selecting a Brazilian isolate, Pf7G8, which is genetically distant from the West African parasite (PfNF54) in our PfSPZ vaccines. Using two regimens to identically immunize US and Malian adults, VE over 24 weeks in the field was as good as or better than against CHMI at 24 weeks in the US. To explain this finding, we quantified differences in the genome, proteome and predicted CD8 T cell epitopes of PfNF54 relative to 709 Pf isolates from Africa and Pf7G8. Pf7G8 is more distant from PfNF54 than any African isolates tested. We propose VE against Pf7G8 CHMI for providing pivotal data for malaria vaccine licensure for travelers to Africa, and potentially for endemic populations, because the genetic distance of Pf7G8 from the Pf vaccine strain makes it a stringent surrogate for Pf parasites in Africa.
Patients with benign breast disease and breast cancer need more COVID-19 vaccines
Authors: Wu Huai-liang , He Zong-lin , Gong Yue , Mo Miao , Liu Guang-yu 
Published: December 2021

AbstractAlbeit the efficacy of COVID-19 vaccines in immunocompromised patients is undermined, it is still found beneficial. Patients with cancer have a much lower COVID-19 vaccination rate globally, and the vaccination coverage in breast cancer patients in China remains elusive. A total of 23029 patients with benign breast diseases and breast cancers were included in the study, and the vaccination rates of patients with benign breast tumors and other benign breast diseases, nonmetastatic and metastatic breast cancer were 44.0%, 54.7%, 19.2% and 9.6%, respectively. Breast cancer in situ patients had a similar vaccination rate with patients with benign breast tumors (45.9% vs 44.0%) while those with invasive breast cancer had much lower vaccination rates. The overall vaccination rate remains meager in breast cancer patients, and gap was found in patients with lower clinical stage. Hence vaccination should be further promoted among patients with benign breast diseases and breast cancer.
ClusTRace, a bioinformatic pipeline for analyzing clusters in virus phylogenies
Authors: Plyusnin Ilya , Nguyen Phuoc Thien Truong , Sironen Tarja , Vapalahti Olli , Smura Teemu , Kant Ravi 
Published: December 2021

ABSTRACTSummarySARS-CoV-2 is the highly transmissible etiologic agent of coronavirus disease 2019 (COVID-19) and has become a global scientific and public health challenge since December 2019. Several new variants of SARS-CoV-2 have emerged globally raising concern about prevention and treatment of COVID-19. Early detection and in depth analysis of the emerging variants allowing pre-emptive alert and mitigation efforts are thus of paramount importance.Here we present ClusTRace, a novel bioinformatic pipeline for a fast and scalable analysis of sequence clusters or clades in large viral phylogenies. ClusTRace offers several high level functionalities including outlier filtering, aligning, phylogenetic tree reconstruction, cluster or clade extraction, variant calling, visualization and reporting. ClusTRace was developed as an aid for COVID-19 transmission chain tracing in Finland and the main emphasis has been on fast and unsupervised screening of phylogenies for markers of super-spreading events and other features of concern, such as high rates of cluster growth and/or accumulation of novel mutations.AvailabilityAll code is freely available fromhttps://bitbucket.org/plyusnin/clustrace/
robustica: customizable robust independent component analysis
Authors: Anglada-Girotto Miquel , Miravet-Verde Samuel , Serrano Luis , Head Sarah A. 
Published: December 2021

ABSTRACTBackgroundIndependent Component Analysis (ICA) allows the dissection of omic datasets into modules that help to interpret global molecular signatures. The inherent randomness of this algorithm can be overcome by clustering many iterations of ICA together to obtain robust components. Existing algorithms for robust ICA are dependent on the choice of clustering method and on computing a potentially biased and large Pearson distance matrix.ResultsWe presentrobustica, a Python-based package to compute robust independent components with a fully customizable clustering algorithm and distance metric. Here, we exploited its customizability to revisit and optimize robust ICA systematically. From the 6 popular clustering algorithms considered,DBSCANperformed the best at clustering independent components across ICA iterations. After confirming the bias introduced with Pearson distances, we created a subroutine that infers and corrects the components’ signs across ICA iterations to enable using Euclidean distance. Our subroutine effectively corrected the bias while simultaneously increasing the precision, robustness, and memory efficiency of the algorithm. Finally, we show the applicability ofrobusticaby dissecting over 500 tumor samples from low-grade glioma (LGG) patients, where we define a new gene expression module with the key modulators of tumor aggressiveness downregulated uponIDH1mutation.Conclusionrobusticabrings precise, efficient, and customizable robust ICA into the Python toolbox. Through its customizability, we explored how different clustering algorithms and distance metrics can further optimize robust ICA. Then, we showcased howrobusticacan be used to discover gene modules associated with combinations of features of biological interest. Taken together, given the broad applicability of ICA for omic data analysis, we envisionrobusticawill facilitate the seamless computation and integration of robust independent components in large pipelines.Contactmiquel.anglada@crg.eu
Plant morphometry matches beetle diversity: effects of natural adjacent vegetation on grain Amaranth crop under small-holder conditions
Authors: Álvarez Hugo Alejandro , Clemente-Orta Gemma , Carrillo-Ruiz Hortensia , López-Olguín Jesús F. , Jiménez-García Daniel , Morón Miguel A. 
Published: December 2021

AbstractGrain Amaranth, Amaranthus hypochondriacus L., is an emerging arable crop cultivated worldwide. One way to obtain resources from the crop, other than grain, is to grow Amaranths in the dry season and harvest only the leaves. In this environmental condition the response of an Amaranth agroecosystem to the presence of natural and semi-natural habitats or other crops has not been studied yet. We analysed the response of (1) Amaranth morphometry and (2) alpha and beta diversity of beetles to the nearness of adjacent vegetation and natural habitats (such as deciduous forest) at the small-holder conditions. Our results showed that A. hypochondriacus crop plants responded positively to the presence of an ecotone (adjacent vegetation) and the natural habitat (deciduous forest), i.e., A. hypochondriacus plants grew bigger in the section nearest to adjacent vegetation, which was a pattern consistent in time. Moreover, for beetles (considered as a bioindicator group), richness was different amongst the study areas and negatively followed the gradient of perturbation. These results suggest that Amaranth crop is sensitive to the presence of natural and semi-natural habitats but not to other crops in the dry season. In addition, beetles match the response of Amaranth plants. This is the first time that this type of data is recorded in grain Amaranth agroecosystem and it will help to understand the interaction amongst grain Amaranth agroecosystems, biodiversity, and natural adjacent vegetation to boost ecosystem services.
High-speed, multi-Z confocal microscopy for voltage imaging in densely labeled neuronal populations
Authors: Weber Timothy D. , Moya Maria V. , Mertz Jerome , Economo Michael N. 
Published: December 2021

ABSTRACTGenetically encoded voltage indicators (GEVIs) hold great promise for monitoring neuronal population activity, but GEVI imaging in dense neuronal populations remains difficult due to a lack of contrast and/or speed. To address this challenge, we developed a novel confocal microscope that allows simultaneous multiplane imaging with high-contrast at near-kHz rates. This approach enables high signal-to-noise ratio voltage imaging in densely labeled populations and minimizes optical crosstalk during concurrent optogenetic photostimulation.
Predicting proprioceptive cortical anatomy and neural coding with topographic autoencoders
Authors: Grogan Max , Blum Kyle P. , Wu Yufei , Harston J. Alex , Miller Lee E. , Aldo Faisal A. 
Published: December 2021

AbstractProprioception is one of the least understood senses, yet fundamental for the control of movement. Even basic questions of how limb pose is represented in the somatosensory cortex are unclear. We developed a topographic variational autoencoder with lateral connectivity (topo-VAE) to compute a putative cortical map from a large set of natural movement data. Although not fitted to neural data, our model reproduces two sets of observations from monkey centre-out reaching: 1. The shape and velocity dependence of proprioceptive receptive fields in hand-centered coordinates despite the model having no knowledge of arm kinematics or hand coordinate systems. 2. The distribution of neuronal preferred directions (PDs) recorded from multi-electrode arrays. The model makes several testable predictions: 1. Encoding across the cortex has a blob-and-pinwheel-type geometry of PDs. 2. Few neurons will encode just a single joint. Our model provides a principled basis for understanding of sensorimotor representations, and the theoretical basis of neural manifolds, with applications to the restoration of sensory feedback in brain-computer interfaces and the control of humanoid robots.Author SummaryIt is well established that proprioception is essential for effective for motor control, yet our understanding of proprioceptive coding in somatosensory cortex is far behind that of more established sensory modalities such as vision and touch. Here, we use unsupervised learning of a deep neural network imposed with biological constraints to reproduce coding properties of proprioceptive neurons in area 2 of primary somatosensory cortex. With this model, we demonstrate that the tendency for area 2 neurons in close physical proximity to share similar directional tuning can be explained by local topographic organisation driven by Mexican hat lateral effects, a phenomenon that is otherwise unobservable with the spatial resolution of available electrode microarray recordings. This provides, to the best of our knowledge, the first evidence of local topographic organisation in area 2 proprioceptive neurons. We also predict that the structure of proprioceptive receptive fields are typically multi-joint rather than single-joint in nature and provide, to the best of our knowledge, and find that our model best reproduces the tuning properties of neural data when training on natural kinematic recordings, rather than those from a stereotyped task, underlining the importance of training on data that reflect the natural distribution of sensory stimuli.
Cell Surface SARS-CoV-2 Nucleocapsid Protein Modulates Innate and Adaptive Immunity
Authors: López-Muñoz Alberto Domingo , Kosik Ivan , Holly Jaroslav , Yewdell Jonathan W. 
Published: December 2021

ABSTRACTSARS-CoV-2 nucleocapsid protein (N) induces strong antibody and T cell responses. Although considered to be localized in the cytosol, we readily detect N on the surface of live cells. N released by SARS-CoV-2 infected cells or N-expressing transfected cells binds to neighboring cells by electrostatic high-affinity binding to heparan sulfate and heparin, but not other sulfated glycosaminoglycans. N binds with high affinity to 11 human chemokines, including CXCL12β, whose chemotaxis of leukocytes is inhibited by N from SARS-CoV-2, SARS-CoV-1, and MERS CoV. Anti-N Abs bound to the surface of N expressing cells activate Fc receptor-expressing cells. Our findings indicate that cell surface N manipulates innate immunity by sequestering chemokines and can be targeted by Fc expressing innate immune cells. This, in combination with its conserved antigenicity among human CoVs, advances its candidacy for vaccines that induce cross-reactive B and T cell immunity to SARS-CoV-2 variants and other human CoVs, including novel zoonotic strains.
Elastin degradation markers are elevated in never-smokers with past history of prolonged exposure to secondhand tobacco smoke and are inversely associated with their lung function
Authors: Rakic Jelena Mustra , Zeng Siyang , Rohdin-Bibby Linnea , Van Blarigan Erin L , Liu Xingjian , Ma Shuren , Kane John P , Redberg Rita , Turino Gerard M. , Stock Eveline Oestreicher , Arjomandi Mehrdad 
Published: December 2021

ABSTRACTBackgroundProlonged past exposure to secondhand tobacco smoke (SHS) in never-smokers is associated with occult obstructive lung disease and abnormal lung function, in particular reduced diffusing capacity. Previous studies have shown ongoing SHS exposure to be associated with increased elastin degradation markers (EDM) desmosine and isodesmosine.Research QuestionAre EDM levels elevated in persons with remote history of SHS exposure, and are those levels associated with reduced lung function?Study Design and MethodsWe measured the plasma levels of EDM from 193 never-smoking flight attendants with history of remote but prolonged SHS exposure in aircraft cabin and 103 nonsmoking flight attendants or sea-level control participants without history of cabin SHS exposure, and examined those levels versus their lung function with adjustment for covariates. The cabin SHS exposure was estimated based on airline employment history and dates of smoking ban enactment. EDM plasma levels were quantified by high-performance liquid chromatography and tandem mass spectrometry.ResultsThe median [interquartile range; IQR] plasma EDM level for all participants was 0.30 [0.24 to 0.36] ng/mL with a total range of 0.16 to 0.65 ng/mL. Plasma EDM levels were elevated in those with history of exposure to cabin SHS compared to those not exposed (0.33±0.08 vs. 0.26±0.06 ng/mL; age- and sex-adjusted P<0.001). In those with history of cabin SHS-exposure, higher EDM levels were associated with lower diffusing capacity (parameter estimate (PE) [95%CI]=4.2 [0.4 to 8.0] %predicted decrease per 0.1 ng/mL increase in EDM; P=0.030). Furthermore, EDM levels were inversely associated with FEV1, FEV1/FVC, and FEF25-75 (PE [95%CI]=5.8 [2.1 to 9.4], 4.0 [2.2 to 5.7], and 12.5 [5.8 to 19.2]% predicted decrease per 0.1 ng/mL increase in EDM, respectively) (P<0.001).InterpretationProlonged past exposure to SHS, even when remote, is associated with higher systemic elastin degradation markers that in turn is associated with lower lung function and in particular reduced diffusing capacity.
Buffering of transcription rate by mRNA half-life is a conserved feature of Rett syndrome models
Authors: Rodrigues Deivid C. , Mufteev Marat , Yuki Kyoko E. , Narula Ashrut , Wei Wei , Piekna Alina , Liu Jiajie , Pasceri Peter , Rissland Olivia S. , Wilson Michael D. , Ellis James 
Published: December 2021

AbstractModels of MECP2 dysfunction in Rett syndrome (RTT) assume that transcription rate changes directly correlate with altered steady-state mRNA levels. However, limited evidence suggests that transcription rate changes are buffered by poorly understood compensatory post-transcriptional mechanisms. Here we measure transcription rate and mRNA half-life changes in RTT patient neurons using RATE-seq, and reinterpret nuclear and whole-cell RNAseq from Mecp2 mice. Genes are dysregulated by changing transcription rate only or half-life only and are buffered when both are changed. We utilized classifier models to understand the direction of transcription rate changes based on gene-body DNA sequence, and combined frequencies of three dinucleotides were better predictors than contributions by CA and CG. MicroRNA and RNA-Binding Protein (RBP) motifs were enriched in 3’UTRs of genes with half-life changes. Motifs for nuclear localized RBPs were enriched on buffered genes with increased transcription rate. Our findings identify post-transcriptional mechanisms in humans and mice that alter half-life only or buffer transcription rate changes when a transcriptional modulator gene is mutated in a neurodevelopmental disorder.
Idea paper: An envelope model of ecological disturbance
Authors: Friedman Nicholas R. 
Published: December 2021

AbstractDisturbance is common in natural ecosystems, but increasingly defines them. While there are many descriptions for the dynamics of an ecosystem’s response to disturbance, there are few descriptions for the dynamics of the disturbance itself. I describe a novel application of a model based on the production of amplitude envelopes in acoustics and electronic music synthesis, with varying parameters Attack, Decay, Sustain, and Release (ADSR). I show that varying the parameters of the ADSR model is sufficient to produce and vary the qualitative disturbance regimes described by previous authors, and is capable of producing dynamics not previously considered. I tested the utility of the ADSR model by applying it to a logistic growth model. I found that manipulating the attack and release parameters of the ADSR model changes the population dynamics estimated by these models. This implies that responses to disturbance are determined not only by the resilience and resistance of the ecological system, but also the dynamics of the disturbance itself. My hope is that the ADSR model will prove useful to researchers in either describing disturbances in long-term ecological data, or in producing disturbances for simulations or experiments.
Acetyltransferases GCN5 and PCAF are required for B lymphocyte maturation in mice
Authors: Oksenych Valentyn , Su Dan , Daniel Jeremy A. 
Published: December 2021

AbstractB lymphocyte development has two DNA recombination processes: V(D)J recombination of the immunoglobulin (Igh) gene variable region and class switching of theIghconstant regions from IgM to IgG, IgA, or IgE. V(D)J recombination is required for successful maturation of B cells from pro-B to pre-B to immature-B and then to mature B cells in the bone marrow. CSR occurs outside of the bone marrow when mature B cells migrate to peripheral lymphoid organs, such as spleen and lymph nodes. Both V(D)J recombination and CSR depend on an open chromatin state that makes DNA accessible to specific enzymes, recombination activating gene (RAG), and activation-induced cytidine deaminase (AID). Acetyltransferases GCN5 and PCAF possess redundant functions acetylating histone H3 lysine 9 (H3K9). Here, we generated a mouse model that lacks both GCN5 and PCAF in B cells. We found that double-deficient mice possess low levels of mature B cells in the bone marrow and peripheral organs, an accumulation of pro-B cells in bone marrow, and reduced CSR levels. We conclude that both GCN5 and PCAF are required for B cell developmentin vivo.
Transcriptional and Cytotoxic Responses of Human Intestinal Organoids to Interferon Types I, II, and III
Authors: Constant David A. , Van Winkle Jacob A. , VanderHoek Eden , Dekker Simone E. , Sofia M. Anthony , Regner Emilie , Modiano Nir , Tsikitis V. Liana , Nice Timothy J. 
Published: December 2021

AbstractThe three types of interferon (IFN) have roles in antimicrobial immunity and inflammation that must be properly balanced to maintain tissue homeostasis. For example, IFNs are elevated in the context of inflammatory bowel disease and may synergize with inflammatory cytokines such as tumor necrosis factor alpha (TNFα) to promote tissue damage. Prior studies suggest that in mouse intestinal epithelial cells (IECs), type III IFNs are preferentially produced during viral infections and are less cytotoxic than type I IFN. Here, we generated human IEC organoid lines from biopsies of ileum, ascending colon, and sigmoid colon of three healthy subjects to establish the baseline responses of normal human IECs to types I, II, and III IFN. We found that all IFN types elicited responses that were qualitatively consistent across intestinal biopsy sites. However, IFN types differed in magnitude of STAT1 phosphorylation and identity of genes in their downstream transcriptional programs. Specifically, there was a core transcriptional module shared by IFN types, but types I and II IFN stimulated unique transcriptional modules beyond this core gene signature. The transcriptional modules of type I and II IFN included pro-apoptotic genes, and expression of these genes correlated with potentiation of TNFα cytotoxicity. These data define the response profiles of healthy human IEC organoids across IFN types, and suggest that cytotoxic effects mediated by TNFα in inflamed tissues may be amplified by a simultaneous high-magnitude IFN response.