bluuebunny/crossref_metadata_2025_split huggingface dataset:
Robust expansion of HIV CAR T cells following antigen boosting in ART-suppressed nonhuman primates
Authors: Rust Blake J. , Kean Leslie S. , Colonna Lucrezia , Brandenstein Katherine E. , Poole Nikhita H. , Obenza Willimark , Enstrom Mark R. , Maldini Colby R. , Ellis Gavin I. , Fennessey Christine M. , Huang Meei-Li , Keele Brandon F. , Jerome Keith R. , Riley James L. , Kiem Hans-Peter , Peterson Christopher W. 
Published: July 2020

AbstractChimeric antigen receptor (CAR) T cells targeting CD19+ hematologic malignancies have rapidly emerged as a promising, novel therapy. In contrast, results from the few CAR T-cell studies for infectious diseases such as HIV-1 have been less convincing. These challenges are likely due to the low level of antigen present in antiretroviral therapy (ART)-suppressed patients in contrast to those with hematologic malignancies. Using our well-established nonhuman primate model of ART-suppressed HIV-1 infection, we tested strategies to overcome these limitations and challenges. We first optimized CAR T-cell production to maintain central memory subsets, consistent with current clinical paradigms. We hypothesized that additional exogenous antigen might be required in an ART-suppressed setting to aid expansion and persistence of CAR T cells. Thus, we studied 4 simian/HIV-infected, ART-suppressed rhesus macaques infused with virus-specific CD4CAR T cells, followed by supplemental infusion of cell-associated HIV-1 envelope (Env). Env boosting led to significant and unprecedented expansion of virus-specific CAR+ T cells in vivo; after ART treatment interruption, viral rebound was significantly delayed compared with controls (P = .014). In 2 animals with declining CAR T cells, rhesusized anti–programmed cell death protein 1 (PD-1) antibody was administered to reverse PD-1–dependent immune exhaustion. Immune checkpoint blockade triggered expansion of exhausted CAR T cells and concordantly lowered viral loads to undetectable levels. These results show that supplemental cell-associated antigen enables robust expansion of CAR T cells in an antigen-sparse environment. To our knowledge, this is the first study to show expansion of virus-specific CAR T cells in infected, suppressed hosts, and delay/control of viral recrudescence.
CAR-modified memory-like NK cells exhibit potent responses to NK-resistant lymphomas
Authors: Gang Margery , Marin Nancy D. , Wong Pamela , Neal Carly C. , Marsala Lynne , Foster Mark , Schappe Timothy , Meng Wei , Tran Jennifer , Schaettler Maximilian , Davila Marco , Gao Feng , Cashen Amanda F. , Bartlett Nancy L. , Mehta-Shah Neha , Kahl Brad S. , Kim Miriam Y. , Cooper Matthew L. , DiPersio John F. , Berrien-Elliott Melissa M. , Fehniger Todd A. 
Published: July 2020

Abstract
Natural killer (NK) cells are a promising cellular immunotherapy for cancer. Cytokine-induced memory-like (ML) NK cells differentiate after activation with interleukin-12 (IL-12), IL-15, and IL-18, exhibit potent antitumor responses, and safely induce complete remissions in patients with leukemia. However, many cancers are not fully recognized via NK cell receptors. Chimeric antigen receptors (CARs) have been used to enhance tumor-specific recognition by effector lymphocytes. We hypothesized that ML differentiation and CAR engineering would result in complementary improvements in NK cell responses against NK-resistant cancers. To test this idea, peripheral blood ML NK cells were modified to express an anti-CD19 CAR (19-CAR-ML), which displayed significantly increased interferon γ production, degranulation, and specific killing against NK-resistant lymphoma lines and primary targets compared with nonspecific control CAR-ML NK cells or conventional CAR NK cells. The 19-CAR and ML responses were synergistic and CAR specific and required immunoreceptor tyrosine-based activation motif signaling. Furthermore, 19-CAR-ML NK cells generated from lymphoma patients exhibited improved responses against their autologous lymphomas. 19-CAR-ML NK cells controlled lymphoma burden in vivo and improved survival in human xenograft models. Thus, CAR engineering of ML NK cells enhanced responses against resistant cancers and warrants further investigation, with the potential to broaden ML NK cell recognition against a variety of NK cell–resistant tumors.
Development of a clinical decision support system for severity risk prediction and triage of COVID-19 patients at hospital admission: an international multicentre study
Authors: Wu Guangyao , Yang Pei , Xie Yuanliang , Woodruff Henry C. , Rao Xiangang , Guiot Julien , Frix Anne-Noelle , Louis Renaud , Moutschen Michel , Li Jiawei , Li Jing , Yan Chenggong , Du Dan , Zhao Shengchao , Ding Yi , Liu Bin , Sun Wenwu , Albarello Fabrizio , D'Abramo Alessandra , Schininà Vincenzo , Nicastri Emanuele , Occhipinti Mariaelena , Barisione Giovanni , Barisione Emanuela , Halilaj Iva , Lovinfosse Pierre , Wang Xiang , Wu Jianlin , Lambin Philippe 
Published: July 2020

BackgroundThe outbreak of coronavirus disease 2019 (COVID-19) has globally strained medical resources and caused significant mortality.ObjectiveTo develop and validate a machine-learning model based on clinical features for severity risk assessment and triage for COVID-19 patients at hospital admission.Method725 patients were used to train and validate the model. This included a retrospective cohort from Wuhan, China of 299 hospitalised COVID-19 patients from 23 December 2019 to 13 February 2020, and five cohorts with 426 patients from eight centres in China, Italy and Belgium from 20 February 2020 to 21 March 2020. The main outcome was the onset of severe or critical illness during hospitalisation. Model performances were quantified using the area under the receiver operating characteristic curve (AUC) and metrics derived from the confusion matrix.ResultsIn the retrospective cohort, the median age was 50 years and 137 (45.8%) were male. In the five test cohorts, the median age was 62 years and 236 (55.4%) were male. The model was prospectively validated on five cohorts yielding AUCs ranging from 0.84 to 0.93, with accuracies ranging from 74.4% to 87.5%, sensitivities ranging from 75.0% to 96.9%, and specificities ranging from 55.0% to 88.0%, most of which performed better than the pneumonia severity index. The cut-off values of the low-, medium- and high-risk probabilities were 0.21 and 0.80. The online calculators can be found atwww.covid19risk.ai.ConclusionThe machine-learning model, nomogram and online calculator might be useful to access the onset of severe and critical illness among COVID-19 patients and triage at hospital admission.
Osteogenesis of adipose-derived stem cells from patients with glucose metabolism disorders
Authors: Skubis-Sikora Aleksandra , Sikora Bartosz , Witkowska Agnieszka , Mazurek Urszula , Gola Joanna 
Published: July 2020

Abstract
Background
Adipose derived stem cells (ADSCs) are clinically widely used somatic stem cells obtained from white adipose tissue. They are characterized by ability to differentiate e.g. into osteoblasts and might successfully regenerate bone tissue in fracture repair. However, the main problem of somatic stem cells is a documented influence of various diseases, drugs or age which can inhibit cells activity. Therefore, in the present study, we investigated the influence of insulin resistance (IR) and type 2 diabetes (T2D) on the proliferation and differentiation potential of ADSCs.

Methods
The fat from subcutaneous abdominal adipose tissue was acquired by lipoaspiration from 23 voluntary participants, divided into three groups: with diabetes type 2, with insulin resistance and control healthy donors. The proliferative potential was analyzed by cell cytotoxicity assays and by mRNA expression of genes connected with proliferation. Flow cytometry was done for identifying proteins characteristic for mesenchymal stem cells and an analysis of osteogenic differentiation potential based on the assessment of osteogenic markers by real time RT-qPCR, and the evaluation of calcium deposition were also performed.

Results
The results showed that diabetes type 2 lowered the activity of ADSCs in proliferation assays and changed their phenotypical characteristics. Interestingly, we observed differences in the proliferation potential of ADSCs in patients with insulin resistance, which is often the first phase of diabetes, compared to the control. It might suggest that insulin resistance, early-stage T2D, alters the activity of cells. Moreover, expression of osteogenesis markers was higher in cells from T2D patients than in cells from patients with IR and control.

Conclusion
We conclude that type 2 diabetes changes the activity of stem cells, and insulin resistance influences on the proliferation of ADSCs.
The effects of cognitive-motor training interventions on executive functions in older people: a systematic review and meta-analysis
Authors: Wollesen Bettina , Wildbredt Alicia , van Schooten Kimberley S. , Lim Mei Ling , Delbaere Kim 
Published: July 2020

Abstract
Background
Ageing is associated with physical and cognitive decline, affecting independence and quality of life in older people. Recent studies show that in particular executive functions are important for daily-life function and mobility. This systematic review investigated the effectiveness of cognitive-motor training including exergaming on executive function (EF, set-shifting, working memory, inhibitory control) in healthy older people.

Methods
An electronic database search for randomised controlled trials (RCT), controlled clinical trials (CCT) and parallel group trials was performed using MEDLINE, EMBASE, and PsychINFO following PRISMA guidelines. Inclusion criteria were: (1) community-dwelling participants > 60 years without a medical condition or medical treatment, (2) reporting at least one cognitive-motor intervention while standing or walking, (3) use of dual-task interventions using traditional methods or modern technology to deliver a cognitive-motor task, (4) inclusion of at least one cognitive outcome. The PEDro scale was used for quality assessment.

Results
A total of 1557 studies were retrieved, of which 25 studies were included in this review. Eleven studies used a technology-based dual-task intervention, while 14 trials conducted a general cognitive-motor training. The age range of the cohort was 69 to 87 years. The interventions demonstrated positive effects on global cognitive function [mean difference 0.6, 95% CI 0.29–0.90] and inhibitory control [mean difference 0.61, 95% CI 0.28–0.94]. Effects were heterogeneous (I2 range: 60–95) and did not remain after a sensitivity analysis. Processing speed and dual-task costs also improved, but meta-analysis was not possible.

Conclusion
Cognitive-motor and technology-based interventions had a positive impact on some cognitive functions. Dual-task interventions led to improvements of domains related global cognitive functions and inhibitory control. Likewise, technology-based exergame interventions improved functions related to processing speed, attentional and inhibitory control. Training interventions with a certain level of exercise load such as progression in difficulty and task specificity were more effective to gain task-related adaptations on cognitive functions.
Re-Analysis of 16S Amplicon Sequencing Data Reveals Soil Microbial Population Shifts in Rice Fields under Drought Condition
Authors: Jang Seok-Won , Yoou Myeong-Hyun , Hong Woo-Jong , Kim Yeon-Ju , Lee Eun-Jin , Jung Ki-Hong 
Published: July 2020

AbstractRice (Oryza sativa. L) has been intensively studied to ensure a stable global supply of this commodity in the face of rapid global climate change. A critical factor that decreases crop yield is drought, which has been analyzed in various ways through many researches. Microbiome-based studies of rice investigate the symbiosis between rice and bacteria, which has been proposed as a way to overcome problems caused by drought. Several rice-associated metagenomic profiles obtained under drought conditions have been reported since the advent of next generation sequencing (NGS) technology. To elucidate the future diversity of plants and microorganisms and to promote sustainable agriculture, we reanalyzed 64 of the publicly available 16S amplicon sequencing data produced under drought condition. In the process of integrating data sets, however, we found an inconsistency that serves as a bottleneck for microbiome-based sustainability research. While this report provides clues about the composition of the microbiome under the drought conditions, the results are affected by differences in the location of the experiments, sampling conditions, and analysis protocols. Re-analysis of amplicon sequencing data of the soil microbiome in rice fields suggests that microbial composition shifts in response to drought condition and the presence of plants. Among the bacteria involved, the phylum Proteobacteria appears to play the most important role in the survival of rice under drought condition.
DiNeR: a Differential graphical model for analysis of co-regulation Network Rewiring
Authors: Zhang Jing , Liu Jason , Lee Donghoon , Lou Shaoke , Chen Zhanlin , Gürsoy Gamze , Gerstein Mark 
Published: July 2020

Abstract
Background
During transcription, numerous transcription factors (TFs) bind to targets in a highly coordinated manner to control the gene expression. Alterations in groups of TF-binding profiles (i.e. “co-binding changes”) can affect the co-regulating associations between TFs (i.e. “rewiring the co-regulator network”). This, in turn, can potentially drive downstream expression changes, phenotypic variation, and even disease. However, quantification of co-regulatory network rewiring has not been comprehensively studied.

Results
To address this, we propose DiNeR, a computational method to directly construct a differential TF co-regulation network from paired disease-to-normal ChIP-seq data. Specifically, DiNeR uses a graphical model to capture the gained and lost edges in the co-regulation network. Then, it adopts a stability-based, sparsity-tuning criterion -- by sub-sampling the complete binding profiles to remove spurious edges -- to report only significant co-regulation alterations. Finally, DiNeR highlights hubs in the resultant differential network as key TFs associated with disease. We assembled genome-wide binding profiles of 104 TFs in the K562 and GM12878 cell lines, which loosely model the transition between normal and cancerous states in chronic myeloid leukemia (CML). In total, we identified 351 significantly altered TF co-regulation pairs. In particular, we found that the co-binding of the tumor suppressor BRCA1 and RNA polymerase II, a well-known transcriptional pair in healthy cells, was disrupted in tumors. Thus, DiNeR successfully extracted hub regulators and discovered well-known risk genes.

Conclusions
Our method DiNeR makes it possible to quantify changes in co-regulatory networks and identify alterations to TF co-binding patterns, highlighting key disease regulators. Our method DiNeR makes it possible to quantify changes in co-regulatory networks and identify alterations to TF co-binding patterns, highlighting key disease regulators.
Genomic characterization of the most barotolerant Listeria monocytogenes RO15 strain compared to reference strains used to evaluate food high pressure processing
Authors: Duru Ilhan Cem , Andreevskaya Margarita , Laine Pia , Rode Tone Mari , Ylinen Anne , Løvdal Trond , Bar Nadav , Crauwels Peter , Riedel Christian U. , Bucur Florentina Ionela , Nicolau Anca Ioana , Auvinen Petri 
Published: July 2020

AbstractBackgroundHigh pressure processing (HPP; i.e. 100–600 MPa pressure depending on product) is a non-thermal preservation technique adopted by the food industry to decrease significantly foodborne pathogens, includingListeria monocytogenes, from food.However, susceptibility towards pressure differs among diverse strains ofL. monocytogenesand it is unclear if this is due to their intrinsic characteristics related to genomic content. Here, we tested the barotolerance of 10 differentL. monocytogenesstrains, from food and food processing environments and widely used reference strains including clinical isolate, to pressure treatments with 400 and 600 MPa. Genome sequencing and genome comparison of the testedL. monocytogenesstrains were performed to investigate the relation between genomic profile and pressure tolerance.ResultsNone of the tested strains were tolerant to 600 MPa. A reduction of more than 5 log10was observed for all strains after 1 min 600 MPa pressure treatment.L. monocytogenesstrain RO15 showed no significant reduction in viable cell counts after 400 MPa for 1 min and was therefore defined as barotolerant. Genome analysis of so far unsequencedL. monocytogenesstrain RO15, 2HF33, MB5, AB199, AB120, C7, and RO4 allowed us to compare the gene content of all strains tested. This revealed that the three most pressure tolerant strains had more than one CRISPR system with self-targeting spacers. Furthermore, several anti-CRISPR genes were detected in these strains. Pan-genome analysis showed that 10 prophage genes were significantly associated with the three most barotolerant strains.ConclusionsL. monocytogenesstrain RO15 was the most pressure tolerant among the selected strains. Genome comparison suggests that there might be a relationship between prophages and pressure tolerance inL. monocytogenes.
Dual indexed library design enables compatibility of in-Drop single-cell RNA-sequencing with exAMP chemistry sequencing platforms
Authors: Southard-Smith Austin N. , Simmons Alan J. , Chen Bob , Jones Angela L. , Ramirez Solano Marisol A. , Vega Paige N. , Scurrah Cherie’ R. , Zhao Yue , Brenan Michael J. , Xuan Jiekun , Shrubsole Martha J. , Porter Ely B. , Chen Xi , Brenan Colin J. H. , Liu Qi , Quigley Lauren N. M. , Lau Ken S. 
Published: July 2020

Abstract
Background
The increasing demand of single-cell RNA-sequencing (scRNA-seq) experiments, such as the number of experiments and cells queried per experiment, necessitates higher sequencing depth coupled to high data quality. New high-throughput sequencers, such as the Illumina NovaSeq 6000, enables this demand to be filled in a cost-effective manner. However, current scRNA-seq library designs present compatibility challenges with newer sequencing technologies, such as index-hopping, and their ability to generate high quality data has yet to be systematically evaluated.

Results
Here, we engineered a dual-indexed library structure, called TruDrop, on top of the inDrop scRNA-seq platform to solve these compatibility challenges, such that TruDrop libraries and standard Illumina libraries can be sequenced alongside each other on the NovaSeq. On scRNA-seq libraries, we implemented a previously-documented countermeasure to the well-described problem of index-hopping, demonstrated significant improvements in base-calling accuracy on the NovaSeq, and provided an example of multiplexing twenty-four scRNA-seq libraries simultaneously. We showed favorable comparisons in transcriptional diversity of TruDrop compared with prior inDrop libraries.

Conclusions
Our approach enables cost-effective, high throughput generation of sequencing data with high quality, which should enable more routine use of scRNA-seq technologies.
Shedding light on cashmere goat hair follicle biology: from morphology analyses to transcriptomic landascape
Authors: Nocelli Cristina , Cappelli Katia , Capomaccio Stefano , Pascucci Luisa , Mercati Francesca , Pazzaglia Irene , Mecocci Samanta , Antonini Marco , Renieri Carlo 
Published: July 2020

AbstractBackgroundCashmere goat is known for its precious undercoat. Being photoperiod-dictated, cashmere growth has been studied focusing mainly on hair follicle cycle phases (anagen, catagen and telogen). An accurate molecular knowledge of the goat hair follicle cycle, disentangling gene expression changes during phases and recognizing timing boundaries, could be useful to improve cashmere goat management and ultimately cashmere production.ResultsTo better describe goat’s hair follicle transcriptome we applied RNA-sequencing to isolated hair follicles from five Italian cashmere goats, during the anagen and catagen phase, identifying total of 214 differentially expressed genes (DEGs): 97 were up-regulated while 117 were down-regulated in catagen with respect to anagen. Gene Ontology and pathway analysis were performed. We detected 144 significant pathways spanning from estrogen, pluripotency of stem cells, thermogenesis and fatty acid metabolism that were strongly expressed during the hair follicle phases analysed. Finally, we validated promising DEGs by RT-qPCR in the same set of samples as well as in hair follicles and entire skin biopsies of another cashmere goats cohort accounting for early anagen, anagen, early catagen, and catagen phases.ConclusionsAs in the isolated hair follicles, some target genes were homogenously modulated during the four hair follicle phases. Ceruloplasmin (CP) and Keratin 4 (K4), confirmed their clear cut expression between growing and resting phase. In fact,K4was almost absent in catagen phases whileCPwas barely expressed in anagen phases. In particular, the strong expression ofK4in early anagen makes it an eligible marker to track the beginning of a new hair cycle, and therefore defining the optimum time for cashmere harvesting.
Pleiotropic effects of RsmA and RsmE proteins in Pseudomonas fluorescens 2P24
Authors: Zhang Yang , Zhang Bo , Wu Haiyan , Wu Xiaogang , Yan Qing , Zhang Li-Qun 
Published: July 2020

Abstract
Background
Pseudomonas fluorescens 2P24 is a rhizosphere bacterium that produces 2,4-diacetyphloroglucinol (2,4-DAPG) as the decisive secondary metabolite to suppress soilborne plant diseases. The biosynthesis of 2,4-DAPG is strictly regulated by the RsmA family proteins RsmA and RsmE. However, mutation of both of rsmA and rsmE genes results in reduced bacterial growth.

Results
In this study, we showed that overproduction of 2,4-DAPG in the rsmA rsmE double mutant influenced the growth of strain 2P24. This delay of growth could be partially reversal when the phlD gene was deleted or overexpression of the phlG gene encoding the 2,4-DAPG hydrolase in the rsmA rsmE double mutant. RNA-seq analysis of the rsmA rsmE double mutant revealed that a substantial portion of the P. fluorescens genome was regulated by RsmA family proteins. These genes are involved in the regulation of 2,4-DAPG production, cell motility, carbon metabolism, and type six secretion system.

Conclusions
These results suggest that RsmA and RsmE are the important regulators of genes involved in the plant-associated strain 2P24 ecologic fitness and operate a sophisticated mechanism for fine-tuning the concentration of 2,4-DAPG in the cells.