bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes following hematopoietic stem cell transplantation in patients treated with standard chemotherapy with or without gemtuzumab ozogamicin for acute myeloid leukemia
Authors: Pautas Cécile , Raffoux Emmanuel , Lambert Juliette , Legrand Ollivier , Chantepie Sylvain , Gastaud Lauris , Marolleau Jean-Pierre , Thomas Xavier , Turlure Pascal , Benner Rebecca J. , Vandendries Erik , Gogat Karïn , Dombret Hervé , Castaigne Sylvie 
Published: February 2021

AbstractThe phase 3 ALFA-0701 trial demonstrated improved outcomes with fractionated-dose gemtuzumab ozogamicin (GO) combined with standard chemotherapy vs. standard chemotherapy alone in adults with de novo acute myeloid leukemia (AML). We examined post-transplant outcomes and occurrence of hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) in patients who received hematopoietic stem cell transplantation (HSCT) as follow-up therapy in ALFA-0701. Patients aged 50–70 years were randomized to standard chemotherapy with or without GO (3 mg/m2 on days 1, 4, and 7 of induction and day 1 on each of two consolidation courses). Allogeneic HSCT was recommended for patients in first complete remission with matched (related or unrelated) donor, except those with core-binding factor AML or normal karyotype and either NPM1+/FLT3-ITDwt or CEBPA+ AML. Eighty-five patients (GO: n = 32; control: n = 53) received HSCT in first complete remission or after relapse/primary induction failure. Three patients (GO: n = 2; control: n = 1 [received GO as follow-up therapy]) developed VOD/SOS after HSCT or conditioning. Post-transplant survival, non-relapse mortality, and relapse were not different between arms. Results indicate fractionated-dose GO as part of induction and consolidation chemotherapy for AML does not induce excess post-transplant VOD/SOS or mortality and thus does not preclude the use of HSCT as consolidation treatment.
Pharmaceutical immunoglobulin G impairs anti-carcinoma activity of oxaliplatin in colon cancer cells
Authors: Shang Yuru , Zhang Xianbin , Lu Lili , Jiang Ke , Krohn Mathias , Matschos Stephanie , Mullins Christina Susanne , Vollmar Brigitte , Zechner Dietmar , Gong Peng , Linnebacher Michael 
Published: February 2021

Abstract
Background
Recent evidence proves that intravenous human immunoglobulin G (IgG) can impair cancer cell viability. However, no study evaluated whether IgG application benefits cancer patients receiving chemotherapeutics.

Methods
Influence of pharmaceutical-grade human IgG on the viability of a series of patient-derived colon cancer cell lines with and without chemotherapeutic intervention was determined. Cell death was analysed flow cytometrically. In addition, the influence of oxaliplatin and IgG on the ERK1/2-signalling pathway was evaluated by western blots.

Results
We evaluated the effects of pharmaceutical IgG, such as PRIVIGEN® IgG and Tonglu® IgG, in combination with chemotherapeutics. We did not observe any significant effects of IgG on tumour cell viability directly; however, human IgG significantly impaired the anti-tumoral effects of oxaliplatin. Primary cancer cell lines express IgG receptors and accumulate human IgG intracellularly. Moreover, while oxaliplatin induced the activation of ERK1/2, the pharmaceutical IgG inhibited ERK1/2 activity.

Conclusions
The present study demonstrates that pharmaceutical IgG, such as PRIVIGEN® IgG and Tonglu® IgG, can impair the anti-carcinoma activity of oxaliplatin. These data strongly suggest that therapeutic IgG as co-medication might have harmful side effects in cancer patients. The clinical significance of these preclinical observations absolutely advises further preclinical, as well as epidemiological and clinical research.
A genome-wide association study for gut metagenome in Chinese adults illuminates complex diseases
Authors: Liu Xiaomin , Tang Shanmei , Zhong Huanzi , Tong Xin , Jie Zhuye , Ding Qiuxia , Wang Dan , Guo Ruidong , Xiao Liang , Xu Xun , Yang Huanming , Wang Jian , Zong Yang , Liu Weibin , Liu Xiao , Zhang Yong , Brix Susanne , Kristiansen Karsten , Hou Yong , Jia Huijue , Zhang Tao 
Published: February 2021

AbstractThe gut microbiome has been established as a key environmental factor to health. Genetic influences on the gut microbiome have been reported, yet, doubts remain as to the significance of genetic associations. Here, we provide shotgun data for whole genome and whole metagenome from a Chinese cohort, identifying no <20% genetic contribution to the gut microbiota. Using common variants-, rare variants-, and copy number variations-based association analyses, we identified abundant signals associated with the gut microbiome especially in metabolic, neurological, and immunological functions. The controversial concept of enterotypes may have a genetic attribute, with the top two loci explaining 11% of the Prevotella–Bacteroides variances. Stratification according to gender led to the identification of differential associations in males and females. Our two-stage metagenome genome-wide association studies on a total of 1295 individuals unequivocally illustrates that neither microbiome nor GWAS studies could overlook one another in our quest for a better understanding of human health and diseases.
Highly efficient neuronal gene knockout in vivo by CRISPR-Cas9 via neonatal intracerebroventricular injection of AAV in mice
Authors: Hana Sam , Peterson Michael , McLaughlin Helen , Marshall Eric , Fabian Attila J. , McKissick Olivia , Koszka Kathryn , Marsh Galina , Craft Michael , Xu Shanqin , Sorets Alexander , Torregrosa Tess , Sun Chao , Henderson Chris E. , Lo Shih-Ching 
Published: February 2021

AbstractCRISPR-Cas systems have emerged as a powerful tool to generate genetic models for studying normal and diseased central nervous system (CNS). Targeted gene disruption at specific loci has been demonstrated successfully in non-dividing neurons. Despite its simplicity, high specificity and low cost, the efficiency of CRISPR-mediated knockout in vivo can be substantially impacted by many parameters. Here, we used CRISPR-Cas9 to disrupt the neuronal-specific gene, NeuN, and optimized key parameters to achieve effective gene knockout broadly in the CNS in postnatal mice. Three cell lines and two primary neuron cultures were used to validate the disruption of NeuN by single-guide RNAs (sgRNA) harboring distinct spacers and scaffold sequences. This triage identified an optimal sgRNA design with the highest NeuN disruption in in vitro and in vivo systems. To enhance CRISPR efficiency, AAV-PHP.B, a vector with superior neuronal transduction, was used to deliver this sgRNA in Cas9 mice via neonatal intracerebroventricular (ICV) injection. This approach resulted in 99.4% biallelic indels rate in the transduced cells, leading to greater than 70% reduction of total NeuN proteins in the cortex, hippocampus and spinal cord. This work contributes to the optimization of CRISPR-mediated knockout and will be beneficial for fundamental and preclinical research.
The effects of drift and selection on latitudinal genetic variation in Scandinavian common toads (Bufo bufo) following postglacial recolonisation
Authors: Thörn Filip , Rödin-Mörch Patrik , Cortazar-Chinarro Maria , Richter-Boix Alex , Laurila Anssi , Höglund Jacob 
Published: February 2021

AbstractClinal variation is paramount for understanding the factors shaping genetic diversity in space and time. During the last glacial maximum, northern Europe was covered by glacial ice that rendered the region uninhabitable for most taxa. Different evolutionary processes during and after the recolonisation of this area from different glacial refugia have affected the genetic landscape of the present day European flora and fauna. In this study, we focus on the common toad (Bufo bufo) in Sweden and present evidence suggesting that these processes have resulted in two separate lineages of common toad, which colonised Sweden from two directions. Using ddRAD sequencing data for demographic modelling, structure analyses, and analysis of molecular variance (AMOVA), we provide evidence of a contact zone located between Uppland and Västerbotten in central Sweden. Genetic diversity was significantly higher in southern Sweden compared to the north, in accordance with a pattern of decreased genetic diversity with increasing distance from glacial refugia. Candidate genes under putative selection are identified through outlier detection and gene–environment association methods. We provide evidence of divergent selection related to stress response and developmental processes in these candidate genes. The colonisation of Sweden by two separate lineages may have implications for how future conservation efforts should be directed by identifying management units and putative local adaptations.
Germline mutational spectrum in Armenian breast cancer patients suspected of hereditary breast and ovarian cancer
Authors: Moradian Mike M. , Babikyan Davit T. , Markarian Sione , Petrosyan Jonny G. , Avanesian Nare , Arutunyan Tereza , Sarkisian Tamara F. 
Published: February 2021

AbstractHereditary breast and ovarian cancer (HBOC) can be identified by genetic testing of cancer-causing genes. In this study, we identified a spectrum of genetic variations among 76 individuals of Armenian descent either with a family history of cancer or breast cancer before the age of 40. We screened 76 suspected HBOC patients and family members as well as four healthy controls using a targeted and hereditary comprehensive cancer panel (127 genes). We found 26 pathogenic (path) and 6 likely pathogenic (LPath)variants in 6 genes in 44 patients (58%); these variants were found in BRCA1 (17), BRCA2 (19), CHEK2 (4), PALB2 (2), and NBN (1). A few different variants were found in unrelated individuals; most notably, variant p.Trp1815Ter in the BRCA1 gene occurred in four unrelated patients. We did not find any known significant variants in five patients. Comprehensive cancer panel testing revealed pathogenic variants in cancer genes other than BRCA1 and BRCA2, suggesting that testing only BRCA1 and BRCA2 would have missed 8 out of 44 suspected HBOC patients (18%). These data also confirm that a comprehensive cancer panel testing approach could be an appropriate way to identify most of the variants associated with hereditary breast cancer.
CAR-T cell-mediated depletion of immunosuppressive tumor-associated macrophages promotes endogenous antitumor immunity and augments adoptive immunotherapy
Authors: Rodriguez-Garcia Alba , Lynn Rachel C. , Poussin Mathilde , Eiva Monika A. , Shaw Lauren C. , O’Connor Roddy S. , Minutolo Nicholas G. , Casado-Medrano Victoria , Lopez Gonzalo , Matsuyama Takami , Powell Daniel J. 
Published: February 2021

AbstractThe immunosuppressive tumor microenvironment (TME) represents a major barrier for effective immunotherapy. Tumor-associated macrophages (TAMs) are highly heterogeneous and plastic cell components of the TME which can either promote tumor progression (M2-like) or boost antitumor immunity (M1-like). Here, we demonstrate that a subset of TAMs that express folate receptor β (FRβ) possess an immunosuppressive M2-like profile. In syngeneic tumor mouse models, chimeric antigen receptor (CAR)-T cell-mediated selective elimination of FRβ+TAMs in the TME results in an enrichment of pro-inflammatory monocytes, an influx of endogenous tumor-specific CD8+T cells, delayed tumor progression, and prolonged survival. Preconditioning of the TME with FRβ-specific CAR-T cells also improves the effectiveness of tumor-directed anti-mesothelin CAR-T cells, while simultaneous co-administration of both CAR products does not. These results highlight the pro-tumor role of FRβ+TAMs in the TME and the therapeutic implications of TAM-depleting agents as preparative adjuncts to conventional immunotherapies that directly target tumor antigens.
Reward-related choices determine information timing and flow across macaque lateral prefrontal cortex
Authors: Tang Hua , Bartolo Ramon , Averbeck Bruno B. 
Published: February 2021

AbstractPrefrontal cortex is critical for cognition. Although much is known about the representation of cognitive variables in the prefrontal cortex, much less is known about the spatio-temporal neural dynamics that underlie cognitive operations. In the present study, we examined information timing and flow across the lateral prefrontal cortex (LPFC), while monkeys carried out a two-armed bandit reinforcement learning task in which they had to learn to select rewarding actions or rewarding objects. When we analyzed signals independently within subregions of the LPFC, we found a task-specific, caudo-rostral gradient in the strength and timing of signals related to chosen objects and chosen actions. In addition, when we characterized information flow among subregions, we found that information flow from action to object representations was stronger from the dorsal to ventral LPFC, and information flow from object to action representations was stronger from the ventral to dorsal LPFC. The object to action effects were more pronounced in object blocks, and also reflected learning specifically in these blocks. These results suggest anatomical segregation followed by the rapid integration of information within the LPFC.
Evidence for SARS-CoV-2 related coronaviruses circulating in bats and pangolins in Southeast Asia
Authors: Wacharapluesadee Supaporn , Tan Chee Wah , Maneeorn Patarapol , Duengkae Prateep , Zhu Feng , Joyjinda Yutthana , Kaewpom Thongchai , Chia Wan Ni , Ampoot Weenassarin , Lim Beng Lee , Worachotsueptrakun Kanthita , Chen Vivian Chih-Wei , Sirichan Nutthinee , Ruchisrisarod Chanida , Rodpan Apaporn , Noradechanon Kirana , Phaichana Thanawadee , Jantarat Niran , Thongnumchaima Boonchu , Tu Changchun , Crameri Gary , Stokes Martha M. , Hemachudha Thiravat , Wang Lin-Fa 
Published: February 2021

AbstractAmong the many questions unanswered for the COVID-19 pandemic are the origin of SARS-CoV-2 and the potential role of intermediate animal host(s) in the early animal-to-human transmission. The discovery of RaTG13 bat coronavirus in China suggested a high probability of a bat origin. Here we report molecular and serological evidence of SARS-CoV-2 related coronaviruses (SC2r-CoVs) actively circulating in bats in Southeast Asia. Whole genome sequences were obtained from five independent bats (Rhinolophus acuminatus) in a Thai cave yielding a single isolate (named RacCS203) which is most related to the RmYN02 isolate found in Rhinolophus malayanus in Yunnan, China. SARS-CoV-2 neutralizing antibodies were also detected in bats of the same colony and in a pangolin at a wildlife checkpoint in Southern Thailand. Antisera raised against the receptor binding domain (RBD) of RmYN02 was able to cross-neutralize SARS-CoV-2 despite the fact that the RBD of RacCS203 or RmYN02 failed to bind ACE2. Although the origin of the virus remains unresolved, our study extended the geographic distribution of genetically diverse SC2r-CoVs from Japan and China to Thailand over a 4800-km range. Cross-border surveillance is urgently needed to find the immediate progenitor virus of SARS-CoV-2.
LC-MS based plant metabolic profiles of thirteen grassland species grown in diverse neighbourhoods
Authors: Marr Sue , Hageman Jos A. , Wehrens Ron , van Dam Nicole M. , Bruelheide Helge , Neumann Steffen 
Published: February 2021

AbstractIn plants, secondary metabolite profiles provide a unique opportunity to explore seasonal variation and responses to the environment. These include both abiotic and biotic factors. In field experiments, such stress factors occur in combination. This variation alters the plant metabolic profiles in yet uninvestigated ways. This data set contains trait and mass spectrometry data of thirteen grassland species collected at four time points in the growing season in 2017. We collected above-ground vegetative material of seven grass and six herb species that were grown in plant communities with different levels of diversity in the Jena Experiment. For each sample, we recorded visible traits and acquired shoot metabolic profiles on a UPLC-ESI-Qq-TOF-MS. We performed the raw data pre-processing in Galaxy-W4M and prepared the data for statistical analysis in R by applying missing data imputation, batch correction, and validity checks on the features. This comprehensive data set provides the opportunity to investigate environmental dynamics across diverse neighbourhoods that are reflected in the metabolomic profile.
Developmental transcriptome profiling uncovered carbon signaling genes associated with almond fruit drop
Authors: Guo Chunmiao , Wei Yu , Yang Bo , Ayup Mubarek , Li Ning , Liu Jun , Liao Kang , Wang Huan 
Published: February 2021

AbstractAlmond is one of the most featured nut crops owing to its high nutritional value. However, due to three different waves of flower and fruitlet drop, fruit drop is a major concern for growers. In this study, we carried out a time-course transcriptome analysis to investigate gene expression differences between normal and abnormal fruitlet development. By de novo assembly analysis, we identified 33,577 unigenes and provided their functional annotations. In total, we identified 7,469 differentially expressed genes and observed the most apparent difference between normal and abnormal fruits at 12 and 17 days after flowering. Their biological functions were enriched in carbon metabolism, carbon fixation in photosynthetic organisms and plant hormone signal transduction. RT-qPCR validated the expression pattern of 14 representative genes, includingglycosyltransferase like family 2,MYB39,IAA13,gibberellin-regulated protein 11-likeandPOD44, which confirmed the reliability of our transcriptome data. This study provides an insight into the association between abnormal fruit development and carbohydrate signaling from the early developmental stages and could be served as useful information for understanding the regulatory mechanisms related to almond fruit drop.
Novel urinary glycan profiling by lectin array serves as the biomarkers for predicting renal prognosis in patients with IgA nephropathy
Authors: Kawakita Chieko , Mise Koki , Onishi Yasuhiro , Sugiyama Hitoshi , Yoshida Michihiro , Yamada Masao , Wada Jun 
Published: February 2021

AbstractIn IgA nephropathy (IgAN), IgA1 molecules are characterized by galactose deficiency in O-glycans. Here, we investigated the association between urinary glycosylation profile measured by 45 lectins at baseline and renal prognosis in 142 patients with IgAN. The primary outcome was estimated glomerular filtration rate (eGFR) decline (> 4 mL/min/1.73 m2/year), or eGFR ≥ 30% decline from baseline, or initiation of renal replacement therapies within 3 years. During follow-up (3.4 years, median), 26 patients reached the renal outcome (Group P), while 116 patients were with good renal outcome (Group G). Multivariate logistic regression analyses revealed that lectin binding signals of Erythrina cristagalli lectin (ECA) (odds ratio [OR] 2.84, 95% confidence interval [CI] 1.11–7.28) and Narcissus pseudonarcissus lectin (NPA) (OR 2.32, 95% CI 1.11–4.85) adjusted by age, sex, eGFR, and urinary protein were significantly associated with the outcome, and they recognize Gal(β1-4)GlcNAc and high-mannose including Man(α1-6)Man, respectively. The addition of two lectin-binding glycan signals to the interstitial fibrosis/tubular atrophy score further improved the model fitness (Akaike’s information criterion) and incremental predictive abilities (c-index, net reclassification improvement, and integrated discrimination improvement). Urinary N-glycan profiling by lectin array is useful in the prediction of IgAN prognosis, since ECA and NPA recognize the intermediate glycans during N-glycosylation of various glycoproteins.
Improved 7 Tesla transmit field homogeneity with reduced electromagnetic power deposition using coupled Tic Tac Toe antennas
Authors: Santini Tales , Wood Sossena , Krishnamurthy Narayanan , Martins Tiago , Aizenstein Howard J. , Ibrahim Tamer S. 
Published: February 2021

AbstractRecently cleared by the FDA, 7 Tesla (7 T) MRI is a rapidly growing technology that can provide higher resolution and enhanced contrast in human MRI images. However, the increased operational frequency (~ 297 MHz) hinders its full potential since it causes inhomogeneities in the images and increases the power deposition in the tissues. This work describes the optimization of an innovative radiofrequency (RF) head coil coupled design, named Tic Tac Toe, currently used in large scale human MRI scanning at 7 T; to date, this device was used in more than 1,300 neuro 7 T MRI scans. Electromagnetic simulations of the coil were performed using the finite-difference time-domain method. Numerical optimizations were used to combine the calculated electromagnetic fields produced by these antennas, based on the superposition principle, resulting in homogeneous magnetic field distributions at low levels of power deposition in the tissues. The simulations were validated in-vivo using the Tic Tac Toe RF head coil system on a 7 T MRI scanner.
Global chromatin organizer SATB1 acts as a context-dependent regulator of the Wnt/Wg target genes
Authors: Ramanujam Praveena L. , Mehrotra Sonam , Kumar Ram Parikshan , Verma Shreekant , Deshpande Girish , Mishra Rakesh K. , Galande Sanjeev 
Published: February 2021

AbstractSpecial AT-rich binding protein-1 (SATB1) integrates higher-order chromatin architecture with gene regulation, thereby regulating multiple signaling pathways. In mammalian cells SATB1 directly interacts with β-catenin and regulates the expression of Wnt targets by binding to their promoters. Whether SATB1 regulates Wnt/wg signaling by recruitment of β-catenin and/or its interactions with other components remains elusive. Since Wnt/Wg signaling is conserved from invertebrates to humans, we investigated SATB1 functions in regulation of Wnt/Wg signaling by using mammalian cell-lines and Drosophila. Here, we present evidence that in mammalian cells, SATB1 interacts with Dishevelled, an upstream component of the Wnt/Wg pathway. Conversely, ectopic expression of full-length human SATB1 but not that of its N- or C-terminal domains in the eye imaginal discs and salivary glands of third instar Drosophila larvae increased the expression of Wnt/Wg pathway antagonists and suppressed phenotypes associated with activated Wnt/Wg pathway. These data argue that ectopically-provided SATB1 presumably modulates Wnt/Wg signaling by acting as negative regulator in Drosophila. Interestingly, comparison of SATB1 with PDZ- and homeo-domain containing Drosophila protein Defective Proventriculus suggests that both proteins exhibit limited functional similarity in the regulation of Wnt/Wg signaling in Drosophila. Collectively, these findings indicate that regulation of Wnt/Wg pathway by SATB1 is context-dependent.