bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of Heavy Metal Pollution in Farmland Soil along the Lancang River in Lincang, Yunnan
Authors: Jing Wang 
Published: June 2021

Abstract
Taking the farmland soil along the Lancang River in Lincang as the research object, through soil sampling test and analysis, using single factor evaluation method, Nemeiro comprehensive pollution index method and relative pollution index method, the heavy metals As, Cd, Pb and Zn pollution characteristics and causes in farmland along the Lancang River were analyzed. The results show that according to the national soil environmental quality standards, the Cd in the farmland along the Lancang River in Lincang seriously exceeded the standard on a large scale, followed by Pb and Zn, while As did not exceed the standard; the soil single factor pollution index is Cd>Zn>Pb>As. It shows that the relative pollution indexes of As, Cd, Pb and Zn in farmland soil all exceed the standard, and the exceeding rate is Pb>Zn>Cd>As. The pollution of heavy metals in the soil of the farmland along the Lancang River in Lincang is not only caused by mine development, but also related to its high background value. The pollution of heavy metals in farmland soil along the north river from upstream to downstream has changed significantly. The correlation between the pollution of As, Cd, Pb and Zn in the farmland along the Lancang River in Lincang is significant, the probability of homology is very high, and there is a danger of combined pollution of four heavy metals.
Decomposition rate and interaction of fungi: A random perturbation differential equation approach
Authors: Zhou Wangbao , Jiang Zonglin , Zhang Ying , Zhang Zhao 
Published: June 2021

Abstract
In order to describe the interaction between different fungi and their effects on lignocellulose decomposition, we established a fungal decomposition rate model, a fungal competition model and a dynamic disturbance model. Function fitting was used to represent the effects of different independent variables on the decomposition rate of fungus, and finally the expression and image of two important independent variables on the decomposition rate of Hyphal extension and moisture trade-off were obtained. Fungal interaction is mainly a competitive relationship, on the basis of which the differential relationship is used to establish a model to analyze the situation when the system reaches a stable state, and the stochastic dynamic disturbance equation is added to simulate the influence of environmental change on the system. The final analysis shows that there are four kinds of stable states: extinction, non-equilibrium persistence, weak equilibrium persistence and strong equilibrium persistence.
Functional connectivity of dorsolateral prefrontal cortex predicts cocaine relapse: implications for neuromodulation treatment
Authors: Zhai Tianye , Salmeron Betty Jo , Gu Hong , Adinoff Bryon , Stein Elliot A , Yang Yihong 
Published: June 2021

Abstract
Relapse is one of the most perplexing problems of addiction. The dorsolateral prefrontal cortex is crucially involved in numerous cognitive and affective processes that are implicated in the phenotypes of both substance use disorders and other neuropsychiatric diseases and has become the principal site to deliver transcranial magnetic stimulation for their treatment. However, the dorsolateral prefrontal cortex is an anatomically large and functionally heterogeneous region, and the specific dorsolateral prefrontal cortex locus and dorsolateral prefrontal cortex-based functional circuits that contribute to drug relapse and/or treatment outcome remain unknown. We systematically investigated the relationship of cocaine relapse with functional circuits from 98 dorsolateral prefrontal cortex regions-of-interest defined by evenly sampling the entire surface of bilateral dorsolateral prefrontal cortex in a cohort of cocaine dependent patients (n = 43, 5 Fr) following a psychosocial treatment intervention. Cox regression models were utilized to predict relapse likelihood based on dorsolateral prefrontal cortex functional connectivity strength. Functional connectivity from only 3 of the 98 dorsolateral prefrontal cortex loci, one in the left and two in the right hemisphere, significantly predicted cocaine relapse with an accuracy of 83.9%, 84.6% and 85.4%, respectively. Combining all three loci significantly improved prediction validity to 87.5%. Protective and risk circuits related to these dorsolateral prefrontal cortex loci were identified that have previously been implicated to support ‘bottom up’ drive to use drug and ‘top down’ control over behaviour together with social emotional, learning and memory processing. Three dorsolateral prefrontal cortex-centric circuits were identified that predict relapse to cocaine use with high accuracy. These functionally distinct dorsolateral prefrontal cortex-based circuits provide insights into the multiple roles played by the dorsolateral prefrontal cortex in cognitive and affective functioning that affects treatment outcome. The identified dorsolateral prefrontal cortex loci may serve as potential neuromodulation targets to be tested in subsequent clinical studies for addiction treatment and as clinically relevant biomarkers of its efficacy. Zhai et al. identify three dorsolateral prefrontal cortex (dlPFC)-centric circuits that predict cocaine relapse with high accuracy, providing insights into the multiple roles of the dlPFC in brain functioning that affects treatment outcome and suggesting the dlPFC loci as potential neuromodulation targets for addiction treatment.
Diagnostic Challenge and Clinical Dilemma: The Long Reach of Clonal Hematopoiesis
Authors: Osman Afaf , Patel Jay L 
Published: June 2021

Abstract

Background
Widespread application of massively parallel sequencing has resulted in recognition of clonal hematopoiesis in various clinical settings and on a relatively frequent basis. Somatic mutations occur in individuals with normal blood counts, and increase in frequency with age. The genes affected are the same genes that are commonly mutated in overt myeloid malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). This phenomenon is referred to as clonal hematopoiesis of indeterminate potential (CHIP).

Content
In this review, we explore the diagnostic and clinical implications of clonal hematopoiesis. In addition to CHIP, clonal hematopoiesis may be seen in patients with cytopenia who do not otherwise meet criteria for hematologic malignancy, a condition referred to as clonal cytopenia of undetermined significance (CCUS). Distinguishing CHIP and CCUS from overt myeloid neoplasm is a challenge to diagnosticians due to the overlapping mutational landscape observed in these conditions. We describe helpful laboratory and clinical features in making this distinction. CHIP confers a risk of progression to overt hematologic malignancy similar to other premalignant states. CHIP is also associated with a proinflammatory state with multisystem implications and increased mortality risk due to cardiovascular events. The current approach to follow up and management of patients with clonal hematopoiesis is described.

Summary
Nuanced understanding of clonal hematopoiesis is essential for diagnosis and clinical management of patients with hematologic conditions. Further data are needed to more accurately predict the natural history and guide management of these patients with respect to both malignant progression as well as nonhematologic sequelae.
What Determines Paternity in Wild Lizards? A Spatiotemporal Analysis of Behavior and Morphology
Authors: Johnson Michele A , Kamath Ambika , Kirby Rebecca , Fresquez Carla C , Wang Su , Stehle Chelsea M , Templeton Alan R , Losos Jonathan B 
Published: June 2021

Abstract
Mating behavior in animals can be understood as a sequence of events that begins with individuals encountering one another and ends with the production of offspring. Behavioral descriptions of animal interactions characterize early elements of this sequence, and genetic descriptions use offspring parentage to characterize the final outcome, with behavioral and physiological assessments of mates and mechanisms of copulation and fertilization comprising intermediate steps. However, behavioral and genetic descriptions of mating systems are often inconsistent with one another, complicating expectations for crucial aspects of mating biology, such as the presence of multiple mating. Here, we use behavioral and genetic data from a wild population of the lizard Anolis cristatellus to characterize female multiple mating and the potential for sexual selection through female mate choice in this species. We find that 48% of sampled females bore offspring sired by multiple males. Moreover, spatiotemporal proximity between males and females was associated with whether a male sired a female’s offspring, and if yes, how many offspring he sired. Additionally, male body size, but not display behavior, was associated with reproductive outcomes for male–female pairs. While much remains to be learned about the mechanisms of mating and targets of sexual selection in A. cristatellus, it is clear that female multiple mating is a substantial component of this species’ mating system in nature.
Open the Gate: German Jews, the Foundation of Tel Aviv Port, and the Imagined Power of the Sea in 1936
Authors: Siegel Björn 
Published: June 2021

Abstract
In 1936, the opening of Tel Aviv port for general cargo had an impact not only on the Yishuv in Palestine, but also on German Jewry. Against the background of increasing ethnic-religious tensions in British Mandatory Palestine, and growing persecution and oppression in National Socialist Germany, the opening of this new access point to the sea became a signifier of hope and self-determination. This article explores the evolving idea of a Zionist turn towards the sea, whose first peak was marked by the opening of Tel Aviv port, and discusses the role of key individuals in the processes of nation-building, survival, and maritime renewal. By examining the influence of the Zionist Organization (ZO) and its interplay with German Jews—especially Hamburg-Jewish shipping experts—the article demonstrates how economic, but also ideological arguments became important in the debates about a Zionist conquest of the sea. Moreover, the article shows that the integration of German-Jewish shipping experts as maritime pioneers into discourses of a Zionist maritime renewal expanded not only the scope of action of the Yishuv’s leaders, but also of German Jews. The interplay of these two groups laid the groundwork for the short-lived dream of Tel Aviv port.
BIOL-01. THE RELATIONSHIP OF BRAIN ENDOTHELIAL WNT SIGNAL INHIBITION ON BLOOD-TUMOR BARRIER INTEGRITY
Authors: Jackson Sadhana , Vezina Amelie , Kundu Nabanita , Robey Robert 
Published: June 2021

Abstract
The blood-tumor barrier (BTB) is the primary site of nutrient and drug transport to tumor cells such as malignant gliomas. Yet, signaling pathways and factors influencing BTB permeability are poorly understood. Previous studies demonstrate the role of WNT/β-catenin signaling in establishing and fortifying blood-brain barrier integrity in a non-diseased state. Additionally, WNT proteins are highly expressed in gliomas and their surrounding vasculature. Thus, we propose inhibition of WNT/β-catenin signaling at the brain endothelium of malignant glioma can impair BTB integrity to enhance permeability for select cytotoxic agents. We used immortalized mouse brain endothelial cells (bEnd.3), akin to brain tumor endothelium, treated for 24 hours with WNT inhibitors (ICG-001, IWR-1, and LGK974). Inhibition of WNT/β-catenin signaling was confirmed by gene expression of transcription factors (Tcf4 and Birc5). Cell viability was confirmed by CellTiter Glo®. Brain endothelial cell-cell interaction was evaluated by cell impedance and resistance via the Agilent xCELLigence and ABP TEER24 systems. Using qPCR and flow cytometry, we observed changes in expression and function of Abcb1 and Abcg2 transporters. Using an in vitro BTB (bEnd.3 cells and mouse H3.3WT/K27 glioma cells) we evaluated the effect of WNT inhibition on permeability and glioma viability. We found that all the inhibitors downregulated Tcf4 and Birc5 in brain endothelium dose-dependently. Viability with inhibitors demonstrated an IC50 of 28μM for ICG-001, and 42μM for both IWR-1 and LGK974. Endothelial cell-cell interaction was transiently decreased by approximately 50% with all inhibitors at 30 minutes; increasing closer to baseline after 2-4hrs. All WNT inhibitors dose-dependently decreased Abcg2 transporter expression and function. While In vitro BTB studies are ongoing, preliminary findings demonstrate increasing permeability of BTB amongst H3.3K27 glioma cells. Our results demonstrate potential of WNT inhibitors to modulate BTB integrity and drug efflux function. More studies are warranted to explore WNT/β-catenin signaling inhibition on BTB in vivo.
BIOL-03. PROTEIN TRANSLATION FROM NON-CODING GENOMIC LOCI PRODUCE BIOLOGICALLY-ACTIVE PROTEINS IMPLICATED IN CANCER CELL SURVIVAL IN PEDIATRIC BRAIN TUMORS
Authors: Prensner John , Golub Todd 
Published: June 2021

Abstract
Protein translation is both a fundamental cellular process essential for life as well as an oncogenic mechanism employed by tumors to enact cancer cell biology. While protein translation is most readily manifest in the ~20,000 known human protein coding genes, there are, in fact, several thousand additional regions of the cancer genome that are translated and contribute the complexity of the molecular milieu of cancer. Here, we systematically addressed the question of whether such uncharacterized genomic regions encode truly biologically active proteins and applied these findings to pediatric brain tumors. We experimentally interrogated 553 candidates selected from non-canonical open reading frame (ORF) datasets. Of these, 57 induced viability defects when knocked out in a broad array of human cancer cell lines. Upon ectopic expression, 257 showed evidence of protein expression and 401 induced gene expression changes. CRISPR tiling and start codon mutagenesis indicated that their biological effects required translation as opposed to RNA-mediated effects. We characterized several of these in the context of pediatric brain tumors, where dense CRISPR tiling screens revealed unique functional relevance of dozens of non-canonical ORFs in pediatric brain cancer cell survival. We found that one of these ORFs, ASNSD1 uORF, encodes a well-folded protein whose translation is a selective genetic dependency distinct from the adjacent ASNSD1 annotated protein. In vitro molecular biology assays confirmed the MYC-amplified medulloblastoma cell lines had a heightened dependency on this protein, and that MYC binds to the promoter of this gene, with MYC expression correlating with ASNSD1 in patient tumors. Co-immunoprecipitation assays defined ASNSD1 uORF as a novel member of the prefoldin complex of cytoplasmic protein stability regulators. Overall, our experiments suggest that the abundant protein translation found in the “non-coding” genome may produce biologically active non-canonical ORFs that are potential therapeutic targets.
BIOL-10. DISTRIBUTION AND VULNERABILITY OF TRANSCRIPTIONAL OUTPUTS ACROSS THE GENOME IN MYC-AMPLIFIED MEDULLOBLASTOMA CELLS
Authors: Yang Rui , Wang Wenzhe , Dong Meichen , Roso Kristen , Bao Xuhui , Pirozzi Christopher , Bigner Darell , Yan Hai , Ashley David , Zhabotynsky Vasyl , Zou Fei , He Yiping 
Published: June 2021

Abstract
Myc plays a central role in tumorigenesis by orchestrating the expression of genes essential to numerous cellular processes. While it is well established that Myc functions by binding to its target genes to regulate their transcription, the distribution of the transcriptional output across human genome in Myc-amplified cancer cells, and the susceptibility of such transcriptional outputs to therapeutic interferences remain to be fully elucidated. Here, we analyze the distribution of transcriptional outputs in Myc-amplified medulloblastoma (MB) cells by profiling nascent total RNAs within a temporal context. This profiling reveals a major portion of transcriptional action in these cells was directed at the genes fundamental to cellular infrastructures, including rRNAs and particularly those in the mitochondrial genome (mtDNA). Notably, even when Myc protein was depleted by as much as 80%, the impact on transcriptional outputs across the genome was limited, with notable reduction mostly in genes of involved in ribosomal biosynthesis, genes residing in mtDNA or encoding mitochondria-localized proteins, and those encoding histones. In contrast to the limited direct impact of Myc depletion, we found that the global transcriptional outputs were highly dependent on the activity of Inosine Monophosphate Dehydrogenases (IMPDHs), rate limiting enzymes for de novo guanine nucleotide synthesis and whose expression in tumor cells was positively correlated with Myc’s expression. Blockage of IMPDHs attenuated the global transcriptional outputs with a particularly strong inhibitory effect on the aforementioned infrastructure genes, which was accompanied by the abrogation of MB cell’s proliferation in vitro and in vivo. Together, our findings reveal a real time action of Myc as a transcriptional factor in tumor cells, gain new insight into the pathogenic mechanism underlying Myc-driven tumorigenesis, and support IMPDHs as a therapeutic vulnerability in MB cells empowered by a high level of Myc oncoprotein.
EMBR-02. OLIG2 REPRESENTS A PROGNOSTIC MARKER AND THERAPEUTIC TARGET IN MYC-AMPLIFIED MEDULLOBLASTOMA RELAPSE AND METASTASIS
Authors: Xu Zhenhua , Murad Najiba , Rivero-Hinojosa Samuel , Schüller Ulrich , Zhang Peng , Liu Xiao , Rood Brian , Packer Roger , Pei Yanxin 
Published: June 2021

Abstract
Medulloblastoma (MB) is one of the most common malignant pediatric brain tumors. Among the multiple MB subtypes, MB with MYC amplification confers an extremely poor prognosis with an overall survival rate of less than 30%. Relapse is often mediated by a small population of therapy-resistant tumor cells which expand and ultimately progress to lethal tumors. Moreover, MYC-amplified MB exhibits a high incidence of leptomeningeal metastases. Approximately one-third of patients with MYC-amplified MB present with metastases and nearly all have this complication at relapse. Metastatic MYC-amplified MB is highly fatal. As such, our ability to effectively treat MYC-amplified MB is largely dependent on our capacity to eradicate the therapy resistant tumor cells, particularly the metastatic tumor cells. The development of clinically effective therapies for this disease will be facilitated by the identification of therapy-resistant tumor cell populations and their molecular signatures involved in tumor metastasis and relapse. Using patient-derived xenograft (PDX) mouse models, we recently discovered that a subset of MYC-amplified MB tumors with strong OLIG2 expression (OLIG2-high) is resistant to radiation and prone to metastasize, whereas MYC-amplified MB tumors without OLIG2 expression (OLIG2-low) are sensitive to radiation without dissemination. Irradiation of OLIG2-high tumors led to either a small number of quiescent OLIG2- cancer stem-like cells (CSLCs) remaining in the cerebellar bed or to the dissemination of highly proliferative OLIG2+ tumor cells along the leptomeninges. All mice harboring these radioresistant CSLCs succumbed to relapse. Further studies demonstrated that the quiescent OLIG2- CSLCs did not contribute to tumor recurrence directly, while elimination of OLIG2+ radioresistant CSLCs with a small molecule OLIG2 antagonist significantly prevented metastatic recurrence, delayed tumor growth and prolonged animal survival. Thus, our studies provide new insights into the role of OLIG2 in radiotherapy resistance and metastasis in MYC-amplified MB and propose a novel therapeutic approach to treating metastatic MYC-amplified MB.
EMBR-05. THE TENTATIVE APPLICATION OF EN BLOC CONCEPT IN THE PEDIATRIC BRAIN TUMOR: EXPERIENCE FROM A LARGE PEDIATRIC CENTER IN CHINA
Authors: Cao Liangliang , Ma Jie 
Published: June 2021

Abstract

Background
The less allowable blood loss and tolerance of intraoperative blood loss of children lead to the high rate of massive blood transfusion in the treatment of brain tumor. The surgical concepts of en bloc resection may contribute to the improvement of brain tumor resection.

Objective
To investigate the effects of en bloc concept on short outcomes of pediatric brain tumors and factors associated with the application of en bloc concept.

Methods
According to the surgical concept involved, the patients were divided into three subgroups-complete en bloc concept, partial en bloc concept and piecemeal concept. The matching-comparison (piecemeal group and en bloc group formed from the first two subgroups) was conducted based on age, tumor location, lesion volume, and pathological diagnosis to investigate effect of the en bloc concept on the short-term outcomes. Then the patient data after January 2018, when the en bloc concept was routinely integrated into brain tumor surgery in our medical center, were reviewed and analyzed to find out the predictors associated with the application of en bloc concept.

Results
In the en bloc group, the perioperative outcomes, including hospital stay (p=0.001), PICU stay (p=0.003), total blood loss(p=0.015), transfusion rate(p=0.005) and complication rate(p=0.039), were all significantly improved. The multinomial logistic regression analysis showed that tumor volume and imaging features, like bottom vessel, encasing nerve or pass-by vessel, finger-like attachment, ratio of “limited line” and ratio of “clear line” remained independent factors for the application of en bloc concept in our medical center.

Conclusion
This study supports the application of complete or partial en bloc concept in the pediatric brain tumor surgery referring to the preoperative imaging features, and compared with piecemeal concept, en bloc concept can improve the short outcomes without significant increases in neurological complication. Large series and Additional supportive evidence are still warranted.