julilili42/papers huggingface dataset:
ETMR-05. Single-cell transcriptomics of ETMR reveals developmental cellular programs and tumor-pericyte communications in the microenvironment
2022-06-01

Abstract BACKGROUND: Embryonal tumors with multilayered rosettes (ETMR) are pediatric brain tumors bearing a grim prognosis, despite intensive multimodal therapeutic approaches. Insights into cellular heterogeneity and cellular communication of tumor cells with cells of the tumor microenvironment (TME), by applying single-cell (sc) techniques, potentially identify mechanisms of therapy resistance and target-directed treatment approaches. MATERIAL AND METHODS: To explore ETMR cell diversity, we used single-cell RNA sequencing (scRNA-seq) in human (n=2) and murine ETMR (transgenic mode; n=4) samples, spatial transcriptomics, 2D and 3D cultures (including co-cultures with TME cells), multiplex immunohistochemistry and drug screens. RESULTS: ETMR microenvironment is composed of tumor and non-tumor cell types. The ETMR malignant compartment harbour cells representing distinct transcriptional metaprograms, (NSC-like, NProg-like and Neuroblast-like), mirroring embryonic neurogenic cell states and fuelled by neurogenic pathways (WNT, SHH, Hippo). The ETMR TME is composed of oligodendrocyte and neuronal progenitor cells, neuroblasts, microglia, and pericytes. Tumor-specific ligand-receptor interaction analysis showed enrichment of intercellular communication between NProg-like ETMR cells and pericytes (PC). Functional network analyses reveal ETMR-PC interactions related to stem-cell signalling and extracellular matrix (ECM) organization, involving factors of the WNT, BMP, and CxCl12 networks. Results from ETMR-PC co-culture and spatial transcriptomics pointed to a pivotal role of pericytes in keeping ETMR in a germinal neurogenic state, enriched in stem-cell signalling. Drug screening considering cellular heterogeneity and cellular communication suggested novel therapeutic approaches. CONCLUSION: ETMR demonstrated diversity in the microenvironment, with enrichment of cell-cell communications with pericytes, supporting stem-cell signalling and interfering in the organization of the tumor extracellular matrix. Targeting ETMR-PC interactions might bring new opportunities for target-directed therapy.
Variable Drug-Target Exposure, Tumor Signatures, and Combinatorial Targeted Treatment: Approaches of Personalized Medicine in Breast Cancer
2022-06-01

The Special Issue “Genome Research and Personalized Medicine in Breast Cancer” presents studies on personalized medicine in breast cancer, originally with a focus on genomic treatment prediction at all stages of disease [...]
Muscle ultrasound in idiopathic Parkinson's disease with deep brain stimulation: Rigidity can be quantified by shear wave elastography.
2022-06-01

Question Rigidity is a cardinal symptom of Parkinson's disease (PD) and is evaluated subjectively by clinicians. By default, the Unified Parkinson’s Disease Rating Scale (UPDRS) is used, which varies even among experienced examiners. Remedy could be shear wave elastography (SWE): Here, tissue elasticity (simply speaking, stiffness) can be estimated non-invasively using an ultrasound device. Since rigidity is basically an increased stiffness of the muscles, it seems reasonable to investigate whether the increased muscle rigidity in PD can be objectified using SWE of the muscles.
Recurrence Score impacts treatment decisions in hormonereceptor-positive, Her2- negative patients with early breast cancer in areal-world setting – results of the IRMA trial
2022-06-01

Background Patients with hormone receptor-positive (HR+), Her2-negative (Her2-) early breast cancer (eBC) with a high risk of relapse often undergo chemotherapy. However, only a few patients will gain benefit from chemotherapy, since classical tumor characteristics (grading, tumor size, lymph node involvement, Ki67) are prognostic but not predictive of efficacy. Thus, many patients are often overtreated. The IRMA trial aims at selecting patients that have a high genomic risk of relapse to undergo chemotherapy and thereby personalize treatment recommendation by assessing the recurrence score (RS) in a real-world setting.
Prevalence of DNA damage repair (DDR) alterations in patients with metastatic hormone-sensitive prostate cancer (mHSPC) receiving enzalutamide (ENZA) or placebo (PBO) plus androgen deprivation therapy (ADT): ARCHES post hoc analysis.
2022-06-01

5074 Background: DDR alterations are associated with poorer prognosis, including shorter overall survival (OS), in patients with mHSPC. In ARCHES (NCT02677896), patients with mHSPC treated with ENZA + ADT had a reduced risk of radiographic progression or death and improved OS versus PBO + ADT. This post hoc analysis assessed the prevalence of DDR alterations and associated baseline characteristics in patients with mHSPC in ARCHES. Methods: Patients with mHSPC (n=1150) were randomized 1:1 to ENZA (160 mg/day) + ADT or PBO + ADT. Germline DDR alteration testing was performed in blood using Ambry Genetics CustomNext-Cancer panel; 16 DDR-related genes were reported in the subset of patients who consented to participate in a pharmacogenomic study (n=664; Table). Descriptive analyses of baseline demographics and disease characteristics by DDR status were performed. Results: Of 664 patient samples tested, 652 were evaluable for analysis (ENZA + ADT, n=326; PBO + ADT, n=326). Baseline characteristics of these patients were similar to the ARCHES intent-to-treat population. The prevalence of DDR+ patients was lower than expected (n=34/652, 5.2%; Table). Of DDR+ patients, 13 (38.2%) had low-volume disease, compared with 228 (36.9%) of DDR− patients. High-volume disease was present in 21 (61.8%) DDR+ and 390 (63.1%) DDR− patients. Of DDR+ patients, 6 (17.6%) had localized disease at initial diagnosis (M0), compared with 145 (23.5%) DDR− patients. De novo metastatic disease at initial diagnosis (M1) was present in 28 (82.4%) DDR+ patients and 465 (75.2%) DDR− patients. Of DDR+ patients, 29 (85.3%) were from Europe, four (11.8%) were from North America, and one (2.9%) was from the Asia-Pacific region. Conclusions: This post hoc analysis found a lower prevalence of DDR alterations in patients with mHSPC in ARCHES, compared with the 7–12% previously reported in patients with metastatic castration-resistant prostate cancer (Lozano et al. Br J Cancer 2021; Pritchard et al. N Engl J Med 2016). We did not identify differences in baseline disease characteristics based on DDR status. Clinical trial information: NCT02677896. [Table: see text]
Trait-anger, hostility, and the risk of incident type 2 diabetes and diabetes-related complications: a systematic review of longitudinal studies
2022-06-01

Introduction There is a well-established association between anger, hostility, and an increased risk of cardiovascular disease. Emerging evidence also suggests associations between anger/hostility and type 2 diabetes (T2D), though evidence from longitudinal studies has not yet been synthesized. Objectives To systematically review findings from existing prospective cohort studies on trait anger/hostility and the risk of T2D and diabetes-related complications. Methods Electronic searches of MEDLINE (PubMed), PsychINFO, Web of Science, and CINAHL were performed for articles/abstracts published up to December 15, 2020. Peer-reviewed longitudinal studies conducted with adult samples, with effect estimates reported for trait anger or hostility and incident T2D or diabetes-related complications, were eligible for inclusion. Risk of bias/study quality was assessed. The review protocol was published a priori in PROSPERO (CRD42020216356) and was in keeping with PRISMA guidelines. Screening for eligibility, data extraction, and quality assessment was conducted by two independent reviewers. Results Four studies with a total of 155,146 participants met the inclusion criteria. A narrative synthesis of extracted data was conducted according to the Synthesis Without Meta-Analysis guidelines. While results were mixed, our synthesis suggested a positive association between high trait-anger/hostility and increased risk of incident T2D. No longitudinal studies were identified relating to anger/hostility and incident diabetes-related complications. Geographical locations of the study samples were limited to the USA and Japan. Conclusions Further research is needed to investigate whether trait-anger/hostility predicts incident type 2 diabetes after adjustments for potential confounding factors. Longitudinal studies are needed to investigate trait-anger/hostility and the risk of diabetes-related vascular complications. Disclosure No significant relationships.
Symptoms of diabetes distress, depression, and anxiety in people with type 2 diabetes: identifying central and bridge symptoms using network analysis
2022-06-01

Introduction People with diabetes are vulnerable to diabetes-related distress and are more likely to experience depressive and anxiety symptoms than the general population. Diabetes distress, depressive, and anxiety symptoms also tend to commonly co-occur. Objectives This study aimed to apply network analysis to explore the associations between diabetes distress, depressive, and anxiety symptoms in a cohort of adults with type 2 diabetes. Methods Data were from the baseline (2011) assessment of the Evaluation of Diabetes Insulin Treatment (EDIT) study ( N = 1,796; 49% female; mean age = 60, SD = 8) from Quebec, Canada. A first network using the 17 items of the diabetes distress scale (DDS-17) was estimated. A second network was estimated using the 17 items of the DDS-17, the 9 depressive items of the PHQ-9, and the 7 anxiety items of the GAD-7. Symptom centrality, network stability, and bridge symptoms were examined. Results Regimen-related and physician-related distress symptoms were amongst the most central (highly connected) in the diabetes distress network. Worrying too much (anxiety), Not feeling motivated to keep up diabetes self-management (diabetes distress), and Feeling like a failure (depression) were the most central symptoms in the combined network. Feeling like a failure (depression) was highly connected to diabetes distress symptoms, representing a potential bridge between diabetes distress and depression. Conclusions Identifying central and bridge symptoms may provide new insights into diabetes distress, depressive, and anxiety symptom maintenance and comorbidity in people with type 2 diabetes. Disclosure No significant relationships.
Kant and the Divine: From Contemplation to the Moral Law. By Christopher J. InsoleKant and Religion. By Allen W. Wood
2022-06-01

Although grasping attempts at secularization are bound to continue, Kant’s philosophy of religion has gained a secure foothold in mainstream Kant scholarship where it is rightly viewed by many as a vital part of his system demanding scholarly attention. Given the mistaken but lingering perception that Kant’s commitment to Enlightenment ideals precludes a robust role for the divine, such scholarly efforts are often preoccupied with providing a defense of Kant’s insistence—recurring throughout his mature philosophical system—that “morality thus inevitably leads to religion” (Insole 262). In new offerings both published in 2020, Christopher J. Insole and Allen W. Wood each provide confident interpretations of this claim that are built upon decades of work and rooted in the shared conviction that the main issue confronting Kant’s reader is not the difficulty of his text but our own ideologically motivated refusal to take him at his word. For both authors, this refusal has far-reaching implications for our own self-understanding and the possibility of individual and communitarian moral progress. As Wood insists in his preface, “A self-inflicted intellectual incapacity to appreciate the human potential of religion is a serious deficiency in the culture of most scientists and most academic humanists” (xix). Whether or not Insole would agree with this specific statement, both authors have built their projects around the claim that Kant’s system reserves a deep-seated and indispensable role for the divine in human moral life that we are worse off for overlooking. Beyond this shared starting point, however, the presuppositions and methods adopted by Wood and Insole pull them in opposite directions and set up two extraordinarily different interpretations of Kant. Reading both books together thereby grants insight into just how much remains unsettled, not only with respect to Kant’s view of religion, but even as regards the broader philosophical influences and commitments that motivate his system as a whole.
EMNIST-DA: A dataset for studying measurement shift
2022-06-01

emnist_large.tar.gz contains the EMNIST-DA dataset consisting of 13 shifted versions of the 47-class extended-MNIST (EMNIST) dataset. As many methods achieve very good performance on MNIST datasets, this dataset was created to be more challenging with 47-classes and some difficult (measurement) shifts. Source code to generate the dataset is available at https://github.com/cianeastwood/bufr/blob/main/data/emnist.py.
EMNIST-DA: A dataset for studying measurement shift
2022-06-01

&lt;p&gt;emnist_large.tar.gz&nbsp;contains the EMNIST-DA&nbsp;dataset consisting of&nbsp;13 shifted versions of the 47-class extended-MNIST (EMNIST) dataset. As many methods achieve very good performance on MNIST datasets, this dataset was created to be more challenging with 47-classes and some difficult (measurement) shifts.&lt;/p&gt; &lt;p&gt;Source code to generate the dataset is available at https://github.com/cianeastwood/bufr/blob/main/data/emnist.py.&lt;/p&gt;
The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee
2022-06-02

Abstract Since the publication of the Revised European-American Classification of Lymphoid Neoplasms in 1994, subsequent updates of the classification of lymphoid neoplasms have been generated through iterative international efforts to achieve broad consensus among hematopathologists, geneticists, molecular scientists, and clinicians. Significant progress has recently been made in the characterization of malignancies of the immune system, with many new insights provided by genomic studies. They have led to this proposal. We have followed the same process that was successfully used for the third and fourth editions of the World Health Organization Classification of Hematologic Neoplasms. The definition, recommended studies, and criteria for the diagnosis of many entities have been extensively refined. Some categories considered provisional have now been upgraded to definite entities. Terminology for some diseases has been revised to adapt nomenclature to the current knowledge of their biology, but these modifications have been restricted to well-justified situations. Major findings from recent genomic studies have impacted the conceptual framework and diagnostic criteria for many disease entities. These changes will have an impact on optimal clinical management. The conclusions of this work are summarized in this report as the proposed International Consensus Classification of mature lymphoid, histiocytic, and dendritic cell tumors.
More than heavy rain turning into fast-flowing water – a landscape perspective on the 2021 Eifel floods
2022-06-02

Abstract. Rapidly evolving floods are rare but powerful drivers of landscape reorganisation that have severe and long-lasting impacts on both the functions of a landscape’s subsystems and the affected society. The July 2021 flood that particularly hit several river catchments of the Eifel region in western Germany and Belgium was a drastic example. While media and scientists highlighted the meteorological and hydrological aspects of this flood, it was not just the rising water levels in the main valleys that posed a hazard, caused damage, and drove environmental reorganisation. Instead, the concurrent coupling of landscape elements and the wood, sediment, and debris carried by the fast-flowing water made this flood so devastating and difficult to predict. Because more intense floods are able to interact with more landscape components, they at times reveal rare non-linear feedbacks, which may be hidden during smaller events due to their high thresholds of initiation. Here, we briefly review the boundary conditions of the 14–15 July 2021 flood and discuss the emerging features that made this event different from previous floods. We identify hillslope processes, aspects of debris mobilisation, the legacy of sustained human land use, and emerging process connections and feedbacks as critical non-hydrological dimensions of the flood. With this landscape scale perspective, we develop requirements for improved future event anticipation, mitigation, and fundamental system understanding.
Genome-wide Association and Meta-analysis of Age at Onset in Parkinson Disease
2022-06-02

Our study further refines the genetic architecture of Chr 4 underlying the AAO of the PD phenotype through the identification of <i>BST1</i> as a novel AAO PD locus. These findings open a new direction for the development of treatments to delay the onset of PD.
Neuroscience Knowledge and Endorsement of Neuromyths among Educators: What Is the Scenario in Brazil?
2022-06-02

The field of neuroscience has seen significant growth and interest in recent decades. While neuroscience knowledge can benefit laypeople as well as professionals in many different areas, it may be particularly relevant for educators. With the right information, educators can apply neuroscience-based teaching strategies as well as protect themselves and their students against pseudoscientific ideas and products based on them. Despite rapidly growing sources of available information and courses, studies show that educators in many countries have poor knowledge of brain science and tend to endorse education-related neuromyths. Poor English skills and fewer resources (personal, institutional and governmental) may be additional limitations in Latin America. In order to better understand the scenario in Latin America’s largest country, we created an anonymous online survey which was answered by 1634 individuals working in education from all five regions of Brazil. Respondents stated whether they agreed with each statement and reported their level of confidence for each answer. Significant differences in performance were observed across regions, between educators living in capital cities versus the outskirts, between those teaching in private versus public schools, and among educators teaching different levels (pre-school up to college/university). We also observed high endorsement of some key neuromyths, even among groups who performed better overall. To the best of our knowledge, this is the first study to conduct a detailed analysis of the profile of a large group of educators in Brazil. We discuss our findings in terms of efforts to better understand regional and global limitations and develop methods of addressing these most efficiently.
A typed continuation-passing translation for lexical effect handlers
2022-06-02

Effect handlers are a language feature which enjoys popularity in academia and is also gaining traction in industry. Programs use abstract effect operations and handlers provide meaning to them in a delimited scope. Each effect operation is handled by the dynamically closest handler. Using an effect operation outside of a matching handler is meaningless and results in an error. A type-and-effect system prevents such errors from happening. Lexical effect handlers are a recent variant of effect handlers with a number of attractive properties. Just as with traditional effect handlers, programs use effect operations and handlers give meaning to them. But unlike with traditional effect handlers, the connection between effect operations and their handler is lexical. Consequently, they typically have different type-and-effect systems. The semantics of lexical effect handlers as well as their implementations use multi-prompt delimited control. They rely on the generation of fresh labels at runtime, which associate effect operations with their handlers. This use of labels and multi-prompt delimited control is theoretically and practically unsatisfactory. Our main result is that typed lexical effect handlers do not need the full power of multi-prompt delimited control. We present the first CPS translation for lexical effect handlers to pure System F. It preserves well-typedness and simulates the traditional operational semantics. Importantly, it does so without requiring runtime labels. The CPS translation can be used to study the semantics of lexical effect handlers as well as as an implementation technique.
Homing of mRNA-Modified Endothelial Progenitor Cells to Inflamed Endothelium
2022-06-02

Endothelial progenitor cells (EPCs) are one of the most important stem cells for the neovascularization of tissues damaged by ischemic diseases such as myocardial infarction, ischemic stroke, or critical limb ischemia. However, their low homing efficiency in the treatment of ischemic tissues limits their potential clinical applications. The use of synthetic messenger RNA (mRNA) for cell engineering represents a novel and promising technology for the modulation of cell behavior and tissue regeneration. To improve the therapeutic potential of EPCs, in this study, murine EPCs were engineered with synthetic mRNAs encoding C-X-C chemokine receptor 4 (CXCR4) and P-selectin glycoprotein ligand 1 (PSGL-1) to increase the homing and migration efficiency of EPCs to inflamed endothelium. Flow cytometric measurements revealed that the transfection of EPCs with CXCR4 and PSGL-1 mRNA resulted in increased expressions of CXCR4 and PSGL-1 on the cell surface compared with the unmodified EPCs. The transfection of EPCs with mRNAs did not affect cell viability. CXCR4-mRNA-modified EPCs showed significantly higher migration potential than unmodified cells in a chemotactic migration assay. The binding strength of the EPCs to inflamed endothelium was determined with single-cell atomic force microscopy (AFM). This showed that the mRNA-modified EPCs required a three-fold higher detachment force to be released from the TNF-α-activated endothelium than unmodified EPCs. Furthermore, in a dynamic flow model, significantly increased binding of the mRNA-modified EPCs to inflamed endothelium was detected. This study showed that the engineering of EPCs with homing factors encoding synthetic mRNAs increases the homing and migration potentials of these stem cells to inflamed endothelium. Thus, this strategy represents a promising strategy to increase the therapeutic potential of EPCs for the treatment of ischemic tissues.
Commentary on “Guidelines for the provision of nutrition support therapy in the adult critically ill patient: The American Society for Parenteral and Enteral Nutrition”
2022-06-02

As authors of recent meta-analyses evaluating lipids for parenteral nutrition1,2 and/or the ESPEN Expert Group: lipids in the intensive care unit3 we welcome the updating of the ASPEN guidelines for clinical nutrition in adult critically ill patients,4 but would like to remark on certain aspects that cause us concern&lt;br/&gt;&lt;br/&gt;This article is protected by copyright. All rights reserved.&lt;br/&gt;&lt;br/&gt;