Miracle-dz/UniFAR-FTUs huggingface dataset:
Loss of SMAD 4 Promotes Colorectal Cancer Progression by Accumulation of Myeloid-Derived Suppressor Cells through the CCL 15 – CCR 1 Chemokine Axis

Purpose: We previously reported that loss of SMAD4 promotes chemokine CCL15 expression to recruit CCR1þ myeloid cells via the CCL15–CCR1 axis, which facilitates metastasis of colorectal cancer to the liver. The purposes of this study were to investigate whether essentially the same mechanism works in tumor invasion of the primary colorectal cancer and to evaluate the clinical importance of CCL15 expression and CCR1þ cell accumulation. Experimental Design: Using human colorectal cancer cell lines with reduced expression of SMAD4 or CCL15, we investigated tumor growth activities in vivo. We used immunohistochemistry (IHC) to investigate expression of SMAD4, CCL15, and CCR1 with 333 clinical specimens of primary colorectal cancer. We next characterized the CCR1þ cells using double immunofluorescence staining with several specific cell-type markers. Finally, we determined the serum CCL15 levels in 132 colorectal cancer patients. Results: In an orthotopic xenograft model, CCL15 secreted from SMAD4-deficient colorectal cancer cells recruited CCR1þ cells, resulting in aggressive tumor growth. IHC indicated that loss of SMAD4 was significantly associated with CCL15 expression, and that CCL15-positive primary colorectal cancers recruited approximately 2.2 times more numbers of CCR1þ cells at their invasion front than CCL15-negative colorectal cancers. Importantly, these CCR1þ cells were of the myeloid-derived suppressor cell (MDSC) phenotype (CD11bþ, CD33þ, and HLA-DR ). Most CCR1þ cells showed the granulocytic-MDSC phenotype (CD15þ), whereas some showed the monocytic-MDSC phenotype (CD14þ). Serum CCL15 levels in colorectal cancer patients were significantly higher than in controls. Conclusions: Blocking the recruitment of CCR1þ MDSCs may represent a novel molecular-targeted therapy, and serum CCL15 concentration can be a novel biomarker for colorectal cancer. Clin Cancer Res; 22(2); 492–501. 2015 AACR.
Consequences of glycan truncation on Fc structural integrity

Effective characterization of protein-based therapeutic candidates such as monoclonal antibodies (mAbs) is important to facilitate their successful progression from early discovery and development stages to marketing approval. One challenge relevant to biopharmaceutical development is, understanding how the stability of a protein is affected by the presence of an attached oligosaccharide, termed a glycan. To explore the utility of molecular dynamics simulations as a complementary technique to currently available experimental methods, the Fc fragment was employed as a model system to improve our understanding of protein stabilization by glycan attachment. Long molecular dynamics simulations were performed on three Fc glycoform variants modeled using the crystal structure of a human IgG1 mAb. Two of these three glycoform variants have their glycan carbohydrates partially or completely removed. Structural differences among the glycoform variants during simulations suggest that glycan truncation and/or removal can cause quaternary structural deformation of the Fc as a result of the loss or disruption of a significant number of inter-glycan contacts that are not formed in the human IgG1 crystal structure, but do form during simulations described here. Glycan truncation/removal can also increase the tertiary structural deformation of CH2 domains, demonstrating the importance of specific carbohydrates toward stabilizing individual CH2 domains. At elevated temperatures, glycan truncation can also differentially affect structural deformation in locations (Helix-1 and Helix-2) that are far from the oligosaccharide attachment point. Deformation of these helices, which form part of the FcRn, could affect binding if these regions are unable to refold after temperature normalization. During elevated temperature simulations of the deglycosylated variant, CH2 domains collapsed onto CH3 domains. Observations from these glycan truncation/removal simulations have improved our understanding on how glycan composition can affect mAb stability.
A New Approach to Interactive Drama: From Intelligent Characters to an Intelligent Virtual Narrator

The limits of current forms of interactive drama have been now clearly identified: - interactive character based stories are poorly interactive, the plot remaining nearly linear; - interactive virtual worlds are poorly dramatic, with no plot at all; the role of the user is confuse. This paper will give guidelines on how those problems should be tackled, by putting Artificial Intelligence (AI) in the right place, within an interactive drama system. Our research aims, in the long term, at building deeply interactive drama, with advanced models of narration.
Epithelial to Mesenchymal Transition in an Epidermal Growth Factor Receptor-Mutant Lung Cancer Cell Line with Acquired Resistance to Erlotinib

Introduction: Mesenchymal status is related to “inherent resistance” to gefitinib or erlotinib in non-small cell lung cancer without epidermal growth factor receptor(EGFR) mutations. In addition, a recent report showed that the epithelial to mesenchymal transition (EMT) plays a role in acquired resistance to gefitinib in A549 cells, which harbor a KRAS mutation. However, recent clinical studies revealed that gefitinib or erlotinib are highly effective in the treatment of non-small cell lung cancer with EGFR mutations. Methods: We developed resistant cells (HCC4006ER) from erlotinib-sensitive HCC4006 cells harboring an EGFR deletion mutation by chronic exposure to increasing concentrations of erlotinib. Acquired resistance mechanisms of HCC4006ER cells were analyzed. Results: Neither known resistance mechanisms nor novel molecules that may confer erlotinib resistance were identified using candidate or comprehensive analyses. In addition, HCC4006ER cells lost dependency for EGFR. However, we found that HCC4006ER cells acquired a mesenchymal phenotype and exhibited down-regulation of E-cadherin expression (2.7 × 10−3 times compared with parental cells). We also found that the histone deacetylase inhibitor, MS-275, restored E-cadherin expression and moderate sensitivity to erlotinib in HCC4006ER cells, on the other hand, transforming growth factor beta, an inducer of EMT, led to moderate erlotinib resistance in HCC4006 parental cells. Conclusions: This is the first report of a relationship between EMT and erlotinib acquired resistance in an erlotinib sensitive EGFR-mutant lung cancer cell line. Our results indicate that it would be important to consider the influence of EMT in the development of treatments against acquired resistance to gefitinib or erlotinib.
Please Scroll down for Article the Quarterly Journal of Experimental Psychology Follow You, Follow Me: Continuous Mutual Prediction and Adaptation in Joint Tapping

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Automatic Construction of Discourse Corpora for Dialogue Translation

In this paper, a novel approach is proposed to automatically construct parallel discourse corpus for dialogue machine translation. Firstly, the parallel subtitle data and its corresponding monolingual movie script data are crawled and collected from Internet. Then tags such as speaker and discourse boundary from the script data are projected to its subtitle data via an information retrieval approach in order to map monolingual discourse to bilingual texts. We not only evaluate the mapping results, but also integrate speaker information into the translation. Experiments show our proposed method can achieve 81.79% and 98.64% accuracy on speaker and dialogue boundary annotation, and speaker-based language model adaptation can obtain around 0.5 BLEU points improvement in translation qualities. Finally, we publicly release around 100K parallel discourse data with manual speaker and dialogue boundary annotation.
Becker Digital

Objective: The need for clinical services in U.S. colleges exceeds the supply. Digital Mental health Interventions (DMHIs) are a potential solution, but successful implementation depends on stakeholder acceptance. This study investigated the relevance of DMHIs from students' perspectives. Methods: In 2020 – 2021, an online cross-sectional survey using mixed methods was conducted with 479 students at 23 colleges and universities. Respondents reported views and use of standard mental health services and DMHIs and rated the priority of various DMHIs to be offered through campus services. Qualitative data included open-ended responses. Findings: Among respondents, 91% reported having experienced mental health problems, of which 91% reported barriers to receiving mental health services. Students highlighted therapy and counseling as desired and saw flexible access to services as important. With respect to DMHIs, respondents had the most experience with physical health apps (46%), mental health questionnaires (41%), and mental well-being apps (39%). Most were unaware of or had not used apps or self-help programs for mental health problems. Students were most likely to report the following DMHIs as high priorities: a crisis text line (76%), telehealth (66%), websites for connecting to services (62%), and text/messaging with counselors (62%). They considered a self-help program with coach support to be convenient but some also perceived such services to be possibly less effective than in-person therapy. Conclusions: Students welcome DMHIs on campus and indicate preference for mental health services that include human support. The findings, with particular focus on characteristics of the DMHIs prioritized, and students' awareness and perceptions of scalable DMHIs emphasized by policymakers, should inform schools looking to implement DMHIs.
A Comparative Evaluation of Term Recognition Algorithms

Automatic Term recognition (ATR) is a fundamental processing step preceding more complex tasks such as semantic search and ontology learning. From a large number of methodologies available in the literature only a few are able to handle both single and multi-word terms. In this paper we present a comparison of five such algorithms and propose a combined approach us¬ing a voting mechanism. We evaluated the six approaches using two different corpora and show how the voting algo¬rithm performs best on one corpus (a collection of texts from Wikipedia) and less well using the Genia corpus (a standard life science corpus). This indicates that choice and design of corpus has a major impact on the evaluation of term recog¬nition algorithms. Our experiments also showed that single-word terms can be equally important and occupy a fairly large proportion in certain domains. As a result, algorithms that ignore single-word terms may cause problems to tasks built on top of ATR. Effective ATR systems also need to take into account both the unstructured text and the structured aspects and this means information extraction techniques need to be integrated into the term recognition process.
JMIR Perioperative Medicine

The purpose of this viewpoint is to provide awareness of the current opportunities to enhance a high-value care approach to blood product transfusion. It provides a historical context to the evolution of blood management, as well as of the patient safety and high-value care movement. Leveraging current technology for enhanced education, as well as clinical decision support, is also discussed
Discussing Death, Dying, and End-of-Life Goals of Care: A Communication Skills Training Module for Oncology Nurses.

BACKGROUND Effective communication, particularly at the end of life, is an essential skill for oncology nurses, but few receive formal training in this area. OBJECTIVES The aim of this article is to adapt an end-of-life care communication skills training (CST) module, originally developed for oncologists, for oncology nurses and to evaluate participants' confidence in using the communication skills learned and their satisfaction with the module. METHODS The adapted end-of-life care module consisted of a 45-minute didactic, exemplary video and 90 minutes of small group interaction and experiential role play with a simulated patient. Using a five-point Likert-type scale, 247 inpatient oncology nurses completed pre-/post-workshop surveys rating their confidence in discussing death, dying, and end-of-life goals of care with patients, as well as overall satisfaction with the module. FINDINGS Nurses' confidence in discussing death, dying, and end-of-life goals of care increased significantly after attending the workshop. Nurse participants indicated satisfaction with the module by agreeing or strongly agreeing to all six items assessing satisfaction 90%-98% of the time. Nurses' CST in discussing death, dying, and end-of-life care showed feasibility, acceptability, and potential benefit at improving confidence in having end-of-life care discussions.
Domain growth by aging in nonequilibrium two-dimensional random Ising systems.

The ac susceptibility in the two-dimensional Ising spin glass Rb 2 Cu 0.67 Co 0.33 F 4 and the twodimensional random-exchange Ising ferromagnet Rb 2 Cu 0.89 Co 0.11 F 4 is observed to relax towards equilibrium on a time scale of hours following fast quenching to 3.9 K. Scaling of the in-phase and out-of-phase susceptibilities yields that the ordered domains grow according to (lnt) 1/ψ , with t expressed in units of a microscopic time, and ψ=1.07±0.10 and 0.20±0.5, respectively. Both values are in agreement with recent theoretical results and numerical simulations
Yat: A Validation Framework for Persistent Memory Software

This paper describes the design and implementation of Yat. Yat is a hypervisor-based framework that supports testing of applications that use Persistent Memory (PM)--byte-addressable, non-volatile memory attached directly to the memory controller. PM has implications on both system architecture and software. The PM architecture extends the memory ordering model to add software-visible support for durability of stores to PM. By simulating the characteristics of PM, and integrating an application-specific checker in the framework, Yat enables validation, correctness testing, and debugging of PM software in the presence of power failures and crashes. We discuss the use of Yat in development and testing of the Persistent Memory File System (PMFS), describing the effectiveness of Yat in catching and debugging several hard-to-find bugs in PMFS.
Teaching Techniques for Designing Physics Learning Activities during the COVID-19 Pandemic: Analysis of Pre-service Teachers’ Lesson Plans

This research had two aims: first, to analyze research articles on physics instruction during the COVID-19 crisis and determine teaching techniques that enhanced upper secondary students’ physics concept understanding, science process skills and five key competencies; second, to analyze the teaching techniques selected by pre-service physics teachers and how they applied them in lesson plans in an online context. A content analysis and an inductive coding were conducted on 79 selected research articles and 85 lesson plans in this study. The results showed that smartphone application, simulation and online clip video were the most frequently used to develop students during the COVID-19 pandemic. In addition, the findings showed that pre-service physics teachers integrated techniques of using digital instructional materials in their physics lesson plans based on various methods, such as explaining concepts, practicing science process skills and learning life skills through online group activities. Besides, the findings showed that the most frequently used teaching techniques were online video clips aimed at building students’ understanding of physics concepts, simulations for developing students’ science process skills, and online video clips with a set of questions for promoting students’ five key competencies.
Hubs and Hyperspheres Reducing Hubness and Improving Transductive Few-Shot Learning with Hyperspherical Embeddings

Distance-based classification is frequently used in trans-ductive few-shot learning (FSL). However, due to the high-dimensionality of image representations, FSL classifiers are prone to suffer from the hubness problem, where a few points (hubs) occur frequently in multiple nearest neighbour lists of other points. Hubness negatively impacts distance-based classification when hubs from one class appear often among the nearest neighbors of points from another class, degrading the classifier’s performance. To address the hubness problem in FSL, we first prove that hubness can be eliminated by distributing representations uniformly on the hypersphere. We then propose two new approaches to embed representations on the hypersphere, which we prove optimize a tradeoff between uniformity and local similarity preservation – reducing hubness while retaining class structure. Our experiments show that the proposed methods reduce hubness, and significantly improves transductive FSL accuracy for a wide range of classifiers 1 .
Assessment of capacity for Health Policy and Systems Research and Analysis in seven African universities: results from the CHEPSAA project

The importance of health policy and systems research and analysis (HPSR+A) is widely recognized. Universities are central to strengthening and sustaining the HPSR+A capacity as they teach the next generation of decision-makers and health professionals. However, little is known about the capacity of universities, specifically, to develop the field. In this article, we report results of capacity self- assessments by seven universities within five African countries, conducted through the Consortium for Health Policy and Systems Analysis in Africa (CHEPSAA). The capacity assessments focused on both capacity ‘assets’ and ‘needs’, and covered the wider context, as well as organizational and individual capacity levels. Six thematic areas of capacity were examined: leadership and governance, organizations’ resources, scope of HPSR+A teaching and research, communication, networking and getting research into policy and practice (GRIPP), demand for HPRS+A and resource environment. The self-assessments by each university used combinations of document reviews, semi-structured interviews and staff surveys, followed by comparative analysis. A framework approach, guided by the six thematic areas, was used to analyse data. We found that HPSR+A is an international priority, and an existing activity in Africa, though still neglected field with challenges including its reliance on unpredictable international funding. All universities have capacity assets, such as ongoing HPSR+A teaching and research. There are, however, varying levels of assets (such as differences in staff numbers, group sizes and amount of HPSR+A teaching and research), which, combined with different capacity needs at all three levels (such as individual training, improvement in systems for quality assurance and fostering demand for HPSR+A work), can shape a future agenda for HPSR+A capacity strengthening. Capacity assets and needs at different levels appear related. Possible integrated strategies for strengthening universities’ capacity include: refining HPSR+A vision, mainstreaming the subject into under- and post-graduate teaching, developing emerging leaders and aligning HPSR+A capacity strengthening within the wider organizational development.
Becker Digital Commons

The genetic basis for the emergence of creativity in modern humans remains a mystery despite sequencing the genomes of chimpanzees and Neanderthals, our closest hominid relatives. Data-driven methods allowed us to uncover networks of genes distinguishing the three major systems of modern human personality and adaptability: emotional reactivity, self-control, and self-awareness. Now we have identi ﬁ ed which of these genes are present in chimpanzees and Neanderthals. We replicated our ﬁ ndings in separate analyses of three high-coverage genomes of Neanderthals. We found that Neanderthals had nearly the same genes for emotional reactivity as chimpanzees, and they were intermediate between modern humans and chimpanzees in their numbers of genes for both self-control and self-awareness. 95% of the 267 genes we found only in modern humans were not protein-coding, including many long-non-coding RNAs in the self-awareness network. These genes may have arisen by positive selection for the characteristics of human well-being and behavioral modernity, including creativity, prosocial behavior, and healthy longevity. The genes that cluster in association with those found only in modern humans are over-expressed in brain regions involved in human self-awareness and creativity, including late-myelinating and phylogenetically recent regions of neocortex for autobiographical memory in frontal, parietal, and temporal regions, as well as related components of cortico-thalamo-ponto-cerebellar-cortical and cortico-striato-cortical loops. We conclude that modern humans have more than 200 unique non-protein-coding genes regulating co-expression of many more protein-coding genes in coordinated networks that underlie their capacities for self-awareness, creativity, prosocial behavior
Cross-Language Speech Retrieval Track

The CLEF-2006 Cross-Language Speech Retrieval (CL-SR) track included two tasks: to identify topically coherent segments of English interviews in a known-boundary condition, and to identify time stamps marking the beginning of topically relevant passages in Czech interviews in an unknown-boundary condition. Five teams participated in the English evaluation, performing both monolingual and cross-language searches of speech recognition transcripts, automatically generated meta-data, and manually generated metadata. Results indicate that the 2006 English evaluation topics are more challenging than those used in 2005, but that cross-language searching continued to pose no unusual challenges when compared with monolingual searches of the same collection. Three teams participated in the monolingual Czech evaluation using a new evaluation measure based on diﬀerences between system-suggested and ground truth replay start times, with results that were broadly comparable to those observed for English