bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fostering student motivation towards community healthcare: a qualitative study
Authors: Yahata Shinsuke , Takeshima Taro , Kenzaka Tsuneaki , Okayama Masanobu 
Published: January 2021

ObjectivesThis study investigated what kinds of experiences influence regional quota (chiikiwaku) medical students’ motivation to practice community healthcare (CH), and the mechanism of this influence, by focusing on their experiences in a community-based medical education (CBME) programme.DesignA qualitative thematic analysis based on interviews.SettingParticipants were recruited from the chiikiwaku students of Kobe University, Japan, using purposive sampling.ParticipantsFourteen students participated. The median (IQR) age of participants was 23 (23–24); half were sixth-year and half fifth-year students.AnalysisFrom September to December 2018, the interviews were audiorecorded and transcribed verbatim. Data were analysed according to the ‘Steps for Coding and Theorisation’ method. Our theoretical framework comprised three internal motives (ie, needs, cognitions and emotions) and their subordinate motivation theories self-determination theory, expectancy-value theories, and positive and negative emotions, respectively.ResultsThree mechanisms and corresponding experiences emerged. The first mechanism, envisioning and preparing for practising CH, included corresponding experiences—empathy for the community, grasping the demands for CH, understanding the practices of CH, finding a role model and diminishing the conflicts between personal life and career. The second mechanism, belonging to a supportive community, included the robust construction of students’ CH community and harmonisation with community residents. The third mechanism, psychological effects included the affect heuristic and framing effect. Student experiences brought about the changes and influences described in the presented mechanisms, and had both positive and negative impacts on their motivation towards CH. These results can be interpreted through the multifaceted lenses of motivation theories.ConclusionsThe authors revealed that motivation mechanisms of medical students towards CH derived from positive interaction with community residents, healthcare professionals and other students, and from exposure to attractive community environments and cultures. These experiences should be incorporated into CBME programmes to further encourage positive attitudes towards CH.
Octogenarian patients’ sleep and delirium experiences in hospital and four years after aortic valve replacement: a qualitative interview study
Authors: Amofah Hege Andersen , Broström Anders , Instenes Irene , Fridlund Bengt , Haaverstad Rune , Kuiper Karel , Ranhoff Anette Hylen , Norekvål Tone M. 
Published: January 2021

ObjectivesSleep disturbances and delirium are frequently observed complications after surgical aortic valve replacement (SAVR) and transcutaneous aortic valve implantation (TAVI), especially in octogenarian patients. However, a knowledge gap exists on patient experiences of sleep and delirium. In particular, patients’ long-term sleep and delirium experiences are unknown. This article explores and describes how octogenarian patients suffering from delirium after aortic valve replacement experience their sleep and delirium situation.DesignAn explorative and descriptive design with a longitudinal qualitative approach was applied. Qualitative content analysis following the recommended steps of Graneheim and Lundman was performed.SettingPatients were included at a tertiary university hospital with 1400 beds. Delirium and insomnia screening was performed at baseline and five postoperative days after aortic valve treatment. For qualitative data, 10 patients were interviewed 6–12 months after treatment with focus on delirium. Five of these patients were reinterviewed 4 years after treatment, with focus on their sleep situation.ParticipantsInclusion criteria; age 80+, treated with SAVR or TAVI and had experienced delirium after treatment.ResultsFor the initial interview, we included five men and five women, four following TAVI and six following SAVR, mean age 83. One overarching theme revealed from the content analyses; Hours in bed represented emotional chaos. Whereas three subthemes described the patients’ experiences with sleep and delirium, a cascade of distressful experiences disturbing sleep, the struggle between sleep and activity and elements influencing sleep. Four years after the treatment, sleep disturbances persisted, and patients still remembered strongly the delirium incidences.ConclusionsFor octogenarian patients, sleep disturbances and delirium are long-term burdens and need a greater attention in order to improve patient care.
Batched Computation of the Singular Value Decompositions of Order Two by the AVX-512 Vectorization
Authors: Novaković Vedran 
Published: January 2021

In this paper a vectorized algorithm for simultaneously computing up to eight singular value decompositions (SVDs, each of the form [Formula: see text]) of real or complex matrices of order two is proposed. The algorithm extends to a batch of matrices of an arbitrary length [Formula: see text], that arises, for example, in the annihilation part of the parallel Kogbetliantz algorithm for the SVD of matrices of order [Formula: see text]. The SVD method for a single matrix of order two is derived first. It scales, in most instances error-free, the input matrix [Formula: see text] such that the scaled singular values cannot overflow whenever the elements of [Formula: see text] are finite, and then computes the URV factorization of the scaled matrix, followed by the SVD of the non-negative upper-triangular middle factor. A vector-friendly data layout for the batch is then introduced, where the same-indexed elements of each of the input and the output matrices form vectors, and the algorithm’s steps over such vectors are described. The vectorized approach is shown to be about three times faster than processing each matrix in the batch separately, while slightly improving accuracy over the straightforward method for the [Formula: see text] SVD.
Stable isotope and chemical stratigraphy of the Eocene Tambaba Formation: correlations with the Paleocene–Eocene Thermal Maximum event
Authors: Veras José Diego Dias , de Souza Neto João Adauto , Sial Alcides Nóbrega , Ferreira Valderez Pinto , Neumann Virgínio Henrique de Miranda Lopes 
Published: January 2021

Abstract

The Paraíba Basin has a well-defined carbonate depositional sequence from the Upper Cretaceous (Campanian) to the Eocene. The carbonate sequence consists of the Itamaracá, Gramame, Maria Farinha and Tambaba formations, which mainly contain calcareous sandstones and carbonates with siliciclastics, limestone–marl alternations, limestones and marls, and limestones, respectively. The Tambaba Formation is composed of reef limestones, ranging from fossil- and ichnofossil-rich calcilutite to calcarenite. We investigated rocks of this unit located in a representative geological section at the Tambaba Beach, northeastern Brazil, in order to elucidate the environmental responses recorded in geochemical proxies (C and O isotopic composition, and distribution of major and trace elements). The
δ
13
C and
δ
18
O values ranged from 1.0 to 2.7‰ VPDB and from −1.3 to 1.1‰ VPDB, respectively. The interpretation of this response suggests environmental changes, such as an increase or decrease in bioproductivity of the organisms that make up these reef limestones. These changes are also recorded in the behaviour of the major and trace elements – for example, the relationship between SiO
2
, Al
2
O
3
, MgO and CaO, characterizing two different cycles during the deposition of these limestones: the first one characterized by a predominantly carbonate deposition, and the second one presenting a pulse of siliciclastic content. In addition, palaeotemperature values (9–15°C, from
δ
18
O data) obtained, together with chemostratigraphic profiles of previous studies (e.g.
δ
13
C, CaO, MgO, SiO
2
, Al
2
O
3
), indicate that the reef limestones of the Tambaba Formation were probably deposited about 5 myr after the Paleocene–Eocene Thermal Maximum event.
Serine-Threonine Kinase TAO3-Mediated Trafficking of Endosomes Containing the Invadopodia Scaffold TKS5α Promotes Cancer Invasion and Tumor Growth
Authors: Iizuka Shinji , Quintavalle Manuela , Navarro Jose C. , Gribbin Kyle P. , Ardecky Robert J. , Abelman Matthew M. , Ma Chen-Ting , Sergienko Eduard , Zeng Fu-Yue , Pass Ian , Thomas George V. , McWeeney Shannon K. , Hassig Christian A. , Pinkerton Anthony B. , Courtneidge Sara A. 
Published: January 2021

AbstractInvadopodia are actin-based proteolytic membrane protrusions required for invasive behavior and tumor growth. In this study, we used our high-content screening assay to identify kinases whose activity affects invadopodia formation. Among the top hits selected for further analysis was TAO3, an STE20-like kinase of the GCK subfamily. TAO3 was overexpressed in many human cancers and regulated invadopodia formation in melanoma, breast, and bladder cancers. Furthermore, TAO3 catalytic activity facilitated melanoma growth in three-dimensional matrices and in vivo. A novel, potent catalytic inhibitor of TAO3 was developed that inhibited invadopodia formation and function as well as tumor cell extravasation and growth. Treatment with this inhibitor demonstrated that TAO3 activity is required for endosomal trafficking of TKS5α, an obligate invadopodia scaffold protein. A phosphoproteomics screen for TAO3 substrates revealed the dynein subunit protein LIC2 as a relevant substrate. Knockdown of LIC2 or expression of a phosphomimetic form promoted invadopodia formation. Thus, TAO3 is a new therapeutic target with a distinct mechanism of action.Significance:An unbiased screening approach identifies TAO3 as a regulator of invadopodia formation and function, supporting clinical development of this class of target.
Double-hit Signature with TP53 Abnormalities Predicts Poor Survival in Patients with Germinal Center Type Diffuse Large B-cell Lymphoma Treated with R-CHOP
Authors: Song Joo Y. , Perry Anamarija M. , Herrera Alex F. , Chen Lu , Skrabek Pamela , Nasr Michel R. , Ottesen Rebecca A. , Nikowitz Janet , Bedell Victoria , Murata-Collins Joyce , Li Yuping , McCarthy Christine , Pillai Raju , Wang Jinhui , Wu Xiwei , Zain Jasmine , Popplewell Leslie , Kwak Larry W. , Nademanee Auayporn P. , Niland Joyce C. , Scott David W. , Gong Qiang , Chan Wing C. , Weisenburger Dennis D. 
Published: January 2021

Abstract

Purpose:
We performed detailed genomic analysis on 87 cases of de novo diffuse large B-cell lymphoma of germinal center type (GCB DLBCL) to identify characteristics that are associated with survival in those treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).

Experimental Design:
The cases were extensively characterized by combining the results of IHC, cell-of-origin gene expression profiling (GEP; NanoString), double-hit GEP (DLBCL90), FISH cytogenetic analysis for double/triple-hit lymphoma, copy-number analysis, and targeted deep sequencing using a custom mutation panel of 334 genes.

Results:
We identified four distinct biologic subgroups with different survivals, and with similarities to the genomic classifications from two large retrospective studies of DLBCL. Patients with the double-hit signature, but no abnormalities of TP53, and those lacking EZH2 mutation and/or BCL2 translocation, had an excellent prognosis. However, patients with an EZB-like profile had an intermediate prognosis, whereas those with TP53 inactivation combined with the double-hit signature had an extremely poor prognosis. This latter finding was validated using two independent cohorts.

Conclusions:
We propose a practical schema to use genomic variables to risk-stratify patients with GCB DLBCL. This schema provides a promising new approach to identify high-risk patients for new and innovative therapies.
ARID1A Mutation May Define an Immunologically Active Subgroup in Patients with Microsatellite Stable Colorectal Cancer
Authors: Mehrvarz Sarshekeh Amir , Alshenaifi Jumanah , Roszik Jason , Manyam Ganiraju C. , Advani Shailesh M. , Katkhuda Riham , Verma Anuj , Lam Michael , Willis Jason , Shen John Paul , Morris Jeffrey , Davis Jennifer S. , Loree Jonathan M. , Lee Hey Min , Ajani Jaffer A. , Maru Dipen M. , Overman Michael J. , Kopetz Scott 
Published: January 2021

AbstractPurpose:AT-rich interactive domain 1A (ARID1A) is commonly mutated in colorectal cancer, frequently resulting in truncation and loss of protein expression. ARID1A recruits MSH2 for mismatch repair during DNA replication. ARID1A deficiency promotes hypermutability and immune activation in preclinical models, but its role in patients with colorectal cancer is being explored.Experimental Design:The DNA sequencing and gene expression profiling of patients with colorectal cancer were extracted from The Cancer Genome Atlas and MD Anderson Cancer Center databases, with validation utilizing external databases, and correlation between ARID1A and immunologic features. IHC for T-cell markers was performed on a separate cohort of patients.Results:Twenty-eight of 417 patients with microsatellite stable (MSS) colorectal cancer (6.7%) had ARID1A mutation. Among 58 genes most commonly mutated in colorectal cancer, ARID1A mutation had the highest increase with frameshift mutation rates in MSS cases (8-fold, P &lt; 0.001). In MSS, ARID1A mutation was enriched in immune subtype (CMS1) and had a strong correlation with IFNγ expression (Δz score +1.91, P &lt; 0.001). Compared with ARID1A wild-type, statistically significant higher expression for key checkpoint genes (e.g., PD-L1, CTLA4, and PDCD1) and gene sets (e.g., antigen presentation, cytotoxic T-cell function, and immune checkpoints) was observed in mutant cases. This was validated by unsupervised differential expression of genes related to immune response and further confirmed by higher infiltration of T cells in IHC of tumors with ARID1A mutation (P = 0.01).Conclusions:The immunogenicity of ARID1A-mutant cases is likely due to an increased level of neoantigens resulting from increased tumor mutational burden and frameshift mutations. Tumors with ARID1A mutation may be more susceptible to immune therapy–based treatment strategies and should be recognized as a unique molecular subgroup in future immune therapy trials.
O desafio de ensinar História em cursos de Relações Internacionais
Authors: Mros Günther Richter 
Published: January 2021

O presente artigo aborda o desafio que existe no ensino de História para cursos de Relações Internacionais. Trata-se de uma breve reflexão sobre conceitos-chave da disciplina de História das Relações Internacionais e de sua aplicabilidade em uma disciplina oferecida no curso de graduação da Universidade Federal de Santa Maria. As reflexões aqui contidas foram inspiradas na carreira exemplar do Professor Emérito da Universidade de Brasília, Amado Luiz Cervo, a quem o autor deve muito de sua formação e escolhas profissionais.
Heterogeneity of Cerebral White Matter Lesions and Clinical Correlates in Older Adults
Authors: Jung Keun-Hwa , Stephens Kimberly A. , Yochim Kathryn M. , Riphagen Joost M. , Kim Chan Mi , Buckner Randy L. , Salat David H. 
Published: January 2021

Background and Purpose:
Cerebral white matter signal abnormalities (WMSAs) are a significant radiological marker associated with brain and vascular aging. However, understanding their clinical impact is limited because of their pathobiological heterogeneity. We determined whether use of robust reliable automated procedures can distinguish WMSA classes with different clinical consequences.

Methods:
Data from generally healthy participants aged >50 years with moderate or greater WMSA were selected from the Human Connectome Project-Aging (n=130). WMSAs were segmented on T1 imaging. Features extracted from WMSA included total and regional volume, number of discontinuous clusters, size of noncontiguous lesion, contrast of lesion intensity relative to surrounding normal appearing tissue using a fully automated procedure. Hierarchical clustering was used to classify individuals into distinct classes of WMSA. Radiological and clinical variability was evaluated across the individual WMSA classes.

Results:
Class I was characterized by multiple, small, lower-contrast lesions predominantly in the deep WM; class II by large, confluent lesions in the periventricular WM; and class III by higher-contrast lesions restricted to the juxtaventricular WM. Class II was associated with lower myelin content than the other 2 classes. Class II was more prevalent in older subjects and was associated with a higher prevalence of hypertension and lower physical activity levels. Poor sleep quality was associated with a greater risk of class I.

Conclusions:
We classified heterogeneous subsets of cerebral white matter lesions into distinct classes that have different clinical risk factors. This new method for identifying classes of WMSA will be important in understanding the underlying pathophysiology and in determining the impact on clinical outcomes.
De and Virtue in Early Confucian Texts: Introduction
Authors: Yao Xinzhong 
Published: January 2021

Abstract
The introduction to this special issue describes the emergence of the virtue ethics approach within the study of Confucian virtues in recent decades. It will first examine scholarly contributions to the discussion of Confucian virtue ethics and then raises questions concerning whether or not de 德 in early Confucian texts is identical with arête or virtue. It will then investigate the meaning and implication of de in Confucian contexts and make an argument for a new type of Confucian de ethics. It will finally come to the project on de and virtue ethics in early Confucian texts and define its purpose and boundaries.
Identifying the sequence specificities of circRNA-binding proteins based on a capsule network architecture
Authors: Wang Zhengfeng , Lei Xiujuan 
Published: January 2021

Abstract
Background
Circular RNAs (circRNAs) are widely expressed in cells and tissues and are involved in biological processes and human diseases. Recent studies have demonstrated that circRNAs can interact with RNA-binding proteins (RBPs), which is considered an important aspect for investigating the function of circRNAs.

Results
In this study, we design a slight variant of the capsule network, called circRB, to identify the sequence specificities of circRNAs binding to RBPs. In this model, the sequence features of circRNAs are extracted by convolution operations, and then, two dynamic routing algorithms in a capsule network are employed to discriminate between different binding sites by analysing the convolution features of binding sites. The experimental results show that the circRB method outperforms the existing computational methods. Afterwards, the trained models are applied to detect the sequence motifs on the seven circRNA-RBP bound sequence datasets and matched to known human RNA motifs. Some motifs on circular RNAs overlap with those on linear RNAs. Finally, we also predict binding sites on the reported full-length sequences of circRNAs interacting with RBPs, attempting to assist current studies. We hope that our model will contribute to better understanding the mechanisms of the interactions between RBPs and circRNAs.

Conclusion
In view of the poor studies about the sequence specificities of circRNA-binding proteins, we designed a classification framework called circRB based on the capsule network. The results show that the circRB method is an effective method, and it achieves higher prediction accuracy than other methods.
Predicting chemosensitivity using drug perturbed gene dynamics
Authors: Mannheimer Joshua D. , Prasad Ashok , Gustafson Daniel L. 
Published: January 2021

Abstract
Background
One of the current directions of precision medicine is the use of computational methods to aid in the diagnosis, prognosis, and treatment of disease based on data driven approaches. For instance, in oncology, there has been a particular focus on development of algorithms and biomarkers that can be used for pre-clinical and clinical applications. In particular large-scale omics-based models to predict drug sensitivity in in vitro cancer cell line panels have been used to explore the utility and aid in the development of these models as clinical tools. Additionally, a number of web-based interfaces have been constructed for researchers to explore the potential of drug perturbed gene expression as biomarkers including the NCI Transcriptional Pharmacodynamic Workbench. In this paper we explore the influence of drug perturbed gene dynamics of the NCI Transcriptional Pharmacodynamics Workbench in computational models to predict in vitro drug sensitivity for 15 drugs on the NCI60 cell line panel.

Results
This work presents three main findings. First, our models show that gene expression profiles that capture changes in gene expression after 24 h of exposure to a high concentration of drug generates the most accurate predictive models compared to the expression profiles under different dosing conditions. Second, signatures of 100 genes are developed for different gene expression profiles; furthermore, when the gene signatures are applied across gene expression profiles model performance is substantially decreased when gene signatures developed using changes in gene expression are applied to non-drugged gene expression. Lastly, we show that the gene interaction networks developed on these signatures show different network topologies and can be used to inform selection of cancer relevant genes.

Conclusion
Our models suggest that perturbed gene signatures are predictive of drug response, but cannot be applied to predict drug response using unperturbed gene expression. Furthermore, additional drug perturbed gene expression measurements in in vitro cell lines could generate more predictive models; but, more importantly be used in conjunction with computational methods to discover important drug disease relationships.