bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gut microbiome and health: mechanistic insights
Authors: de Vos Willem M , Tilg Herbert , Van Hul Matthias , Cani Patrice D 
Published: February 2022

The gut microbiota is now considered as one of the key elements contributing to the regulation of host health. Virtually all our body sites are colonised by microbes suggesting different types of crosstalk with our organs. Because of the development of molecular tools and techniques (ie, metagenomic, metabolomic, lipidomic, metatranscriptomic), the complex interactions occurring between the host and the different microorganisms are progressively being deciphered. Nowadays, gut microbiota deviations are linked with many diseases including obesity, type 2 diabetes, hepatic steatosis, intestinal bowel diseases (IBDs) and several types of cancer. Thus, suggesting that various pathways involved in immunity, energy, lipid and glucose metabolism are affected.In this review, specific attention is given to provide a critical evaluation of the current understanding in this field. Numerous molecular mechanisms explaining how gut bacteria might be causally linked with the protection or the onset of diseases are discussed. We examine well-established metabolites (ie, short-chain fatty acids, bile acids, trimethylamine N-oxide) and extend this to more recently identified molecular actors (ie, endocannabinoids, bioactive lipids, phenolic-derived compounds, advanced glycation end products and enterosynes) and their specific receptors such as peroxisome proliferator-activated receptor alpha (PPARα) and gamma (PPARγ), aryl hydrocarbon receptor (AhR), and G protein-coupled receptors (ie, GPR41, GPR43, GPR119, Takeda G protein-coupled receptor 5).Altogether, understanding the complexity and the molecular aspects linking gut microbes to health will help to set the basis for novel therapies that are already being developed.
Exosomes derived from γδ-T cells synergize with radiotherapy and preserve antitumor activities against nasopharyngeal carcinoma in immunosuppressive microenvironment
Authors: Wang Xiwei , Zhang Yanmei , Mu Xiaofeng , Tu Chloe Ran , Chung Yuet , Tsao Sai Wah , Chan Godfrey Chi-Fung , Leung Wing-Hang , Lau Yu-lung , Liu Yinping , Tu Wenwei 
Published: February 2022

BackgroundRadiotherapy is the first-line treatment for patients nasopharyngeal carcinoma (NPC), but its therapeutic efficacy is poor in some patients due to radioresistance. Adoptive T cell-based immunotherapy has also shown promise to control NPC; however, its antitumor efficacy may be attenuated by an immunosuppressive tumor microenvironment. Exosomes derived from γδ-T cells (γδ-T-Exos) have potent antitumor potentials. However, it remains unknown whether γδ-T-Exos have synergistic effect with radiotherapy and preserve their antitumor activities against NPC in an immunosuppressive tumor microenvironment.Methodsγδ-T-Exos were stained with fluorescent membrane dye, and their interactions with NPC were determined both in vitro and in vivo. NPC cell deaths were detected after treatment with γδ-T-Exos and/or irradiation. Moreover, effects of γδ-T-Exos on radioresistant cancer stem-like cells (CSCs) were determined. The therapeutic efficacy of combination therapy using γδ-T-Exos and irradiation on NPC tumor progression was also monitored in vivo. Finally, the tumor-killing and T cell-promoting activities of γδ-T-Exos were determined under the culture in immunosuppressive NPC supernatant.Resultsγδ-T-Exos effectively interacted with NPC tumor cells in vitro and in vivo. γδ-T-Exos not only killed NPC cells in vitro, which was mainly mediated by Fas/Fas ligand (FasL) and death receptor 5 (DR5)/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathways, but also controlled NPC tumor growth and prolonged tumor-bearing mice survival in vivo. Furthermore, γδ-T-Exos selectively targeted the radioresistant CD44+/highCSCs and induced profound cell apoptosis. The combination of γδ-T-Exos with radiotherapy overcame the radioresistance of CD44+/highNPC cells and significantly improved its therapeutic efficacy against NPC in vitro and in vivo. In addition, γδ-T-Exos promoted T-cell migration into NPC tumors by upregulating CCR5 on T cells that were chemoattracted by CCR5 ligands in the NPC tumor microenvironment. Although NPC tumor cells secreted abundant tumor growth factor beta to suppress T-cell responses, γδ-T-Exos preserved their direct antitumor activities and overcame the immunosuppressive NPC microenvironment to amplify T-cell antitumor immunity.Conclusionsγδ-T-Exos synergized with radiotherapy to control NPC by overcoming the radioresistance of NPC CSCs. Moreover, γδ-T-Exos preserved their tumor-killing and T cell-promoting activities in the immunosuppressive NPC microenvironment. This study provides a proof of concept for a novel and potent strategy by combining γδ-T-Exos with radiotherapy in the control of NPC.
Immune Activity and Response Differences of Oncolytic Viral Therapy in Recurrent Glioblastoma: Gene Expression Analyses of a Phase IB Study
Authors: Miller Katherine E. , Cassady Kevin A. , Roth Justin C. , Clements Jennifer , Schieffer Kathleen M. , Leraas Kristen , Miller Anthony R. , Prasad Nripesh , Leavenworth Jianmei W. , Aban Inmaculada B. , Whitley Richard J. , Gillespie G. Yancey , Mardis Elaine R. , Markert James M. 
Published: February 2022

Abstract

Purpose:
Previously, clinical trials of experimental virotherapy for recurrent glioblastoma multiforme (GBM) demonstrated that inoculation with a conditionally replication–competent Δγ134.5 oncolytic herpes simplex virus (oHSV), G207, was safe. Following the initial safety study, a phase Ib trial enrolled 6 adult patients diagnosed with GBM recurrence from which tumor tissue was banked for future studies.

Patients and Methods:
Here, we analyzed tumor RNA sequencing (RNA-seq) data obtained from pre- and posttreatment (collected 2 or 5 days after G207 injection) biopsies from the phase Ib study patients.

Results:
Using a Spearman rank-order correlation analysis, we identified approximately 500 genes whose expression pattern correlated with survival duration. Many of these genes were enriched for the intrinsic IFN-mediated antiviral and adaptive immune functional responses, including immune cell chemotaxis and antigen presentation to T-cells. Furthermore, we show that the expression of several T-cell–related genes was highest in the patient with the longest survival after G207 inoculation.

Conclusions:
Our data support that the oHSV-induced type I IFN production and the subsequent recruitment of an adaptive immune response differed between enrolled patients and showed association with survival duration in patients with recurrent malignant glioma after treatment with an early generation oHSV.
Blocking PI3K p110β Attenuates Development of PTEN-Deficient Castration-Resistant Prostate Cancer
Authors: Gao Xueliang , Wang Yubao , Ribeiro Caroline F. , Manokaran Cherubin , Chang Hyeyoun , Von Thanh , Rodrigues Silvia , Cizmecioglu Onur , Jia Shidong , Korpal Manav , Korn Joshua M. , Wang Zhigang , Schmit Fabienne , Jiang Lan , Pagliarini Raymond , Yang Yi , Sethi Isha , Signoretti Sabina , Yuan Guo-Cheng , Loda Massimo , Zhao Jean J. , Roberts Thomas M. 
Published: February 2022

Abstract

A common outcome of androgen deprivation in prostate cancer therapy is disease relapse and progression to castration-resistant prostate cancer (CRPC) via multiple mechanisms. To gain insight into the recent clinical findings that highlighted genomic alterations leading to hyperactivation of PI3K, we examined the roles of the commonly expressed p110 catalytic isoforms of PI3K in a murine model of Pten-null invasive CRPC. While blocking p110α had negligible effects in the development of Pten-null invasive CRPC, either genetic or pharmacologic perturbation of p110β dramatically slowed CRPC initiation and progression. Once fully established, CRPC tumors became partially resistant to p110β inhibition, indicating the acquisition of new dependencies. Driven by our genomic analyses highlighting potential roles for the p110β/RAC/PAK1 and β-catenin pathways in CRPC, we found that combining p110β with RAC/PAK1 or tankyrase inhibitors significantly reduced the growth of murine and human CRPC organoids in vitro and in vivo. Because p110β activity is dispensable for most physiologic processes, our studies support novel therapeutic strategies both for preventing disease progression into CRPC and for treating CRPC.

Implications:
This work establishes p110β as a promising target for preventing the progression of primary PTEN-deficient prostate tumors to CRPC, and for treating established CRPC in combination with RAC/PAK1 or tankyrase inhibitors.
Robustness of Competing Climatic States
Authors: Ragon Charline , Lembo Valerio , Lucarini Valerio , Vérard Christian , Kasparian Jérôme , Brunetti Maura 
Published: February 2022

AbstractThe climate is a nonequilibrium system undergoing the continuous action of forcing and dissipation. Under the effect of a spatially inhomogeneous absorption of solar energy, all the climate components dynamically respond until an approximate steady state (or attractor) is reached. However, multiple steady states can coexist for a given forcing and with the same boundary conditions. Here, we apply the Thermodynamic Diagnostic Tool (TheDiaTo) to investigate the statistical properties of five coexisting climates, ranging from a snowball to an ice-free aquaplanet, obtained in MITgcm coupled simulations. The aim is to explore the multistability of the climate model setup by highlighting differences in competing steady states and their characteristic signatures regarding the meridional transport of heat and water mass, the Lorenz energy cycle, and the material entropy production. We also investigate how such attractors change when the model configuration is varied. We consider, in particular, the effect of changing the representation of the cloud albedo, and of implementing an improved closure of the energy budget. We find that, even if the dynamics remain on the same attractor, state variables are modified. The set of metrics in TheDiaTo quantifies such modifications and represents a valuable tool for model evaluation.
Iron Pill-Induced Chemical Laryngitis
Authors: Sethia Rishabh , Bishop Ryan , Gordian-Arroyo Adlin , Matrka Laura 
Published: February 2022

Objective: To discuss the presentation and management of pill-induced chemical laryngitis by illustrating a rare case. Methods: We report a unique case of a patient with iron pill-induced laryngitis. Results: A 71-year-old male presented for evaluation of dysphonia. Five weeks prior, the patient had reportedly aspirated an iron pill. The pill was lodged in his throat for several hours before being coughed up, soft but still intact. Since that event, the patient noted complete voice loss and in clinic was found to have a very breathy and asthenic voice. Stroboscopy revealed aperiodicity with severe false fold compression and significant ulceration of the infraglottic region associated with thick exudate. Vocal folds were mobile but atrophic, with overlying crusted secretions. A sensory deficit was suspected based on scope tolerance. The patient was treated with nebulized ciprodex and humidified air with some improvement in mucosal crusting but had persistent glottic insufficiency and dysphonia, prompting bilateral hyaluronic acid injection. Conclusions: Pill-induced laryngitis is an extremely rare phenomenon. While typically associated with bisphosphonates, this condition should be considered in any patient presenting with dysphonia and history of aspiration of a pill, including iron supplements. Regardless of the inciting medication, pill-induced laryngitis may be treated with humidified air, nebulized steroids, and antibiotics. Injection augmentation of the vocal folds may be made considered when glottic insufficiency and weak cough contribute to the presentation.
The Arts and Civic Space: An Experiment in Community Education
Authors: Mccue Frances 
Published: February 2022

Background/Context While the arts are being elbowed out of school curricula, new community-based education venues for the arts are emerging in cities across the country. This article describes Richard Hugo House, an arts center for creative writing in Seattle, which attracts people of different ages and sociocultural backgrounds who participate in not only writing studios, but in a wide range of activities such as literary readings and plays. Hugo House also maintains a gallery, a café, and a “zine” library, an underground collection of almost 16,000 homemade magazines from around the world. It has come to function as a civic space for the arts that fosters in participants not only a range of real-life skills, but also a sense of democratic values. Purpose This essay explores the theoretical underpinnings of a community learning place for the arts and includes some observations about how people of different backgrounds, ages, and skill levels engage with an art form and how the art becomes a pivot of dialogue for a larger community. Research Design In this particular civic arts space, I am identifying traits that make the learning environment a vibrant and inspiring one. For example, at Richard Hugo House, we are able to ask: “What do people need as they are learning to write? What does anyone coming to an artistic enterprise need? How does she sustain her work and improve her craft?” and we can trace the responses to these questions through the experiences of particular students and their teachers. Conclusions/Recommendations Good teaching in this informal setting is idealistic and pragmatic: it gives voice to more stories, and more stories help us see the “what ifs” of the world. Teaching at Hugo House facilitates more than it instructs—it's a process theory approach and our observations are grounded similarly—in action research. While good teaching lets more people be the tellers of their stories, it also helps to hone and craft them, making both the story and the telling of it culturally urgent. That, at its best, is highly democratic.
Contact Intervention Programs for Peace Education and the Reality of Dynamic Conflicts
Authors: Yablon Yaacov Boaz 
Published: February 2022

Background Great efforts are made to develop and implement contact activities for groups in conflict, yet studies of effects of planned contact interventions yielded mixed results. Previous attempts to explain why contact interventions do not fulfill their promise focused on the contact itself. However, the main focus of the present study was the underlying prevention strategy and the implementation of contact interventions. This was done in the context of planned face-to-face encounters between Jewish and Arab high school students in Israel. Purpose of Study The aim of this study was to examine whether there is a unique embodiment of a social conflict in different subgroups of one prototypical social group. It has been suggested that one of the reasons for the failure of contact intervention programs is that they are usually based on a primary prevention strategy, which does not consider intragroup differences or developments over time. Population The research sample consisted of 255 Israeli Jewish and Israeli Arab students who intended to participate in a peace education encounter program. Participants in the study were 17-year-old 11th-grade students from 12 classes—6 in Jewish high schools and 6 in Arab high schools. Research Design Quantitative analysis was used to measure differences within and between groups at the onset of a contact intervention program. Data were collected at three waves (three different points in time). Each wave was held for a few days, usually within a week, before the onset of the planned encounters. In each wave, two schools, one Jewish and one Arab, were sampled. The waves were 2 months apart, so that all questionnaires were collected within a 6-month period. Findings Results revealed significant differences within the subgroups in the perceptional and affective domains but not in variables indicating behavioral aspects of social relationships. Additional findings regarding differences between groups (majority and minority) suggested that the majority group was less negative toward the minority group than the minority group was toward the majority. Conclusions Results suggest that although mutual relationships between groups are negatively based, they are neither stable nor monolithic. Within a social group, different subgroups hold and present different attitudes, perceptions, and feelings toward their counterparts. Therefore, peace education programs, and especially face-to-face contact intervention, should be based on secondary intervention strategies and not, as is often the case, on primary prevention strategies.
William C. Bagley and the Founding of Essentialism: An Untold Story in American Educational History
Authors: Null J. Wesley 
Published: February 2022

Background/Context Most people who study the history and philosophy of education have heard of essentialism, but few people know the story behind how, when, and why the movement came to exist. This paper tells this story for the first time. Purpose/Conclusions This essay has three purposes. First, it provides an introduction to the life and career of William Chandler Bagley, a prominent professor of education at Teachers College, Columbia University, from 1917 until his retirement in 1939. Following an introduction to Bagley's life, this work describes the founding of essentialism by drawing upon numerous primary and secondary sources to place this movement within the social and historical context in which it developed. The author pays careful attention to the story of how and why the founding of essentialism took place on the same day that John Dewey delivered his “Experience and Education” lecture at the 12th biennial convocation of Kappa Delta Pi. The paper then argues that what came to be known as essentialism represents a forgotten tradition in American educational history, one that is much richer than contemporary calls for “standards and accountability,” which grew out of the economically driven “A Nation at Risk” report of 1983. To conclude, the essay calls for more substantive attention to liberal education, purpose, moral philosophy, and curriculum for teaching teachers, all of which were at the heart of essentialist educational thought, but are now forgotten in an age obsessed with economic efficiency. The author calls upon contemporary leaders in American education to reconsider essentialism as a powerful philosophy that has great potential for the future of the teaching profession. Research Design This paper is written from the perspective of history and is based upon the long-established methodology from the field of historiography.
The March of Remembrance and Hope: Teaching and Learning about Diversity and Social Justice through the Holocaust
Authors: Spalding Elizabeth , Savage Todd A. , Garcia Jesus 
Published: February 2022

Background Experiential learning has been posited as an approach to influencing preservice teachers’ understanding of diversity and social justice. The research reported here examined the impact of a field-based experience in Poland focused on the Holocaust as it pertained to the beliefs and actions of 12 future education professionals. This program, the March of Remembrance and Hope (MRH), took place in Poland in May 2003; the pretrip preparation occurred in January-May 2003 at a large southeastern university. Five of the participants were preservice teachers, and 7 were graduate students in either counseling psychology or school psychology. The MRH is an international interfaith trip to Holocaust sites in Poland, sponsored by the March of the Living, Israel. The MRH educates participants, primarily Gentiles, about the Holocaust and the dangers of intolerance and racism. Purpose of Study The authors are teacher educators committed to multicultural teacher education and teaching about social justice. Thus, we generated the following questions to guide this research: (1) How did the experience of the MRH influence participants’ knowledge of, attitudes about, and actions regarding diversity? (2) How, if at all, did participants connect the MRH experience to issues of social justice? Research Design Three case studies, exemplars of the impact of this experience, are presented and discussed in relation to the literature on effective multicultural teacher education, experiential education, and Holocaust education. Conclusions Results indicated that the MRH had a significant effect on the thinking and actions of students related to diversity and social justice. If the goal of multicultural education is to facilitate changes in future education professionals’ knowledge, beliefs, and actions, then it is important to take note of the aspects of the MRH experience that so affected Silas, Rachel, and Penny, the students described in the case studies. The literature on teacher education for diversity indicates that traditional approaches to multicultural education have minimal long-term impact. By contrast, the effects of the MRH took time to process and, as of this writing, appear not to have faded over time. And, although the academic preparation was critical to their understanding of the Holocaust, the authentic experience of the MRH had the greatest impact on these students’ thinking about diversity and their willingness to take action against social injustice.