Conversion of Anergic T Cells Into Foxp3−^- IL-10+^+ Regulatory T Cells by a Second Antigen Stimulus In Vivo

T cell anergy is a common mechanism of T cell tolerance. However, although anergic T cells are retained for longer time periods in their hosts, they remain functionally passive. Here, we describe the induction of anergic CD4$^+$ T cells in vivo by intravenous application of high doses of antigen and their subsequent conversion into suppressive Foxp3$^-$ IL-10$^+$ Tr1 cells but not Foxp3$^+$ Tregs. We describe the kinetics of up-regulation of several memory-, anergy- and suppression-related markers such as CD44, CD73, FR4, CD25, CD28, PD-1, Egr-2, Foxp3 and CTLA-4 in this process. The conversion into suppressive Tr1 cells correlates with the transient intracellular CTLA-4 expression and required the restimulation of anergic cells in a short-term time window. Restimulation after longer time periods, when CTLA-4 is down-regulated again retains the anergic state but does not lead to the induction of suppressor function. Our data require further functional investigations but at this stage may suggest a role for anergic T cells as a circulating pool of passive cells that may be re-activated into Tr1 cells upon short-term restimulation with high and systemic doses of antigen. It is tentative to speculate that such a scenario may represent cases of allergen responses in non-allergic individuals

Why do Asian-American women have lower rates of breast conserving surgery: results of a survey regarding physician perceptions

<p>Abstract</p> <p>Background</p> <p>US Asian women with early-stage breast cancer are more likely to receive a modified radical mastectomy (MRM) than White women, contrary to clinical recommendations regarding breast conserving treatment (BCT).</p> <p>Methods</p> <p>We surveyed physicians regarding treatment decision-making for early-stage breast cancer, particularly as it applies to Asian patients. Physicians were identified through the population-based Greater Bay Area Cancer Registry. Eighty (of 147) physicians completed a questionnaire on sociodemographics, professional training, clinical practices, and perspectives on the treatment decision-making processes.</p> <p>Results</p> <p>The most important factors identified by physicians in the BCT/MRM decision were clinical in nature, including presence of multifocal disease (86% identified this as being an important factor for selecting MRM), tumor size (71% for MRM, 78% for BCT), cosmetic result (74% for BCT), and breast size (50% for MRM, 55% for BCT). The most important reasons cited for the Asian treatment patterns were patient attitudes toward not needing to preserve the breast (53%), smaller breast sizes (25%), and fear and cultural beliefs (12%).</p> <p>Conclusion</p> <p>These survey results suggest that physicians perceive major roles of both clinical and cultural factors in the BCT/MRM decision, but cultural factors may be more relevant in explaining surgical treatment patterns among Asians.</p

Syllable Weakening in Kagoshima Japanese An Element-Based Analysis

This paper examines syllable weakening or nisshōka (入声化) in Kagoshima Japanese (KJ), where high vowel apocope feeds lenition, leading to correspondences such as Tōkyō Japanese (TJ) [kaki] ‘persimmon’ and Kagoshima [kaʔ]. The traditional pattern noted in the literature is quite clear. Apocope elides stem-final /u/ or /i/. The preceding onset is lenited in one of four ways: 1) stops and affricates are debuccalised (/kaki/ > [kaʔ] ‘persimmon’); 2) fricatives undergo voicing neutralisation (TJ [kazu] > KJ [kas] ‘number’); 3) nasals undergo place loss (TJ [kami] > KJ [kaɴ] ‘paper’); 4) rhotics undergo gliding (TJ [maru] > [maj] ‘round’). This paper presents an initial analysis of the data within Element Theory representational framework

PATHWAYS TO AND FROM SOCIAL WITHDRAWAL: ANTECEDENTS, CORRELATES, CONSEQUENCES, AND CONSIDERATIONS FOR EVALUATING DIMENSIONS OF SOCIAL WITHDRAWAL IN ADOLESCENTS

Research into child and adolescent social withdrawal has identified multiple forms of withdrawal behavior, most of which fall under the subtypes of shyness or preference for solitude. Social withdrawal can lead to a variety of maladjustment outcomes, though there is evidence to suggest that the trajectory might differ depending on the form and function of social withdrawal experienced. However, much of the previous research in this area has failed to account for the moderate correlation between shyness and preference for solitude, which calls into question findings on distinctions between these two forms. We investigated the antecedents, correlates, and consequences of shyness and preference for solitude with a sample of 408 adolescents over a three-year period. Each analysis examining one form of social withdrawal included the other form of withdrawal as a covariate in order to control for the impact of their shared variance. Similar concurrent and longitudinal adjustment correlates were found in shyness and preference for solitude. We discovered that controlling for the other form of social withdrawal revealed a significant decrease in numerous found effects, particularly those on or from internalizing behavior. We hope to emphasize the magnitude of this correlation between social withdrawal subtypes and encourage researchers in this area to control for this shared variance in future work, especially when examining distinctions between shyness and preference for solitude. Given the documented importance of childhood peer relationships for long-term personal and social development, accurately assessing these constructs is critical

Open science is good science, so what’s getting in the way?

The replication crisis in psychology has revealed that questionable research practices may have undermined the credibility of previously published research. This has led to meta-scientific efforts dedicated to improving research integrity and credibility by prioritizing transparency and reproducibility of research. This can be done through the use of open science practices, such as study preregistration, open data sharing, open source/code sharing, open-source publishing, and prioritizing replication studies. Many scientists agree that open science practices align with their scientific values, yet they are not currently standard practice. It is proposed that incentive structures that reduce the likelihood of adopting open science practices play a role in scientists’ decision-making as they design, conduct, analyze, and disseminate results from their research. In order to improve the quality of the scientific record, systemic paradigm shift must occur at each step along the way

Flt3L, LIF, and IL‐10 combination promotes the selective in vitro development of ESAMlow^{low} cDC2B from murine bone marrow

The development of two conventional dendritic cells (DC) subsets (cDC1 and cDC2) and the plasmacytoid DC (pDC) in vivo and in cultures of bone marrow (BM) cells is mediated by the growth factor Flt3L. However, little is known about the factors that direct the development of the individual DC subsets. Here, we describe the selective in vitro generation of murine ESAM$^{low}$ CD103$^{-}$ XCR1$^{-}$ CD172a$^{+}$ CD11b$^{+}$ cDC2 from BM by treatment with a combination of Flt3L, LIF, and IL‐10 (collectively named as FL10). FL10 promotes common dendritic cell progenitors (CDP) proliferation in the cultures, similar to Flt3L and CDP sorted and cultured in FL10 generate exclusively cDC2. These cDC2 express the transcription factors Irf4, Klf4, and Notch2, and their growth is reduced using BM from Irf4$^{-/-}$ mice, but the expression of Batf3 and Tcf4 is low. Functionally they respond to TLR3, TLR4, and TLR9 signals by upregulation of the surface maturation markers MHC II, CD80, CD86, and CD40, while they poorly secrete proinflammatory cytokines. Peptide presentation to TCR transgenic OT‐II cells induced proliferation and IFN‐γ production that was similar to GM‐CSF‐generated BM‐DC and higher than Flt3L‐generated DC. Together, our data support that FL10 culture of BM cells selectively promotes CDP‐derived ESAM$^{low}$ cDC2 (cDC2B) development and survival in vitro

Integration of nano- and biotechnology for beta-cell and islet transplantation in type-1 diabetes treatment.

Regenerative medicine using human or porcine β-cells or islets has an excellent potential to become a clinically relevant method for the treatment of type-1 diabetes. High-resolution imaging of the function and faith of transplanted porcine pancreatic islets and human stem cell-derived beta cells in large animals and patients for testing advanced therapy medicinal products (ATMPs) is a currently unmet need for pre-clinical/clinical trials. The iNanoBIT EU H2020 project is developing novel highly sensitive nanotechnology-based imaging approaches allowing for monitoring of survival, engraftment, proliferation, function and whole-body distribution of the cellular transplants in a porcine diabetes model with excellent translational potential to humans. We develop and validate the application of single-photon emission computed tomography (SPECT) and optoacoustic imaging technologies in a transgenic insulin-deficient pig model to observe transplanted porcine xeno-islets and in vitro differentiated human beta cells. We are progressing in generating new transgenic reporter pigs and human-induced pluripotent cell (iPSC) lines for optoacoustic imaging and testing them in transplantable bioartificial islet devices. Novel multifunctional nanoparticles have been generated and are being tested for nuclear imaging of islets and beta cells using a new, high-resolution SPECT imaging device. Overall, the combined multidisciplinary expertise of the project partners allows progress towards creating much needed technological toolboxes for the xenotransplantation and ATMP field, and thus reinforces the European healthcare supply chain for regenerative medicinal products

Integration of nano‐ and biotechnology for beta‐cell and islet transplantation in type‐1 diabetes treatment

Regenerative medicine using human or porcine β-cells or islets has an excellent potential to become a clinically relevant method for the treatment of type-1 diabetes. High-resolution imaging of the function and faith of transplanted porcine pancreatic islets and human stem cell-derived beta cells in large animals and patients for testing advanced therapy medicinal products (ATMPs) is a currently unmet need for pre-clinical/clinical trials. The iNanoBIT EU H2020 project is developing novel highly sensitive nanotechnology-based imaging approaches allowing for monitoring of survival, engraftment, proliferation, function and whole-body distribution of the cellular transplants in a porcine diabetes model with excellent translational potential to humans. We develop and validate the application of single-photon emission computed tomography (SPECT) and optoacoustic imaging technologies in a transgenic insulin-deficient pig model to observe transplanted porcine xeno-islets and in vitro differentiated human beta cells. We are progressing in generating new transgenic reporter pigs and human-induced pluripotent cell (iPSC) lines for optoacoustic imaging and testing them in transplantable bioartificial islet devices. Novel multifunctional nanoparticles have been generated and are being tested for nuclear imaging of islets and beta cells using a new, high-resolution SPECT imaging device. Overall, the combined multidisciplinary expertise of the project partners allows progress towards creating much needed technological toolboxes for the xenotransplantation and ATMP field, and thus reinforces the European healthcare supply chain for regenerative medicinal products

Attitudes and perceptions of radiologists towards online (virtual) oncologic multidisciplinary team meetings during the COVID-19 pandemic-a survey of the European Society of Oncologic Imaging (ESOI)

Objectives To explore radiologists' opinions regarding the shift from in-person oncologic multidisciplinary team meetings (MDTMs) to online MDTMs. To assess the perceived impact of online MDTMs, and to evaluate clinical and technical aspects of online meetings. Methods An online questionnaire including 24 questions was e-mailed to all European Society of Oncologic Imaging (ESOI) members. Questions targeted the structure and efficacy of online MDTMs, including benefits and limitations. Results A total of 204 radiologists responded to the survey. Responses were evaluated using descriptive statistical analysis. The majority (157/204; 77%) reported a shift to online MDTMs at the start of the pandemic. For the most part, this transition had a positive effect on maintaining and improving attendance. The majority of participants reported that online MDTMs provide the same clinical standard as in-person meetings, and that interdisciplinary discussion and review of imaging data were not hindered. Seventy three of 204 (35.8%) participants favour reverting to in-person MDTs, once safe to do so, while 7/204 (3.4%) prefer a continuation of online MDTMs. The majority (124/204, 60.8%) prefer a combination of physical and online MDTMs. Conclusions Online MDTMs are a viable alternative to in-person meetings enabling continued timely high-quality provision of care with maintained coordination between specialties. They were accepted by the majority of surveyed radiologists who also favoured their continuation after the pandemic, preferably in combination with in-person meetings. An awareness of communication issues particular to online meetings is important. Training, improved software, and availability of support are essential to overcome technical and IT difficulties reported by participants