bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cell metabolism in graft-versus-host disease
Authors: Zou Yujing , Chen Benny J. 
Published: November 2020

Abstract
Graft-versus-host disease (GVHD) is a major source of morbidity and mortality following allogeneic hematopoietic stem cell transplant (allo-HSCT), one of the most effective approaches to treat hematopoietic malignancies.
1
However, current prophylaxis regimens and treatments that reduce the detrimental effect of acute GVHD can be offset by increased incidence in opportunistic infections and relapse of the primary malignancy.
2
In addition, the majority of the approaches that inhibit T cell responses are non-specific, resulting in the inhibition of both alloreactive T cells and protective T cells from the donor. Therefore, there is an increase in the demand to develop novel approaches that selectively target alloreactive T cells. One potential means to address this issue is to take advantage of the unique metabolic profile of activated T cells.
Dynamic regulation of GATA2 in fate determination in hematopoiesis: possible approach to hPSC-derived hematopoietic stem/progenitor cells
Authors: Zhou Ya , Mao Bin , Chen Yijin , Xue Yuan , Chen Bo , Zhang Yonggang , Ma Feng 
Published: November 2020

Abstract
GATA2, a principal member of the GATA family, plays important roles in the generation and maintenance of hematopoietic stem/progenitor cells. Among the three mRNA transcripts, the distal first exon of GATA2 (IS exon) is specific for hematopoietic and neuronal cells. GATA2 mutants with abnormal expression are often present in acute myeloid leukemia-related familial diseases and myelodysplastic syndrome, indicating the crucial significance of GATA2 in the proper maintenance of blood system functions. This article offers an overview of the regulation dynamics and function of GATA2 in the generation, proliferation, and function of hematopoietic stem cells in both mouse and human models. We acknowledge the current progress in the cell fate determination mechanism by dynamic GATA2 expression. The gene modification approaches for inspecting the role of GATA2 in definitive hematopoiesis demonstrate the potential for acquiring hPSC-derived hematopoietic stem cells via manipulated GATA2 regulation.
Abnormal miR-214/A20 expression might play a role in T cell activation in patients with aplastic anemia
Authors: Yu Zhi , Chen Cunte , Xiao Yankai , Chen Xiaohui , Guo Lixing , Tan Guangxiao , Huang Guixuan , Luo Weifeng , Zhou Ming , Li Yumiao , Lin Chen , Shen Qi , Zhang Yuping , Li Bo 
Published: November 2020

Abstract
Aberrant T cell activation is a major cause of aplastic anemia (AA) pathogenesis. Recent studies have shown that miRNAs regulate T cell activation and are involved in AA. A previous study found that miR-214 was significantly up-regulated upon T cell activation in a CD28-dependent fashion by targeting PTEN. However, the expression characteristics of miR-214 and its target genes in AA have not been defined. In this study, target genes for miR-214 were predicted and confirmed by bioinformatics and luciferase reporter assays. The expression levels of miR-214 and target genes were detected in 36 healthy individuals and 35 patients with AA in peripheral blood mononuclear cells by real-time quantitative reverse transcriptase-polymerase chain reaction. Bioinformatics and luciferase reporter assays identified that miR-214 could bind to the A20 3′ untranslated regions. Significantly increased miR-214 and the decreased A20 expression level were detected in the AA patients compared with the healthy group. In addition, significantly increased miR-214 was found in non-severe aplastic anemia compared with severe aplastic anemia patients. These results suggested that the A20 gene was a potential target of miR-214, and elevated miR-214 might medicate T cell activation at least in part by regulating A20 expression in AA. We firstly confirmed that miR-214 regulated A20 expression, and aberrant miR-214/A20 expression might contribute to immunopathology in AA. The miR-214 expression might be used as a potential biomarker that assisted in diagnosing AA severity.
Loss of Tet2 affects platelet function but not coagulation in mice
Authors: Wang Bichen , Xia Meijuan , Chen Ting , Li Mengke , Shi Deyang , Wang Xiaomin , Pang Aiming , Zhou Jiaxi , Yuan Weiping , Chu Yajing 
Published: November 2020

Abstract
Ten-eleven translocation 2 (TET2) functions as a methylcytosine dioxygenase that catalyzes the iterative oxidation of 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine. TET2 has been shown to be crucial for the maintenance and differentiation of hematopoietic stem cells, and its deletion and/or mutations results in the expansion of HSPCs, and leads to hematological malignancies. TET2 mutations were found in a variety of hematological disorders such as CMML (60%), MDS (30%), MPN (13%) and AML (20%). Interestingly, it was shown that CMML patients with TET2 mutation exhibited fewer platelets than CMML patients without TET2 mutation. However, the role and function of TET2 in platelet hemostasis and thrombogenesis is not well defined. Here in this study, using a genetically engineered Tet2 deletion mouse model, we found that the absence of Tet2 caused a decrease in the proportion of MEP cells and hyperploid megakaryocytes. Additionally, Tet2-deficient mice displayed impaired platelet activation and aggregation under stimulation of ADP and low concentrations of thrombin, although the modestly compromised platelet function and MEP differentiation in Tet2-deficient mice could be compensated without affecting blood coagulation function. Our study indicate that Tet2 deficiency leads to mild impairment of platelet function and thrombopoiesis in mice.
ALKBH3 is dispensable in maintaining hematopoietic stem cells but forced ALKBH3 rectified the differentiation skewing of aged hematopoietic stem cells
Authors: He Hanqing , Wang Yuqian , Wang Jianwei 
Published: November 2020

Abstract
ALKBH3, a demethylase responsible for demethylating N1-methyladenosine (m1A) in mRNA and N1-methyldeoxyadenosine in single-stranded DNA, plays an important role in DNA repair and cancer cell proliferation. However, its function in hematopoietic stem cells (HSCs) is unknown. In this study, we generated Alkbh3 knockout mice and observed that the deletion of Alkbh3 does not impair the reconstitution capacity of HSCs in both primary and secondary transplantation. Aged hematopoietic stem and progenitor cells exhibit increased expression of ALKBH3. Forced ALKBH3 rescued the differentiation skewing without affecting the reconstitution capacity of aged HSCs. In brief, our study for the first time investigated the functional role of ALKBH3 in hematopoietic system, and observed that ALKBH3 is dispensable for HSCs maintenance and differentiation, but overexpression of ALKBH3 rectified the differentiation skewing of aged HSCs.
Long-term Outcomes of Gamma Knife Radiosurgery for Treating Vestibular Schwannoma With a Lower Prescription Dose of 12 Gy Compared With Higher Dose Treatment
Authors: Kawashima Mariko , Hasegawa Hirotaka , Shin Masahiro , Takahashi Wataru , Shinya Yuki , Iwasaki Shinichi , Kashio Akinori , Nakatomi Hirofumi , Saito Nobuhito 
Published: November 2020

Objective:
Gamma knife radiosurgery (GKRS) is commonly used to treat vestibular schwannomas (VSs). The risk of complications from GKRS decreases at lower doses, but it is unknown if long-term tumor control is negatively affected by dose reduction.

Study Design:
This was a retrospective case review and analysis of patient data.

Setting:
Tertiary referral center.

Patients:
Patients with VSs who underwent GKRS between 1990 and 2007 at the authors’ institution.

Intervention(s):
The subjects were divided into two cohorts based on the prescribed doses of radiation received: a 12 Gy cohort (96 patients) with a follow-up period of 124 months and a >12 Gy cohort (118 patients) with a follow-up period of 143 months.

Main Outcome Measures:
Tumor control rates at 10 to 15 years, frequency of facial and trigeminal nerve complications, and hearing function.

Results:
The 10 to 15-year tumor control rates were 95% in the 12 Gy cohort and 88% in the > 12 Gy cohort, but the differences were not significant. Compared with the >12 Gy cohort, facial and trigeminal nerve deficits occurred significantly less frequently in the 12 Gy cohort, with the 10-year cumulative, permanent deficit-free rates being 2% and 0%, respectively. Multivariate analyses revealed that treatment doses exceeding 12 Gy were associated with a significantly higher risk for cranial nerve deficits. The percentage of subjects retaining pure-tone average ≤ 50 dB at the final follow-up did not significantly differ between the cohorts (12 Gy cohort, 30% and >12 Gy cohort, 33%; p = 0.823).

Conclusions:
Dose reduction to 12 Gy for GKRS to treat VSs decreased facial and trigeminal nerve complications without worsening tumor control rates.
Activating Immune Recognition in Pancreatic Ductal Adenocarcinoma Using Autophagy Inhibition, MEK blockade and CD40 Agonism
Authors: Jiang Honglin , Courau Tristan , Lupin-Jimenez Leonard , Borison Joseph , Ritchie Alexa J. , Mayer Aaron T. , Krummel Matthew F. , Collisson Eric A. 
Published: November 2020

AbstractPancreatic ductal adenocarcinoma (PDA) patients have not yet benefitted from the revolution in cancer immunotherapy due in large part to the dominantly immunosuppressive tumor microenvironment (TME). MEK inhibition combined with autophagy inhibition leads to transient tumor responses in some PDA patients. We find that co-inhibition of MEK (using cobimetinib, COBI) and autophagy (using mefloquine, MFQ), but not either treatment alone, activates the Type I Interferon/STING pathway in tumor cells which in turn reprogram tumor associated macrophages (TAMs) in paracrine to foster an immunogenic switch. This effect is augmented by a CD40 agonist (aCD40). Triple therapy (COBI+MFQ+aCD40) achieved cytotoxic T cell activation in an immunologically “cold” mouse PDA model, leading to enhanced anti-tumor immunity. Collectively, MEK and autophagy co-inhibition coupled with CD40 agonism invokes immuno-reprograming and is an attractive therapeutic approach for PDA immunotherapy development.
Progesterone specifically dampens disease-associated TH1- and TH17-related immune responses during T cell activationin vitro
Authors: Hellberg Sandra , Raffetseder Johanna , Rundquist Olof , Magnusson Rasmus , Papapavlou Georgia , Jenmalm Maria C. , Ernerudh Jan , Gustafsson Mika 
Published: November 2020

ABSTRACTThe changes in progesterone (P4) levels during and after pregnancy coincide with the temporary improvement and worsening of several autoimmune diseases like multiple sclerosis (MS) and rheumatoid arthritis (RA). Most likely immune-endocrine interactions play a major role in these pregnancy-induce effects. In this study, we used next generation sequencing to investigate the direct effects of P4 on CD4+T cell activation, of central importance in pregnancy and disease. We found that P4 had a profound dampening effect on T cell activation, altering the gene and protein expression profile and opposing many of the changes induced during the activation. The transcriptomic changes induced by P4 were significantly enriched for genes associated with diseases known to be modulated during pregnancy such as MS, RA and psoriasis. The TH1-and TH17-associated transcription factors STAT1 and STAT3 were significantly downregulated by P4 and their downstream targets were significantly enriched among the diseases-associated genes. Several of these genes included well-known and disease-relevant cytokines, such as IL-12β, CXCL10 and OSM, that were further validated also at the protein level using proximity extension assay. Our results extend the previous knowledge of P4 as an immune regulatory hormone and supports its importance during pregnancy for regulating potentially detrimental immune responses towards the semi-allogenic fetus. Further, our results also point toward a potential role for P4 in the pregnancy-induced disease immunomodulation, suggestively through dampening of TH1 and TH17-associated immune responses and highlights the need for further studies evaluating P4 as a future treatment option.
EEG frequency tagging reveals neural entrainment to people moving in synchrony
Authors: Cracco Emiel , Lee Haeeun , van Belle Goedele , Quenon Lisa , Haggard Patrick , Rossion Bruno , Orgs Guido 
Published: November 2020

AbstractHumans and other animals have evolved to act in groups, but how does the brain distinguish multiple people moving in group from multiple people moving independently? Across three experiments, we test whether biological motion perception depends on the spatiotemporal relationships among people moving together. In Experiment 1, we apply EEG frequency tagging to apparent biological motion and show that fluently ordered sequences of body postures drive brain activity at three hierarchical levels of biological motion processing: image, body sequence, and movement. We then show that movement-, but not body- or image-related brain responses are enhanced when observing four agents moving in synchrony. Neural entrainment was strongest for fluently moving synchronous groups (Experiment 2), displayed in upright orientation (Experiment 3). Our findings show that the brain preferentially entrains to the collective movement of human agents, deploying perceptual organization principles of synchrony and common fate for the purpose of social perception.
International rotational assignments: women's challenge to occupational gender segregation
Authors: Shortland Susan 
Published: November 2020

PurposeThe purpose of this exploratory research is to understand how women have accessed male-dominated oil and gas international rotational assignments and why they believe these roles to be professionally worthwhile.Design/methodology/approachThis cross-sectional qualitative study is based on semi-structured interviews and correspondence with female international rotational assignees, and interviews with HR professionals involved in selection and deployment for such assignments.FindingsHR personnel stereotype women as unsuitable for international rotational assignments. Women must be exceptionally determined and/or circumvent selection processes to access such roles. Women value the professional and personal development gained from international rotational assignments which helps them widen their occupational skills capacity.Research limitations/implicationsTo extend these findings, larger samples of female international rotational assignees and research in a wider range of industries are required. Longitudinal studies could further our understanding of women’s career progression building upon their international rotational assignment experience.Practical implicationsTo reduce stereotyping of women's perceived unsuitability, greater understanding of international rotational assignment roles/environments is required by managers involved in selection. Transparent selection processes are required to support diversity. Greater interest in the work performed by international rotational assignees will raise their profile and assist with wider labour market opportunities.Social implicationsOrganisational representatives unintentionally reinforce occupational segregation by stereotyping women as less appropriate workers than men for international rotational assignments.Originality/valueThis research hears women's voices as they begin to make inroads into the masculine world of oil and gas international rotational assignments. Research propositions and recommendations for practice are suggested to assist in breaking down male monopoly in this context.
Feasibility and reliability of screening on mild to borderline intellectual disabilities using SCIL through video-administration
Authors: Spaan Nienke Agnes , Verzaal Matthijs , Kaal Hendrien Lourine 
Published: November 2020

Purpose
In the Netherlands, the Screener for Intelligence and Learning Disabilities (SCIL) was developed to aid recognition of mild to borderline intellectual disability (MBID) early in the criminal justice system or health-care trajectory. In situations where physically meeting the suspect or client is not feasible, administration of the SCIL using a video-link might be a solution. This paper aims to examine whether the SCIL is still reliable when administered remotely instead of face-to-face.

Design/methodology/approach
The SCIL was administered twice to a total of 89 respondents: once face-to-face, once using a video link, in varying order and with an interval of at least six weeks. A laptop with a Skype connection was used for the remote administration, while an assistant was present to make sure the respondents did not have to perform technical actions. After the second SCIL administration, respondents were asked to answer a series of evaluation questions.

Findings
Respondents were generally satisfied with both methods of administration of the SCIL. However, they were in general more positive about face-to-face administration. Nevertheless, most respondents would be willing to undergo administration through video-link in future. On average, respondents scored slightly lower on the SCIL when administered remotely (µ = 16.31, SE = 0 0.77) than with face-to-face administration (µ = 16.94, SE = 0.78), t(88) = 2.47, p = 0 0.015. Calculation of the reliability of the assessment “suspected MBID” showed a (linear weighted) Kappa of 0.77, p = 0.000, 95% RI: 0.64-0.90.

Originality/value
The results of this study show that with some caution, the SCIL can be administered remotely. When doing this, the SCIL will only lead to a small number of respondents being wrongly labelled as “suspected MBID”.
A “North star:” spirituality and decision-making among strategic leaders
Authors: Phipps Kelly A. , Shelton Charlotte 
Published: November 2020

PurposeThe purpose of this study was to examine the experience of strategic-level leaders whose spiritual beliefs or practices inform their organizational decision making.Design/methodology/approachUsing a phenomenological methodology, 25 executives were interviewed to understand their lived experience. All participants held executive level positions, engaged in spiritual practices at least once a week and described spirituality as important in their lives.FindingsThematic analysis revealed themes that pointed to the locus of spirituality in the lives of the executives (innate but not overt) and the types of decisions for which they turned to their spirituality (decisions concerning people). When facing these types of decisions, leaders described an additional step we named “executive discernment.” This additional step sought to establish a connection with the transcendent and was described as heightening their decision-making abilities, serving as a model or “North Star,” or guiding them to a decision.Originality/valueThis study builds on prior theoretical work and gives insight into a process not usually visible: executives' reliance on spirituality during organizational decision making. These insights highlight the potential benefits and provide specificity to the potential risks for leaders who turn to spirituality when making organizational decisions. These risks include an overconfidence in one's decision-making abilities, reliance on an authority inconsistent with organizational aims or failing to convince others of the wisdom of the chosen direction.
Stress gradients interact with disturbance to reveal alternative states in salt marsh: Multivariate resilience at the landscape scale
Authors: Jones Scott F. , Stagg Camille L. , Yando Erik S. , James W. Ryan , Buffington Kevin J. , Hester Mark W. 
Published: November 2020

Abstract

Stress gradients influence many ecosystem processes and properties, including ecosystem recovery from and resistance to disturbance. While recent analytical approaches have advanced multivariate metrics of ecosystem resilience that allow quantification of conceptual resilience models and identification of thresholds of state change, these approaches are not often translated to landscape scales.

Using natural and restored salt marshes in Louisiana, USA, we quantified plant community recovery and resistance metrics along flooding stress gradients. n‐dimensional hypervolumes of plant community biomass and structure were simulated using field data collected from disturbance‐recovery experiments. The relationships between multivariate resilience metrics and flooding stress gradients were then mapped at community‐ and landscape‐relevant scales by scaling with airborne‐derived data across the region.

Greater pre‐disturbance abiotic stress decreased live below‐ground, but not above‐ground, biomass, and ultimately led to lower post‐disturbance total recovery, recovery rates and resistance of plant communities. Vegetated plots flooded >52% of the time transitioned to an alternative, unvegetated state after disturbance. Mapping revealed differences in spatial patterns of resilience—highlighting low, interior marsh edges as especially vulnerable to the combination of chronic flooding stress and acute disturbance. At the landscape scale, approximately half of the area (48%) is vulnerable to state change after pulse disturbances.

Synthesis. Ultimately, we quantify the ball‐and‐cup conceptual model for a salt marsh ecosystem and its alternative state, mudflat. We find that increasing abiotic stress due to climate change diminishes ecosystem resilience, but the interaction with common episodic disturbances is necessary to reveal transitions to alternative states and quantify state change thresholds. Quantifying and mapping resilience and where alternative states may exist in this fashion improves ecologists' ability to investigate the mechanisms of stress gradient control on emergent ecosystem properties while providing spatially explicit resources for managing ecosystems according to their projected resilience.
Effects of implementing flipped classroom elements and dynamic in‐class discussion on student performance
Authors: Cao Loan Thi Thanh , Swada Jeffrey Gerard 
Published: November 2020

AbstractIn a Food Processing–Unit Operations course, students learn the basic equipment that comprises unit operations and techniques commonly used in the food industry to prepare, process, and preserve a variety of food products. Due to the complexity of these operations, students frequently struggle with applying food processing principles to predict how unit operations influence the physical, biochemical, sensory, and nutritional properties of foods. This study is designed to evaluate how pre‐class readings and in‐class group activities improve the students’ learning in a Food Processing course. The survey after the exams shows that 48 and 60% of students agree that reading assignments and in‐class group activities help them understand the course material better, respectively. The mean value of exam scores shows that the students in the intervention section (Spring 2018) had significantly higher scores (88.4%) than that of the two previous sections without intervention (77.6%, Spring 2016 and 82.8%, Spring 2017) (P < .05). It is concluded that using a flipped class element like providing reading assignments and quizzes before the lecture can be an effective preparation technique for students as well as providing the instructors with critical insight into the students’ level of understanding before the lecture. This allows the instructor to focus time spent in class on areas in which students struggle the most.