bluuebunny/crossref_metadata_2025_split huggingface dataset:
Common trajectories of highly effective CD19-specific CAR T cells identified by endogenous T cell receptor lineages
Authors: Wilson Taylor L. , Kim Hyunjin , Chou Ching-Heng , Langfitt Deanna , Allen E. Kaitlynn , Métais Jean-Yves , Pogorelyy Mikhail V. , Kottapalli Pratibha , Trivedi Sanchit , Olsen Scott R. , Lockey Timothy , Willis Catherine , Meagher Michael M. , Triplett Brandon M. , Talleur Aimee C. , Gottschalk Stephen , Crawford Jeremy Chase , Thomas Paul G. 
Published: December 2021

AbstractCurrent chimeric antigen receptor-modified (CAR) T cell therapy products are evaluated in bulk, without assessment of the possible heterogeneity in effector potential between cells. Conceivably, only a subset of the pre-infusion product differentiates into optimal effectors. We generated a comprehensive single-cell gene expression and T cell receptor (TCR) sequencing dataset using both pre- and post-infusion CD19-CAR T cells from peripheral blood and bone marrow of pediatric patients with B cell acute lymphoblastic leukemia (B-ALL). We identified potent effector post-infusion cells with identical TCRs to a subset of pre-infusion CAR T cells. Effector precursor CAR T cells exhibited a unique transcriptional profile compared to other pre-infusion cells, and the number of effector precursor cells infused correlated with peak CAR T cell expansion. Additionally, we identified an unexpected cell surface phenotype (TIGIT+, CD62Llo, CD27-), conventionally associated with inhibiting effective T cell responses, that we used to successfully enrich for subsequent effector potential. Collectively, these results demonstrate that highly diverse effector potentials are present among cells in pre-infusion cell products, which can be exploited for diagnostic and therapeutic applications. Furthermore, we provide an integrative experimental and analytical framework for elucidating the biological mechanisms underlying effector development in other CAR T cell therapy products.
Detection of brain somatic variation in epilepsy-associated developmental lesions
Authors: Bedrosian Tracy A. , Miller Katherine E. , Grischow Olivia E. , Yoon Hyojung , Schieffer Kathleen M. , LaHaye Stephanie , Miller Anthony R. , Navarro Jason , Westfall Jesse , Leraas Kristen , Choi Samantha , Williamson Rachel , Fitch James , Lee Kristy , McGrath Sean , Cottrell Catherine E. , Magrini Vincent , Leonard Jeffrey , Pindrik Jonathan , Shaikhouni Ammar , Boué Daniel R. , Thomas Diana L. , Pierson Christopher R. , Wilson Richard K. , Ostendorf Adam P. , Mardis Elaine R. , Koboldt Daniel C. 
Published: December 2021

AbstractEpilepsy-associated developmental lesions, including malformations of cortical development and low-grade developmental tumors, represent a major cause of drug-resistant seizures requiring surgical intervention in children. Brain-restricted somatic mosaicism has been implicated in the genetic etiology of these lesions; however, many contributory genes remain unidentified. We enrolled 50 children undergoing epilepsy surgery into a translational research study. We performed exome and RNA-sequencing of resected brain tissue samples to identify somatic variation. We uncovered candidate disease-causing somatic variation affecting 28 patients (56%), as well as candidate germline variants affecting 4 patients (8%). We confirmed somatic findings using high-depth targeted DNA sequencing. In agreement with previous studies, we identified somatic variation affecting SLC35A2 and MTOR pathway genes in patients with focal cortical dysplasia. Somatic gains of chromosome 1q were detected in 30% (3 of 10) Type I FCD patients. Somatic variation of MAPK pathway genes (i.e., FGFR1, FGFR2, BRAF, KRAS) was associated with low-grade epilepsy-associated developmental tumors. Somatic structural variation accounted for over one-half of epilepsy-associated tumor diagnoses. Sampling across multiple anatomic regions revealed that somatic variant allele fractions vary widely within epileptogenic tissue. Finally, we identified putative disease-causing variants in genes (EEF2, NAV2, PTPN11) not yet associated with focal cortical dysplasia. These results further elucidate the genetic basis of structural brain abnormalities leading to focal epilepsy in children and point to new candidate disease genes.
Study Design: Validation of clinical acceptability of deep-learning-based automated segmentation of organs-at-risk for head-and-neck radiotherapy treatment planning
Authors: Anand Aman , Beltran Chris J. , Brooke Mark D. , Buroker Justine R. , DeWees Todd A. , Foote Robert L. , Foss Olivia R. , Hughes Cían O. , Hunzeker Ashley E. , Lucido J. John , Morigami Megumi , Moseley Douglas J. , Pafundi Deanna H. , Patel Samir H. , Patel Yojan , Ridgway Ana K. , Tryggestad Erik J. , Wilson Megan Z. , Xi Lihong , Zverovitch Alexei 
Published: December 2021

AbstractThis document reports the design of a retrospective study to validate the clinical acceptability of a deep-learning-based model for the autosegmentation of organs-at-risk (OARs) for use in radiotherapy treatment planning for head & neck (H&N) cancer patients.
Reduced Neutralization of SARS-CoV-2 Omicron Variant by Vaccine Sera and Monoclonal Antibodies
Authors: Wilhelm Alexander , Widera Marek , Grikscheit Katharina , Toptan Tuna , Schenk Barbara , Pallas Christiane , Metzler Melinda , Kohmer Niko , Hoehl Sebastian , Helfritz Fabian A. , Wolf Timo , Goetsch Udo , Ciesek Sandra 
Published: December 2021

AbstractDue to numerous mutations in the spike protein, the SARS-CoV-2 variant of concern Omicron (B.1.1.529) raises serious concerns since it may significantly limit the antibody-mediated neutralization and increase the risk of reinfections. While a rapid increase in the number of cases is being reported worldwide, until now there has been uncertainty about the efficacy of vaccinations and monoclonal antibodies. Our in vitro findings using authentic SARS-CoV-2 variants indicate that in contrast to the currently circulating Delta variant, the neutralization efficacy of vaccine-elicited sera against Omicron was severely reduced highlighting T-cell mediated immunity as essential barrier to prevent severe COVID-19. Since SARS-CoV-2 Omicron was resistant to casirivimab and imdevimab, genotyping of SARS-CoV-2 may be needed before initiating mAb treatment. Variant-specific vaccines and mAb agents may be required to treat COVID-19 due to Omicron and other emerging variants of concern.
Fiber orientation downsampling compromises the computation of white matter tract-related deformation
Authors: Zhou Zhou , Wang Teng , Jörgens Daniel , Li Xiaogai 
Published: December 2021

AbstractIncorporating neuroimaging-revealed structural details into finite element (FE) head models opens vast new opportunities to better understand brain injury mechanisms. Recently, growing efforts have been made to integrate fiber orientation from diffusion tensor imaging (DTI) into FE models to predict white matter (WM) tract-related deformation that is biomechanically characterized by tract-related strains. Commonly used approaches often downsample the spatially enriched fiber orientation to match the FE resolution with one orientation per element (i.e., element-wise orientation implementation). However, the validity of such downsampling operation and corresponding influences on the computed tract-related strains remain elusive. To address this, the current study proposed a new approach to integrate voxel-wise fiber orientation from one DTI atlas (isotropic resolution of 1 mm3) into FE models by embedding orientations from multiple voxels within one element (i.e., voxel-wise orientation implementation). By setting the responses revealed by the newly proposed voxel-wise orientation implementation as the reference, we evaluated the reliability of two previous downsampling approaches by examining the downsampled fiber orientation and the computationally predicted tract-related strains secondary to one concussive impact. Two FE models with varying element sizes (i.e., 6.37 ± 1.60 mm and 1.28 ± 0.55 mm, respectively) were incorporated. The results showed that, for the model with a large voxel-mesh resolution mismatch, the downsampled element-wise fiber orientation, with respect to its voxel-wise counterpart, exhibited an absolute deviation over 30° across the WM/gray matter interface and the pons regions. Accordingly, this orientation deviation compromised the computation of tract-related strains with normalized root-mean-square errors up to 30% and underestimated the peak tract-related strains up to 10%. For the other FE model with finer meshes, the downsampling-induced effects were lower, both on the fiber orientation and tract-related strains. Taken together, the voxel-wise orientation implementation is recommended in future studies as it leverages the DTI-delineated fiber orientation to a larger extent than the element-wise orientation implementation. Thus, this study yields novel insights on integrating neuroimaging-revealed fiber orientation into FE models and may better inform the computation of WM tract-related deformation, which are crucial for advancing the etiological understanding and computational predictability of brain injury.Graphic abstract
Mechanical ventilation affects the microecology of the rat respiratory tract
Authors: Xue-Meng Chen , Gao-Wang Liu , Xiao-Mei Ling , Fan-Fang Zeng , Jin-Fang Xiao 
Published: December 2021

AbstractBackgroundThe most common ‘second strike’ in mechanically ventilated patients is a pulmonary infection caused by the ease with which bacteria can invade and colonize the lungs due to mechanical ventilation. At the same time, metastasis of lower airway microbiota may have significant implications in the development of intubation mechanical ventilation lung inflammation. Thus, we establish a rat model of tracheal intubation with mechanical ventilation and explore the effects of mechanical ventilation on lung injury and microbiological changes in rats.MethodsSprague-Dawley rats were randomized into control, Spontaneously Breathing (1, 3, 6 hours), Mechanical ventilation(1, 3, 6 hours) groups. Lung wet to dry weight ratio (W/D weight ratio) and Lung histopathological injury score were evaluated.16SrDNA sequencing was performed to explore respiratory flora changes.ResultsBacterial diversity was comparable between healthy and intubation mechanical ventilation rats, with time relation. Ordination analyses revealed that samples clustered more dispersing by tracheal intubation and mechanical ventilation. Finally, predicted metagenomes suggested a substantial increase in biofilm formation phenotype during early tracheal intubation and mechanical ventilation.ConclusionCollectively, these results establish a link between the duration of mechanical ventilation and alterations to the respiratory tract microecology. In future studies, we hope to discover the effectiveness of new immunomodulatory or probiotic bacteria to prevent airway diseases associated with ventilator therapy.
Dual engagement of the nucleosomal acidic patches is essential for deposition of histone H2A.Z by SWR1C
Authors: Baier Alexander S. , Gioacchini Nathan , Eek Priit , Leith Erik M. , Tan Song , Peterson Craig L. 
Published: December 2021

ABSTRACTThe SWR1C chromatin remodeling enzyme catalyzes the ATP-dependent exchange of nucleosomal histone H2A for the histone variant H2A.Z, a key variant involved in a multitude of nuclear functions. How the 14-subunit SWR1C engages the nucleosomal substrate remains largely unknown. Numerous studies on the ISWI, CHD1, and SWI/SNF families of chromatin remodeling enzymes have demonstrated key roles for the nucleosomal acidic patch for remodeling activity, however a role for this nucleosomal epitope in nucleosome editing by SWR1C has not been tested. Here, we employ a variety of biochemical assays to demonstrate an essential role for the acidic patch in the H2A.Z exchange reaction. Utilizing asymmetrically assembled nucleosomes, we demonstrate that the acidic patches on each face of the nucleosome are required for SWR1C-mediated dimer exchange, suggesting SWR1C engages the nucleosome in a “pincer-like” conformation, engaging both patches simultaneously. Loss of a single acidic patch results in loss of high affinity nucleosome binding and nucleosomal stimulation of ATPase activity. We identify a conserved arginine-rich motif within the Swc5 subunit that binds the acidic patch and is key for dimer exchange activity. In addition, our cryoEM structure of a Swc5-nucleosome complex suggests that promoter proximal, histone H2B ubiquitinylation may regulate H2A.Z deposition. Together these findings provide new insights into how SWR1C engages its nucleosomal substrate to promote efficient H2A.Z deposition.
Chlorine redox chemistry is not rare in biology
Authors: Barnum Tyler P. , Coates John D. 
Published: December 2021

AbstractChlorine is abundant in cells and biomolecules, yet the biology of chlorine oxidation and reduction is poorly understood. Some bacteria encode the enzyme chlorite dismutase (Cld), which detoxifies chlorite (CIO2-) by converting it to chloride (Cl-) and molecular oxygen (O2). Cld is highly specific for chlorite and aside from low hydrogen peroxide activity has no known alternative substrate. Here, we reasoned that because chlorite is an intermediate oxidation state of chlorine, Cld can be used as a biomarker for oxidized chlorine species in microorganisms and microbial habitats. Cld was abundant in metagenomes from soils and freshwater to water treatment systems. About 5% of bacterial and archaeal genera contain an organism encoding Cld in its genome, and within some genera Cld is nearly conserved. Cld has been subjected to extensive horizontal gene transfer, suggesting selection by chlorite is episodic yet strong. Cld was also used as a biomarker to predict genes related to chlorine redox chemistry. Genes found to have a genetic association with Cld include known genes for responding to reactive chlorine species and uncharacterized genes for transporters, regulatory elements, and putative oxidoreductases that present targets for future research. Cld was repeatedly co-located in genomes with genes for enzymes that can inadvertently reduce perchlorate (CIO4-) or chlorate (CIO3-), confirming that in nature (per)chlorate reduction does not only occur in specialized anaerobic respiratory metabolisms. The presence of Cld in genomes of obligate aerobes without such enzymes suggested that chlorite, like hypochlorous acid (HOCl), might be formed by oxidative processes within natural habitats. In summary, the comparative genomics of Cld has provided an atlas for a deeper understanding of chlorine oxidation and reduction reactions that are an underrecognized feature of biology.
The paradoxical consequences of leader feedback seeking for subordinates: a theoretical framework
Authors: Carvalho Sheldon , Carvalho Fallan Kirby , Carvalho Charles 
Published: December 2021

Purpose
Scholars in the feedback seeking domain have predominantly focused on subordinate feedback seeking. The authors still know very little about feedback seeking when the leader is the “seeker” and subordinates are the “targets” of such seeking. This paper aims to develop a theoretical framework that explores the potential benefits and costs of leader feedback seeking, specifically, leader feedback inquiry for subordinates.

Design/methodology/approach
The authors draw upon the transactional theory of stress to propose a framework in which leader feedback inquiry influences two subordinate behaviors (in-role and proactive skill development behaviors) via appraisal processes (challenge and threat appraisals). With insights from regulatory focus theory, the authors propose that individual characteristics, namely, the regulatory focus of subordinates (promotion and prevention focus), determine the appraisals of leader feedback inquiry, subsequently influencing subordinate behavioral outcomes.

Findings
The authors contend that leader feedback inquiry can be appraised as a challenge which then produces beneficial subordinate behaviors (i.e. higher in-role and proactive skill development behaviors). However, leader feedback inquiry can also be appraised as a threat which then elicits detrimental subordinate behaviors (i.e. lower in-role and proactive skill development behaviors). The authors then argue that subordinates with a high promotion focus appraise leader feedback inquiry as challenging, thereby enabling beneficial behaviors. Subordinates with a high prevention focus, by contrast, appraise leader feedback inquiry as threatening, thereby prompting detrimental behaviors.

Originality/value
The authors shed light on the benefits and costs of leader feedback seeking for subordinates. The resulting framework underlines the importance of including individual characteristics and cognitive appraisal processes in research investigating the effects of leader feedback inquiry on subordinate outcomes.
How does regulatory framework impact sectoral performance? A systematic literature review
Authors: Mishra Brajesh , Kumar Avanish 
Published: December 2021

PurposeThe regulatory framework may be construed as the existence of supporting infrastructure that assists in control, direction/implementation of a proposed course of law, rule or action. The regulatory order is now more formalized, expert-driven, transparent, independent and pervasive across countries and sectors. As a result, regulatory reforms enable markets to function efficiently by providing a supportive environment for increased investment, private sector growth and market-led economic growth. This study aims to review previous literature for understanding the impact of sectoral regulatory framework on sectoral performance.Design/methodology/approachThis paper has adopted a systematic literature review to understand dynamics between the sectoral regulatory framework and sectoral performance. While seven multidisciplinary databases were used to identify 51 research articles, the bibliometric research profiling was executed to broaden academic research.FindingsThe results are organized into three broad categories: research context, research area and research methods. The identified articles exhibited association with 12 distinct sectors/industries, with maximum articles belonging to telecom, energy and finance industries. The study has focused on evolution of regulatory studies, impact of regulatory framework on sectoral performance and commonality in regulatory studies. Among the 15 distinct research contexts identified in this systematic literature review (SLR), the highest mapping was registered (from 23 articles) by the research context “impact of regulatory framework on the sector–institutions, infrastructure and performance indicators.”Practical implicationsPublic administration researchers are increasingly using mixed methods research approaches to add diverse and novel perspectives on wicked problems. The qualitative approach (grounded theory, action research, phenomenology and participant observations) is appropriate for understanding the native viewpoints of regulatory practitioners and reducing the gap between rigor and relevance.Originality/valueThe study addresses lack of systematic review of articles covering the impact of regulatory framework on sectoral performance encompassing all sectors by, inter alia, collating important bibliometric profiles of the identified articles.
Principals' perspectives of inclusive education involving students with autism spectrum conditions – a Swedish case study
Authors: Lüddeckens Johanna , Anderson Lotta , Östlund Daniel 
Published: December 2021

PurposeThe aim of this case study is to describe what commitment and actions are needed in the Swedish school so that principals — within the Swedish school policy framework and with the goal of creating an inclusive school culture and practice — can positively affect schooling for students with disabilities, with a particular focus on students with autism spectrum conditions (ASC). Three research questions guide the study: (1) What commitment and actions do principals consider important for developing an inclusive school for all students, with a particular focus on students with ASC? (2) How do the principals reflect on their own leadership in the development of inclusive education, with a particular focus on students with ASC? (3) Based on the results, what are the implications of the study in practice?Design/methodology/approachAs part of a three-step data collection method, a snowball sampling was conducted in which n = 6 principals were initially interviewed and the data analyzed by an inductive thematic content analysis.Findings(1) Certain structures are needed when planning how to develop mutual values when organizing an inclusive school involving students with ASC, (2) the principals could, at times, feel a sense of loneliness in relation to their superiors and decision-makers and (3) more accountability from educators and greater consideration for the student perspective in decision-making are needed.Practical implicationsIt was found that (1) certain structures are needed when planning how to develop mutual values when organizing an inclusive school involving students with ASC, (2) the principals could, at times, feel a sense of isolation in relation to their superiors and decision-makers and (3) more accountability from educators and greater consideration for the student perspective in decision-making are needed.Originality/valueIndex for inclusion and elements from the inclusive leadership model were used in the data collection and analysis.
Impact of COVID-19 on food outlets: symmetric or asymmetric? A case study of Amritsar
Authors: Dhillon Dilpreet Kaur , Kaur Kuldip 
Published: December 2021

PurposeThe present study is an intra-industry analysis, which aims to investigate whether the impact of COVID-19 on employment level, clientele rate, liquidity constraints and sustainability aspect of different food outlets is symmetric or asymmetric in nature.Design/methodology/approachWith the help of well-structured questionnaire, the study has surveyed 80 food outlets in total by interviewing the managers and owners of these outlets. Food outlets have been classified into four categories namely international, national, local and street food outlets. Econometric techniques like MANOVA and Garret ranking have been employed to fulfil the objective of the study.FindingsThe results depict that the impact of COVID-19 on employment level and liquidity constraints is significantly asymmetric amongst different groups of food outlets, even though the decline in extent of clientele is somewhat same for all groups. The survival aspect of outlets also witnesses clear-cut asymmetry in results as big outlets have greater potential to survive for longer if lockdown happens again when compared to street food outlets as their financial availability and stability differ.Research limitations/implicationsThe sample size of study is restricted, mainly due to lesser number of national franchise's food outlets available in Amritsar, though other categories of eateries were sufficient in number. Further, the study is restricted only to one district of Punjab state, whereas for future research, inter-district comparison can be done.Practical implicationsThe findings reveal that the street food outlets may gain by fostering its online functioning. Similarly national food outlets are encouraged to alter their business strategies to revive their sales against their competitors.Originality/valueThis study is one of the explorer studies to analyse the impact of COVID-19 by making an intra-industry comparison for the eatery industry – considering four different categories of eateries. The classification of eateries helps in analysing whether the employment level, clientele rate, liquidity constraints and survival perspective have been affected symmetrically for the whole eateries industry or does severity of being affected differ asymmetrically. The study makes a contribution by adding a new string of dimension to the existing load of literature in the domain of hospitality.