bluuebunny/crossref_metadata_2025_split huggingface dataset:
Steroid-induced osteonecrosis of the humeral head in a 20-year-old man treated with an osteochondral autograft: A case report
Authors: Hotta Tadahiro , Kozono Naoya , Takeuchi Naohide , Nabeshima Akira , Kawahara Shinya , Hamai Satoshi , Akasaki Yukio , Tsushima Hidetoshi , Tashiro Eiji , Konishi Toshiki , Nakashima Yasuharu 
Published: April 2022

ABSTRACT
To our knowledge, only one previous report described the treatment of osteochondral autograft for steroid-induced osteonecrosis of the humeral head (ONHH) in a middle-aged patient. The present report describes a 20-year-old man who was found to have avascular osteonecrosis of the right humeral head after corticosteroid pulse treatment, followed by oral corticosteroid therapy. The patient complained of serious right shoulder pain and limited range of motion (ROM). Anteroposterior (AP) radiographs of the right shoulder revealed a crescent sign at the humeral head, indicating subchondral bone collapse with a linear sclerotic change and normal articular surface of the glenoid. The case was categorized as Stage 3 according to the Cruess classification. In general, Cruess classification Stage 3 is treated with humeral head replacement and shoulder arthroplasty. The patient underwent surgical treatment involving osteochondral autograft transplantation. Autografts were harvested from the right knee. At the 1.5-year follow-up, the patient was pain-free and showed an improved active ROM. Furthermore, AP radiographs demonstrated that the glenohumeral joint space was maintained, and no progression of humeral head collapse was observed. This case may be helpful in decision-making if young patients with ONHH require surgical treatment. Furthermore, osteochondral autograft transplantation may be an effective treatment for ONHH.
Stress fractures in the forefoot after arthrodesis of the hindfoot in a patient with rheumatoid arthritis: A case report
Authors: Yano Koichoro , Ikari Katsunori , Okazaki Ken 
Published: April 2022

ABSTRACT
Rheumatoid arthritis (RA) is an autoimmune disease that attacks multiple joints throughout the body. Ankle arthrodesis (AA) has been the gold standard surgery for end-stage ankle arthritis in patients with RA. Here, we report the case of a 67-year-old woman with RA who had displacement and loosening of total ankle arthroplasty. The ankle was converted to AA using a metal spacer and an intramedullary nail. The patient had no complications in perioperative terms of arthrodesis. However, multiple fractures were found in the metatarsal bones at the routine 3-year follow-up. Although the patient did not remember any symptoms, the clinical outcome deteriorated compared to that a year before. The hindfoot in this case report was fixed completely by an intramedullary nail, while the midfoot had already involved ankylosis because of severe joint destruction present before the surgery. As a result, the range of motion in the joints of the midfoot and hindfoot was lost, and it is probable that an excessive load was applied to the forefoot during push-off by the toes, resulting in a stress fracture. Patients with RA remain at risk of future progressive joint destruction in every joint of their body. Therefore, surgeons should choose a surgery that preserves ankle motion to decrease the rate of adjacent joint degeneration for severe ankle arthropathy in patients with RA.
The metaphorical swiss army knife: The multitude and diverse roles of HEAT domains in eukaryotic translation initiation
Authors: Friedrich Daniel , Marintchev Assen , Arthanari Haribabu 
Published: April 2022

AbstractBiomolecular associations forged by specific interaction among structural scaffolds are fundamental to the control and regulation of cell processes. One such structural architecture, characterized by HEAT repeats, is involved in a multitude of cellular processes, including intracellular transport, signaling, and protein synthesis. Here, we review the multitude and versatility of HEAT domains in the regulation of mRNA translation initiation. Structural and cellular biology approaches, as well as several biophysical studies, have revealed that a number of HEAT domain-mediated interactions with a host of protein factors and RNAs coordinate translation initiation. We describe the basic structural architecture of HEAT domains and briefly introduce examples of the cellular processes they dictate, including nuclear transport by importin and RNA degradation. We then focus on proteins in the translation initiation system featuring HEAT domains, specifically the HEAT domains of eIF4G, DAP5, eIF5, and eIF2Bϵ. Comparative analysis of their remarkably versatile interactions, including protein–protein and protein–RNA recognition, reveal the functional importance of flexible regions within these HEAT domains. Here we outline how HEAT domains orchestrate fundamental aspects of translation initiation and highlight open mechanistic questions in the area.
Control of bacterial immune signaling by a WYL domain transcription factor
Authors: Blankenchip Chelsea L , Nguyen Justin V , Lau Rebecca K , Ye Qiaozhen , Gu Yajie , Corbett Kevin D 
Published: April 2022

Abstract
Bacteria use diverse immune systems to defend themselves from ubiquitous viruses termed bacteriophages (phages). Many anti-phage systems function by abortive infection to kill a phage-infected cell, raising the question of how they are regulated to avoid cell killing outside the context of infection. Here, we identify a transcription factor associated with the widespread CBASS bacterial immune system, that we term CapW. CapW forms a homodimer and binds a palindromic DNA sequence in the CBASS promoter region. Two crystal structures of CapW suggest that the protein switches from an unliganded, DNA binding-competent state to a ligand-bound state unable to bind DNA. We show that CapW strongly represses CBASS gene expression in uninfected cells, and that phage infection causes increased CBASS expression in a CapW-dependent manner. Unexpectedly, this CapW-dependent increase in CBASS expression is not required for robust anti-phage activity, suggesting that CapW may mediate CBASS activation and cell death in response to a signal other than phage infection. Our results parallel concurrent reports on the structure and activity of BrxR, a transcription factor associated with the BREX anti-phage system, suggesting that CapW and BrxR are members of a family of universal defense signaling proteins.
The ‘Alu-ome’ shapes the epigenetic environment of regulatory elements controlling cellular defense
Authors: Costallat Mickael , Batsché Eric , Rachez Christophe , Muchardt Christian 
Published: April 2022

Abstract
Promoters and enhancers are sites of transcription initiation (TSSs) and carry specific histone modifications, including H3K4me1, H3K4me3, and H3K27ac. Yet, the principles governing the boundaries of such regulatory elements are still poorly characterized. Alu elements are good candidates for a boundary function, being highly abundant in gene-rich regions, while essentially excluded from regulatory elements. Here, we show that the interval ranging from TSS to first upstream Alu, accommodates all H3K4me3 and most H3K27ac marks, while excluding DNA methylation. Remarkably, the average length of these intervals greatly varies in-between tissues, being longer in stem- and shorter in immune-cells. The very shortest TSS-to-first-Alu intervals were observed at promoters active in T-cells, particularly at immune genes, where first-Alus were traversed by RNA polymerase II transcription, while accumulating H3K4me1 signal. Finally, DNA methylation at first-Alus was found to evolve with age, regressing from young to middle-aged, then recovering later in life. Thus, the first-Alus upstream of TSSs appear as dynamic boundaries marking the transition from DNA methylation to active histone modifications at regulatory elements, while also participating in the recording of immune gene transcriptional events by positioning H3K4me1-modified nucleosomes.
EGFR suppresses p53 function by promoting p53 binding to DNA-PKcs: a noncanonical regulatory axis between EGFR and wild-type p53 in glioblastoma
Authors: Ding Jie , Li Xiaolong , Khan Sabbir , Zhang Chen , Gao Feng , Sen Shayak , Wasylishen Amanda R , Zhao Yang , Lozano Guillermina , Koul Dimpy , Alfred Yung W K 
Published: April 2022

Abstract

Background
Epidermal growth factor receptor (EGFR) amplification and TP53 mutation are the two most common genetic alterations in glioblastoma multiforme (GBM). A comprehensive analysis of the TCGA GBM database revealed a subgroup with near mutual exclusivity of EGFR amplification and TP53 mutations indicative of a role of EGFR in regulating wild-type-p53 (wt-p53) function. The relationship between EGFR amplification and wt-p53 function remains undefined and this study describes the biological significance of this interaction in GBM.

Methods
Mass spectrometry was used to identify EGFR-dependent p53-interacting proteins. The p53 and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) interaction was detected by co-immunoprecipitation. We used CRISPR-Cas9 gene editing to knockout EGFR and DNA-PKcs and the Edit-R CRIPSR-Cas9 system for conditional knockout of EGFR. ROS activity was measured with a CM-H2DCFDA probe, and real-time PCR was used to quantify expression of p53 target genes.

Results
Using glioma sphere-forming cells (GSCs), we identified, DNA-PKcs as a p53 interacting protein that functionally inhibits p53 activity. We demonstrate that EGFR knockdown increased wt-p53 transcriptional activity, which was associated with decreased binding between p53 and DNA-PKcs. We further show that inhibition of DNA-PKcs either by siRNA or an inhibitor (nedisertib) increased wt-p53 transcriptional activity, which was not enhanced further by EGFR knockdown, indicating that EGFR suppressed wt-p53 activity through DNA-PKcs binding with p53. Finally, using conditional EGFR-knockout GSCs, we show that depleting EGFR increased animal survival in mice transplanted with wt-p53 GSCs.

Conclusion
This study demonstrates that EGFR signaling inhibits wt-p53 function in GBM by promoting an interaction between p53 and DNA-PKcs.
Cardiac dysfunction in medulloblastoma survivors treated with photon irradiation
Authors: Cacciotti Chantel , Chordas Christine , Valentino Katie , Allen Rudy , Lenzen Alicia , Burns Karen , Nagarajan Rajaram , Manley Peter , Pillay-Smiley Natasha 
Published: April 2022

Abstract

Background
Medulloblastoma is an aggressive central nervous system (CNS) tumor that occurs mostly in the pediatric population. Treatment often includes a combination of surgical resection, craniospinal irradiation (CSI), and chemotherapy. Children who receive standard photon CSI are at risk for cardiac toxicities including coronary artery disease, left ventricular scarring and dysfunction, valvular damage, and atherosclerosis. Current survivorship guidelines recommend routine echocardiogram (ECHO) surveillance. In this multi-institutional study, we describe markers of cardiac dysfunction in medulloblastoma survivors.

Methods
A retrospective chart review of medulloblastoma patients who had photon beam CSI was followed by ECHO between 1980 and 2010 at Lurie Children’s Hospital and Dana-Farber/Boston Children’s Hospital.

Results
During the 30-year study period, 168 medulloblastoma patient records were identified. Included in this study were the 75 patients who received CSI or spinal radiation and ECHO follow-up. The mean age at CSI was 8.6 years (range, 2.9-20), and the mean number of years between radiation therapy (RT) completion and first ECHO was 7.4 (range, 2-16). Mean ejection fraction (EF) was 60.0% and shortening fraction (SF) was 33.8%. Five patients (7%) had abnormal ECHO results: three with EF &lt;50% and two with SF &lt;28%.

Conclusion
The majority of medulloblastoma patients who received CSI have relatively normal ECHOs post-treatment; however, 7% of patients had abnormal ECHOs. The implication of our study for medulloblastoma survivors is that further investigations are needed in this population with a more systematic, longitudinal assessment to determine predictors and screenings.
Being LGBTQ+ and Disabled, a Socially Contradicting
Experience
Authors: Egner Justine E. 
Published: April 2022

Abstract
This chapter explores the ways in which disability and sexuality have been conceptualized and understood as incompatible and how this perceived incompatibility renders LGBTQ+ disabled people invisible within both popular society as well as their identity communities. Employing virtual ethnography, the chapter focuses on the unique experience of intersectional invisibility as described by LGBTQ+ disabled people and organizations in virtual spaces. It explores the relationship between disability and sexuality and disability identities and LGBTQ+ identities through an empirical examination of organizational discourses and personal narratives present in online spaces. Findings suggest that LGBTQ+ disabled people and advocacy groups seek to reject and resist current narratives that render them invisible by broadcasting their experiences through virtual communities and media.
“The beauty of a man is his cattle”
Authors: Whittaker Laryssa 
Published: April 2022

Abstract
“Ubuhle bendoda” is a Zulu song about lobolo, the exchange of bridewealth in the form of cattle. A practice that was never conceptualized simply as transactional, lobolo indexed and cemented social contract between families, and represented the capacity of individuals and families to fulfil their social roles. The song is a favorite in the repertoire of the Field Band Foundation (FBF), a national non-profit youth development organization that provides music education in underprivileged communities in South Africa. This chapter analyzes “Ubuhle bendoda” in the context of the FBF’s work, revealing social and economic change due to colonialism, apartheid, and post-apartheid capitalism. I argue the song provides a heuristic for understanding the way that the FBF addresses present-day socioeconomic inequality through teaching, musical practice, and financial partnerships, resulting in new ethical and economic bases for gender roles, new forms of reciprocity, and new economic vehicles for establishing social relations.
Claims Across Outcomes and Population Ethics
Authors: Adler Matthew D. 
Published: April 2022

Abstract
Prioritarians, unlike utilitarians, believe that well-being has diminishing marginal moral value. This difference is captured in the Pigou-Dalton axiom: a transfer of well-being from a better-off person to a worse-off person, which (a) is non-leaky in the sense that the worse-off one gains exactly what the better-off one loses, (b) still leaves the better-off one at least as well off as the worse-off one, and (c) affects no one else, is a moral improvement. Prioritarianism satisfies the Pigou-Dalton axiom, while utilitarianism does not. Prioritarianism also satisfies the Pareto axioms and an axiom of Anonymity. The axiom cluster Pareto, Pigou-Dalton, and Anonymity can be defended with reference to individuals’ “claims across outcomes.” A claim is a tripartite relation between an individual and two outcomes, which is valenced in terms of her well-being. The moral ranking of two outcomes, in turn, depends upon the valence and strength of individuals’ claims between them. The claims-across-outcome framework helps make the case for prioritarianism as against utilitarianism and other outcome-ranking criteria that fail to satisfy the combination of Pareto, Pigou-Dalton, and Anonymity. Can the claims-across-outcomes framework be extended to the case of variable population, in which the individuals who exist in a given outcome x need not be identical to those who exist in another outcome y? This chapter argues that the framework can be thus extended and that it supports generalized versions of the Pareto, Pigou-Dalton and Anonymity axioms. These axioms, in turn, have implications for a range of topics in population ethics.
Integrated Methods
Authors: Tröndle Martin , Greenwood Steven , Ramakrishnan Chandrasekhar , Uhde Folkert , Egermann Hauke , Tschacher Wolfgang 
Published: April 2022

AbstractIntegration of methods is an option for interdisciplinary research settings, allowing insights into the fleeting moments of aesthetic experience. This chapter aims to exemplify such research settings by introducing two research projects: eMotion: MappingMuseum Experience and ECR—Experimental Concert Research. eMotion concerned aesthetic experiences in the environment of a fine arts museum, and ECR investigates music experience in concerts. Both projects were conducted in ecologically valid environments: the fine art museum and the classical concert hall, respectively. The technical setup of both projects merged different data levels—body movement, heart rate, skin conductance, facial expressions, sociological variables, and emotional and aesthetic evaluations of specific artworks or musical pieces—into an integrated dataset. In both projects, scientists (from musicology, art history, psychology, cultural studies, etc.), technicians, and programmers, as well as practitioners like artists, musicians, and curators, were brought together to intensively cooperate. The chapter elaborates on the aspects of such inter- and transdisciplinary research endeavors.
Movement behaviours and health of children and youth with disabilities: Impact of the 2020 COVID-19 pandemic
Authors: Arbour-Nicitopoulos Kelly P , James Maeghan E , Moore Sarah A , Sharma Ritu , Martin Ginis Kathleen A 
Published: April 2022

Abstract

Objectives
This study examined the acute and longer-term impacts of the COVID-19 pandemic on the movement behaviours and health of children and youth with disabilities (CYD) in Canada.

Methods
Eighty-six parents of CYD completed an online survey twice (May 2020 and November 2020). Interviews were completed with seven families in March 2021.

Results
At both time points, &lt;20% of CYD met the physical activity and sedentary behaviour guidelines, and &gt;50% of CYD met the sleep guideline. No CYD met all three movement guidelines. Nearly one-quarter of CYD reported declines in health from pre-pandemic levels. Interview themes revealed that shifting of routines, unoccupied time, reduced physiotherapy opportunities, parental capacity, and the social and built environment all impacted the movement behaviours of CYD.

Conclusions
Movement behaviours and health of CYD must be prioritized in COVID-19 recovery efforts through quality programming, highly trained instructors, accessible and inclusive infrastructure, and family-centred health.
OA25 Is it time for patient-initiated methotrexate monitoring?
Authors: Wood Natasha A. E , Farmer Leila , Manhas Roope , Lewis Tom , Kyle Stuart 
Published: April 2022

Abstract

Background/Aims
Regular blood monitoring is recommended to ensure safety in patients on methotrexate (MTX). During the COVID pandemic, British Society of Rheumatology (BSR) sanctioned a reduction in monitoring for patients stable on MTX for 12 months. In accordance Devon CCG approved changing local Shared Care Guidelines (SCG), reducing the frequency to six monthly in stable MTX patients. Our aim was to assess whether monitoring frequency changed during the pandemic, and if so whether any patients came to harm.

Methods
Patients stable on MTX monotherapy for at least a year to 31.3.2020 were identified via hospital pathology. 854 patients identified; the mean number of days between monitoring requests was calculated for the year to April 2020, and year to April 2021, respectively. A sub-analysis of 229 patients who had reduced from monthly to three monthly blood tests at similar time points was undertaken. Tests included: platelets (PLT), mean cell volume (MCV), neutrophils (NEUT), estimated glomerular filtration rate (eGFR), and alanine aminotransferase (ALT). Confidence intervals evaluated any differences in the results between monthly and three-monthly frequencies, in terms of overall distribution as well as at an individual patient level. Additionally, the numbers of ‘catastrophic' test results, as defined by the Royal College of Pathologists, were calculated for the higher frequency and reduced frequency years.

Results
Testing frequency in the year to April 2020 approximated to monthly, and three-monthly in the year to April 2021. Sub-analysis in 229 patients showed the overall distributions of PLT, MCV, NEUT, eGFR and ALT results were no more likely to be outside normal laboratory parameters when tested less frequently. Furthermore, individual patients were no more likely to have results outside normal laboratory parameters with less frequent testing. Overall, our analysis indicated that reduced monitoring did not lead to more abnormal results. Additionally, ‘catastrophic’ results were extremely uncommon, and did not increase with reduced testing. Routine MTX monitoring revealed no catastrophic results, these only occurred in patients being managed for co-existing morbidities.

Conclusion
MTX monitoring reduced during the pandemic but not in adherence to updated SCG. We evidence that reducing frequency of routine blood monitoring did not increase abnormal results or cause harm in stable MTX patients. Significant blood abnormalities were rare and universally occurred only with co-existing morbidities. Across primary and secondary care workloads are increasing, resources are limited, and cost efficiencies needed. These findings support a review of the frequency of routine blood monitoring; is now the time to shift to patient-initiated testing in those stable on MTX monotherapy?

Disclosure
N.A.E. Wood: None. L. Farmer: None. R. Manhas: None. T. Lewis: None. S. Kyle: None.