bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intravenous administration of anakinra in children with macrophage activation syndrome
Authors: Phadke Omkar , Rouster-Stevens Kelly , Giannopoulos Helen , Chandrakasan Shanmuganathan , Prahalad Sampath 
Published: June 2021

Abstract
Background
Subcutaneous anakinra is an interleukin-1 inhibitor used to treat juvenile idiopathic arthritis. Recent reports suggest anakinra can be a valuable addition to the treatment of COVID-19 associated cytokine storm syndrome and the related multisystem inflammatory syndrome (MIS-C) in children. Herein, we describe our experience with intravenously administered anakinra.

Findings
19 Patients (9 male) received intravenous (IV) anakinra for treatment of macrophage activation syndrome (MAS) secondary to systemic lupus erythematosus (SLE), systemic JIA (SJIA) or secondary hemophagocytic lymphohistiocytosis (sHLH). In most cases the general trend of the fibrinogen, ferritin, AST, and platelet count (Ravelli criteria) improved after initiation of IV anakinra. There were no reports of anaphylaxis or reactions associated with administration of IV anakinra.

Conclusion
Intravenous administration of anakinra is an important therapeutic option for critically ill patients with MAS/HLH. It is also beneficial for those with thrombocytopenia, subcutaneous edema, neurological dysfunction, or very young, hospitalized patients who need multiple painful subcutaneous injections.
Cutaneous mucinosis of infancy: a rare case of joint involvement
Authors: Morreale Cristina , Bleidl Dario , Sementa Angela Rita , Malattia Clara 
Published: June 2021

Abstract
Background
Primary cutaneous mucinosis are a heterogeneous group of diseases characterized by the deposition of glycosaminoglycans in the dermis and the follicles. These diseases are rare in children therefore their diagnosis and management are still challenging. Joint involvement has been reported in patients with secondary cutaneous mucinosis and, rarely, in primary mucinosis. We describe a case of Cutaneous Mucinosis of Infancy with joint involvement.

Case presentation
An healthy 5-year-old boy showed acute arthritis of the left knee and left elbow confirmed by ultrasound. Laboratory tests were within normal range. Symptoms disappeared after a course of nonsteroid anti-inflammatory drugs. One year later, the knee swelling reappeared; juvenile idiopathic arthritis was diagnosed and intra-articular steroid injection was performed. Due to persistence of arthritis of the knee he was admitted to our hospital. On physical examination variable skin-colored lesions were observed, which had been in existence for over 2 years.
We performed a skin biopsy that showed an interstitial mucine deposition in the reticular dermis. Cutaneous Mucinosis of Infancy was diagnosed.

Discussion and conclusions
Cutaneous Mucinosis of Infancy is a persistent dermatosis with benign prognosis and no treatment is generally required. Our case report is particularly interesting because it is the first in which joint involvement has been reported in CMI, a disorder that has so far been described as limited to skin involvement. Further studies will be necessary in order to clarify the pathogenesis of joint involvement in primary mucinosis.
Rehabilitation of extremely atrophic edentulous mandible in elderly patients with associated comorbidities: a case report and proof of concept
Authors: Filipov Iulian , Chirila Lucian , Cristache Corina Marilena 
Published: June 2021

Abstract
Background
Oral rehabilitation of the atrophic mandible is, most of the time, a challenging procedure, especially in elderly patients with associated comorbidities.

Case presentation
This clinical report describes the rehabilitation of an extremely atrophic mandible using an overdenture supported by four splinted implants, two of which are placed in the interforaminal region and the other two bypassing the inferior alveolar nerve at the level of the antegonial notch. A passive-fit bar structure splinting the four inserted implants was designed to compensate for mandibular flexure, to reduce the amount of strain on the implants, and avoid bone resorption and prosthetic failure. The 14-month postoperative cone-beam computed tomography (CBCT) and the clinical follow-up showed the bilateral integrity of the inferior alveolar nerve and the successful restoration of the atrophic edentulous mandible with a significant improvement in the patient’s quality of life.

Conclusions
The applied technique depicts several benefits such as a minimally invasive approach, reduced number of surgical interventions, reduced total treatment time, reduced treatment costs, and higher psychological acceptability.
Factors influencing the provision of care for Inuit in a mainstream residential addiction rehabilitation centre in Southern Canada, an instrumental case study into cultural safety
Authors: Lauzière Julie , Fletcher Christopher , Gaboury Isabelle 
Published: June 2021

AbstractBackgroundProvision of culturally safe care has been proposed to address health inequity, including in the areas of mental health and addiction. The factors that influence the provision of culturally safe care remain understudied. This paper explores the factors influencing the efforts of a mainstream residential addiction rehabilitation centre to provide culturally appropriate and quality care for Inuit.MethodsAn instrumental case study was conducted, informed by ethnographic and creative research methods. Over 700 h of participant observation were carried out between March 2018 and January 2020, in addition to qualitative semi-structured interviews (34 participants) and/or member-checking activities (17 participants) conducted with a total of 42 individuals: 20 Inuit residents, 18 clinical/specialized staff, and 4 clinical/administrative managers. An interpretive thematic analysis was performed to examine the factors that may influence the provision of culturally safe care for Inuit residents.ResultsTen categories of interrelated factors were identified and classified according to whether they relate to individual, programmatic, organizational, or systemic levels. These categories covered: (1) residents’ and staff’s life experiences; (2) personal and relational qualities and skills; (3) the model of care; (4) model flexibility; (5) ways in which relational aspects were considered; (6) sensitivity of the organization towards the population served; (7) human resources and professional development issues; (8) social climate; (9) political, relational, and funding climate; and (10) legislative, regulatory, and professional environment. While system-level factors generally had a negative effect on experiences of cultural safety, most factors at other levels had both favourable and unfavourable effects, depending on the context and dimensions examined.ConclusionsThe results offer insight into the interplay between the challenges and barriers that mainstream organizations face when working with Inuit, and the opportunities and enablers that organizations can build on to improve their services. This paper contributes to a better understanding of the challenges and opportunities to providing culturally safe addiction programs to Inuit within a complex intervention setting. It concludes by highlighting some areas for improvement to advance cultural safety in this context.
Metabolic and immunological phenotype of rare lipomatoses: Dercum’s disease and Roch-Leri mesosomatic lipomatosis
Authors: Lemaitre Madleen , Chevalier Benjamin , Jannin Arnaud , Le Mapihan Kristell , Boury Samuel , Lion Georges , Labalette Myriam , Vantyghem Marie-Christine 
Published: June 2021

Abstract
Context
Dercum’s disease (DD) and Roch-Leri mesosomatic lipomatosis (LMS) are rare and poorly characterized diseases. The clinical presentation combines multiple lipomas, painful in DD in contrast with LMS, without lipoatrophy.

Objective
To identify any specific metabolic and immune phenotype of DD and LMS.

Design and patients
This monocentric retrospective study included 46 patients: 9 DD, 11 LMS, 18 lean and 8 obese controls. Metabolic and immunohematological characteristics of each group were compared.

Results
The median age of the patients was similar in the 3 groups (31 years). The number of women, and of basophils, and CD3+, CD4+ and CD8+ T lymphocytes was significantly higher in the DD versus the LMS group, without any difference of the metabolic parameters. Weight, BMI, blood pressure, gamma-GT, leptin, fasting insulin and C-peptide levels, fat mass percentage, and intra/total abdominal fat ratio were significantly higher in each lipomatosis group compared with the lean group. Compared with the lean group, the DD group had significantly higher fasting blood glucose, LDL-cholesterol, platelets, leukocytes, basophils, and a lower NK cell count, whereas the LMS group had a significantly lower rate of CD3, CD4, and CD8 lymphocytes. Compared with the obese controls, basophils remained higher in DD and T lymphocytes subpopulations lower in LMS groups.

Conclusion
DD and LMS show a common background of obesity and metabolic phenotype, but a distinct immunohematological profile characterized by a higher number of basophils in DD patients, an inflammatory profile that could contribute to pain. T lymphocyte depletion was present in LMS. These findings could offer specific therapeutic opportunities, especially for painful DD.
AMPK hyperactivation promotes dendrite retraction, synaptic loss, and neuronal dysfunction in glaucoma
Authors: Belforte Nicolas , Agostinone Jessica , Alarcon-Martinez Luis , Villafranca-Baughman Deborah , Dotigny Florence , Cueva Vargas Jorge L. , Di Polo Adriana 
Published: June 2021

Abstract
Background
The maintenance of complex dendritic arbors and synaptic transmission are processes that require a substantial amount of energy. Bioenergetic decline is a prominent feature of chronic neurodegenerative diseases, yet the signaling mechanisms that link energy stress with neuronal dysfunction are poorly understood. Recent work has implicated energy deficits in glaucoma, and retinal ganglion cell (RGC) dendritic pathology and synapse disassembly are key features of ocular hypertension damage.

Results
We show that adenosine monophosphate-activated protein kinase (AMPK), a conserved energy biosensor, is strongly activated in RGC from mice with ocular hypertension and patients with primary open angle glaucoma. Our data demonstrate that AMPK triggers RGC dendrite retraction and synapse elimination. We show that the harmful effect of AMPK is exerted through inhibition of the mammalian target of rapamycin complex 1 (mTORC1). Attenuation of AMPK activity restores mTORC1 function and rescues dendrites and synaptic contacts. Strikingly, AMPK depletion promotes recovery of light-evoked retinal responses, improves axonal transport, and extends RGC survival.

Conclusions
This study identifies AMPK as a critical nexus between bioenergetic decline and RGC dysfunction during pressure-induced stress, and highlights the importance of targeting energy homeostasis in glaucoma and other neurodegenerative diseases.
Comprehensive high-throughput meta-analysis of differentially expressed microRNAs in transcriptomic datasets reveals significant disruption of MAPK/JNK signal transduction pathway in Adult T-cell leukemia/lymphoma
Authors: Shadabi Shahrzad , Delrish Nargess , Norouzi Mehdi , Ehteshami Maryam , Habibian-Sezavar Fariba , Pourrezaei Samira , Madihi Mobina , Ostadali Mohammadreza , Akhgar Foruhar , Shayeghpour Ali , Razavi Pashabayg Cobra , Aghajanian Sepehr , Mozhgani Sayed-Hamidreza , Jazayeri Seyed-Mohammad 
Published: June 2021

Abstract
Background
Human T-lymphotropic virus 1 (HTLV-1) infection may lead to the development of Adult T-cell leukemia/lymphoma (ATLL). To further elucidate the pathophysiology of this aggressive CD4+ T-cell malignancy, we have performed an integrated systems biology approach to analyze previous transcriptome datasets focusing on differentially expressed miRNAs (DEMs) in peripheral blood of ATLL patients.

Methods
Datasets GSE28626, GSE31629, GSE11577 were used to identify ATLL-specific DEM signatures. The target genes of each identified miRNA were obtained to construct a protein-protein interactions network using STRING database. The target gene hubs were subjected to further analysis to demonstrate significantly enriched gene ontology terms and signaling pathways. Quantitative reverse transcription Polymerase Chain Reaction (RTqPCR) was performed on major genes in certain pathways identified by network analysis to highlight gene expression alterations.

Results
High-throughput in silico analysis revealed 9 DEMs hsa-let-7a, hsa-let-7g, hsa-mir-181b, hsa-mir-26b, hsa-mir-30c, hsa-mir-186, hsa-mir-10a, hsa-mir-30b, and hsa-let-7f between ATLL patients and healthy donors. Further analysis revealed the first 5 of DEMs were directly associated with previously identified pathways in the pathogenesis of HTLV-1. Network analysis demonstrated the involvement of target gene hubs in several signaling cascades, mainly in the MAPK pathway. RT-qPCR on human ATLL samples showed significant upregulation of EVI1, MKP1, PTPRR, and JNK gene vs healthy donors in MAPK/JNK pathway.

Discussion
The results highlighted the functional impact of a subset dysregulated microRNAs in ATLL on cellular gene expression and signal transduction pathways. Further studies are needed to identify novel biomarkers to obtain a comprehensive mapping of deregulated biological pathways in ATLL.
The effect of prophylactic bilateral salpingectomy on ovarian reserve in patients who underwent laparoscopic hysterectomy
Authors: Wang Shizhuo , Gu Jiahui 
Published: June 2021

Abstract
Background
Bilateral salpingectomy has been proposed to reduce the risk of ovarian cancer, but it is not clear whether the surgery affects ovarian reserve. This study compares the impact of laparoscopic hysterectomy for benign disease with or without prophylactic bilateral salpingectomy on ovarian reserve.

Methods
Records were reviewed for 373 premenopausal women who underwent laparoscopic hysterectomy with ovarian reserve for benign uterine diseases. The serum anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and three-dimensional antral follicle count (AFC) were assessed before surgery and 3 and 9 months postoperatively to evaluate ovarian reserve. Patients were divided into two groups according to whether they underwent prophylactic bilateral salpingectomy. The incidence of pelvic diseases was monitored until the ninth month after surgery.

Results
There was no significant difference between the two surgery groups in terms of baseline AMH, E2, FSH, LH, and AFC (all P > 0.05). There was no difference in potential bias factors, including patient age, operative time, and blood loss (all P > 0.05). There was also no significant difference between the two groups 3 months after surgery with respect to AMH (P = 0.763), E2 (P = 0.264), FSH (P = 0.478), LH (P = 0.07), and AFC (P = 0.061). Similarly, there were no differences between groups 9 months after surgery for AMH (P = 0.939), E2 (P = 0.137), FSH (P = 0.276), LH (P = 0.07) and AFC (P = 0.066). At 9 months after the operation, no patients had malignant ovarian tumors. The incidences of benign ovarian tumors in the salpingectomy group were 0 and 2.68 % at 3 and 9 months after surgery, respectively, and the corresponding values in the control group were 0 and 5.36 %. The incidences of pelvic inflammatory disease in the salpingectomy group were 10.72 and 8.04 % at 3 and 9 months after surgery, respectively, while corresponding values in the control group were 24.13 and 16.09 %.

Conclusions
Prophylactic bilateral salpingectomy did not damage the ovarian reserve of reproductive-age women who underwent laparoscopic hysterectomy. Prophylactic bilateral salpingectomy might be a good method to prevent the development of ovarian cancer. Larger clinical trials with longer follow-up times are needed to further evaluate the risks and benefits.
The role of routine FIBERoptic bronchoscopy monitoring during percutaneous dilatational TRACHeostomy (FIBERTRACH): a study protocol for a randomized, controlled clinical trial
Authors: Añón José M. , Arellano María Soledad , Pérez-Márquez Manuel , Díaz-Alvariño Claudia , Márquez-Alonso José A. , Rodríguez-Peláez Jorge , Nanwani-Nanwani Kapil , Martín-Pellicer Ana , Civantos Belén , López-Fernández Alba , Seises Irene , García-Nerín Jorge , Figueira Juan C. , Casero Henar , Vejo Javier , Agrifoglio Alexander , Cachafeiro Lucía , Díaz-Almirón Mariana , Villar Jesús 
Published: June 2021

AbstractBackgroundTracheostomy is one of the most frequent techniques in intensive care units (ICU). Fiberoptic bronchoscopy (FB) is a safety measure when performing a percutaneous dilatational tracheostomy (PDT), but the controversy surrounding the routine use of FB as part of the procedure remains open. National surveys in some European countries showed that the use of FB is non-standardized. Retrospective studies have not shown a significant difference in complications between procedures performed with or without a bronchoscope. International guidelines have not been able to establish recommendations regarding the use of FB in PDT due to lack of evidence.DesignThis is a multicenter (three centers at the time of publishing this paper) randomized controlled clinical trial to examine the safety of percutaneous tracheostomy using FB. We will include all consecutive adult patients admitted to the ICU in whom percutaneous tracheostomy for prolonged mechanical ventilation is indicated and with no exclusion criteria for using FB. Eligible patients will be randomly assigned to receive blind PDT or PDT under endoscopic guidance. All procedures will be performed by experienced intensivists in PDT and FB. A Data Safety and Monitoring Board (DSMB) will monitor the trial. The primary outcome is the incidence of perioperative complications.DiscussionFB is a safe technique when performing PDT although its use is not universally accepted in all ICUs as a routine practice. Should PDT be monitored routinely with endoscopic guidance? This study will assess the role of FB monitoring during PDT.Trial registrationClinicalTrials.gov NCT04265625. Registered on February 11, 2020
Sheep scab spatial distribution: the roles of transmission pathways
Authors: Nixon Emily Joanne , Brooks-Pollock Ellen , Wall Richard 
Published: June 2021

Abstract
Background
Ovine psoroptic mange (sheep scab) is a highly pathogenic contagious infection caused by the mite Psoroptes ovis. Following 21 years in which scab was eradicated in the UK, it was inadvertently reintroduced in 1972 and, despite the implementation of a range of control methods, its prevalence increased steadily thereafter. Recent reports of resistance to macrocyclic lactone treatments may further exacerbate control problems. A better understanding of the factors that facilitate its transmission are required to allow improved management of this disease. Transmission of infection occurs within and between contiguous sheep farms via infected sheep-to-sheep or sheep–environment contact and through long-distance movements of infected sheep, such as through markets.

Methods
A stochastic metapopulation model was used to investigate the impact of different transmission routes on the spatial pattern of outbreaks. A range of model scenarios were considered following the initial infection of a cluster of highly connected contiguous farms.

Results
Scab spreads between clusters of neighbouring contiguous farms after introduction but when long-distance movements are excluded, infection then self-limits spatially at boundaries where farm connectivity is low. Inclusion of long-distance movements is required to generate the national patterns of disease spread observed.

Conclusions
Preventing the movement of scab infested sheep through sales and markets is essential for any national management programme. If effective movement control can be implemented, regional control in geographic areas where farm densities are high would allow more focussed cost-effective scab management.

Graphical Abstract
The zinc finger protein CLAMP promotes long-range chromatin interactions that mediate dosage compensation of the Drosophila male X-chromosome
Authors: Jordan William , Larschan Erica 
Published: June 2021

Abstract
Background
Drosophila dosage compensation is an important model system for defining how active chromatin domains are formed. The male-specific lethal dosage compensation complex (MSLc) increases transcript levels of genes along the length of the single male X-chromosome to equalize with that expressed from the two female X-chromosomes. The strongest binding sites for MSLc cluster together in three-dimensional space largely independent of MSLc because clustering occurs in both sexes. CLAMP, a non-sex specific, ubiquitous zinc finger protein, binds synergistically with MSLc to enrich the occupancy of both factors on the male X-chromosome.

Results
Here, we demonstrate that CLAMP promotes the observed three-dimensional clustering of MSLc binding sites. Moreover, the X-enriched CLAMP protein more strongly promotes longer-range three-dimensional interactions on the X-chromosome than autosomes. Genome-wide, CLAMP promotes three-dimensional interactions between active chromatin regions together with other insulator proteins.

Conclusion
Overall, we define how long-range interactions which are modulated by a locally enriched ubiquitous transcription factor promote hyper-activation of the X-chromosome to mediate dosage compensation.
Contribution of genetic and epigenetic changes to escape from X-chromosome inactivation
Authors: Balaton Bradley P. , Brown Carolyn J. 
Published: June 2021

Abstract
Background
X-chromosome inactivation (XCI) is the epigenetic inactivation of one of two X chromosomes in XX eutherian mammals. The inactive X chromosome is the result of multiple silencing pathways that act in concert to deposit chromatin changes, including DNA methylation and histone modifications. Yet over 15% of genes escape or variably escape from inactivation and continue to be expressed from the otherwise inactive X chromosome. To the extent that they have been studied, epigenetic marks correlate with this expression.

Results
Using publicly available data, we compared XCI status calls with DNA methylation, H3K4me1, H3K4me3, H3K9me3, H3K27ac, H3K27me3 and H3K36me3. At genes subject to XCI we found heterochromatic marks enriched, and euchromatic marks depleted on the inactive X when compared to the active X. Genes escaping XCI were more similar between the active and inactive X. Using sample-specific XCI status calls, we found some marks differed significantly with variable XCI status, but which marks were significant was not consistent between genes. A model trained to predict XCI status from these epigenetic marks obtained over 75% accuracy for genes escaping and over 90% for genes subject to XCI. This model made novel XCI status calls for genes without allelic differences or CpG islands required for other methods. Examining these calls across a domain of variably escaping genes, we saw XCI status vary across individual genes rather than at the domain level. Lastly, we compared XCI status calls to genetic polymorphisms, finding multiple loci associated with XCI status changes at variably escaping genes, but none individually sufficient to induce an XCI status change.

Conclusion
The control of expression from the inactive X chromosome is multifaceted, but ultimately regulated at the individual gene level with detectable but limited impact of distant polymorphisms. On the inactive X, at silenced genes euchromatic marks are depleted while heterochromatic marks are enriched. Genes escaping inactivation show a less significant enrichment of heterochromatic marks and depletion of H3K27ac. Combining all examined marks improved XCI status prediction, particularly for genes without CpG islands or polymorphisms, as no single feature is a consistent feature of silenced or expressed genes.