bluuebunny/crossref_metadata_2025_split huggingface dataset:
SNAI1 is upregulated during muscle regeneration and represses FGF21 and ATF3 expression by directly binding their promoters
Authors: Elia Ines , Realini Giulia , Di Mauro Vittoria , Borghi Sara , Bottoni Laura , Tornambè Salvatore , Vitiello Libero , Weiss Stephen J. , Chiariello Mario , Tamburrini Annalaura , Oliviero Salvatore , Neri Francesco , Orlandini Maurizio , Galvagni Federico 
Published: June 2022

AbstractDuring skeletal myogenesis, the zinc‐finger transcription factors SNAI1 and SNAI2, are expressed in proliferating myoblasts and regulate the transition to terminally differentiated myotubes while repressing pro‐differentiation genes. Here, we demonstrate that SNAI1 is upregulated in vivo during the early phase of muscle regeneration induced by bupivacaine injury. Using shRNA‐mediated gene silencing in C2C12 myoblasts and whole‐transcriptome microarray analysis, we identified a collection of genes belonging to the endoplasmic reticulum (ER) stress pathway whose expression, induced by myogenic differentiation, was upregulated in absence of SNAI1. Among these, key ER stress genes, such as Atf3, Ddit3/Chop, Hspa5/Bip, and Fgf21, a myokine involved in muscle differentiation, were strongly upregulated. Furthermore, by promoter mutant analysis and Chromatin immune precipitation assay, we demonstrated that SNAI1 represses Fgf21 and Atf3 in proliferating myoblasts by directly binding to multiple E boxes in their respective promoter regions. Together, these data describe a new regulatory mechanism of myogenic differentiation involving the direct repressive action of SNAI1 on ER stress and Fgf21 expression, ultimately contributing to maintaining the proliferative and undifferentiated state of myoblasts.
Calcific aortic valve stenosis and COVID-19: clinical management, valvular damage, and pathophysiological mechanisms
Authors: Bäck Magnus , Hashem Mohammed , Giani Anna , Pawelzik Sven-Christian , Franco-Cereceda Anders 
Published: June 2022

Abstract
Patients with corona virus disease (COVID)-19 are prone to a variety of myocardial and vascular complications. Recent studies suggest that cardiac valves are also potential targets for the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Calcific aortic valve stenosis (CAVS) is the most common valvular heart disease. Severe COVID-19 has been associated with main risk factors for CAVS, including male sex, older age, cardiovascular co-morbidities, obesity, hypertension, diabetes, and chronic kidney disease. Prognostic implications for concomitant CAVS and SARS-CoV-2 infection have been reported. Changes in CAVS diagnostic, interventional, and follow-up clinical processes have occurred during the COVID-19 pandemic. SARS-CoV-2 may damage aortic valves via both direct injury and indirect mechanisms that include hyperinflammation, oxidative stress, and valve thrombosis. The injury is often acute but may be irreversible and thus favor future CAVS development. Rheumatic heart disease, which develops as a sequel of rheumatic fever, is one example of a possible relation between an acute infection and chronic valvular heart disease. A persistent prothrombotic state, prolonged endothelial dysfunction, and incomplete resolution of inflammation after COVID-19 convalescence may expose the aortic valves to chronic stimulation toward CAVS. Priority of CAVS management in COVID-19 includes avoiding treatment delay and managing underlying pathophysiological state that promotes CAVS.
Aldehyde dehydrogenase 2-associated metabolic abnormalities and cardiovascular diseases: current status, underlying mechanisms, and clinical recommendations
Authors: Xu Lei , Cui Xiao-Tong , Chen Zhang-Wei , Shen Ling-Hong , Gao Xiu-Fang , Yan Xiao-Xiang , Wang Cong , Zhang Xiao-Kai , Hu Kai , Ge Jun-Bo , Sun Ai-Jun 
Published: June 2022

Abstract
Cardiovascular diseases originate from various pathogeneses, among which metabolic abnormalities are common. An integrated metabolic disturbance in common cardiovascular diseases has been suggested, particularly in the Asian population. This speculation is supported by the finding that aldehyde dehydrogenase 2 (ALDH2) gene mutations are present in nearly half of the Asian population. ALDH2 mutations significantly reduce ALDH2 enzyme activity and increase production of toxic aldehydes, including 4-hydroxynonenal, and are involved in the pathophysiology of several cardiovascular disorders such as atherosclerosis and myocardial infarction. Additionally, individuals with ALDH2 mutations are more susceptible to hypertension and diabetes, and these mutations are significantly correlated with heart failure. Until now there are no actionable clinical recommendations with regards to screening for ALDH2 mutations. A comprehensive understanding of the relationship between ALDH2 and these etiologies may greatly help in better prevention and treatment of cardiovascular diseases in populations, especially Asian, where ALDH2 mutations are common.
Signaling pathways of inflammation in myocardial ischemia/reperfusion injury
Authors: Hu Shi-Yu , Yang Ji-E , Zhang Feng 
Published: June 2022

Abstract
Primary percutaneous coronary intervention is the current standard treatment for myocardial infarction, but is associated with ischemia/reperfusion injury for which inflammation is an important part. This review summaries the recent findings in the study of pro- and anti-inflammatory signaling pathways (eg, TLR4/Myd88/NF-κB, MAPKs/NF-κB, NLRP3 inflammasome, JAK2/STAT3, and Nrf2/HO-1) in myocardial ischemia/reperfusion injury, as well as relevant drug development efforts. Despite of the vast body of literature, no concrete advances have been made in translating the new knowledge into clinical practice, but we do anticipate major breakthroughs in the foreseeable future.
Maternal and fetal health outcomes of cesarean sections (CS) in Ethiopia: results from retrospective cross-sectional study of Southern Ethiopia Gurage Zone Governmental Hospitals
Authors: Belay Helina M. , Kassa Roza T. , Negeri Haweni A. , Woldesenbet Ermiyas B. , Belachew Fitsum K. 
Published: June 2022

Background:
The most common obstetric surgery performed nowadays is a cesarean section (CS). Even though cesarean delivery is the safest mode of delivery in high-risk scenarios, it also appears to have a higher risk of maternal and newborn morbidity and mortality than vaginal delivery, and in low-resource settings, the risks are doubled. In this study we investigated fetal and maternal outcomes following CS in southern Ethiopia, specifically in the Gurage region, to better understand and quantify the prevalence of these outcomes and to provide recommendations based on the findings.

Methods:
Institutional based retrospective cross-sectional study was conducted in Gurage Zone in 5 governmental hospitals from February 21, 2021 to March 13, 2021, on the hospital medical records of mothers who delivered by CS from February 2019 to January 2021. The collected data was entered and analyzed using STATA version 15. Binary and Multiple Logistic regressions were used to identify associated factors for maternal outcome and fetal outcome.

Results:
Among the 368 mothers included in the study, 86 (23.4%) had poor maternal outcomes, and the 3 most common causes were postop infection 19 (25.6%), the need for blood transfusion 16 (21.6%), and anesthesia-related complications 9 (12.1%). On the other hand, from the 384 neonates studied, 75 (19.74%) had poor outcomes with 16 (4.2%) perinatal death, and 60 (15,6%) had low first-minute APGAR scores needing close monitoring. Obstetric complications, medical diseases, and AntePartum Hemorrhage as an indication for CS were statistically significant factors for poor maternal outcomes. Similarly, medical disease and cephalic pelvic disproportion as an indication for CS were statistically significant factors for poor fetal outcomes.

Conclusion and recommendation:
The numbers are not uniformly high or low when compared with other regions of Ethiopia, but they are closely related, suggesting a need for immediate collaborative evidence-based interventions to improve hospital capacities and preoperative optimization strategies, since pregnancy-related complications, preoperative hemorrhages, and preoperative medical conditions all contributed to poor maternal and neonatal outcomes.
Risk factors for ocular neovascularization after central retinal artery occlusion
Authors: Lo Wen-Jung , Lin Yu-Ching , Chang Hsin-Yi , Chen Mei-Ju 
Published: June 2022

Background:
To report the incidence and risk factors associated with ocular neovascularization (NV) in patients with central retinal artery occlusion (CRAO).

Methods:
This retrospective study included patients diagnosed with acute CRAO in a single tertiary center. Medical charts were reviewed for ocular NV occurrences. We analyzed systemic and ocular conditions on first visit and demographic data.

Results:
Eighty-seven eyes were eligible for this study. Among these, 13 eyes had ocular NV after CRAO, with an incidence of 15%. The prevalences of hypertension, diabetes mellitus, history of stroke, chronic kidney disease (CKD), and age at first visit were higher among patients with ocular NV than among patients without ocular NV after CRAO. Moreover, most patients with CKD in the ocular NV group had undergone dialysis. A multivariate regression analysis revealed that CKD (hazard ratio [HR]: 9.27, 95% CI, 1.87-46.05, p = 0.006) and glaucoma history (HR: 7.52, 95% CI, 1.14-49.46, p = 0.036) were significant risk factors for developing ocular NV among patients with CRAO.

Conclusion:
CKD and glaucoma history were significant risk factors for developing ocular NV after CRAO, particularly among patients that underwent dialysis.
Recalcitrant cutaneous mastocytosis treated with genetically informed targeted therapy
Authors: Gleason Laura , Tekmen Volkan , Cohen Alexa , Bhatti Safiyyah , Beksac Burcu , Cha Jisun , Porcu Pierluigi , Nikbakht Neda 
Published: June 2022

Introduction:
Mastocytosis, a clonal proliferation of mast cells commonly involving the skin and bone marrow, has a varied clinical presentation ranging from skin-limited lesions to systemic disease. Cutaneous mastocytosis is managed symptomatically, but systemic mastocytosis is treated with targeted therapy against the mutated receptor tyrosine kinase c-KIT, the pathogenic driver of mastocytosis. However, there are no guidelines for the treatment of cutaneous mastocytosis refractory to symptomatic management.
We herein report a method to select genetically informed therapy for symptomatic and recalcitrant cutaneous mastocytosis.

Case Presentation:
We performed a mutational analysis of dermal mast cells after enrichment by laser capture in a 23-year-old woman with recalcitrant cutaneous mastocytosis. The analysis revealed a aspartic acid to valine substitution at codon 816 (D816V) mutation in the protein c-KIT. Based on these results, we initiated treatment with the multi-kinase/KIT inhibitor midostaurin, a treatment effective against the D816V c-KIT mutation. After 3 months of treatment, the patient exhibited a reduction in the number and size of cutaneous lesions and reported resolution of pruritus and decreased severity of other mast cell-related symptoms.

Discussion:
The treatment of mastocytosis relies heavily on whether the disease is limited to the skin or systemic. However, there are no guidelines for cutaneous mastocytosis that does not respond to symptomatic management. In the present report describing a patient with recalcitrant cutaneous mastocytosis, we describe a strategy in which skin mutational analysis is used to guide the selection of targeted therapy.

Conclusion:
Performing mast cell mutational analyses in the skin provides a means to select targeted therapy for symptomatic and refractory cutaneous mastocytosis.
Livedoid Vasculopathy Secondary to Protein C Deficiency: A Case Successfully Treated With Rivaroxaban
Authors: Chaisrimaneepan Nattanicha , Tienthavorn Tanongkiet 
Published: June 2022

Introduction:
Livedoid vasculopathy is a chronic noninflammatory skin disease secondary to hypercoagulable states. No therapeutic guideline has yet been established for livedoid vasculopathy.
We herein report a case of livedoid vasculopathy secondary to protein C deficiency that was successfully treated with rivaroxaban.

Case presentation:
A 31-year-old Thai woman who had been diagnosed with livedoid vasculopathy 10 years previously presented with a 2-month history of worsening leg ulcers and failure to respond to aspirin, colchicine, and pentoxifylline. Further investigations confirmed protein C deficiency. Rivaroxaban was initiated, and clinical improvement was achieved in 8 weeks.

Discussion:
When livedoid vasculopathy is confirmed by skin biopsy, additional investigations for hypercoagulable states should be performed to exclude secondary causes. Identification of the causes of livedoid vasculopathy can direct physicians to therapeutic options based on previously reported cases of successful treatment. Our patient, whose livedoid vasculopathy was caused by protein C deficiency, responded well to rivaroxaban.

Conclusion:
Protein C deficiency results in a hypercoagulable state, and affected patients can present with livedoid vasculopathy. The anticoagulant rivaroxaban has been beneficial in the treatment of livedoid vasculopathy.
Meeting the need for nurse practitioner clinicals: A survey of practitioners
Authors: Gigli Kristin H. , Gonzalez John D. 
Published: June 2022

ABSTRACT

Background:
The increase in the number of nurse practitioner (NP) students requires increased clinical practice sites and prepared preceptors.

Purpose:
This study describes NPs' clinical experiences as a student and their current practices as an NP preceptor.

Methodology:
A descriptive study design used a 38-item web-based survey conducted in June and July 2021.

Results:
A total of 334 NPs practicing in Texas responded; most had been NPs for 10 or fewer years (58.2%) and in their positions less than 5 years (50.3%). A plurality of respondents was required to find their own clinical placements (46%). The most common challenge in obtaining clinical placements was finding preceptors (33%). Nurse practitioners reported excellent clinical experiences (39.3%) as a student and believed that they were generally well prepared for the NP role (38.9%) and to care for their specialty patient population (46.1%) upon graduation. Sixty percent of respondents reported not currently precepting, 37.6% had never been asked to precept, whereas 32.8% reported that employers restricted precepting. Family NPs were the least likely to precept.

Conclusions:
Nurse practitioners report positive clinical experiences that prepare them for NP careers. Multiple opportunities exist to enlist additional NPs as preceptors for NP students.

Implications:
There is capacity within the current NP workforce to meet the clinical educational needs of NP students. Future work should examine best practices to engage NPs who are not currently preceptors. As policies change NP education, research should examine the implications of the preparation for NP roles at the time of graduation, organizational outcomes, and quality of care.
Provider Communication and Fever Protocol for Children With Sickle Cell Disease in the Emergency Department
Authors: Awe Mofoluwake , Robbins Adelaide , Chandi Mohit , Cortright Lindsay , Tumin Dmitry , Whitfield Andrea 
Published: June 2022

Objective
We assessed whether prior communication between pediatric hematologists and emergency department (ED) providers reduced time to administration of parenteral antibiotics for children with sickle cell disease presenting with fever.

Methods
Patients 2 months to 21 years of age were retrospectively identified if they were followed up at our center's pediatric hematology clinic and presented to the pediatric ED with fever. Emergency department–hematology communication before patient arrival was ascertained by chart review. The primary outcome was time to administration of parenteral antibiotics after ED arrival, with 60 minutes being the recommended maximum.

Results
Forty-nine patients were included in the analysis. Prior communication occurred in 43% of cases, with a median time to antibiotic administration of 79 minutes in this group (interquartile range, 59–142), compared with 136 minutes for patients without prior communication (interquartile range, 105–181 minutes; P = 0.012). The groups did not differ in hospital length of stay at the index visit.

Conclusions
Advance communication between the pediatric hematologist and ED physician was associated with reduced time to antibiotic administration for febrile children with sickle cell disease. Further interventions should be explored to achieve timely antibiotics administration within 60 minutes of ED arrival.
Care Pattern for Fontan-Associated Liver Disease by Academic Pediatric Hepatologists in Canada
Authors: Kehar Mohit , Jimenez-Rivera Carolina 
Published: June 2022

Background:
Fontan-Associated Liver Disease (FALD) is a common extracardiac complication seen in patients following the Fontan procedure. There are no consensus guidelines on screening and management of children with FALD.

Objective:
The current study aims to determine academic pediatric hepatologists’ practices and identify variability in management provided to children with FALD in Canada.

Methods:
Using the infrastructure of the Canadian Pediatric Hepatology Research Group, a nationwide survey was distributed electronically to all pediatric hepatologists practicing in university-affiliated hospitals.

Results:
Twelve pediatric hepatologists from 12 of 13 academic centers (92%) responded to the survey. The institutions of only 2 (17%) physicians offer post-Fontan care with a multidisciplinary team, both from different provinces. The screening for other comorbidities, use of noninvasive modality, and timing of liver biopsy for estimation of liver fibrosis and screening for esophageal varices differ from program to program. The frequency of outpatient clinic follow-up varies significantly. Education and counseling concerning liver health are generally used as treatment; only 58% of academic centers have a formal adult care transition plan.

Conclusions:
Significant discrepancies exist in the care provided to children with FALD by hepatologists practicing in academic centers across Canada. Future study is needed to develop a standardized protocol for managing and following children and youth with FALD.
Elevated CD4+ T-cell glucose metabolism in HIV+ women with diabetes mellitus
Authors: Butterfield Tiffany R. , Hanna David B. , Kaplan Robert C. , Xue Xiaonan , Kizer Jorge R. , Durkin Helen G. , Kassaye Seble G. , Nowicki Marek , Tien Phyllis C. , Topper Elizabeth T. , Floris-Moore Michelle A. , Titanji Kehmia , Fischl Margaret A. , Heath Sonya , Palmer Clovis S. , Landay Alan L. , Anzinger Joshua J. 
Published: June 2022

Objective:
Immune dysfunction and chronic inflammation are characteristic of HIV infection and diabetes mellitus, with CD4+ T-cell metabolism implicated in the pathogenesis of each disease. However, there is limited information on CD4+ T-cell metabolism in HIV+ persons with diabetes mellitus. We examined CD4+ T-cell glucose metabolism in HIV+ women with and without diabetes mellitus.

Design:
A case–control study was used to compare CD4+ T-cell glucose metabolism in women with HIV with or without diabetes mellitus.

Methods:
Nondiabetic (HIV+DM−, N = 20) or type 2 diabetic HIV+ women with (HIV+DM+, N = 16) or without (HIV+DMTx+, N = 18) antidiabetic treatment were identified from the WIHS and matched for age, race/ethnicity, smoking status and CD4+ cell count. CD4+ T-cell immunometabolism was examined by flow cytometry, microfluidic qRT-PCR of metabolic genes, and Seahorse extracellular flux analysis of stimulated CD4+ T cells.

Results:
HIV+DM+ displayed a significantly elevated proportion of CD4+ T cells expressing the immunometabolic marker GLUT1 compared with HIV+DMTx+ and HIV+DM− (P = 0.04 and P = 0.01, respectively). Relative expression of genes encoding key enzymes for glucose metabolism pathways were elevated in CD4+ T cells of HIV+DM+ compared with HIV+DMTx+ and HIV+DM−. T-cell receptor (TCR)-activated CD4+ T cells from HIV+DM+ showed elevated glycolysis and oxidative phosphorylation compared with HIV+DM−.

Conclusion:
CD4+ T cells from HIV+DM+ have elevated glucose metabolism. Treatment of diabetes mellitus among women with HIV may partially correct CD4+ T-cell metabolic dysfunction.
Fluoxetine reduces organ injury and improves motor function after traumatic brain injury in mice
Authors: Weaver Jessica L. , Eliceiri Brian , Costantini Todd W. 
Published: June 2022

BACKGROUND
Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in trauma patients worldwide. Brain injury is associated with significant inflammation, both within the brain and in the peripheral organs. This inflammatory response in TBI leads to a secondary injury, worsening the effects of the original brain injury. Serotonin is also linked to inflammation in the intestine and inflammatory bowel disease, but its role in the gut-brain axis is not known. We hypothesized that using fluoxetine to block serotonin reuptake would reduce organ inflammation and improve outcomes after TBI.

METHODS
C57/B6 mice were given a severe TBI using a controlled cortical impact. To measure intestinal permeability, a piece of terminal ileum was resected, the lumen was filled with 4-kDa fluorescein isothiocyanate (FITC)-dextran, and the ends were tied. The intestinal segment was submerged in buffer and fluorescence in the buffer measured over time. To measure lung permeability, 70-kDa FITC-dextran is injected retro-orbitally. Thirty minutes later, the left lung was homogenized and the fluorescence was measured. To measure performance on the rota-rod, mice were placed on a spinning rod, and the time to fall off was measured. Those treated with fluoxetine received a single dose of 5 mg/kg via intraperitoneal injection immediately after injury.

RESULTS
Traumatic brain injury was associated with an increase in intestinal permeability to FITC-dextran, increased lung vascular permeability, and worse performance on the rota-rod. Fluoxetine significantly reduced lung and intestinal permeability after TBI and improved performance on the rota-rod after TBI.

CONCLUSION
Use of fluoxetine has the potential to reduce lung injury and improve motor coordination in severe TBI patients. Further study will be needed to elucidate the mechanism behind this effect.
Efficient direct and limited environmental transmission of SARS-CoV-2 lineage B.1.22 in domestic cats
Authors: Gerhards Nora M. , Gonzales Jose L. , Vreman Sandra , Ravesloot Lars , van den Brand Judith M.A. , Doekes Harmen P. , Egberink Herman F. , Stegeman Arjan , Oreshkova Nadia , van der Poel Wim H.M. , de Jong Mart C.M. 
Published: June 2022

AbstractSusceptibility of domestic cats for infection with SARS-CoV-2 has been demonstrated by several experimental studies and field observations. We performed an extensive study to further characterize transmission of SARS-CoV-2 between cats, both by direct contact as well as by indirect contact. To that end, we estimated the transmission rate parameter and the decay parameter for infectivity in the environment. Using four groups of pair-transmission experiment, all donor (inoculated) cats became infected, shed virus and seroconverted, while three out of four direct contact cats got infected, shed virus and two of those seroconverted. One out of eight cats exposed to a SARS-CoV-2-contaminated environment became infected but did not seroconvert. Statistical analysis of the transmission data gives a reproduction number R0 of 2.18 (95% CI: (0.92-4.08), a transmission rate parameter β of 0.23 day-1 (95% CI: 0.06-0.54), and a virus decay rate parameter μ of 2.73 day-1 (95% CI: 0.77-15.82). These data indicate that transmission between cats can be sustained (R0>1), however, infectiousness of a contaminated environment decays rapidly (mean duration of infectiousness 1/2.73 days). Infections of cats via exposure to a SARS-CoV-2-contaminated environment cannot be excluded if cats are exposed shortly after contamination.