bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Different Challenges in Being an Adult Versus a Pediatric Intensivist
Authors: Dennis Diane , van Heerden Peter , Khanna Rahul , Knott Cameron , Zhang Simone , Calhoun Aaron 
Published: March 2022

OBJECTIVES:
There is little current research comparing stress, burnout, and resilience in pediatric and adult intensive care practitioners. This article analyzes data derived from a 2018 qualitative study of burnout and resilience among ICU providers to explore differences that may exist between the pediatric and adult domains of practice.

DESIGN:
This study represents a thematic subanalysis of textual data derived from a larger qualitative study of ICU provider burnout and resilience.

SETTING:
Six international critical care units (Australia, Israel, United States).

SUBJECTS:
Physicians working at the above sites who had been practicing as intensivists for a minimum period of 4 years.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Data were collected using a semistructured interview process, and resulting transcripts were analyzed using postpositivist framework analysis. A secondary analysis was then performed separately on pediatric and adult datasets using the initial coding framework as a template. Three themes related to perceived differences were noted: differences in the patient characteristics within both cohorts, differences in the relationships between staff and family, and personal biases of individual intensivists. Pediatric and adult practitioners differed in their perceptions of the patient’s perceived responsibility for their illness. Emotional responses to the stressor of child abuse (particularly as they related to clinician-family relationships) also differed. The stress of dealing with family expectations of patient survival even in dire circumstances was unique to the pediatric environment. Both pediatric and adult practitioners commented on the perceived difficulty of assuming the opposite role. Differences in life expectancy and mortality rate were significant factors in this.

CONCLUSIONS:
Although similar stressors exist within each group, meaningful differences in how these are perceived and personally processed by individual clinicians exist. Better understanding of these differences will assist attempts to enhance the resilience and provide career guidance to aspiring intensive care clinicians.
Cardioprotective Effect of Growth Differentiation Factor 15 Against Isoproterenol-Induced Cardiomyocyte Apoptosis via Regulation of the Mitochondrial Fusion
Authors: Zhang Yan , Mei Zhu , Jia Xiaodong , Song Haixu , Liu Jing , Tian Xiaoxiang 
Published: March 2022

Abstract

Objective:
Pressure overload-induced myocardial apoptosis is a critical pathologically initiated process leading to heart failure (HF). Growth differentiation factor 15 (GDF15) dramatically increases during cardiac hypertrophy and dysfunction, but its functions and mechanisms are barely known. This study aims to elucidate the role and mechanism of GDF15 in HF.

Methods:
Between January 2017 and August 2018, 57 patients diagnosed with chronic HF (aged >18  years, with left ventricular ejection fraction (LVEF) ≤35%) and 57 non-HF patients (aged >18  years, LVEF >35%) were prospectively enrolled in this study based on the balance of the baseline characteristics. Other acute or chronic diseases and pregnant/lactating women were excluded. The serum concentrations of GDF15 were detected. Isoproterenol (ISO)-induced HF mouse model was established by pumping with ISO (30 mg/(kg·day)) for 4  weeks, and the GDF15 expression in serum and heart tissue was evaluated in vivo. Primary cardiomyocytes were cultured and treated with ISO to induce cardiomyocytes damage. The apoptosis of cardiomyocytes and the effect of GDF15 on ISO-induced cardiomyocytes injury was evaluated in vitro.

Results:
After adjusting the baseline characteristic, serum levels of GDF15 were significantly higher in HF subjects than in non-HF patients. Similarly, in the ISO-induced HF mouse model, the significant increase in GDF15 was associated with the process of HF in vivo. Moreover, the elevation of GDF15 occurred prior to heart remodeling in the ISO-induced HF mouse model. Furthermore, using primary cardiomyocytes, we demonstrated that the GDF15 was remarkably enhanced in serum from pathological HF patients and cardiac tissue from the ISO-induced mouse model. Reducing GDF15 exaggerated the ISO-induced cell apoptosis by blocking mitochondrial fusion and increasing oxidative stress. In contrast, the silence of GDF15 aggravated the ISO-induced cardiomyocytes damage.

Conclusions:
GDF15 acts as a protective factor against cardiomyocyte apoptosis by improving mitochondria fusion during HF. These findings indicate that GDF15 may be a potential therapeutic target for HF.
YAP1 Expression in Lichen Planus and Squamous Cell Carcinoma: Role in Disease Pathogenesis and Potential Therapeutic Target
Authors: Neinaa Yomna Mazid El-Hamd , El-Aziz Mohamed Dareen Abd , Ali Shereen Abd El-Moula , Gaballah Hanaa Hibishy , El-Tatawy Rania Ahmed 
Published: March 2022

Background:
Lichen planus (LP), especially oral type, reported a potential risk of malignant transformation to squamous cell carcinoma (SCC). Yes-Associated Protein (YAP1), a key component of the Hippo pathway, acts as a transcription cofactor regulating expression of genes involved in cell proliferation, apoptosis, and migration. Therefore, it has been implicated in carcinogenesis of a wide variety of human cancers.

Objectives:
To study YAP1 expression in LP and SCC in comparison to normal control (NC) specimens.

Patients and methods:
This study was conducted on 50 NC specimens, 50 LP specimens, and 50 SCC specimens. They were categorized into 2 main groups; cutaneous (25 NC, 25 LP, 25 SCC), and oral (25 NC, 25 LP, 25 SCC). All specimens were examined for YAP1 antibody expression by immunohistochemistry and YAP1 mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR).

Results:
In both cutaneous and oral groups; significant upregulation of YAP1 expressions was observed in SCC specimens followed by LP and then NC specimens in the same sequence. Its expression in SCC was found to be significantly higher in poorly and moderately differentiated types than well differentiated types.

Conclusion:
YAP1 may have a potential role in the pathogenesis of LP and oncogenesis and progression of SCC. Moreover, it could be considered as a novel therapeutic target for such cases.
An Atypical Myelomonocytic Cell Infiltrate: Use of Next-Generation Sequencing to Diagnose Indeterminate Cell Histiocytosis
Authors: Belina Morgan E. , Kwock Jeffery T. , Al-Rohil Rami , Fresco Amber 
Published: March 2022

Abstract:
Indeterminant cell histiocytosis (ICH) is a rare lymphoproliferative disorder that demonstrates features of Langerhans and non-Langerhans cell histiocytoses and diagnosis can be challenging. We present a case of a 62 year old woman with a generalized eruption of erythematous papules on the face, trunk and extremities. Skin biopsies demonstrated a dermal mononuclear cell infiltrate with monocytic (CD4, CD33), histiocytic (CD68, CD163), and dendritic cell (CD1a) immunophenotype but negative for Langerhans' cell marker (CD207). The differential diagnosis included leukemia cutis and ICH, and further workup revealed a normal bone marrow biopsy. To confirm the diagnosis of ICH, next generation sequencing with ETV3-NCOA2 gene fusion was performed and was positive. The patient's condition improved with methotrexate and narrow band UVB phototherapy. Our case adds to the existing literature supporting the use of next-generation sequencing to test for ETV3-NCOA2 gene fusion in suspected cases of ICH.
ALK-Negative Primary Cutaneous Anaplastic Large Cell Lymphoma With Systemic Involvement or Systemic ALCL With Cutaneous Lesion. A Diagnostic Dilemma
Authors: Gupta Ishan , Ramteke Prashant , Narwal Anubhav , Sharma Mehar Chand , Bakhshi Sameer , Mallick Saumyaranjan 
Published: March 2022

Abstract:
Primary cutaneous anaplastic large-cell lymphoma (C-ALCL) is a cutaneous CD30-positive lymphoproliferative disorder. The patients usually present with single or multiple cutaneous nodules or papules and about 10% cases present with extracutaneous manifestations, which are predominantly in the form of regional lymph nodal involvement. Visceral involvement especially pulmonary or hepatic involvement in C-ALCL is only rarely described in the scientific literature. Approximately 20%–42% cases show spontaneous regression, about 50% cases may recur; however, C-ALCL generally carries a good prognosis. We present a rare case of primary C-ALCL in a 66-year-old man with regional lymph nodal and hepatic involvement. Differential diagnostic entities are discussed in this report with the review of the literature.
The development from hyperuricemia to gout: key mechanisms and natural products for treatment
Authors: Liu Lin , Wang Dan , Liu Mengyang , Yu Haiyang , Chen Qian , Wu Yuzheng , Bao Ruixia , Zhang Yi , Wang Tao 
Published: March 2022

Abstract
Gout is a common of inflammatory arthritis and is caused by the deposition of monosodium urate (MSU) crystals as a result of hyperuricemia (HUA). Although HUA is considered to be the main risk factor for gout, only approximately 10% of the individuals with HUA will eventually experience a gout attack. In this review, we first briefly introduce the development of gout and then summarize several possible reasons for its development. Genetic factors play a more prominent role in gout than in other diseases; functional mutations related to urate control and innate immunity components have been found to be associated with gout. Here, we list some of the most prominent genes involved in the pathogenesis of gout. In joints with MSU deposition, mature macrophages may uptake MSU crystals without causing inflammation, and this helps to maintain joints in an asymptomatic state. As an auxiliary inflammation pathway, the ATP-P2X7R-NLRP3 axis may contribute to the amplification of MSU-induced inflammation to affect the development of gout. Finally, this review summarizes the research progress on natural products that can be used in the treatment of HUA and gout.
INTRAVITREAL NESVACUMAB (ANTIANGIOPOIETIN 2) PLUS AFLIBERCEPT IN DIABETIC MACULAR EDEMA
Authors: Brown David M. , Boyer David S. , Csaky Karl , Vitti Robert , Perlee Lorah , Chu Karen W. , Asmus Friedrich , Leal Sergio , Zeitz Oliver , Cheng Yenchieh , Schmelter Thomas , Heier Jeffrey S. ,   On behalf of the RUBY Investigators
Published: March 2022

Purpose:
The purpose of this study was to compare intravitreal nesvacumab (anti-angiopoietin 2) plus aflibercept with intravitreal aflibercept injection (IAI) in diabetic macular edema.

Methods:
The eyes (n = 302) were randomized (1:2:3) to nesvacumab 3 mg + aflibercept 2 mg (LD combo), nesvacumab 6 mg + aflibercept 2 mg (HD combo), or IAI 2 mg at baseline, Weeks 4 and 8. LD combo continued every 8 weeks (q8w). HD combo was rerandomized at Week 12 to q8w or every 12 weeks (q12w); IAI to q8w, q12w, or HD combo q8w through Week 32.

Results:
Week 12 best-corrected visual acuity gains for LD and HD combo versus IAI were 6.8, 8.5, and 8.8 letters; Week 36 changes were similar. Central subfield retinal thickness reductions at Week 12 were −169.4, −184.0, and −174.6 µm (nominal P = 0.0183, HD combo vs. IAI); Week 36 reductions for LD combo and HD combo q8w and q12w versus IAI were −210.4, −223.4, and −193.7 versus −61.9 µm (nominal P < 0.05). At Week 12, 13.3% and 21.3% versus 15.2% had ≥2-step Diabetic Retinopathy Severity Scale improvement (LD and HD combos vs. IAI) and 59.6% and 66.3% versus 53.7% had complete foveal center fluid resolution. Safety was comparable across groups.

Conclusion:
Nesvacumab + aflibercept demonstrated no additional visual benefit over IAI. Anatomic improvements with HD combo may warrant further investigation.
Homozygous Nonsense Mutation in SDR9C7 in a Chinese Patient With Autosomal Recessive Congenital Ichthyosis
Authors: Huang Xin , Chen Zhi-Ming , Yang Yong 
Published: March 2022

Introduction:
Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of cornification disorders. To date, 14 genes have been found to be related to ARCI.
We herein describe a patient with ARCI who carried a homozygous nonsense mutation in the SDR9C7 gene and presented with generalized erythroderma, scales, recurrent blisters, and onychomycosis.

Case presentation:
A 23-year-old woman developed generalized erythroderma and scales over her trunk and limbs shortly after birth, followed by recurrent blisters and nail deformities. A diagnosis of ARCI was made based on her clinical manifestations, family history, and genetic analysis, which revealed a homozygous mutation in SDR9C7 (c.187C>T, p.Q63X).

Discussion:
Most genes responsible for ARCI are associated with epidermal lipid metabolism, which contributes to the cutaneous barrier. SDR9C7, which encodes short-chain dehydrogenase/reductase family 9C member 7, has also been recently found to play vital roles in this process by regulating ceramide binding to the epidermal cornified cell envelope. For patients clinically suspected to have ARCI, recurrent onychomycosis is a strong indication that they carry a SDR9C7 gene mutation.

Conclusion:
Remarkable phenotypic and genotypic heterogeneity exists among patients with ARCI. Genetic analysis is an effective tool in diagnosing this and other hereditary diseases. Our patient developed recurrent onychomycosis, a typical presentation of ARCI caused by SDR9C7 mutation, and the unusual blisters further expand the clinical phenotypic spectrum of ARCI.
Elite Athletes Successfully Return to the Preinjury Level of Sport Following Ankle Syndesmosis Injuries: A Systematic Review and Meta-Analysis
Authors: Bolia Ioanna K. , Bogdanov Jacob , Schoell Kyle , Ouyang Yuxin , Petrigliano Frank A. , Weber Alexander E. , Tan Eric W. 
Published: March 2022

Objective:
To comprehensively review and report the outcomes of ankle syndesmotic injury management in elite athletes.

Data sources:
Three databases were searched for articles reporting the rate of return to sport following treatment of ankle syndesmotic injuries in elite athletes (collegiate or professional level). Ten articles and 440 athletes were included. Articles reporting the rate of return to sport following high ankle sprain injury in elite athletes. Data collected included demographics, type of treatment received, and return to sport (RTS) information. A random effects model was used.

Main results:
The estimated overall rate of RTS was 99% (95% CI, 95.5-99.9). The mean time to RTS was 38 ± 18 (range, 14-137) days. Of the 440 athletes, 269 (269/440%, 61%) were treated nonoperatively (nonoperative group); the rate of RTS was 99.6%, and the athletes returned at a mean time of 29 ± 14 (range, 13-45) days. A total of 171 athletes (171 of 440%, 39%) underwent surgical treatment (operative group). All (171 of 171%, 100%) athletes returned at a mean time of 50.3 ± 13 (range, 41-137) days. Almost all athletes who underwent surgery had suture button fixation (164 of 171 athletes, 96%), and the mean time to RTS was 7 weeks with 9.1% complication rate.

Conclusions:
Elite athletes with ankle syndesmosis injury return to sport at an extremely high rates, following operative or nonoperative treatment. Return to the preinjury level of competition should be expected at 4 weeks and 7 weeks in high-level athletes who undergo nonoperative and operative management, respectively. Suture button fixation was used by the majority of studies reporting surgical management of ankle syndesmosis injuries in athletes.
HIV Testing at Visits to US Emergency Departments, 2018
Authors: Clay Carson E. , Ling Albee Y. , Bennett Christopher L. 
Published: March 2022

Background:
An early HIV diagnosis improves patient outcomes, reduces the burden of undiagnosed HIV, and limits transmission. There is a need for an updated assessment of HIV testing rates in the emergency department (ED).

Setting:
The National Hospital Ambulatory Medical Care Survey sampling ED visits were weighted to give an estimate of ED visits across all US states in 2018.

Methods:
We analyzed patients aged 13–64 years without known HIV and estimated ED visits with HIV testing and then stratified by race, ethnicity, and region. Descriptive statistics and mapping were used to illustrate and compare patient, visit, and hospital characteristics for visits with HIV testing.

Results:
Of 83.0 million weighted visits to EDs in 2018 by patients aged 13–64 years without a known HIV infection (based on 13,237 National Hospital Ambulatory Medical Care Survey sample visits), HIV testing was performed in 1.05% of visits. HIV testing was more frequent for patients aged 13–34 years compared with that for patients aged 35–64 years (1.32% vs. 0.82%, P = 0.056), Black patients compared with that for White and other patients (1.73% vs. 0.79% and 0.41%, P = 0.002), Hispanic or Latino patients compared with that for non-Hispanic or Latino patients (2.18% vs. 0.84%, P = 0.001), and patients insured by Medicaid compared with that for patients insured by private or other insurance (1.71% vs. 0.64% and 0.96%, P = 0.003). HIV testing rates were the highest in the Northeast (1.72%), followed by the South (1.05%).

Conclusions:
HIV testing occurred in a minority of ED visits. There are differences in rates of HIV testing by race, ethnicity, and location. Although rates of testing have increased, rates of ED-based HIV testing remain low.
89Zr-PSMA-617 PET/CT May Reveal Local Recurrence of Prostate Cancer Unidentified by 68Ga-PSMA-11 PET/CT
Authors: Rosar Florian , Bartholomä Mark , Maus Stephan , Privé Bastiaan M. , Khreish Fadi , Franssen Gerben M. , Derks Yvonne H.W. , Nagarajah James , Ezziddin Samer 
Published: March 2022

Abstract
For localization of biochemical recurrence of prostate cancer, 68Ga-PSMA-11 PET/CT imaging was performed in a 66-year-old man with no suspicious findings at 1 hour p.i. Additional 89Zr-PSMA-617 PET/CT revealed a small local recurrence in the prostate bed, facilitating consecutive local therapy. This interesting image points to the potential of PET/CT with 89Zr-labeled PSMA ligands, for example, 89Zr-PSMA-617, for identifying the source of biochemical recurrence despite otherwise negative imaging including conventional PSMA PET/CT.
68Ga-FAPI-04 Versus 18F-FDG PET/CT in a Case of Peutz-Jeghers Syndrome
Authors: Dong Aisheng , Zhang Zeyu , Zhang Lu , Cheng Chao , Zuo Changjing 
Published: March 2022

Abstract
Peutz-Jeghers syndrome is a rare inherited hamartomatous polyposis syndrome. We describe 68Ga-FAPI-04 and 18F-FDG PET/CT findings in a case of Peutz-Jeghers syndrome with primary duodenal clear cell sarcoma, peritoneal metastases, and multiple intestinal polyps varying in size. The duodenal tumor and its metastases showed increased FDG and FAPI uptake. The peritoneal metastases were delineated more clearly on FAPI PET/CT compared with FDG PET/CT. More interestingly, the intestinal polyps showed increased FDG uptake and no FAPI uptake.
YY1 PROMOTES MICROGLIA M2 POLARIZATION THROUGH THE MIR-130A-3P/TREM-2 AXIS TO ALLEVIATE SEPSIS-ASSOCIATED ENCEPHALOPATHY
Authors: Peng Liang-Shan , Xu Yan , Wang Qiao-Sheng 
Published: March 2022

ABSTRACT

Purpose: Sepsis-associated encephalopathy (SAE) induces cognitive dysfunction via mechanisms that commonly involve neuroinflammation. Yin Yang 1 (YY1) is an important transcription factor that acts as a key role in sepsis and neuroepithelium development. However, the function of YY1 in SAE remains unclear. Our study aimed to probe the intrinsic and concrete molecular mechanism of YY1 in SAE. Methods: SAE cell model and SAE animal model were constructed by lipopolysaccharide (LPS) treatment and cecal ligation and puncture surgery, respectively. Behavioral tests were performed to analyze the cognitive function. The polarization state of mouse microglia (BV-2 cells) was assessed by flow cytometry assay. The mRNA and protein expressions were assessed by qRT-PCR and western blot. Finally, the binding relationships between YY1, miR-130a-3p, andTREM-2were verified by dual luciferase reporter gene assay and/or ChIP assay. Results: Here our results described that YY1 and TREM-2 were downregulated and miR-130a-3p was upregulated in SAE. YY1 overexpression could promote M2 polarization of microglia, and alleviate neuroinflammation and behavioral deficits in vitro and in vivo. YY1 could inhibit miR-130a-3p promoter activity. As expected, miR-130a-3p overexpression abolished the effects of YY1 overexpression on LPS-treated BV-2 cells. Besides, TREM-2 was identified as the target of miR-130a-3p. TREM-2 silencing could reverse the effects of miR-130a-3p inhibition on LPS-treated BV-2 cells. Conclusion: Taken together, YY1 promoted microglia M2 polarization via upregulating TREM-2 by interacting with miR-130a-3p promoter, suggesting YY1 overexpression might be a novel therapeutic strategy of SAE.
Surgical Correction of the Genital Hiatus at the Time of Sacrocolpopexy—Are Concurrent Posterior Repairs Cost-Effective?
Authors: Chang Olivia H. , Shepherd Jonathan P. , St. Martin Brad , Sokol Eric R. , Wallace Shannon 
Published: March 2022

Objective
The objective was to perform a cost-effectiveness analysis of posterior repair performed at the time of sacrocolpopexy (SCP).

Methods
We used TreeAge Pro to construct a decision model comparing laparoscopic hysterectomy with SCP with and without concurrent posterior repair (SCP and SCP + PR). Using a time horizon of 1 year, we modeled prolapse recurrence, prolapse retreatment, and complications, including rectal injury, rectovaginal hematoma requiring surgical take-back, and postoperative dyspareunia. Costs included index surgery, surgical retreatment, and complications. We modeled effectiveness as quality-adjusted life years (QALYs). Cost-effectiveness was defined using the incremental cost-effectiveness ratio and willingness to pay of $100,000/QALY. Sensitivity analyses were performed.

Results
Sacrocolpopexy was the dominant strategy with a cost of $65,714 and an effectiveness of 0.84. It was cost-effective at willingness to pay threshold less than $100,000/QALY. The SCP + PR costs more ($75,063) with lower effectiveness (0.83). The effectiveness of the 2 strategies was similar, differing only by 0.01 QALY, which is less than the minimally important difference for utilities. Tornado plots showed CEA results were most influenced by the cost of SCP, cost of SCP + PR, and probability of dyspareunia after SCP. In 1-way sensitivity analyses, the model outcome would change only if the cost of SCP was increased by 12.8% or if the cost of SCP + PR decreased by 14.5%. For dyspareunia, our model would only change if the probability of dyspareunia after SCP alone was 75.9% (base case, 18.6%), whereas the probability of dyspareunia after SCP + PR was 26.8%.

Conclusion
In this cost-effectiveness analysis, SCP without concurrent PR was the dominant strategy.