bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single Nucleotide Variant in FAS Associates With Organ Failure and Soluble Fas Cell Surface Death Receptor in Critical Illness
Authors: Mikacenic Carmen , Bhatraju Pavan , Robinson-Cohen Cassianne , Kosamo Susanna , Fohner Alison E. , Dmyterko Victoria , Long S. Alice , Cerosaletti Karen , Calfee Carolyn S. , Matthay Michael A. , Walley Keith R. , Russell James A. , Christie Jason D. , Meyer Nuala J. , Christiani David C. , Wurfel Mark M. 
Published: October 2021

OBJECTIVES:
Multiple organ failure in critically ill patients is associated with poor prognosis, but biomarkers contributory to pathogenesis are unknown. Previous studies support a role for Fas cell surface death receptor (Fas)-mediated apoptosis in organ dysfunction. Our objectives were to test for associations between soluble Fas and multiple organ failure, identify protein quantitative trait loci, and determine associations between genetic variants and multiple organ failure.

DESIGN:
Retrospective observational cohort study.

SETTING:
Four academic ICUs at U.S. hospitals.

PATIENTS:
Genetic analyses were completed in a discovery (n = 1,589) and validation set (n = 863). Fas gene expression and flow cytometry studies were completed in outpatient research participants (n = 250).

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
In discovery and validation sets of critically ill patients, we tested for associations between enrollment plasma soluble Fas concentrations and Sequential Organ Failure Assessment score on day 3. We conducted a genome-wide association study of plasma soluble Fas (discovery n = 1,042) and carried forward a single nucleotide variant in the FAS gene, rs982764, for validation (n = 863). We further tested whether the single nucleotide variant in FAS (rs982764) was associated with Sequential Organ Failure Assessment score, FAS transcriptional isoforms, and Fas cell surface expression. Higher plasma soluble Fas was associated with higher day 3 Sequential Organ Failure Assessment scores in both the discovery (β = 4.07; p < 0.001) and validation (β = 6.96; p < 0.001) sets. A single nucleotide variant in FAS (rs982764G) was associated with lower plasma soluble Fas concentrations and lower day 3 Sequential Organ Failure Assessment score in meta-analysis (–0.21; p = 0.02). Single nucleotide variant rs982764G was also associated with a lower relative expression of the transcript for soluble as opposed to transmembrane Fas and higher cell surface expression of Fas on CD4+ T cells.

CONCLUSIONS:
We found that single nucleotide variant rs982764G was associated with lower plasma soluble Fas concentrations in a discovery and validation population, and single nucleotide variant rs982764G was also associated with lower organ dysfunction on day 3. These findings support further study of the Fas pathway as a potential mediator of organ dysfunction in critically ill patients.
Q-15 Minutes Vital Sign Documentation Is a Poor Surrogate for Assessing Quality of Care After Acute Ischemic Stroke
Authors: Stone Suzanne , Zhao Huihan , Nyancho Daniel , Schneider Nathan J. , Shang Ty , Olson DaiWai M. 
Published: October 2021

Objective
Documenting vital signs and National Institutes of Health Stroke Scale (NIHSS) once every 15 minutes after intravenous thrombolytic therapy for acute ischemic stroke is often used as a metric to assess the quality of care. This study explores the association between “once every 15 minutes” documentation and stroke outcomes.

Methods
This is a retrospective study of the first 2 hours of vital signs and NIHSS documentation after thrombolytic stroke therapy. Sociodemographic and clinical data, including NIHSS, temperature, heart rate, systolic blood pressure, diastolic blood pressure, mean arterial blood pressure, and respiratory rate, were abstracted from the medical record. Missing documentation was examined for association with modified Rankin Scale (mRS) scores and neurologic changes.

Result
Among 84 patients with a mean age of 68.8 years, there were 2276 documented assessments from an expected 3780. There were 104 clinically significant changes in 1 or more index variables. The most commonly missed documentation occurred during interventional radiology. After controlling for admission NIHSS, there was no significant relationship between the completeness of documentation and discharge mRS score (r
2 = 0.047, P = .0561), nor between vital sign documentation and discharge mRS (r
2 = 0.003, P = .6338).

Conclusion
Frequency of documentation does not reflect the quality of care during the early phase of acute stroke treatment.
Doubling Intensive Care Unit Capacity by Surging Onto Medical-Surgical Units During the COVID-19 Pandemic
Authors: O'Donoghue Sharon C. , Donovan Barbara , Anderson Joanna , Foley Jane , Gillis Jean , Maloof Kimberly , Milano Andrea , Whitlock John , DeSanto-Madeya Susan 
Published: October 2021

Introduction
The ability of an organization to accommodate a large influx of patients during a prolonged period is dependent on surge capacity. The aim of this article is to describe the surge experience with space, supplies, and staff training in response to COVID-19 and provide guidance to other organizations.

Background
A hospital's response to a large-scale event is greatly impacted by the ability to surge and, depending on the type of threat, to maintain a sustained response. To identify surge capacity, an organization must first consider the type of event to appropriately plan resources.

Preparation Process
An epidemic surge drill, conducted in 2012, served as a guide in planning for the COVID-19 pandemic. The principles of crisis standards of care and a hospital incident command structure were used to clearly define roles, open lines of communication, and inform our surge plan. Preparation began by collaborating with multidisciplinary groups to acquire the most appropriate space, as well as adequate supplies, and identify and train staff.

Implementation
Teams were formed to identify the necessary resources to expand the intensive care unit (ICU) environment quickly and efficiently. Educational training was developed for redeployed staff.

Outcomes
Beth Israel Deaconess Medical Center experienced the largest surge of ICU patients within a hospital system in the state of Massachusetts. The ICU capacity was expanded by 93% from 77 to 149 beds, and the surge was maintained for approximately 9 weeks. Shadowing experiences before the actual surge were extremely valuable.

Conclusions
Planning for the surge of critically ill patients required a thoughtful, collaborative approach. Ongoing staff support and communication from nursing leadership were necessary to ensure safe, effective care for critically ill patients in a new and dynamic environment.
Nicorandil Decreases Renal Injury in Patients With Coronary Heart Disease Complicated With Type I Cardiorenal Syndrome
Authors: Du Xiaozhi , Ma Zhiyong , Li Li , Zhong Xuezhen 
Published: October 2021

Abstract:
Cardiorenal syndrome (CRS) is a group of disorders in which heart or kidney dysfunction worsens each other. This study aimed to explore the improvement effect of nicorandil on cardiorenal injury in patients with type I CRS. Patients with coronary heart disease complicated with type I CRS were enrolled. Based on the conventional treatment, the patients were prospectively randomized into a conventional treatment group and a nicorandil group, which was treated with 24 mg/d nicorandil intravenously for 1 week. Fasting peripheral venous blood serum and urine were collected before and at the end of treatment. An automatic biochemical analyzer and enzyme linked immunosorbent assay were used to detect B-type brain natriuretic peptide (BNP), serum creatinine (Scr) and cystatin C (Cys-C), renal injury index–kidney injury molecule-1 (KIM-1), neutrophil gelatinase–associated lipocalin (NGAL), and interleukin-18 (IL-18) levels. The left ventricular ejection fraction was measured by echocardiography. All measurements were not significantly different between the nicorandil and conventional treatment groups before treatment (all P > 0.05), and BNP, Scr, Cys-C, NGAL, KIM-1, and IL-18 were decreased in the 2 groups at the end of treatment (all P < 0.05). Compared with the conventional treatment group, BNP, Scr, Cys-C, NGAL, KIM-1, and IL-18 were more significantly decreased in the nicorandil group (all P < 0.05) and left ventricular ejection fraction was more significantly increased (P < 0.05). Therefore, nicorandil could significantly improve the cardiac and renal function of patients with type I CRS. This may prove to be a new therapeutic tool for improving the prognosis and rehabilitation of type I CRS.
CUL5-Mediated Visfatin (NAMPT) Degradation Blocks Endothelial Proliferation and Angiogenesis via the MAPK/PI3K-AKT Signaling
Authors: Shi Zanhua , Yao Jiamei , Ma Xinhua , Xu Daomiao , Ming Guangfeng 
Published: October 2021

Abstract:
Endothelial dysfunction participates in the pathogenesis of various cardiovascular disorders, and dysregulated angiogenesis involves the vascular endothelial growth factor (VEGF)–matrix metalloproteinases (MMP) system. Nicotinamide phosphoribosyltransferase (NAMPT) is known to enhance endothelial function and angiogenesis. The study found that NAMPT overexpression protected human coronary artery endothelial cells (HCAECs) from H2O2-induced injury through promoting cell viability, inhibiting cell apoptosis, enhancing cell motility, and promoting tube formation. Through analyses based on 2 Protein–Protein Interaction databases, Mentha and BioGrid, we identified CUL5 as a protein that may interact with NAMPT, which was then validated by Co-IP experiments. Through interacting with NAMPT, CUL5 inhibited NAMPT expression. In contrast to NAMPT, CUL5 overexpression further aggravated H2O2-induced HCAEC dysfunction. In the meantime, CUL5 overexpression reduced, whereas NAMPT overexpression increased the phosphorylation of p38 and Akt and the protein levels of VEGF and MMP2. More importantly, NAMPT overexpression partially reversed the effects of CUL5 overexpression on H2O2-stimulated HCAECs and the MAPK/phosphatidylinositol 3-kinase-Akt/VEGF/MMP signaling. In conclusion, CUL5 interacts with NAMPT in H2O2-stimulated HCAECs, suppressing cell viability, promoting cell apoptosis, and inhibiting cell mobility and tube formation. NAMPT overexpression protects against H2O2-induced HCAEC dysfunction by promoting cell viability, inhibiting cell apoptosis, and enhancing cell mobility and tube formation.
The “Brookhaven Brassie” and the Response to the Three Mile Island Accident
Authors: Studer Nicholas M. 
Published: October 2021

Abstract
In the mid-1970s, American civil defense authorities became increasingly concerned with the potential threat of fission reactor accidents. Research from the Defense Civil Preparedness Agency began to be aimed not just at the ever-present threat of nuclear warfare but also peacetime emergencies as part of a “dual use” philosophy. The Brookhaven National Laboratory received funding to create a prototype radioiodine air sampling system, with multiple publications detailing the creation of the air sampler itself and a special CD V-700 survey meter that accompanied it. In late March 1979, the system found its first operational employment at the reactor accident at Three Mile Island in Pennsylvania. Despite successful use and further study, the BNL Air Sampler was not widely fielded by the federal government. However, lessons learned from its employment and development may be applicable to contemporary radiological emergency response.
Optic Nerve Head Vessel Density Changes from Graves’ Disease without TED to TED Dysthyroid Optic Neuropathy: Does Optic Nerve Head Ischemia Play a Role?
Authors: Abdolalizadeh Parya , Kashkouli Mohsen Bahmani , Moradpasandi Farideh , Falavarjani Khalil Ghasemi , Mirshahi Reza , Akbarian Shadi 
Published: October 2021

Purpose:
To compare the retinal peripapillary capillary (RPC) vessel density (VD) between 5 groups of patients on the spectrum of thyroid eye disease (TED).

Method:
This is a prospective comparative study looking at 5 groups of patients who were consecutively included from January 2018 to March 2021. They were composed of: Healthy volunteers (39 eyes and 20 subjects), patients with Graves’ disease without TED (26 eyes and 13 patients), mild TED (28 eyes and 14 patients), moderate-severe TED (30 eyes and 17 patients), and TED with dysthyroid optic neuropathy (DON) (21 eyes and 12 patients). Ocular and periocular examination, visual field indices, RPC-VD (with optical coherence tomography angiography), and retinal nerve fiber layer, and macular ganglion cell complex thickness were recorded.

Result:
An initial insignificant (0.5 < p < 0.9) rise in the peripapillary-VD (pp-VD) and whole image-VD (wi-VD) from the healthy subject to the Graves’ disease without TED was followed by a significant (p = 0.001) fall in RPC-VD in different severity grades of the TED. Paired comparison between the 5 groups showed that the statistically significant fall from the Graves’ disease group occurred in the moderate-severe and DON groups (0.001 ≤ p ≤ 0.04). No variable significantly affected the VD (0.08 ≤ p ≤ 0.9). A lower wi-VD and pp-VD were significantly (0.001 ≤ p ≤ 0.009) correlated with the impaired optic nerve functional and structural tests. The sensitivity and specificity of wi-VD (81% and 76%) and pp-VD (69% and 71%) for detecting the DON were statistically significant (p < 0.001).

Conclusion:
Despite an insignificant rise in the wi- and pp-VD from the healthy volunteers to the patients with Graves’ disease without TED, VD showed a declining trend in the course of patients with TED, which was statistically significant in the moderate-severe TED and DON groups.
Prevalence of pseudophakia: U.S. population–based study
Authors: Erie Ellen A. , Hodge David O. , Mahr Michael A. 
Published: October 2021

Purpose:
To determine the current prevalence and trends of pseudophakia in a well-defined U.S. population, calculating values for Olmsted County, Minnesota, from 1988 through 2018.

Setting:
Mayo Clinic, Rochester, Minnesota.

Design:
Population-based cohort study.

Methods:
Rochester Epidemiology Project (REP) databases were used to identify all cases of pseudophakia in Olmsted County, Minnesota, between January 1, 1988, and December 31, 2018. Age- and sex-specific prevalence rates were calculated in 1988, 1998, 2008, and 2018 using REP census population estimates and mortality counts. Poisson regression analysis was used to assess changes in prevalence over time. Mortality rates were estimated by Kaplan-Meier analysis.

Results:
In 2018, 10 024 county residents were pseudophakic in at least 1 eye, for a total population prevalence of 6.5%. The prevalence increased 67% in the last 10 years and 590% in the last 30 years (P < .001). By 2018, 51% of residents aged 75 years and 88% of residents aged 85 years and older were pseudophakic in at least 1 eye, 53% of residents with pseudophakia aged 65 years and older were bilaterally pseudophakic, and 29% of residents with pseudophakia had lived with pseudophakia for more than 10 years. The prevalence was higher among women than men and increased with age (P < .001). Overall, pseudophakia had a lower all-cause mortality compared with the general Minnesota population (P < .001).

Conclusions:
In 2018, most residents aged 75 years and older were pseudophakic in at least 1 eye. These numbers underscore the changing visual status of older adults and the large number of adults who benefit from cataract surgery.
Characterization of Androgen Receptor Complex Associated Protein (ARCAP) in hepatocellular carcinoma and liver
Authors: Chang Tai-Jay , Hsia Cheng-Yuan , Chau Gar-Yang , Hsiao Liang-Tsai , Huang Kuang-Tzu , King Kung-Liang , Lui Wing-Yiu , Li Anna F.-Y. , Wang Chia-Lin , Tsai Pin-Hsing , Chien Yueh , Lin Ta-Hsien 
Published: October 2021

Background:
Hepatocellular carcinoma (HCC) ranks many tasks in clinical oncology due to possibly developing a general tumor in men and, usually lead to malignant to death within years. Researches had reported about major factors for being HCC was male sex and HCC associated with cirrhosis in childhood was found more common in males than females. In certain mouse strains as studied, breeding with testosterone significantly increases the development of HCC. Furthermore, castration of male mice diminished the frequency of the development of liver tumors. Meanwhile male hepatitis B virus transgenic mice have a greater occurrence of HCC than females.

Methods:
We apply degenerate priming PCR to observe the expression of various steroid receptors in livers. Yeast-two hybrid screening to search a novel RNA fragment helps to find a new full-length gene by RACE experiment. RT-PCR is applied to detect various expressions in tissues and cell lines. In situ hybridization detects DNA in Chromosome mapping. GFP-constructs transfection proves the gene localization in cells. Immunoprecipitation pulldown assay verifies protein interaction. Gene transfection followed with luciferase assay demonstrates the interaction of genes within cellular signaling. Genomic alignment analysis for observing sequences data perform from NCBI database website (http://www.ncbi.nim.nih.gov/genebank/).

Results:
The androgen receptor (AR) expression level is found at the highest level among the steroid receptors families detected in liver tumors. By yeast-two hybrid screening, we cloned an Androgen Receptor Complex Associated Protein (ARCAP), of 95 Kd in molecular weight and its cDNA. ARCAP locates at Chromosome 1. Our findings indicate ARCAP is highly expressed in hepatoma cell lines and liver tumors and their adjacent tumors as observed. Yeast two-hybrid assay and in vitro immunoprecipitation assays demonstrated an interaction between AR and ARCAP.

Conclusion:
We aim to search for different types and levels of steroid receptors expressed within human HCCs and in the adjacent liver tissues. To verify possible molecular mechanisms by which AR might affect hepatoma cells, we had characterized a novel protein ARCAP which functions as a coregulator to interact with AR within liver. The ligand-dependent AR with its cofactor, ARCAP, can induce a signal cascade by transactivation.
End-of-Life Healthcare Service Needs Among Children With Neurological Conditions: A Latent Class Analysis
Authors: Lindley Lisa C. , Svynarenko Radion , Mooney-Doyle Kim , Mendola Annette , Naumann Wendy C. , Fortney Christine A. 
Published: October 2021

ABSTRACT

BACKGROUND: At the end of life, children with neurological conditions have complex healthcare needs that can be met by providing care of their life-limiting conditions concurrently with hospice care (ie, concurrent care). Given the limited literature on concurrent care for children with neurologic conditions, this investigation aimed to identify patterns of nonhospice, healthcare service needs and to assess characteristics of children within each group. METHODS: A nationally representative sample children with neurological conditions enrolled in concurrent hospice care was used. Latent class analysis and descriptive statistics were calculated to identify patterns of healthcare needs and characteristics of children within the groups. A subgroup analysis of infants was conducted. RESULTS: Among the 1601 children, the most common types of services were inpatient hospitals, durable medical equipment, and home health. Two classes of service needs were identified: moderate intensity (58%) and high intensity (42%). Children in the moderate-intensity group were predominantly between 1 and 5 years old, male, White, and non-Hispanic. The most common neurological condition was central nervous system degeneration. They also had significant comorbidities, mental/behavioral health conditions, and technology dependence. They commonly resided in urban areas in the South. Children in the high-intensity group had a wide range of neurological conditions and high acuity. The subgroup analysis of infants indicated a different neurological profile. CONCLUSIONS: Two distinct classes of nonhospice, healthcare service needs emerged among children with neurological conditions at the end of life. The groups had unique demographic profiles.
Transcatheter aortic valve replacement via a transsubclavian approach in a patient with severe aortic stenosis who had previously undergone kidney transplantation
Authors: Oh Seok , Kim Ju Han , Hyun Dae Young , Cho Kyung Hoon , Kim Min Chul , Sim Doo Sun , Hong Young Joon , Ahn Youngkeun , Jeong Myung Ho , Lee Kyo Seon 
Published: October 2021

Abstract

Rationale:
Although the transfemoral approach is the gold standard for transcatheter aortic valve replacement (TAVR), it is not feasible in a considerable number of patients. We report a case of successful transsubclavian TAVR (TS-TAVR) in a patient with severe aortic stenosis (AS) who was ineligible for transfemoral TAVR because she was a kidney transplant recipient.

Patient concerns:
A 72-year-old Korean woman, who had previously undergone kidney transplantation in the right iliac fossa for end-stage kidney disease, was admitted to our center with dyspnea. Upon auscultation, grade IV systolic murmurs were detected in both upper sternal borders and the left lower sternal border, suggestive of valvular heart disease.

Diagnosis:
Two-dimensional transthoracic echocardiography revealed heavy calcification of the aortic valve with a high peak velocity (4.54 m/s) and mean pressure gradient (48.49 mm Hg), indicative of severe AS.

Interventions:
TS-TAVR was performed by a heart team comprised of interventional cardiologists, cardiac surgeons, and anesthesiologists. A self-expandable valve prosthesis (CoreValveTM Evolut RTM, Medtronic Inc., Minneapolis, MN) was successfully deployed via the left subclavian artery.

Outcomes:
Post-TAVR 2-dimensional transthoracic echocardiography demonstrated a well-functioning valve with mild paravalvular leakage. The peak velocity had declined from 4.54 m/s to 2.22 to 2.24 m/s, and the mean pressure gradient had declined from 48.49 to 8.57–9.61 mmHg. The patient was discharged successfully and uneventfully.

Lessons:
Because kidney transplant recipients with severe AS are considered poor candidates for transfemoral TAVR, TS-TAVR is a suitable alternative to consider.
Association of total cholesterol and atherosclerotic cardiovascular disease in patients with follicular thyroid cancer
Authors: Huang Guoding , Lu Hongquan , Li Meigui , Lv Qiongxiu , Chen Qizhu 
Published: October 2021

Abstract
The association between serum total cholesterol (TC) level and incident atherosclerotic cardiovascular disease (ASCVD) in patients with follicular thyroid cancer postthyroidectomy is unknown.
This was a retrospective study and patients (n = 384) were divided into low and high TC groups according to the median TC level. Incidence of composite ASCVD (myocardial infarction, ischemic stroke, and cardiovascular death) was compared between these 2 groups and factors contributing to the association of TC and ASCVD were evaluated.
Patients in the high TC group were older and more likely to have diabetes and have higher C-reactive protein level. After thyroidectomy, serum levels of free triiodothyronine and free thyroxine were lower while thyroid-stimulating hormone level was higher in the high TC group. 31.6% and 39.7% of patients developed hypothyroidism in the low and high TC groups (P < .05) postthyroidectomy. The incidence rate of composite ASCVD was higher in the high TC versus low TC groups, with incidence rate ratio of 1.69 (95% confidence interval [CI]: 1.07–2.69), which was mainly driven by a higher incidence rate of myocardial infarction in the high TC group (incidence rate ratio: 2.11 and 95% CI: 1.10–4.20). In unadjusted model, higher TC was associated with 73% higher risk of composite ASCVD. After adjustment for hypothyroidism, the association of higher TC and composite ASCVD was attenuated into insignificance, with hazard ratio of 0.92 and 95% CI: 0.81 to 1.34.
Increased TC level was associated with composite ASCVD, which might be attributed to hypothyroidism postthyroidectomy. The use of levothyroxine might help to prevent hypercholestemia and reduce the incidence of ASCVD.