bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oncogenic GNAQ and GNA11 Drive Tumorigenesis and Hyper‐Pigmentation in a Zebrafish Model of Human Uveal Melanoma
Authors: Henle Andrea , Hoelzli Emily , Perez Dahlia , Amsterdam Adam , Lees Jacqueline 
Published: June 2021

Uveal melanoma is the most common intraocular cancer, with an estimated 2000 cases diagnosed yearly in the U.S. Tumors arise from melanocytes in the choroid, iris, and ciliary body. Treatment typically includes proton beam therapy, and as such, the availability of tissue samples for research is limited. Approximately 50% of patients diagnosed with the disease develop untreatable liver metastases within 15 years. There is an urgent need to develop an animal model for uveal melanoma, in order to discover new therapeutics and understand disease initiation and progression. Approximately 83% of human uveal melanoma tumors have activating mutations in GNAQ or GNA11. Signaling pathways known to cause cell proliferation and survival are active downstream of mutated GNAQ or GNA11, but the exact signals responsible for metastasis remain to be discovered. We have developed a zebrafish model for human uveal melanoma by expressing mutated human GNA11Q209L or GNAQQ209L under control of the zebrafish melanocyte‐restricted mitfa promoter. Several lines have been identified that stably express either of the transgenes, Tg(mitfa:GNAQQ209L) or Tg(mitfa:GNA11Q209L). These fish have been crossed to p53M214K fish to facilitate tumor onset through a multi‐hit tumorigenic process. Tg(mitfa:GNAQQ209L);p53M214K and Tg(mitfa:GNA11Q209L);p53M214K zebrafish show hyper‐pigmentation in their skin and eyes. Fish develop tumors as early as 6 months of age. Our current efforts focus on the characterization of the tumors and the pigmentation defects. This model has revealed new mechanisms in pigmentation development and has provided insight into disease pathogenesis and metastasis.
Dietary Inflammatory Index during Pregnancy and Maternal Systemic Inflammation
Authors: Sen Sarbattama , Rifas‐Shiman Sheryl , Shivappa Nitin , Wirth Michael , Hebert James , Gold Diane , Gillman Matthew , Oken Emily 
Published: June 2021

BackgroundHigher levels of inflammation during pregnancy have been associated with complications in pregnancy and childhood. Dietary influences on inflammation during pregnancy have not been well studied. Objective: We examined the association of maternal Dietary Inflammatory Index (DII), a validated predictor of dietary inflammatory potential with C‐Reactive Protein (CRP) in the 2nd trimester of pregnancy. Methods: We included 795 women from Project Viva, a pre‐birth cohort in MA. We calculated the DII from FFQs completed in the 1st and 2nd trimesters, which were strongly correlated (Pearson r = 0.61, p<0.001). A higher DII score indicates a more pro‐inflammatory diet. We used Pearson correlations and multivariable linear regression models, adjusted for time of blood draw, age, pre‐pregnancy BMI, education, parity, race/ethnicity, smoking status and income to examine associations between DII scores with CRP. Results: Mean (SD) maternal DII was ‐2.6 (1.4) and was higher with greater maternal BMI and smoking; 2nd trimester CRP was 1.5 mg/L (1.3). Intake of trans, saturated, and monounsaturated fats were the strongest positive correlates of the DII score and intake of vitamin A, β carotene, fiber and magnesium were the strongest negative correlates. The maternal DII was directly associated with CRP (β=0.07; 95% CI = 0.00, 0.13). ConclusionInflammatory potential of the maternal diet is a modifiable factor that affects systemic inflammation during pregnancy.
Endothelial Cell Senescence with Age is Associated with Oxidative Stress‐Mediated Suppression of Endothelial Function in Healthy Adults
Authors: Hill S , McNamara M , Seals D , Kaplon R 
Published: June 2021

Senescence is emerging as a key mechanism of vascular aging, but evidence in healthy humans is lacking. We hypothesized that endothelial cells (EC) become senescent with age in healthy adults and that this is associated with endothelial dysfunction. In biopsied venous EC, expression of the cell cycle inhibitors p16 and p21 was greater in middle‐aged and older (MA/O, n=10, 60±1 yr) vs. young (Y, n=9, 22±1 yr) healthy adults (p16: 0.45±0.04 vs. 0.28±0.03 AU, P<0.01; p21: 0.63±0.06 vs. 0.34±0.03 AU, P<0.01; quantitative immunofluorescence) whereas p53 did not reach significance (P>0.05). Similarly, EC expression of p16, p21, and p53 was positively related to age (p16: r=0.65, p<0.01; p21: r=0.72, P<0.01; p53: r=0.42, P<0.01). Flow‐mediated dilation (FMD), a measure of endothelial function, was 47% lower in MA/O vs. Y (4.7±0.6 vs. 8.9±0.9%, P<0.01) and was inversely related to EC p21 expression (r=‐0.43, P<0.05). MA/O also had elevated EC abundance of nitrotyrosine (NT), a marker of oxidative protein damage, compared with Y (0.53±0.05 vs. 0.33±0.04 AU, P<0.01) and greater expression of the pro‐oxidant enzyme NADPH oxidase (‐0.28±0.11 vs. ‐0.57±0.08 log(AU), P<0.05). Oxidative stress‐mediated suppression of endothelial function, as indicated in the percent change in FMD following intravenous vitamin C (FMDvc), was greater in MA/O vs. Y (38±17 vs. ‐2±6 %Δ, P<0.05). FMDvc was positively related to EC expression of p16, p21, and p53 (p16: r=0.63, P<0.01; p21: r=0.46, P=0.05; p53: r=0.58, P<0.05). These findings provide novel evidence that senescence occurs in human EC with age in healthy adults and is associated with oxidative stress‐mediated suppression of endothelial function.NIH AG044031 TR001082 AG013038
Limb Specific Vascular Adjustments at Exercise Onset
Authors: Fenuta Alyssa , Bravo Michael , Hartnett John , Tschakovsky Michael 
Published: June 2021

ObjectiveTo compare the rate of vascular adjustment at the onset of arm vs. leg exercise using the same exercise modality and hydrostatic conditions.Methods10 healthy recreationally active males (21.9±1.9 yrs) completed step increase dynamic exercise protocols (1s contract/2s relax) at 40%, 80% and 100% of peak vascular conductance response. Forearm handgrip and knee extension was performed in supine position with the exercising muscles at heart level. Continuous measures of brachial (forearm) and femoral (leg) artery blood flow (FBF, LBF; Doppler and Echo ultrasound) and arterial blood pressure (MAP; Finometer) were used to calculate forearm (FVC) and leg (LVC) vascular conductance.ResultsFor all exercise intensities, LVC was (p<0.001) but FVC was not (P=0.705) characterized by a subsequent vasoconstriction at ~10 s (Phase IB) following the rapid initial vasodilation (Phase IA). Phase IA LVC amplitude was greater than steady state in the leg at 40% and no different at 80% (P<0.05), but for FVC it was lower than steady state at all exercise intensities (P<0.05). Phase IA had a greater contribution to the total response amplitude in the leg vs. forearm at all exercise intensities (P<0.05) representing an overshoot compared to the Phase II plateau at 40% and 80% (P<0.05). There was a main effect of limb for the Phase II time constant (leg faster than forearm, P<0.05).ConclusionWhen contraction/relaxation modality and hydrostatic environment are controlled for, rapid vasodilatory mechanisms are more sensitive to the onset of exercise in lower vs. upper limbs and can overshoot steady state. Transient vasoconstriction between the initial rapid and secondary slower adjustment is specific to the lower limb. Funding: NSERC 250367‐06.
How to minimize bleeding in laparoscopic myomectomy
Authors: Barbosa Priscila Almeida , Villaescusa Marina , Andres Marina Paula , Fernandes Luiz Flavio Cordeiro , Abrão Mauricio S. 
Published: June 2021

Purpose of review
Laparoscopic myomectomy is a common surgical procedure for symptomatic myomas. However, bleeding control during surgery may pose a challenge. Therefore, the aim of this study was to review recent evidence regarding interventions to control bleeding during laparoscopic myomectomy.

Recent findings
The use of vasopressin resulted in less blood loss compared to placebo. Barbed sutures reduced blood loss compared to conventional sutures. Intravenous infusion of tranexamic acid (TXA) in the intraoperative period of large myomectomies showed no significant difference compared to placebo. Uterine artery occlusion (UAO) and emergency uterine artery embolization were reported to be feasible and may reduce and treat bleeding before conversion to laparotomy.

Summary
Several methods can control bleeding during laparoscopic myomectomy. Vasopressin and barbed sutures resulted in decreased blood loss, and TXA did not have an impact on bleeding control. The use of UAO and emergency embolization techniques can contribute to the control of bleeding; however, further studies are needed to prove the efficacy of these and other agents.
Coronary artery calcium score above 250 confirms the presence of significant stenosis in coronary CT angiography of symptomatic patients
Authors: Alshumrani Ghazi A. 
Published: June 2021

Objectives
Evaluation of coronary artery calcium score (CACS) at multiple low and high cutoff values for the detection of significant coronary stenosis at two different cutoffs (50 and 70%) in a large number of symptomatic patients was not investigated previously in one study. This study aims to investigate if there are a correlation and statistical significance between different CACS cutoffs and the severity of coronary artery stenosis by coronary CT angiography (CCTA) in symptomatic patients.

Methods
This is a retrospective study that included all symptomatic patients who had CCTA in a tertiary care hospital over a period of 7 years.

Results
CCTA of 502 patients was evaluated (406 included, mean age 56.2 years); 230 were males (56.7%). The prevalence of stenosis at any percentage was 53.7%, ≥50% was 26.6% and ≥70% was 12.3%. The mean CACS was 84.5 (range 0–1860), for males was 124.5 and for females was 32.1. Patients with CACS of zero (59%) and CACS of ≥1 (41%) had a mean stenosis of 8.9% (range 0–75%) and 52.6% (range 0–100%), respectively. All patients with a CACS of ≥250 were found to have ≥50% stenosis (100% specificity and positive predictive value, 35.2% sensitivity, 81% negative predictive value and 82.6% accuracy). The percentage of stenosis increased as CACS increased with strong statistical significance (P value < 0.0001) and a positive correlation (r = 0.58).

Conclusions
CACS is a valuable diagnostic tool to predict the severity of coronary artery stenosis. A cutoff value of 250 confirmed the presence of at least 50% stenosis in symptomatic patients.
Administration of Purified Exosome Product in a Rat Sciatic Serve Reverse Autograft Model
Authors: Ikumi Akira , Gingery Anne , Toyoshima Yoichi , Zhao Chunfeng , Moran Steven L. , Livia Christopher , Rolland Tyler , Peterson Timothy , Sabbah Michael S. , Boroumand Soulmaz , Saffari Tiam M. , Behfar Atta , Shin Alexander Y. , Amadio Peter C. 
Published: June 2021

Background:
The nerve autograft remains the gold standard when reconstructing peripheral nerve defects. However, although autograft repair can result in useful functional recovery, poor outcomes are common, and better treatments are needed. The purpose of this study was to evaluate the effect of purified exosome product on functional motor recovery and nerve-related gene expression in a rat sciatic nerve reverse autograft model.

Methods:
Ninety-six Sprague-Dawley rats were divided into three experimental groups. In each group, a unilateral 10-mm sciatic nerve defect was created. The excised nerve was reversed and used to reconstruct the defect. Group I animals received the reversed autograft alone, group II animals received the reversed autograft with fibrin glue, and group III animals received the reversed autograft with purified exosome product suspended in the fibrin glue. The animals were killed at 3 and 7 days and 12 and 16 weeks after surgery. Evaluation included compound muscle action potentials, isometric tetanic force, tibialis anterior muscle wet weight, nerve regeneration–related gene expression, and nerve histomorphometry.

Results:
At 16 weeks, isometric tetanic force was significantly better in group III (p = 0.03). The average axon diameter of the peroneal nerve was significantly larger in group III at both 12 and 16 weeks (p = 0.015 at 12 weeks; p < 0.01 at 16 weeks). GAP43 and S100b gene expression was significantly up-regulated by purified exosome product.

Conclusions:
Local administration of purified exosome product demonstrated improved nerve regeneration profiles in the reverse sciatic nerve autograft rat model. Thus, purified exosome product may have beneficial effects on nerve regeneration, gene profiles, and motor outcomes.
Hymenobacter caeli sp. nov., an airborne bacterium isolated from King George Island, Antarctica
Authors: Roldán Diego M. , Kyrpides Nikos , Woyke Tanja , Shapiro Nicole , Whitman William B. , Králová Stanislava , Sedláček Ivo , Busse Hans-Jürgen , Menes Rodolfo Javier 
Published: June 2021

A rod-shaped and Gram-stain-negative bacterial strain 9AT, was isolated from an air sample collected at King George Island, maritime Antarctica. Phylogenetic analysis based on 16S rRNA gene sequence reveals that strain 9AT belongs to the genus

Hymenobacter

and shows the highest similarity to

Hymenobacter coccineus

CCM 8649T (96.8 %). The DNA G+C content based on the draft genome sequence is 64.9 mol%. Strain 9AT is strictly aerobic, psychrophilic, catalase-positive, oxidase-positive and non-motile. Growth is observed at 0–20 °C (optimum 10 °C), pH 6.0–8.0 (optimum pH 7.0), and in the absence of NaCl. The predominant menaquinone of strain 9AT is MK-7 and the major fatty acids comprise Summed Feature 3 (C16 : 1
ω7c and/or C16 : 1
ω6c; 25.2 %), iso-C15 : 0 (23.2 %), C16 : 1
ω5c (11.6 %), Summed Feature 4 (anteiso-C17 : 1 B/iso-C17 : 1 I) (9.6 %) and anteiso-C15 : 0 (9.6 %). The polar lipid profile consists of the major lipid phosphatidylethanolamine and moderate to minor amounts of phosphatidylserine, unidentified aminolipids, aminophospholipids, aminophosphoglycolipids, polar lipids lacking a functional group and an unidentified phospholipid and a glycolipid. In the polyamine pattern sym-homospermidine is predominant. On the basis of the results obtained, strain 9AT is proposed as a novel species of the genus

Hymenobacter

, for which the name Hymenobacter caeli sp. nov. is suggested. The type strain is 9AT (=CCM 8971T=LMG 32109T=DSM 111653T).
A prospective observational cohort study to identify inflammatory biomarkers for the diagnosis and prognosis of patients with sepsis
Authors: D’Onofrio Valentino , Heylen Dries , Pusparum Murih , Grondman Inge , Vanwalleghem Johan , Meersman Agnes , Cartuyvels Reinoud , Messiaen Peter , Joosten Leo AB , Netea Mihai G. , Valkenborg Dirk , Ertaylan Gökhan , Gyssens Inge C. 
Published: June 2021

AbstractBackgroundSepsis is a life-threatening organ dysfunction. A fast diagnosis is crucial for patient management. Proteins that are synthesized during the inflammatory response can be used as biomarkers, helping in a rapid clinical assessment or an early diagnosis of infection. The aim of this study was to identify biomarkers of inflammation for the diagnosis and prognosis of infection in patients with suspected sepsis.MethodsIn total 406 episodes were included in a prospective cohort study. Plasma was collected from all patients on the first day of a new episode. Samples were analysed using a 92-plex proteomic panel based on a proximity extension assay with oligonucleotide-labelled antibody probe pairs (OLink, Uppsala, Sweden). Supervised and unsupervised differential expression analyses and pathway enrichment analyses were performed.ResultsSupervised differential expression analysis revealed 21 proteins that were significantly lower in circulation of patients with viral infections compared to patients with bacterial infections. More strongly, higher expression levels were observed for 38 proteins in patients with high SOFA scores (>4), and for 21 proteins in patients with worse outcome. These proteins are mostly involved in pathways known to be activated early in the inflammatory response. Unsupervised, hierarchical clustering confirmed that inflammatory response was more strongly related to disease severity than to aetiology.ConclusionSeveral differentially expressed inflammatory proteins were identified that could be used as biomarkers for sepsis. These proteins are mostly related to disease severity. Within the setting of an emergency department, they could be used for outcome prediction, patient monitoring, and directing diagnostics.Registrationclinicaltrial.gov identifier NCT03841162
Using aggregate patient data at the bedside via an on-demand consultation service
Authors: Callahan Alison , Gombar Saurabh , Cahan Eli M. , Jung Kenneth , Steinberg Ethan , Polony Vladimir , Morse Keith , Tibshirani Robert , Hastie Trevor , Harrington Robert , Shah Nigam H. 
Published: June 2021

AbstractUsing evidence derived from previously collected medical records to guide patient care has been a long standing vision of clinicians and informaticians, and one with the potential to transform medical practice. As a result of advances in technical infrastructure, statistical analysis methods, and the availability of patient data at scale, an implementation of this vision is now possible. Motivated by these advances, and the information needs of clinicians in our academic medical center, we offered an on-demand consultation service to derive evidence from patient data to answer clinician questions and support their bedside decision making. We describe the design and implementation of the service as well as a summary of our experience in responding to the first 100 requests. Consultation results informed individual patient care, resulted in changes to institutional practices, and motivated further clinical research. We make the tools and methods developed to implement the service publicly available to facilitate the broad adoption of such services by health systems and academic medical centers.
Predicting arterial age using carotid ultrasound images, pulse wave analysis records, cardiovascular biomarkers and deep learning
Authors: Le Goallec Alan , Collin Sasha , Diai Samuel , Vincent Théo , Patel Chirag J. 
Published: June 2021

AbstractCardiovascular disease --an age-related disease-- is the leading cause of death worldwide. We built an arterial age predictor by training deep learning models to predict age from 233,388 pulse wave analysis records, 8,279 carotid ultrasound images and arterial health biomarkers (e.g blood pressure) collected from 502,000 UKB participants. We predicted age with a R-Squared of 67.1+/-0.6% and a root mean squared error of 4.29+/-0.04 years. Attention maps for carotid ultrasound images suggest that the predictions are driven by vascular features, for the largest part. Accelerated arterial aging is 32.6+/-7.3% GWAS-heritable, and we identified 192 single nucleotide polymorphisms in 109 genes (e.g NPR3, involved in blood volume and pressure) significantly associated with this phenotype. Similarly, we identified biomarkers (e.g electrocardiogram features), clinical phenotypes (e.g chest pain), diseases (e.g hypertension), environmental (e.g smoking) and socioeconomic (e.g income and education) variables associated with accelerated arterial aging. Finally, carotid ultrasound images, pulse wave analysis records and blood pressure biomarkers capture different facets of arterial aging. For example, carotid ultrasound-measured and pulse wave analysis-measured accelerated arterial aging phenotypes are only .164+/-.009 correlated. In conclusion, our predictor suggests potential lifestyle and therapeutic interventions to slow arterial aging, and could be used to assess the efficiency of emerging rejuvenating therapies on the arterial system.
Increased Risk of Severe COVID-19 Disease in Pregnancy in a Multicenter Propensity Score-Matched Study
Authors: Cojocaru Liviu , Noe Myint , PahlavaN Autusa , Werzen Alissa , Seung Hyunuk , Jessica Yoo Young Chae , Tyson Patricia , Narayanan Shivakumar , Turan Shifa , Turan Ozhan M. , Chua Joel V. 
Published: June 2021

AbstractBackgroundRespiratory infections have long been associated with higher maternal and perinatal morbidity. Early data did not report an increased risk of SARS-CoV-2 infection or disease severity in pregnancy. However, surveillance data from the Center for Disease Control and Prevention (CDC) indicates a higher risk of severe disease and death in pregnant women with symptomatic SARS-CoV-2 infection, although this data is subject to ascertainment bias.ObjectiveTo explore the association between COVID-19 disease severity and pregnancy in our university-based hospital system using measures such as COVID-19 ordinal scale severity score, hospitalization, intensive care unit admission, oxygen supplementation, invasive mechanical ventilation, and death.Study designWe conducted a retrospective, multicenter case-control study to understand the association between COVID-19 disease severity and pregnancy. We reviewed consecutive charts of adult females, ages 18-45, with laboratory-confirmed SARS-CoV-2 infection in six months between March 1, 2020, and August 31, 2020. Cases were patients diagnosed with COVID-19 during pregnancy, whereas controls were not pregnant at the time of COVID-19 diagnosis. Primary endpoints were the COVID-19 severity score at presentation (within four hours) and the nadir of the clinical course. The secondary endpoints were the proportion of patients requiring hospitalization, intensive care unit admission, oxygen supplementation, invasive mechanical ventilation, and death.ResultsA higher proportion of pregnant women had moderate to severe COVID-19 disease at the nadir of the clinical course than nonpregnant women (25% vs. 16.1%, p=0.04, respectively). While there was a higher rate of hospitalization (25.6% vs. 17.2%), ICU admission (8.9% vs. 4.4%), need for vasoactive substances (5.0% vs. 2.8%), and invasive mechanical ventilation (5.6% vs. 2.8%) in the pregnant group, this difference was not significant after the propensity score matching was applied.We found a high rate of pregnancy complications in our population (40.7%). The most worrisome is the rate of hypertensive disorders of pregnancy (20.1%).ConclusionsIn our propensity score-matched study, COVID-19 in pregnancy is associated with an increased risk of disease severity and an increased risk of pregnancy complications.