bluuebunny/crossref_metadata_2025 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

Background

Higher 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).

Conclusion

Inflammatory potential of the maternal diet is a modifiable factor that affects systemic inflammation during pregnancy.
Prenatal Exposure to Inflammation Decreases Endothelial Cell Proliferation in the Mouse Intestinal Mucosa
Authors: Yan Xiaocai , Liu Xueli , Managlia Elizabeth , De Plaen Isabelle
Published: June 2021

Necrotizing enterocolitis (NEC) is the most devastating gastrointestinal disease affecting premature infants. Chorioamnionitis has been shown to increase its incidence. However, the mechanism by which prenatal infection increases susceptibility to NEC remains elusive. Our lab has shown that VEGF is decreased in human NEC. VEGF may play a role in NEC pathogenesis by compromising vascular network integrity. Here we hypothesized that antenatal inflammation decreases the expression of vascular endothelial growth factor (VEGF) in intestine tissues and mucosal vascular endothelial cell proliferation. To test our hypothesis, pregnant mice were injected i.p. at E16 with LPS or normal saline. VEGF protein of Day 0 pup intestines was analyzed by western blot and band density values normalized to b‐actin. To quantify endothelial cell (E.C.) proliferation, pups were injected with BrdU i.p. 4 hours prior to euthanasia, and the number of BrdU positive cells co‐staining for CD31, an endothelial cell marker, were counted in the villi (3 fields/ sample at 10x magnification). We found that intestinal VEGF expression was significantly lower in pups from LPS‐treated dams compared to controls (mean±SEM: 1.40 ± 0.14 v.s 2.80 ± 0.15; p<0.0005). Also, the number of proliferating endothelial cells was significantly decreased in newborn pups from LPS‐treated dams compared to controls (8.0 ± 0.88 v.s 26.0 ± 1.60; p<0.0001). In conclusion, prenatal exposure to inflammation decreases intestinal VEGF protein and intestinal mucosal endothelial cell proliferation. This suggests that antenatal inflammation may predispose to intestinal injury and NEC by affecting mucosal microvasculature (supported by NIH grant RO1HD060876).
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

Objective

To compare the rate of vascular adjustment at the onset of arm vs. leg exercise using the same exercise modality and hydrostatic conditions.

Methods

10 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.

Results

For 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).

Conclusion

When 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.
Phosphoenolpyruvate Carboxykinase: Possible Therapeutic Targets for Insulin Resistant Type‐II Diabetes
Authors: Wall Susan , Chow Jonathan , Huang Justin , Jiang Max , Yang Amanda , Jones Kyra
Published: June 2021

Maintaining blood glucose levels is not just the responsibility of insulin and glucagon but also of a rate‐controlling enzyme known as Phosphoenolpyruvate Carboxykinase (PEPCK). This molecule plays a central role in glucose homeostasis by controlling hepatic gluconeogenesis. Developing functional inhibitors of PEPCK would be useful in the treatment of diabetes and the model of PEPCK reveals several sites of interest. Cytosolic, mammalian PEPCK is a GTP‐dependent enzyme that catalyzes the rate‐controlling step in gluconeogenesis: conversion of oxaloacetate to phosphoenolpyruvate. Two divalent metal ions are required for enzyme activity. The positively charged active site creates an electrostatic environment tailored to stabilize the localized negative charge of the enzyme's substrates. There is no consensus on the order in which substrates bind but upon binding, a mobile lid domain (Ω‐loop) closes, causing the substrates to be positioned closer to one another. Only upon closure of the lid, does another structural feature, the P‐loop, move which repositions the GTP molecule. Finally, the N‐ and C‐terminal lobes move inward, All of these steps are required for catalysis to occur and so are possible targets for the inactivation of PEPCK. The Ashbury College SMART team (Students Modeling A Research Topic) used Jmol interactive software and 3D printed using Zcorp plaster modeling to create PEPCK.
Characteristics of pneumonia in children with cerebral palsy
Authors: Starosvetova Ekaterina , Razumov Sergey , Skuchalina Lubov , Aishauova Raushan
Published: June 2021

The analysis of course of pneumonia in 33 children with various forms of infantile cerebral palsy (ICP) had been conducted. It is determined that more severe course of pneumonia with distinct, long‐lasting symptoms of respiratory failure and fever was observed in double hemiplegia with spastic tetraplegia and distinct muscle hypertension; atonic‐astatic with low muscle tone and impairment of cortical‐subcortical connections; hyperkinetic with hyperkinesia. These patients had stayed long in the intensive care department (an average of 29 ± 3,2) with artificial lung ventilation. Persistence and distinction of respiratory symptoms were supported by the presence of GORD, microaspiration, vomiting, impaired swallowing reflex (85.7%). This entails that all patients with ICP should regularly examine lung function, even in the absence of respiratory symptoms, examine for finding the presence of pathology of aspiration, select special breathing techniques in ineffective cough reflex.
Chenodeoxycholate (CDCA) Activation of Ca2+‐Dependent Cl‐ Transport in Human Embryonic Kidney‐293 Cells (HEK‐293) is CFTR‐Independent
Authors: George Alvin , Domingue J , Ao M , Sarathy J , Rao M.C.
Published: June 2021

Bile acids (BAs) are increasingly recognized to have hormone‐like functions. For example, the dihydroxy BA CDCA stimulates Cl‐ transport in the human colonic cell line T84 via the cystic fibrosis transmembrane conductance regulator (CFTR). To explore CDCA signaling, we examined its action in CFTR‐transfected HEK (HEK‐CFTR) by iodide efflux (IE), a method used to measure Cl‐ channel activity. CDCA (500μM)‐induced IE was not inhibited by CFTRinh172 (20μM, n=4) in HEK‐CFTR, suggesting CDCA stimulates a non‐CFTR Cl‐ channel in HEK. Screening for mRNA transcripts in HEK revealed expression of Ca2+‐activated TMEM16A, voltage‐gated ClC2, but not CFTR Cl‐ channels (Physiol Rep. 2(9): 1‐16, '14). Also, CDCA—but not the cAMP activator forskolin—increases IE in HEK (max IE in fold increase of baseline: CDCA: 5.8±1; Forskolin [10µM]: 3.7±0.4). To assess if CDCA action in HEK is Ca2+ dependent (n=3), cells were pretreated with the Ca2+ chelator BAPTA (40μM) or the IP3 receptor inhibitor 2‐APB (200μM). BAPTA and 2‐APB reduced CDCA‐induced IE by 21% and 52% respectively, indicating a role for [Ca2+]i. The muscarinic M3 receptor—coupled to Ca2+ release by Gαq—has been shown to be activated by BAs and stimulate cell proliferation,but has yet to be linked to BA‐induced Cl‐ transport. Of the muscarinic receptor isoforms (M1‐5), HEK express only M3 mRNA, but the receptor antagonist atropine (10μM) had no effect on CDCA action. Thus, CDCA‐induced IE in HEK is CFTR independent and is mediated by [Ca2+]i and IP3 receptors. Our data suggest a role for TMEM16A in CDCA‐induced Cl‐ secretion in HEK and demonstrate that HEK can serve as a model for studying BA‐action unrelated to CFTR.
Efficacy of Malaria Intermittent Preventive Treatment in Angolan Endemic Areas
Authors: Ferreira da Cruz Maria de Fatima , Daniel Elsa , Oliveira Natalia , Daniel‐Ribeiro Claudio Tadeu , Fortes Filomeno
Published: June 2021

P. falciparum parasites are responsible for severe morbidity and its chemoresistance is notorious. Thus, is necessary to evaluate the effectiveness of intermittent preventive treatment (IPT). For this purpose, 107 malaria patient samples were DNA sequenced against pfdhps and pfdhfr genes. The results showed: 46% with double mutant haplotypes ACNRNVI in codons 59 and 108; 27% with double mutations in codons 51 and 108 with haplotype ACICNVI, 17% triple mutant at codons 51, 59 and 108 with haplotypes ACIRNVI; 2% triple mutant at codons 50, 51, ​​108 and 59, 108, and 164 with haplotypes ARICNVI ACNRNVL; 6% with a single mutation at codon 108, showing ACNCNVI haplotype and; only wild type sample ‐ ACNCSVI (2%). The 108N mutation (change of serine for asparagine ‐ S108N) in pfdhfr gene ‐ a mutation described as the predecessor for all resistant emergence strains ‐ was the most prevalent (98%) followed by 59R (65%) and 51I (47% ). Regarding pfdhps gene, a total prevalence of 437G mutation, with the exception of one sample (4%) with wild haplotype SAKAA were noted. Among the mutant samples, 88% had a single mutation presenting haplotype SGKAA; 6% showed double mutants at codons 437 and 540 with haplotype SGEAA and; 6% with double mutant at codons 436 and 437 (AGKAA). Quadruple (triple pfdhfr + single pfdhps) and triple mutants (double pfdhfr + single pfdhps) were recorded. Considering the significant percentage of P. falciparum parasites circulating in Lubango with a resistance profile associated with pyrimethamine and sulphadoxine tolerance, we conclude that the IPT should not be effective in Angola.
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.

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

Background

Sepsis 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.

Methods

In 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.

Results

Supervised 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.

Conclusion

Several 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.

Registration

clinicaltrial.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

Using 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

Cardiovascular 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

Background

Respiratory 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.

Objective

To 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 design

We 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.

Results

A 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%).

Conclusions

In 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.
Plasma gradient of soluble urokinase-type plasminogen activator receptor is linked to pathogenic plasma proteome and immune transcriptome and stratifies outcomes in severe COVID-19
Authors: Sarif Jafar , Raychaudhuri Deblina , D’Rozario Ranit , Bandopadhyay Purbita , Singh Praveen , Mehta Priyanka , Hoque Md. Asmaul , Sinha Bishnu Prasad , Kushwaha Manoj , Sahni Shweta , Devi Priti , Chattopadhyay Partha , Paul Shekhar Ranjan , Ray Yogiraj , Chaudhuri Kausik , Banerjee Sayantan , Majumdar Debajyoti , Saha Bibhuti , Sarkar Biswanath Sharma , Bhattacharya Prasun , Chatterjee Shilpak , Paul Sandip , Ghosh Pramit , Pandey Rajesh , Sengupta Shantanu , Ganguly Dipyaman
Published: June 2021

Disease caused by SARS-CoV-2 coronavirus (COVID-19) has resulted in significant morbidity and mortality world-wide. A systemic hyper-inflammation characterizes the severe COVID-19 disease often associated with acute respiratory distress syndrome (ARDS). Blood biomarkers capable of risk stratification are of great importance in effective triage and critical care of severe COVID-19 patients. In the present study we report higher plasma abundance of soluble urokinase-type plasminogen activator receptor (sUPAR), expressed by an abnormally expanded circulating myeloid cell population, in severe COVID-19 patients with ARDS. Plasma sUPAR level was found to be linked to a characteristic proteomic signature of plasma, linked to coagulation disorders and complement activation. Receiver operator characteristics curve analysis identified a cut-off value of sUPAR at 1996.809 pg/ml that could predict survival in our cohort (Odds ratio: 2.9286, 95% confidence interval 1.0427-8.2257). Lower sUPAR level than this threshold concentration was associated with a differential expression of the immune transcriptome as well as favourable clinical outcomes, both in terms of survival benefit (Hazard ratio: 0.3615, 95% confidence interval 0.1433-0.912) and faster disease remission in our patient cohort. Thus we identified sUPAR as a key pathogenic circulating molecule linking systemic hyperinflammation to the hypercoagulable state and stratifying clinical outcomes in severe COVID-19 patients with ARDS.
Intranasal oxytocin reduces pre-courtship aggression and increases paternal response in California mice (Peromyscus californicus)
Authors: Guoynes Caleigh D. , Marler Catherine A.
Published: June 2021

Oxytocin (OXT) is a neuropeptide that can facilitate prosocial behavior and decrease social stress and anxiety. We investigated whether acute pulses of intranasal (IN) OXT influenced social behavior during social challenges that are likely to occur throughout the lifespan of a wild mouse. To test this, we examined the acute effects of IN OXT in the male California mouse (Peromyscus californicus), a monogamous, biparental, and territorial rodent, using a within-subjects longitudinal design. Social challenges included a pre-courtship male-female encounter conducted during the initial aggressive and not the following affiliative phase of courtship, same-sex resident intruder test, and parental care test, with each test and dose separated by at least two weeks. Males were treated with intranasal infusions of 0.8 IU/kg OXT or saline controls 5-min before each behavioral test, receiving a total of three treatments of either IN OXT or saline control. We predicted that IN OXT would 1) decrease aggression and increase affiliation during the pre-courtship aggression phase, 2) increase aggression during resident intruder paradigms and 3) increase paternal care and vocalizations during a paternal care test. As predicted, during pre-courtship aggression with a novel female, IN OXT males displayed less contact aggression than control males, although with no change in affiliative behavior. However, post-pairing, during the resident intruder test, IN OXT males did not differ from control males in contact aggression. During the paternal care test, IN OXT males were quicker to approach their pups than control males but did not differ in vocalizations produced, unlike our previous research demonstrating an effect on vocalizations in females. In summary, during pre-courtship aggression and the paternal care test, IN OXT promoted prosocial approach; however, during the resident intruder test IN OXT did not alter social approach. These data suggest that IN OXT promotes prosocial approach specifically in social contexts that can lead to affiliation.

HIGHLIGHTS

IN OXT attenuates male aggression during pre-courtship encounters

IN OXT does not attenuate male aggression during resident intruder encounters

IN OXT increases paternal responsiveness during a paternal care challenge

IN OXT in fathers does not influence total paternal care or vocalizations

GRAPHICAL ABSTRACT
Executives and career shocks: observations from coaching practice
Authors: Korotov Konstantin
Published: June 2021

Purpose

The study provides practice-based vignettes describing career shocks as experienced by executives. It also offers a brief description of the approaches taken by the coach in helping executives to cope with their initial reactions. This work informs the readers about examples of career shocks in the executive population and provides access to normally rarely available information about sensitive aspects of psychological life of executives.

Design/methodology/approach

This paper is a qualitative exploration of managers' career shock experiences reflected in executive coaching interventions. It takes an anecdotal look at how executives react to shocks of various valences, and how coaching attempts to assist them by processing their first reactions and choosing a response. The paper particularly looks at managers' responses almost immediately following a shocking event triggering their request for coaching help.

Findings

Coaching conversation serves as opportunities for handling immediate emotional reactions to career disruptions. Even shocks with positive valence can cause ambivalent reactions. Processing of career shocks through coaching conversations can activate agency in dealing with abrupt career events. Coaches can offer further support in career deliberations. In one of the cases, an instance of anticipation of a negative career event was associated with positive hopes, and the non-occurrence of the event led to further elaboration about one's career options.

Research limitations/implications

This work is based on a small sample of executives experiencing career shocks.

Practical implications

This work informs executives about opportunities provided by executive coaching in handling difficult reactions to external career events. Coaches or coaches-in-training receive an overview of coaching requests associated with career shocks.

Social implications

With the increasing instability in careers the paper draws the attention to the helping potential of coaching to those experiencing career shocks. It also contributes to normalization of turning for support in psychologically burdening situations.

Originality/value

This work is a trigger for further consideration of the experiences of career shocks by business executives. It provides a first look into immediate reactions of this career population to unexpected external disruptions. It also offers opportunities for further exploration of the role executive coaching can play in career deliberations.
Creating a case for innovation acceleration in the New Zealand building industry
Authors: Adafin Johnson , Wilkinson Suzanne , Rotimi James O.B. , MacGregor Casimir , Tookey John , Potangaroa Regan
Published: June 2021

Purpose

This study aims to examine how innovation can be accelerated within the New Zealand (NZ) building industry to improve the productivity and efficiency of the industry.

Design/methodology/approach

The study adopted a mixed philosophical approach combining interpretivism and post-positivism. Data for the study were obtained through a focus group of 50 practitioners that were selected using a stratified sampling procedure. All focus group data were audio-recorded, notes of the discussions were taken and then transcribed, de-identified and managed using NVivo software. Data analysis was undertaken using thematic analysis and inductive reasoning consistent with interpretative phenomenological analysis.

Findings

The study findings revealed that the industry could benefit from the adoption of new and emerging technologies to improve its performance, especially its productivity and efficiency. Key drivers for the adoption of innovative practices included the adaptation of “local best practices” from case studies that would consist of stories of successful innovations that could foster confidence in future innovation. It was also identified that Government and industry should nurture innovation through collaborative contracts, policies and regulations. Further, it was highlighted that a culture of innovation needed to be developed to help nurture competencies and capability within the industry workforce.

Research limitations/implications

This study provides an in-depth examination of the need for innovation from the point of view of building industry practitioners. This study provides a useful starting-off point for further research and for the creation of policies that could help to support and accelerate innovation within the NZ building industry.

Practical implications

NZ’s building industry productivity and efficiency have been sub-optimal relative to other industries. But using evidence from the experiences and knowledge of industry practitioners, strategies can be developed to accelerate innovation within the NZ building industry that could help reverse industry performance. Further, the research findings can help inform government policies to develop support mechanisms that could encourage innovation in the industry in NZ. In addition, it is anticipated that the findings will provide a useful set of guidance for other countries that have similar market and physical constraints as those encountered by NZ.

Originality/value

There is a dearth of empirical studies on innovation in the NZ building industry which the current study contributes to. By sharing industry practitioners’ experiences and knowledge of innovation, the paper seeks to counteract more technocratic and technological optimist accounts of innovation within the building industry. Further, the paper provides insights into how the NZ building industry can transform its performance through innovation.
Exploring the impact of the COVID-19 pandemic on the perceptions and sentiments of tourism employees: evidence from a small island tourism economy in the Caribbean
Authors: Peterson Ryan R. , DiPietro Robin B.
Published: June 2021

Purpose

Building on tourism crisis studies and behavioral economics, this study describes a national survey conducted among 439 Aruban tourism and nontourism employees.

Design/methodology/approach

Regression analysis was subsequently conducted to analyze the relationship between experienced well-being, crisis duration and tourism and nontourism employee sentiments.

Findings

The findings indicate that tourism employee sentiments are generally, and significantly, more negative and their concerns about the future are significantly more pessimistic than nontourism employees. The results show that the experienced well-being and expected duration of the COVID-19 crisis have a significant negative effect on tourism employees' sentiments. The paper provides several policies and industry recommendations for strengthening tourism employee well-being and economic resilience. Several avenues for future research are presented.

Originality/value

The current study contributes to this literature by showing that the increased pessimism and negativity of the tourism employees as compared to nontourism employees during the current pandemic influence their thoughts about future income and earnings as well as future purchases.
Digital transformations and supply chain management: a Lean Six Sigma perspective
Authors: Tay Huay Ling , Loh Hui Shan
Published: June 2021

Purpose

With the advent of technological connectivity and access to massive data, the possibilities of augmenting Lean Six Sigma’s Define-Measure-Analyze-Improve-Control (LSS’s DMAIC) problem-solving approach with advanced technologies are enormous. This paper aims to examine digital transformations (DT) of supply chains from a process improvement angle using the LSS DMAIC approach.

Design/methodology/approach

This paper uses a case study approach. Three exemplary case studies were examined to shed light on how LSS can aid in DT to achieve enterprise-wide improvements and enhance value across the supply chains.

Findings

The paper provides a conceptual framework based on a structured DMAIC problem-solving approach to drive improvements in supply chains. The conceptual framework also provides a systematic approach for big data to be integrated in LSS initiatives to achieve greater supply chain performance.

Originality/value

This paper extends research in LSS supply chains by providing a guidance through a conceptual framework that integrate DT and LSS supply chains to support successful digital transformation and LSS supply chains.
Considerations in the use of local and national data for evaluating innovation in children’s social care
Authors: Preston Oli , Godar Rebecca , Lefevre Michelle , Boddy Janet , Firmin Carlene
Published: June 2021

Purpose

This paper aims to explore the possibilities in using such national, statutory data sets for evaluating change and the challenges of understanding service patterns and outcomes in complex cases when only a limited view can be gained using existing data. The discussion also explores how methodologies can adapt to an evaluation in these circumstances.

Design/methodology/approach

This paper examines the use of data routinely collected by local authorities (LAs) as part of the evaluation of innovation. Issues entailed are discussed and illustrated through two case studies of evaluations conducted by the research team within the context of children’s social care in England.

Findings

The quantitative analysis of LA data can play an important role in evaluating innovation but researchers will need to address challenges related to: selection of a suitable methodology; identifying appropriate comparator data; accessing data and assessing its quality; and sustaining and increasing the value of analytic work beyond the end of the research. Examples are provided of how the two case studies experienced and addressed these challenges.

Research limitations/implications

• Quasi-experimental methods can be beneficial tools for understanding the impact of innovation in children’s services, but researchers should also consider the complexity of children’s social care and the use of mixed and appropriate methods. • Those funding innovative practice should consider the additional burden on those working with data and the related data infrastructure if wishing to document and analyse innovation in a robust way. • Data, which may be assumed to be uniform may in fact not be when considered at a multi-area or national level, and further study of the data recording practice of social care professionals is required.

Originality/value

The paper discusses some common issues experienced in quasi-experimental approaches to the quantitative evaluation of children’s services, which have, until recently, been rarely used in the sector. There are important considerations, which are of relevance to researchers, service leads in children’s social care, data and performance leads and funders of innovation.
Establishment of a maturity model to assess the development of industrial AI in smart manufacturing
Authors: Chen Wenting , Liu Caihua , Xing Fei , Peng Guochao , Yang Xi
Published: June 2021

Purpose

The benefits of artificial intelligence (AI) related technologies for manufacturing firms are well recognized, however, there is a lack of industrial AI (I-AI) maturity models to enable companies to understand where they are and plan where they should go. The purpose of this study is to propose a comprehensive maturity model in order to help manufacturing firms assess their performance in the I-AI journey, shed lights on future improvement, and eventually realize their smart manufacturing visions.

Design/methodology/approach

This study is based on (1) a systematic review of literature on assessing I-AI-related technologies to identify relevant measured indicators in the maturity model, and (2) semi-structured interviews with domain experts to determine maturity levels of the established model.

Findings

The I-AI maturity model developed in this study includes two main dimensions, namely “Industry” and “Artificial Intelligence”, together with 12 first-level indicators and 35 second-level indicators under these dimensions. The maturity levels are divided into five types: planning level, specification level, integration level, optimization level, and leading level.

Originality/value

The maturity model integrates indicators that can be used to assess AI-related technologies and extend the existing maturity models of smart manufacturing by adding specific technical and nontechnical capabilities of these technologies applied in the industrial context. The integration of the industry and artificial intelligence dimensions with the maturity levels shows a road map to improve the capability of applying AI-related technologies throughout the product lifecycle for achieving smart manufacturing.