bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P461: Phospho-regulated Spatial Regulation Of α-tat1 Mediates Dynamic Microtubule Acetylation
Authors: Deb Roy Abhijit , Gross Evan G , Pillai Gayatri S , Seetharaman Shailaja , Etienne-Manneville Sandrine , Inoue Takanari
Published: November 2021

Microtubules (MTs) provide mechanical strength to cardiomyocytes and dysregulation of MT network is implicated in cardiac diseases. MT acetylation mediates mechanotransduction, provides structural flexibility to cardiomyocytes and protects against proteinopathy-induced cardiac failure. MT acetylation is exclusively catalyzed by α-TAT1, whose only known substrate is α-tubulin in polymerized MTs. However, little is known about how α-TAT1 itself is regulated. Here we report that intracellular spatial localization of α-TAT1 mediates MT acetylation. Specifically, we identified a conserved signal motif in the intrinsically disordered C-terminus of α-TAT1, consisting of three competing regulatory elements - nuclear export, nuclear import and cytosolic retention. Inhibition of Exportin 1-mediated nuclear export induced nuclear accumulation of α-TAT1 and loss of MT acetylation. We found that α-TAT1 nuclear localization is inhibited by CDKs, CK2 and PKA kinases, pharmacological inhibition of which increased nuclear localization of α-TAT1 and inhibited MT acetylation. We identified a critical phosphoThreonine (T
322
) that binds to 14-3-3 proteins (β, γ, ε and ζ isoforms) downstream of kinases and mediates cytosolic retention of α-TAT1. Inhibition of 14-3-3 proteins also increased nuclear accumulation of α-TAT1. Fibroblastic cells expressing a phosphodeficient α-TAT1 (T322A) show defects in DNA damage response and increased cell proliferation, which may be pertinent to cardiac hypertrophy. Based on these observations, we developed an optogenetic tool, named optoATAT1, which rapidly and reversibly shuttled from the nucleus to the cytosol on blue light stimulation. HeLa cells expressing optoATAT1 exposed to light showed increased MT acetylation unlike those kept in dark, validating the tool. In summary, we have identified a novel role for the C-terminal region of α-TAT1 in regulating its function through dynamic intracellular localization downstream of kinases and 14-3-3 proteins. We have identified multiple pharmacological agents to modulate MT acetylation through spatial regulation of α-TAT1. We have also developed an optogenetic tool to control MT acetylation that will help in elucidating the role of MT acetylation in disease states.
Abstract P473: Obstructive Sleep Apnea Results In Microbial Bile Acid Biotransformations To Promote Atherosclerosis
Authors: Lingaraju Amulya , Flores Ramos Stephany , Gentry Emily , Poulsen Orit , Dorrestein Pieter C , Haddad Gabriel G , Zarrinpar Amir
Published: November 2021

Obstructive sleep apnea (OSA) is an independent exacerbator of cardiovascular disease (CVD). However, it is unclear how OSA or it’s characteristic components, intermittent hypoxia and hypercapnia (IHC), increase CVD risk. Our previous work has shown that IHC reproducibly changes the gut microbiome dynamics in murine models of atherosclerosis and that these changes could affect host cardiovascular physiology through bile acids and phosphocholines. In our initial targeted metabolomics approach, changes in particular bile acids, such as taurocholic acid, taurodeoxycholic acid, and muricholic acid, were associated with and were predictive of IHC exposure in atherosclerotic Ldlr-/- mice. In a more recent study, we identified the formation of novel, microbially-synthesized conjugated bile acids by the gut microbiome that are more potent farnesoid X receptor agonists than other previously described bile acids, and thus, potentially can affect atherosclerosis formation. To determine whether these novel bile acids are associated with IHC-induced atherosclerosis, we characterized luminal bile acid changes in Ldlr-/- mice in an OSA model. We hypothesize that IHC alters the amount of microbially-synthesized novel bile acids and that these bile acids are associated with IHC-induced atherosclerosis. To test this hypothesis, we subjected atherogenic diet-fed Ldlr-/- mice to either room-air (control) or IHC conditions (n=10/condition) and assessed atherosclerotic lesion formation after 12 weeks post-diet. Mice under IHC conditions had significantly higher aortic lesion formation compared to controls. Assessment of fecal bile acid metabolites indicated changes in novel bile acid levels under IHC conditions. Moreover, correlational analysis showed that these novel bile acid changes were positively correlated with atherosclerotic lesion amounts, mainly driven by IHC conditions. Our results demonstrate that bile acid changes through microbial biotransformations occur under IHC conditions and could be the mechanistic link between OSA-induced microbiome changes and atherosclerosis.
Abstract P479: Pathogenesis And Altered Cardiac Transcriptomic Landscape In Western Diet Treated Aged Mice Overexpressing Human Angiotensin Type 1 Receptor
Authors: Ketkar Harshada , Tang Samantha , Jain Sudhir
Published: November 2021

Overexpression of human angiotensin II type 1 receptor (hAT1R) may lead to pathophysiological outcomes due to overactivation of the renin angiotensin system. We have shown that transgenic (TG) mice containing Hap-I (hypertensive genotype) of human AT1R gene are more prone to develop metabolic syndrome (MetS) as compared to TG mice with Hap-II (normotensive genotype). The increased risk of MetS, especially in hypertension, compounded by the effects of aging and Western diet (WD), which may lead to cardiac complications. However, the underlying mechanisms are not well examined. For this purpose, we studied the pathophysiological changes and gene expression profile alterations in the heart of aged Hap-I and Hap-II TG mice following exposure to WD. Aged mice (20-24 months of age) were maintained on a regular diet or high fat diet with 2% NaCl (WD) for 16 weeks. On regular diet, aged Hap-I mice presented higher (~9 mmHg) systolic blood pressure with respect to age-matched Hap-II animals. Following administration of WD, blood pressure increased in both groups of mice, but to a larger extent in Hap-I animals (~15 mmHg), in comparison to Hap-II (~7 mmHg). With respect to Hap-II, aged Hap-I mice on regular diet tended to have larger heart weight-to-body weight ratio and higher levels of fibrosis. Western Diet treatment exacerbated these differences. RNA sequencing data from cardiac tissue of WD treated Hap-I aged mice (compared to control diet treated age-matched mice) revealed that WD significantly altered the expression of >500 genes (p-adj. <0.05). Bioinformatics analysis, using Qiagen IPA software, identified major alterations in main canonical pathways involved in cardiac function, inflammation, and oxidative damage. Top hits in the disease and biological function category included arrhythmia, chamber enlargement, and cell death. Importantly, IRF3, IRF7, IFNG and STAT1 were among the top upstream regulators significantly affected by WD. Overall, these results indicate that Western diet promotes hypertension, hypertrophy, and fibrosis in the heart of aged mice. Results from these studies will assist in the identification of novel molecules and mechanisms involved in hypertension and associated cardiac pathophysiology.
Abstract P492: Putative Protein Biomarkers For Reductive Stress Cardiomyopathy
Authors: Namakkal-Soorappan Rajasekaran , David Cynthia L , Parsawar Krishna
Published: November 2021

Background:
Nuclear factor erythroid 2-related factor 2 (NRF2) signaling is vital for redox homeostasis. We reported that transgenic mice expressing constitutively active Nrf2 (CaNrf2) exhibit reductive stress (RS). Here in, we identified novel protein signatures reacting to RS-induced cardiomyopathy.

Methods:
Tandem Mass Tag (TMT) proteomic analysis was performed in the heart tissues of Ca-Nrf2-transgenic (TG-low & TG-high) and non-transgenic (NTg) mice at 6 months of age (N= 4/group). Differentially expressed proteins (DEPs) were then identified using Scaffold. Validated the key DEPs using immunoblotting. PANTHER and STRING analysis were used to identify potential targets and their interactions.

Results:
A total of 1105 proteins were extracted from 24369 spectra. Of note, 226 and 261 proteins were differentially expressed in TG-L and TG-H vs. NTg hearts indicating a unique proteome signature for RS. Heat map analysis revealed a clear distinction between the TG-L and TG-H due to the dose-dependent effects of transgene/RS. Majority of the DEPs that are significantly altered in RS mice found to involve in stress related pathways such as antioxidants, NADPH, protein quality control (PQC), etc. Interestingly, some of these proteins were redox modified at their cysteine residues under chronic RS setting.

Conclusions:
TMT based proteomic analyses revealed unique proteome signatures for RS. The cysteine modifications in multiple proteins likely to cause pathological alterations via impaired PQC mechanisms. Molecular studies related to RS-mediated redox modifications in structural and functional cardiac proteome are underway.
Abstract P493: Histone Reader PHF7 Cooperates With The SWI/SNF Complex At Cardiac Super Enhancers To Promote Direct Reprogramming
Authors: Garry Glynnis A , Bezprozvannaya Svetlana , Zhou Huanyu , Hashimoto Hisayuki , Chen Kenian , Liu Ning , Bassel-duby Rhonda S , Olson Eric N
Published: November 2021

Ischemic heart disease is the leading cause of death worldwide. Direct reprogramming of resident cardiac fibroblasts (CFs) to induced cardiomyocytes (iCLMs) has emerged as a potential therapeutic approach to treat heart failure and ischemic disease. Cardiac reprogramming was first achieved through forced expression of the transcription factors Gata4, Mef2c, and Tbx5 (GMT); our laboratory found that Hand2 (GHMT) and Akt1 (AGHMT) markedly enhanced reprogramming efficiency in embryonic and postnatal cell types. However, adult mouse and human fibroblasts are resistant to reprogramming due to staunch epigenetic barriers. We undertook a screen of mammalian gene regulatory factors to discover novel regulators of cardiac reprogramming in adult fibroblasts and identified the epigenetic reader PHF7 as the most potent activating factor. We validated the findings of this screen and found that PHF7 augmented reprogramming of adult fibroblasts ten-fold. Mechanistically, PHF7 localized to cardiac super enhancers in fibroblasts by reading H3K4me2 marks, and through cooperation with the SWI/SNF complex, increased chromatin accessibility and transcription factor binding at these multivalent enhancers. Further, PHF7 recruited cardiac transcription factors to activate a positive transcriptional autoregulatory circuit in reprogramming. Importantly, PHF7 achieved efficient reprogramming through these mechanisms in the absence of Gata4. Collectively, these studies highlight the underexplored necessity of cardiac epigenetic readers, such as PHF7, in harnessing chromatin remodeling and transcriptional complexes to overcome critical barriers to direct cardiac reprogramming.
Abstract P501: Comprehensive Analysis Of Alternative Polyadenylation In Human Left Ventricle Failure By Using The Novel Algorithm: Polya-miner
Authors: Neupane Rahul , Yalamanchili Hari Krishna , Mahalingam Rajasekaran , Collum Scott D , Youker Keith , Wagner Eric J , Bhimaraj Arvind , Karmouty-quintana Harry , Ashrith Guha , Amirthalingam Thandavarayan Rajarajan
Published: November 2021

Background:
Alternative polyadenylation (APA) is an emerging post-transcriptional mechanism for gene regulation that generates distinct isoforms of mRNA with different 3′ untranslated regions (3’UTR) lengths. APA plays an important role in different biological processes and dysregulation of APA leads to many human diseases. However, the functional consequences of APA events in the left ventricle (LV) failure in humans remain unexplored.

Objective:
To identify whether the 3′UTR length is modulated by APA in the LV failure in humans compared to healthy LV.

Methods and Results:
We used Poly(A)-ClickSeq RNA sequencing and PolyA-miner algorithm to measure the global patterns of APA in healthy and failing human LV specimens. We determined shortening versus lengthening of 3′UTRs based on the PolyA index, a metric unit that determines the length of 3′UTR. Based on these scores, we identified 129 genes with a significant shift of cleavage site usage in failing LV compared to healthy LV specimens. By examining polyadenylation events in these hearts, we identified disease-specific APA signatures in many genes. In addition, differential APA events in LV failure regulate many pathways important for the progression of LV failure. Finally, the regulator proteins of APA including cleavage and polyadenylation specificity factor (CPSF) 6 and 7, cleavage factor Im (CFIm) 25 and 59 have been regulated in LV failure compared to healthy LV specimens.

Conclusions:
Our results provide genome-wide, polyadenylation maps of the human heart and show that APA of mRNA is dynamic in the progression of LV failure in humans. Demonstrating that APA mediated 3’UTR length regulation provides the additional layer of gene expressions in LV failure.
Abstract P509: Novel Protein Kinase C Epsilon Inhibitor Attenuates Uncoupled Endothelial Nitric Oxide Synthase And Vascular Endothelial Dysfunction
Authors: Galbreath Brogan , Nair Arjun , Ringe John , Madison Ian T , Dean Tameka C , Lopez Alexandra , Chen Qian , Young Lindon
Published: November 2021

Endothelial nitric oxide synthase (eNOS) uncoupling reduces nitric oxide (NO) production when tetrahydrobiopterin (BH
4
) is oxidized to dihydrobiopterin (BH
2
), resulting in endothelial dysfunction and leukocyte adherence. Renovascular damage following shockwave lithotripsy (SWL) may occur via the potentiation of this mechanism. We aim to modulate uncoupled eNOS activity with myristoylated protein kinase C epsilon inhibitor (
myr
-PKCε–; N-
myr
-EAVSLKPT) and activator (
myr
-PKCε+; N-
myr
-HDAPIGYD). We hypothesize that
myr
-PKCε– with uncoupled eNOS (i.e., bound to BH
2
) should reduce leukocyte-endothelial interactions in postcapillary venules and H
2
O
2
levels after SWL.
Myr
-PKCε+ should promote similar effects when eNOS is coupled (i.e., bound to BH
4
).

Mesenteric venules of anesthetized male SD rats (300g) were superfused for 120 min with 100 μM BH
2
and test solutions (Krebs’ buffer, 10 μM
myr
-PKCε+, or 10 μM
myr
-PKCε–) with or without 100 μM BH
4
. Leukocyte activity was evaluated via intravital microscopy. In separate SD rats, SWL was performed on left kidneys (16 kV, 500 shocks at 60 shocks/min and at 120 shocks/min). Then, normal saline or test solution cocktail (
myr
-PKCε+ [0.9 mg/kg]/
myr
-PKCε- [0.8 mg/kg] with BH
2
[2mg/kg] or BH
4
[0.8 mg/kg]) was given i.v. NO or H
2
O
2
levels were measured with 100 μm microsensors in left renal veins at baseline, end of SWL, and 5-min intervals for 30 min post-SWL. Data were analyzed using ANOVA Student-Newman-Keuls test.

BH
2
-induced leukocyte rolling, adherence, and transmigration were significantly increased by
myr
-PKCε+ (
n
= 6) and attenuated with
myr-
PKCε– (
n
= 5) compared to control (n=5) at 120 min (p<0.01). Following SWL, all treatments except
myr
-PKCε+ with BH
2
significantly reduced H
2
O
2
(
n
= 5,
p
< .01) and increased NO levels (
n
= 5,
p
< .01) compared to control. NO and H
2
O
2
levels following administration of
myr
-PKCε+ with BH
2
were similar to SWL control.

Results suggest that
myr
-PKCε– attenuates uncoupled eNOS activity and H
2
O
2
release in rat renal veins, after SWL. Promoting coupled eNOS activity with BH
4
yields similar results. Promoting eNOS coupling with BH
4
or inhibiting uncoupled eNOS with
myr-
PKCε– attenuates oxidative stress and endothelial dysfunction following SWL and BH
2
-induced inflammation.
Cerebrovascular Risk-Factors of Prevalent and Incident Brain Infarcts in the General Population: The AGES-Reykjavik Study
Authors: Sigurdsson Sigurdur , Aspelund Thor , Kjartansson Olafur , Gudmundsson Elias , Jonsson Palmi V. , van Buchem Mark A. , Gudnason Vilmundur , Launer Lenore J.
Published: November 2021

Background:

Studies on the association of cerebrovascular risk factors to magnetic resonance imaging detected brain infarcts have been inconsistent, partly reflecting limits of assessment to infarcts anywhere in the brain, as opposed to specific brain regions. We hypothesized that risk-factors may differ depending on where the infarct is located in subcortical-, cortical-, and cerebellar regions.

Methods:

Participants (n=2662, mean age 74.6±4.8) from the longitudinal population-based AGES (Age, Gene/Environment Susceptibility)-Reykjavik Study underwent brain magnetic resonance imaging at baseline and on average 5.2 years later. We assessed the number and location of brain infarcts (prevalent versus incident). We estimated the risk-ratios of prevalent (PRR) and incident (IRR) infarcts by baseline cerebrovascular risk-factors using Poisson regression.

Results:

Thirty-one percent of the study participants had prevalent brain infarcts and 21% developed new infarcts over 5 years. Prevalent subcortical infarcts were associated with hypertension (PRR, 2.7 [95% CI, 1.1–6.8]), systolic blood pressure (PRR, 1.2 [95% CI, 1.1–1.4]), and diabetes (PRR, 2.8 [95% CI, 1.9–4.1]); incident subcortical infarcts were associated with systolic (IRR, 1.2 [95% CI, 1.0–1.4]) and diastolic (IRR, 1.3 [95% CI, 1.0–1.6]) blood pressure. Prevalent and incident cortical infarcts were associated with carotid plaques (PRR, 1.8 [95% CI, 1.3–2.5] and IRR, 1.9 [95% CI, 1.3–2.9], respectively), and atrial fibrillation was significantly associated with prevalent cortical infarcts (PRR, 1.8 [95% CI, 1.2–2.7]). Risk-factors for prevalent cerebellar infarcts included hypertension (PRR, 2.45 [95% CI, 1.5–4.0]), carotid plaques (PRR, 1.45 [95% CI, 1.2–1.8]), and migraine with aura (PRR, 1.6 [95% CI, 1.1–2.2]). Incident cerebellar infarcts were only associated with any migraine (IRR, 1.4 [95% CI, 1.0–2.0]).

Conclusions:

The risk for subcortical infarcts tends to increase with small vessel disease risk-factors such as hypertension and diabetes. Risk for cortical infarcts tends to increase with atherosclerotic/coronary processes and risk for cerebellar infarcts with a more mixed profile of factors. Assessment of risk-factors by location of asymptomatic infarcts found on magnetic resonance imaging may improve the ability to target and optimize preventive therapeutic approaches to prevent stroke.
Black-White Differences in Ischemic Stroke Risk Factor Burden in Young Adults
Authors: Aradine Elizabeth M. , Ryan Kathleen A. , Cronin Carolyn A. , Wozniak Marcella A. , Cole John W. , Chaturvedi Seemant , Dutta Tara L.M. , Hou Yan , Mehndiratta Prachi , Motta Melissa , Phipps Michael S. , Yarbrough Karen L. , McArdle Patrick F. , Kittner Steven J.
Published: November 2021

Background and Purpose:

Although the US Black population has a higher incidence of stroke compared with the US White population, few studies have addressed Black-White differences in the contribution of vascular risk factors to the population burden of ischemic stroke in young adults.

Methods:

A population-based case-control study of early-onset ischemic stroke, ages 15 to 49 years, was conducted in the Baltimore-Washington DC region between 1992 and 2007. Risk factor data was obtained by in-person interview in both cases and controls. The prevalence, odds ratio, and population-attributable risk percent (PAR%) of smoking, diabetes, and hypertension was determined among Black patients and White patients, stratified by sex.

Results:

The study included 1044 cases and 1099 controls. Of the cases, 47% were Black patients, 54% were men, and the mean (±SD) age was 41.0 (±6.8) years. For smoking, the population-attributable risk percent were White men 19.7%, White women 32.5%, Black men 10.1%, and Black women 23.8%. For diabetes, the population-attributable risk percent were White men 10.5%, White women 7.4%, Black men 17.2%, and Black women 13.4%. For hypertension, the population-attributable risk percent were White men 17.2%, White women 19.3%, Black men 45.8%, and Black women 26.4%.

Conclusions:

Modifiable vascular risk factors account for a large proportion of ischemic stroke in young adults. Cigarette smoking was the strongest contributor to stroke among White patients while hypertension was the strongest contributor to stroke among Black patients. These results support early primary prevention efforts focused on smoking cessation and hypertension detection and treatment.
Whose Past and Whose Future: Free Love and Love Marriage among “Kafirs” of the Hindukush in an Early Nineteenth-Century Persian Ethnography
Authors: Cacopardo Alberto , Pellò Stefano
Published: November 2021

This paper deals with some practices and conceptions relating to love and marriage in a now-extinct pre-Islamic culture of the Hindukush, as described in an extremely precious, yet very little-known, Persian ethnographical source (ca. 1840). Written by a munshī from Peshawar under instructions from the French general Claude-Auguste Court, who was then in the service of Maharaja Ranjit Singh, this is probably the single most important pre-Robertson source about the “Kafir” cultures of Nuristan. While a complete translation and thorough study of the unpublished document, by Stefano Pellò and Alberto Cacopardo, is now forthcoming, in these brief notes we show how free love and love marriage, often perceived as “modern” concepts in many parts of Asia, were envisioned by Tak and Shamlar, two elders from pre-Islamic Kamdesh.
Proto-Indo-European Initial *r Revisited
Authors: Kocharov Petr , Shatskov Andrey
Published: November 2021

The ante-rhotic vocalic prothesis has been postulated for the history of Hittite, Greek, Armenian, and Albanian—languages, which are often believed to have no inherited PIE words beginning with a rhotic. With the advance of the laryngeal theory, the existence of the ante-rhotic prothesis has been critically revised for Hittite, Greek, and Albanian. However, a closer look at the available evidence leaves one with a wide scale of possibilities of analysis not limited to postulating laryngeals before any PIE initial rhotic. Given that all of the aforementioned branches are primarily localized in Asia Minor or adjacent territories and that they most likely had split from the proto-language at different periods, the hypothesis of the ante-rhotic vocalic prothesis as an aerial feature may prove to be the most economic explanation of facts.
The first assessment of genetic diversity among Turkish leek accessions using molecular and morphological markers
Authors: Hanci Fatih
Published: November 2021

Considering the high importance of leek as a vegetable crop, this species is rarely an object of molecular genetic studies. In this study, SRAP and ISSR markers were used for the first time to investigate the genetic diversity in Turkish leek accessions together with some morphological characters. The study was conducted in Erciyes University Faculty of Agriculture in 2018–2020. Thirty-seven local varieties were collected from different towns in Turkey. Also, nineteen leek accessions, which originated from different regions of Turkey, had been kindly obtained from Plant Gene Banks, USDA. Seventeen SRAP and three ISSR markers were screened; all of them exposing 137 reproducible bands, of which 114 resulted in polymorphic. Polymorphism information content (PIC) varied between 0.209 and 0.840. Genetic similarities varied from 0.563 to 0.960, with an average of 0.789. In addition to molecular markers, the entire gene pool was morphologically characterized over two-year data. For this purpose, eight characters, which play a key role in leek breeding, were measured. At the end of the study, the analyzes made according to the molecular and morphological data were compared both separately and in combination. In all groupings, it was found remarkable that the accessions numbered 98*3, 40*1, 40*4, and 40*6 were positioned differently from the others. These results have provided important insights into the genetic variability of Turkish leek accessions for the first time. Also, the diversity analysis performed in this study provides valuable information to researchers for future studies.
Two new species of Pyrgulopsis Call & Pilsbry, 1886 (Mollusca: Caenogastropoda: Hydrobiidae) from springs in the Rio Grande watershed in Texas
Authors: PEREZ KATHRYN E. , LEAL MANUEL SPOR , GLOVER HOUSTON , CHASTAIN REBECCA T. , HUTCHINS BENJAMIN T. , SCHWARTZ BENJAMIN
Published: November 2021

Pyrgulopsis Call & Pilsbry, 1886 is a genus of small (<5 mm) spring snails, usually endemic to single freshwater springs. Two new populations of Pyrgulopsis found in very small, isolated springs and spring runs in the mainstem Rio Grande watershed of western Texas are distinguished from congeners. Mitochondrial and nuclear sequences, morphometrics, and morphological characteristics support Pyrgulopsis rubra sp. nov. and Pyrgulopsis harrymilleri sp. nov. as distinct from other known Pyrgulopsis species, including the geographically proximate P. metcalfi.
Design of chitosan-poloxamer nanogel and evaluation of its therapeutic effect on skin burn
Authors: Zou Jianfei , Lv Lianshuang , Qi Xiuli
Published: November 2021

Wound infection is the main cause of slow healing and complications of skin burns. Wound dressings can temporarily replace the skin to isolate the contamination and can be anti-infective, which is conducive to wound healing. In this study, a chitosan-Poloxamer-apigenin nanogel dressing
(CTS-Plo-Api) was constructed using CTS and Plo, as carriers, and Api. In comparison with traditional treatments, the speed of wound healing is improved with the use of CTS-Plo-Api; moreover, it enhances bacteriostatic and anti-infection ability and has certain analgesic effects. Therefore,
we demonstrate that CTS-Plo-Api is an exciting new clinical avenue for the treatment of burn patients.
Advances in the Application and Utility of Subseasonal-to-Seasonal Predictions
Authors: White Christopher J. , Domeisen Daniela I. V. , Acharya Nachiketa , Adefisan Elijah A. , Anderson Michael L. , Aura Stella , Balogun Ahmed A. , Bertram Douglas , Bluhm Sonia , Brayshaw David J. , Browell Jethro , Büeler Dominik , Charlton-Perez Andrew , Chourio Xandre , Christel Isadora , Coelho Caio A. S. , DeFlorio Michael J. , Delle Monache Luca , Di Giuseppe Francesca , García-Solórzano Ana María , Gibson Peter B. , Goddard Lisa , González Romero Carmen , Graham Richard J. , Graham Robert M. , Grams Christian M. , Halford Alan , Huang W. T. Katty , Jensen Kjeld , Kilavi Mary , Lawal Kamoru A. , Lee Robert W. , MacLeod David , Manrique-Suñén Andrea , Martins Eduardo S. P. R. , Maxwell Carolyn J. , Merryfield William J. , Muñoz Ángel G. , Olaniyan Eniola , Otieno George , Oyedepo John A. , Palma Lluís , Pechlivanidis Ilias G. , Pons Diego , Ralph F. Martin , Reis Dirceu S. , Remenyi Tomas A. , Risbey James S. , Robertson Donald J. C. , Robertson Andrew W. , Smith Stefan , Soret Albert , Sun Ting , Todd Martin C. , Tozer Carly R. , Vasconcelos Francisco C. , Vigo Ilaria , Waliser Duane E. , Wetterhall Fredrik , Wilson Robert G.
Published: November 2021

The subseasonal-to-seasonal (S2S) predictive time scale, encompassing lead times ranging from 2 weeks to a season, is at the frontier of forecasting science. Forecasts on this time scale provide opportunities for enhanced application-focused capabilities to complement existing weather and climate services and products. There is, however, a “knowledge–value” gap, where a lack of evidence and awareness of the potential socioeconomic benefits of S2S forecasts limits their wider uptake. To address this gap, here we present the first global community effort at summarizing relevant applications of S2S forecasts to guide further decision-making and support the continued development of S2S forecasts and related services. Focusing on 12 sectoral case studies spanning public health, agriculture, water resource management, renewable energy and utilities, and emergency management and response, we draw on recent advancements to explore their application and utility. These case studies mark a significant step forward in moving from potential to actual S2S forecasting applications. We show that by placing user needs at the forefront of S2S forecast development—demonstrating both skill and utility across sectors—this dialogue can be used to help promote and accelerate the awareness, value, and cogeneration of S2S forecasts. We also highlight that while S2S forecasts are increasingly gaining interest among users, incorporating probabilistic S2S forecasts into existing decision-making operations is not trivial. Nevertheless, S2S forecasting represents a significant opportunity to generate useful, usable, and actionable forecast applications for and with users that will increasingly unlock the potential of this forecasting time scale.
Optimization of twisted blade of pump as turbine based on high dimensional surrogate model
Authors: Jiang Bingxiao , Yang Junhu , Wang Xiaohui , Shi Fengxia , Bai Xiaobang
Published: November 2021

In order to improve the operation efficiency of the twisted blade pump as turbine (PAT), a medium specific speed PAT was selected as the research object. The variables of the twisted blade plane blade profile were defined, the twisted blade was transformed into three plane blade profiles, and the blade profiles were parameterized by MATLAB 9.7 software. MATLAB 9.7, CFturbo 2020 and Fluent 19.2 were used to build the support vector machine-high dimensional model representation (SVM-HDMR) surrogate model function for efficiency optimization of PAT. Genetic algorithm was run on MATLAB 9.7 to optimize the surrogate model function, and the optimized blade profiles were fed back. The optimization results were verified by numerical simulation and experiment. The results show that the simulation efficiency of the PAT after optimization at the design operating point is 3.51% higher than the efficiency of the PAT before optimization, and the output power is increased by 5.3%. The test efficiency of the PAT after optimization at the design operating point is 3.4% higher than the efficiency of the PAT before optimization, and the output power is increased by 5.1%.
Familial Mentor Support and Black Youths’ Connectedness to Parents Across Adolescence
Authors: Billingsley Janelle T. , Rivens Ariana J. , Charity-Parker Bianka M. , Chang Stephanie H. , Garrett Shedrick L. , Li Tianjiao , Hurd Noelle M.
Published: November 2021

This mixed method study explored whether and how familial mentor support may have influenced the parent-adolescent relationship, and whether the impact of familial mentor support on the parent-adolescent relationship may have differed across adolescents’ developmental stage. Findings from analyses of survey data from 106 Black adolescents indicated that familial mentor support may be equally beneficial for youths’ connectedness to parents across developmental stage. Interview data from a subset of 12 adolescents, their primary caregivers, and familial mentors were analyzed to better understand how familial mentors supported the parent-adolescent bond and whether the nature of mentor support differed between early and middle adolescents. Qualitative findings indicated that mentors supported the parent-adolescent relationship by acting as sounding boards; coaching positive communication strategies; and promoting understanding between youth and their parents. Additionally, findings indicated that familial mentors may be attuned to developmental changes experienced by their adolescent relatives.
Platform NHS: Reconfiguring a Public Service in the Age of Digital Capitalism
Authors: Faulkner-Gurstein Rachel , Wyatt David
Published: November 2021

The platform is emerging as a key organizational form and operational logic of contemporary capitalism, intimately tied to financialization and assetization. However, discussions to date have focused on platforms and platformization in the context of the private, corporate, and technology sectors. In this paper, we develop an analysis of how platformization operates in the context of public policy. Using the UK’s National Health Service as a case study, we explore how platformization is altering the form and function of the state. The platformization of the NHS has its roots in the UK government’s strategic interest in the development of the bioeconomy. This led to the creation of a research infrastructure within the health service. Subsequently, the NHS has leveraged various assets into a range of data- and technology-focused initiatives. We argue that platformization has been a major form of neoliberalization within the NHS. The paper concludes with a discussion of what an analysis of public platformization can teach us about ongoing transformations of the state.
The door swings in and out: The impact of family support and country stability on success of women entrepreneurs in the Arab world
Authors: Welsh Dianne HB , Kaciak Eugene , Mehtap Salime , Pellegrini Massimiliano M , Caputo Andrea , Ahmed Siddiga
Published: November 2021

Women-owned businesses represent a significant segment of the contemporary economy upon a global basis. However, women entrepreneurs still experience more obstacles than men depending on cultural context; for example, research on the Arab world concerning the interaction between women entrepreneurs and their families remains under-developed. Consequently, we ground our study upon an enhanced framework of agency theory, which includes family altruism. We examined the relationships between business-family interface (BFI) enrichment components and the performance of firms headed by female entrepreneurs women in Jordan and Sudan. Specifically, we investigated if and how the country level of political and social stability moderates these relationships. The findings suggest that the relationship between the family-related objective factor (family financial support) and the performance of firms headed by female entrepreneurs is not affected by the country’s political and social stability context. Conversely, the family-related subjective factor (family moral support) is affected by this context. Our study bridges the gap in contextual studies on the Arab world concerning the success of women-owned businesses and confirms how institutional elements affect business in addition to family-related matters. Implications for future research and public policy are discussed.
Ensuring hemodialysis adequacy by dialysis dose monitoring with UV spectroscopy analysis of spent dialyzate
Authors: Zhang Li , Liu Wenhu , Hao Chuanming , He Yani , Tao Ye , Sun Shiren , Jakob Marten , Marcelli Daniele , Barth Claudia , Chen Xiangmei
Published: November 2021

Introduction:

Patients’ session-to-session variation has been shown to influence outcomes, making critical the monitoring of dialysis dose in each session. The aim of this study was to detect the intra-patient variability of blood single pool Kt/V as measured from pre-post dialysis blood urea and from the online tool Adimea®, which measures the ultraviolet absorbance of spent dialyzate.

Methods:

This open, one-armed, prospective non-interventional study, evaluates patients on bicarbonate hemodialysis or/and on hemodiafiltration. Dialysis was performed with B. Braun Dialog+ machines equipped with Adimea®. In the course of the prospective observation, online monitoring with Adimea® in each session was established without the target warning function being activated. A sample size of 97 patients was estimated.

Results:

A total of 120 patients were enrolled in six centers in China (mean age 51.5 ± 12.2 years, 86.7% males, 24.2% diabetics). All had an AV-fistula. The proportion of patients with blood Kt/V < 1.20 at baseline was 48.3%. During follow-up with Adimea®, the subgroup with Kt/V > 1.20 at baseline remains at the same adequacy level for more than 90% of the patients. Those with a Kt/V < 1.20 at baseline, showed a significant increase of Kt/V to 60% of the patients reaching the adequacy level >1.20. The coefficient of variation for spKt/V as evaluated by Adimea® was 9.6 ± 3.4%, not significantly different from the 9.6 ± 8.6% as blood Kt/V taken at the same time.

Conclusion:

Online monitoring of dialysis dose by Adimea® improves and maintains dialysis adequacy. Implementing online monitoring by Adimea into daily practice moves the quality of dialysis patient care a significant step forward.
ST-Elevation Myocardial Infarction Among Septic Shock and Coronary Interventions: A National Emergency Database Study
Authors: Mir Tanveer , Uddin Mohammed , Qureshi Waqas T. , Abohashem Shady , Alqalyoobi Shehabaldin , Sheikh Mujeeb , Soubani Ayman , Saydain Ghulam , Albertson Timothy E.
Published: November 2021

Objective

To study coronary interventions and mortality among patients with ST-elevated myocardial infarction (STEMI) who were admitted with septic shock.

Methods

Data from the national emergency department sample (NEDS) that constitutes 20% sample of hospital-owned emergency departments in the United States was analyzed for the septic shock related visits from 2016 to 2018. Septic shock was defined by the ICD codes.

Results

Out of 1 375 507 adult septic shock patients, 521 300 had a primary diagnosis of septic shock (mean age 67.41±15.67 years, 51.1% females) in the national emergency database for the years 2016 to 2018. Of these patients, 2768 (0.53%) had STEMI recorded during the hospitalization. Mortality rates for STEMI patients were higher than patients without STEMI (52.3% vs 23.5%). Mortality rates improved with PCI among STEMI patients (43.8% vs 56.2%). Coronary angiography was performed among 16% of patients of which percutaneous coronary intervention (PCI) rates were 7.7% among patients with STEMI septic shock. PCI numerically improved mortality, however, had no significant difference than patients without PCI on multivariate logistic regression and univariate logistic regression post coarsened exact matching of baseline characteristics among STEMI patients. Among the predictors, STEMI was a significant predictor of mortality in septic shock patients (OR 2.87, 95% CI 2.37-3.49; P<.001). Age, peripheral vascular disease, were predominant predictors of mortality in STEMI with septic shock subgroup ( P <.001). Pneumonia was the predominant underlying infection among STEMI (36.4%) and without STEMI group (29.5%).

Conclusion

STEMI complicating septic shock worsens mortality. PCI and coronary angiography numerically improved mortality, however, had no significant difference from patients without PCI. More research will be needed to improve mortality in such a critically ill subgroup of patients.
Examining the Use of a Brief Online Intervention in Primary Care for Changing Low-Income Caregivers’ Attitudes Toward Spanking
Authors: Richardson Hilary L. , Damashek Amy
Published: November 2021

There is a robust and growing literature base indicating that spanking is a common, but potentially problematic, discipline strategy. Goals: Using a randomized controlled trial design, this study examined whether participation in a brief online program, Play Nicely, would result in favorable changes in caregivers’ attitudes toward spanking. The study also examined whether the intervention was equally effective for participants of color (POC) and White participants, and it assessed caregivers’ perceptions of the program’s cultural sensitivity. Methods: Participants were 52 caregivers from 1- to 5-year-old children who were visiting a pediatric clinic. Participants were enrolled and randomly assigned to either engage in the Play Nicely online program ( n = 21) or view a control condition website ( n = 31) in a clinic exam room. Results: There was not a statistically significant difference between the treatment and control groups’ scores on attitudes toward spanking (ATS) at post-test ( F (1, 49) = 1.515, p = 0.224), but a small between-group effect size was detected ( d = 0.20). Within the treatment condition, desired changes in ATS scores were significantly higher among White participants than POC ( t (17) = −2.125, p = 0.049), but there was not a significant difference in reported perceptions of Play Nicely’s cultural acceptability between White participants and POC ( t (19) = 0.469, p = 0.644). Conclusions: Findings suggest a need for further investigation of Play Nicely’s impact on caregivers’ ATS with a larger sample to clarify the program’s utility as a potential population-based tool for parent education and violence prevention. Additional research is needed to identify sociocultural factors that may moderate the effects of spanking interventions for families across diverse racial backgrounds.
The Effects of Exclusive Walking on Lipids and Lipoproteins in Women with Overweight and Obesity: A Systematic Review and Meta-Analysis
Authors: Ballard Anjulyn M. , Davis Ashlee , Wong Brett , Lyn Rodney , Thompson Walter R.
Published: November 2021

Objective

To evaluate the effects of walking, independent of diet and weight-loss, on lipids and lipoproteins in women with overweight and obesity.

Data Source

Academic Search Complete, Alternative Health Watch, Global Health, Health Source, CINAHL, MEDLINE, EMBASE, SportDiscus, and ProQuest.

Study Inclusion and Exclusion Criteria

(1) experiment-control design; (2) women with overweight or obesity; (3) walking as the experiment’s independent variable; (4) four or more weeks; and (5) pre- to post-assessment of lipids and/or lipoproteins. Excluded studies reported use of lipid-lowering medication, diet or other modes of physical activity, and alternative interventions as the control.

Data Extraction

Data extraction and study quality were completed by the first 2 authors using the Cochrane review protocol and risk of bias assessment.

Data Synthesis

Raw mean difference between the experiment and control groups using a random effects model.

Results

Meta-analyses of 21 interventions (N = 1129) demonstrated exclusive walking improves total cholesterol (raw mean difference = 6.67 mg/dL, P = .04) and low-density lipoproteins (raw mean difference = 7.38 mg/dL, P = .04). Greater improvement in total cholesterol, triglycerides, high-density lipoproteins, and low-density lipoproteins existed in women with obesity.

Conclusions

Exclusive walking aids in normalizing total cholesterol and LDLs in women with overweight and obesity. Exclusive walking can be used as a non-pharmacologic therapy, which may have positive clinical outcomes for individuals who especially struggle with diet and weight-reduction.
With or without U(nions)? Understanding the diversity of gig workers’ organizing practices in Italy and the UK
Authors: Cini Lorenzo , Maccarrone Vincenzo , Tassinari Arianna
Published: November 2021

Since 2016, mobilizations of gig workers across European countries have become increasingly common within location-based services, such as food delivery. Despite remarkable similarities in workers’ mobilization dynamics, their organizational forms have varied considerably, ranging from self-organization, to work councils, to unionization through rank-and-file or longstanding unions. To start making sense of this diversity in organizing practices, we compare two cases of mobilization in the food delivery sector: in Italy, where workers have initially opted for self-organization, and in the UK, where they have organized through rank-and-file unions. Drawing on interview and observational data gathered between 2016 and 2018, we find that the diversity of organizational forms across the two cases derives from the interaction between agential and contextual factors, namely: the capabilities of rank-and-file unions and the political tradition of militant organizing of the environment within which gig workers are embedded. These findings contribute to the emerging debate on labour relations in the gig economy by showing the central role that factors external to the labour process and to the institutional context play in shaping the structuring of labour antagonism in a still lowly institutionalized sector characterized by transnationally homogenous challenges.
Rationalizing the irrational: Making sense of (in)consistency among union members and non-members
Authors: Hadziabdic Sinisa , Frangi Lorenzo
Published: November 2021

Focusing on 13 OECD countries over 25 years, we examine the factors that explain why a sizable fraction of wage-earners exhibit an inconsistency between their union membership status and their confidence in unions by being either confident non-members or non-confident members. While structural factors associated with joining constraints generate inconsistency in specific labour market categories, wage-earners who have extreme ideological orientations and are highly interested in politics are much less likely to exhibit inconsistency across time and countries. For individuals who have intermediate ideological orientations and are not very interested in politics, differences in terms of non-member and member inconsistency between countries are explainable through contextual variables such as economic conditions, the level of employment protection, and historical legacies. Implications for union membership research and union strategies are discussed.
Renal function deterioration is an independent mortality determinant in Koreans diagnosed with lupus nephritis
Authors: Jeon Howook , Lee Jennifer , Ju Ji Hyeon , Kim Wan-Uk , Park Sung-Hwan , Moon Su-Jin , Kwok Seung-Ki
Published: November 2021

Objective

To evaluate the predictors of mortality, mortality rate, and causes of death in patients with lupus nephritis (LN) depending on final renal function.

Methods

The cohort included 401 Korean patients diagnosed with LN between 1985 and 2019. We retrospectively analyzed the clinical and laboratory indices, treatment response, and the final renal function. The final renal function was defined by the last stable level of eGFR measured in an out-patient department more than 3 times before death occurred and was categorized into five groups depending on CKD stage.

Results

The median follow-up time after the diagnosis of LN was 131 months. No difference in baseline demographic characteristics and laboratory findings was found except for the proportion of Hb less than 10 mg/dl and baseline eGFR ( p = 0.011 and 0.037). We found no significant differences in therapeutic parameters, but all the response parameters including treatment response at 6 months ( p = 0.004) and 12 months ( p = 0.004), time to remission ( p < 0.001), final renal response ( p < 0.001), and the final renal function ( p < 0.001) differed significantly between the two groups. In multivariate Cox proportional hazards analysis, the final renal function was an independent risk factor predicting mortality. The main causes of death were infection and SLE flare. Contrary to existing knowledge, SLE flare also triggered mortality in a few patients with LN progressed to end-stage renal disease (ESRD). Only two cases of mortality occurred in the kidney transplantation (KT) group ( n = 25) with a median follow-up period of 224 months. The overall mortality rates calculated using the Kaplan–Meier method were 6.8%, 10.3%, 19.7%, and 28.0% at 5, 10, 20, and 30 years, respectively.

Conclusion

Renal function deterioration was an independent determinant of mortality in Korean patients with LN. SLE flare also caused mortality in patients with LN who required maintenance dialysis, suggesting the benefit of KT on lupus activity and survival.