bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P250: A High-throughput Nitric Oxide Measurement Assay Reveals That Angiotensin-(1-5) Is An AT2 Receptor Agonist
Authors: Souza Silva Igor M , Kjærgaard Kenneth , Mortensen Christina , Santos Robson A , Verano-Braga Thiago , Stage Tore B , Steckelings Ulrike M
Published: August 2021

The angiotensin AT2-receptor (AT2R) is a key component within the protective arm of the renin-angiotensin system (RAS), being involved in nitric oxide (NO) production and vasodilation. To this date, no quantitative high-throughput assay is available to identify AT2R agonists
in vitro
, which may be a reason for the low number of AT2R selective ligands in drug development programs.

Objective:
To design and validate a high-throughput method for detection of AT2R activation
in vitro
.

Methods and Results:
NO release was selected as readout for AT2R activation in AT2R transfected (CHO-AT2) and non-transfected (CHO-NT) CHO cells using DAF-FM (5x10-6 mol/L) as NO probe. Cells were seeded on 96-well plates and stimulated for 15 minutes with C21 or Ang II (established AT2R agonists, 10-6mol/L), Ang-(1-5) (molecule with unknown biological status, 10-6 mol/L) or Ang-(1-7) (Mas-receptor agonist, 10-7 mol/L). After fixation of cells, fluorescence signals were captured by fluorescence microscopy using an automated imaging system (ImageXpress Pico, Molecular Devices, San Jose, USA) and image analysis by ImageJ. In CHO-AT2, C21 (+34.78 ± 12.09%), Ang II (+28.76 ± 17.65%) and Ang-(1-5) (+78.00 ± 23.82%) increased NO release (one-way ANOVA, p < 0.05 vs control, at least 3 independent experiments), while Ang-(1-7) had no effect (+ 0.13 ± 4.74%). In CHO-NT, none of the compounds stimulated release of NO (C21 -4.91 ±10.24%; Ang II -4.79 ± 12.44%; Ang (1-5) -8.88 ± 18.16%; Ang-(1-7) -11.57 ± 19.95%) indicating that the responses in CHO-AT2 were AT2R specific.

Conclusion:
Measurement of NO release from AT2R transfected CHO cells by DAF-FM fluorescence in an automated way is suitable as high-throughput assay for the identification of AT2R-agonistic compounds
in vitro
, Application of the assay revealed that Ang-(1-5), which is commonly regarded as an inactive metabolite of Ang II, has AT2R agonistic properties.
Abstract P258: The Use Of Ace Inhibitors And Angiotensin Receptor Blockers Is Associated With Decreased Mortality And Increased Hospitalization Rate In Covid-19 Patients
Authors: Douen Aaron , Oh Jeremy , Romney Wesley , Panetti Ryan , Ramdass Prakash , Toreli Aleksandre , Juang George
Published: August 2021

Introduction:
Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are well known for upregulating ACE2 receptors. SARS-Cov-2 (COVID-19) infection utilizes the ACE2 receptor for proliferation and infection of host cells.

Hypothesis:
We hypothesize that the use of ACEI/ARBs will lead to a higher mortality and hospitalization rate among COVID-19 infected patients.

Methods:
The electronic health database at a public hospital in New York City was queried retrospectively for patients 18 years and older with a positive test for COVID-19 between 3/1/2020 - 4/1/2021. We examined baseline characteristics including comorbidities and whether they were prescribed ACEI/ARBs versus other medications including beta-blockers, calcium channel blockers, thiazides, or hydralazine. We categorized patients based on ACEI/ARB. The primary outcomes were all-cause mortality and hospitalization. The secondary outcomes were acute kidney injury, ventricular arrhythmia, myocardial infarction, heart failure, and intubation. We adjusted for comorbidities using multivariate logistic regression.

Results:
We identified 23,068 patients positive for SARS-CoV-2; 1,385 on ACEI/ARBs and 21,683 not on ACE/ARBs. The mean age in years was 65.90 +- 14.35 (SEM 0.386) and 44.01+-16.76, (SEM 0.114) for ACEI/ARB and non-ACEI/ARB respectively (p<0.001). The incidence of all cause mortality and hospitalization rate were significantly greater in the ACEI/ARB group. However, when adjusted for comorbidities using multivariate logistic regression, OR for mortality was 0.41 (CI 0.32-0.52, p<0.001) and for hospitalization was 4.12 (CI 3.49-4.86 p<0.001). For the secondary outcomes, non-ACEI/ARB patients had significantly increased unadjusted odds of all outcomes (p<0.001), except for ventricular tachycardia (p<0.618) and intubation (p< 0.214).

Conclusion:
Patients in the ACEI/ARB group demonstrated significantly lower mortality and increased hospitalization rates. Increased hospitalization may be due to more comorbidities. These results highlight the importance of continuing the use of ACEI and ARBs in COVID-19 patients for treatment of comorbidities and cardioprotective effects.
Abstract P261: Is Hypertension A Clinically Important Independent Risk Factor For Critical Illness In Covid-19?
Authors: Katsouli Anthi , Gazi Sadia , Marfia Paula , Lee Helen , Qazi Sameer , Komorowski Monica , Bertino Ann-Marie , Joshi Neeraj
Published: August 2021

Reports from major COVID-19 epicenters revealed higher morbidity and mortality rates among patients with a history of hypertension, coronary artery disease, diabetes mellitus, chronic kidney disease, and obesity. A large US study of 5,700 hospitalized patients with COVID-19 revealed an overall hypertension rate of 56%. Evidence from meta-analysis suggested that hypertension was independently associated with a significantly increased risk of critical COVID-19. The link between hypertension and COVID-19 is unclear and severity of COVID-19 illness is skewed towards the elderly population who have a higher prevalence of hypertension and number of comorbidities. A cohort of 661 positive COVID patients admitted to the Loyola hospital from 3/11/2020 to 10/12/2020 was used to validate previously published results with the composite outcome of ‘critically ill’, defined as invasive ventilation, ICU admission, or in-hospital death. The proportions of hypertension in critical COVID-19 were 77% when compared with 69% of noncritical COVID-19 patients (p 0.022), the proportion of CVD (cardiovascular heart disease) was 72% and 64% respectively (p 0.036) and diabetes was 50% and 42% respectively (p 0.029). Obesity and chronic kidney disease did not meet statistical significance as independent variables. The mean systolic pressure on admission was about the same 128 and 120 for critical ill and non critical ill respectively with p 0.864. All statistical analyses were performed using SAS 9.4 (Cary, NC). Two-sided p-values of <0.05 were deemed statistically significant. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for development of predictor risk score. LASSO identified 8 variables for a multivariable model (HR, SBP, SPO2<90%, Fever, LDH, Ferritin, D-dimer).In the multivariable model: SpO2 <90, fever at admission, and increasing LDH were found to be statistically associated with our outcome. This multivariable model resulted in an AUC of 0.71 (95% CI: 0.67, 0.74) which was increased to 0.73 by adding age and number of comorbidities. In our study, the prevalence of hypertension was higher but age and number or comorbidities are important variables that when used in a multivariable logistic regression model increased the AUC.
Abstract P265: Hypertension, Vascular Dysfunction And Downregulation Of The Renin Angiotensin System Sequelae Of COVID-19
Authors: McCallum Linsay , Lip Stefanie , Rios Francisco J , Neves Karla B , Kilmartin Jason , Murray Eleanor , Reetoo Salil , Knox Laura , Rostron Maggie , Lucas-herald Angela , du Toit Clea , Guzik Tomasz J , Delles Christian , Montezano Augusto C , Dominiczak Anna F , Padmanabhan Sandosh , Touyz Rhian M
Published: August 2021

Hypertension, vascular dysfunction and downregulation of the renin angiotensin system as sequelae of COVID-19

The long-term CV consequences of COVID are unknown however the potential for ongoing cardiac and vascular inflammation with RAAS alteration may increase the risk of developing hypertension and CV disease. Non-hypertensive patients hospitalised in April-May 2020 with either confirmed COVID19 (cases) or non-COVID (controls) diagnosis were recruited ≥12 weeks post-discharge. All underwent detailed BP and vascular/immune and RAAS phenotyping. The primary outcome was ABPM 24-hr SBP. Paired t-tests and multivariable regression models used to assess differences. Thirty cases and eighteen controls completed the study. Cases were older (51±7
vs
45±9 years) with lower discharge SBP (121±10 vs 128±15 mmHg; p0.01). ABPM at study visit was higher in the cases compared to controls (24-hour SBP (OR[95%CI]: 8.6[0.9-16.3]; p0.03), day-time SBP (8.6[1.5-17.3]; p0.02), day-time DBP (4.6[0.1-9.1]; p<0.05). Paired analysis of office BP showed a 11 mmHg difference between cases and controls (11.5[3.12];19.8; p=0.008; figure) Cases had lowerRenin and Ang-1-10 levels (-0.4[-0.9-0.1]; p0.08; -0.7[-1.2- -0.1]; p0.02 respectively) and higher TNF-alpha (0.5[0.1-0.9]; p0.01). Confirmed COVID requiring hospitalisation is associated with elevated SBP, reduced renin and Ang-1-10 and elevated TNF-alpha at ≥12 weeks post-discharge.
Abstract P269: Influence Of Sex, Race, And Changes In Vital Signs In Covid-19 And Flu Diagnosed Patients In Mississippi
Authors: Martin Brigitte E , Garrett Michael R
Published: August 2021

Early detection of viral infections, such as COVID-19 and flu, have the potential to reduce risk of morbidity, mortality, and disease transmission through earlier intervention strategies. Distinguishing patterns among vital signs, including body temperature, pulse rate, respiration rate, and blood pressure, can help to diagnose a potential respiratory virus more rapidly and accurately. The objective of this study was to utilize the University of Mississippi Medical’s extensive clinical database (EPIC) to investigate the potential association between temperature, pulse rate, blood pressure, and respiration with influenza and COVID-19. COVID-19 (March 3, 2020 to February 27, 2021) and flu (October 1, 2017 to September 30, 2018) diagnosed patients were identified from over 1 million patients (of a total population of 3 million) and 36 million encounters of Mississippi residents from the electronic health record. Data from patients with reported demographic dimensions (age, first race, and sex) and office visit dimensions (BMI, diastolic blood pressure (BP), pulse rate, respiration rate, systolic BP, and temperature) was obtained for 1,363 COVID-19 and 507 flu diagnosed patients, including day of diagnosis and additional encounter visits within 60 days before and after first unique viral disease diagnosis. Patients with COVID-19 or flu were disproportionately obese, with 93% of COVID-19 and 79% of flu patients with BMI ≥30. Most striking was that black women in 50-64 years disproportionately carried the burden of disease. For all patients at the time of infection, temperature was significantly increased for both respiratory viruses, pulse rate was significantly increased for flu, and BP was not significantly increased in either infection. We compared flu patients with no pre-existing diagnoses (n= 57) to those with essential (primary) hypertension (n= 234) and found significantly higher systolic BP at day of infection in flu only patients. Our findings show the need for more complete demographic and office visit dimension data from patients during epidemic and pandemic events.
Abstract P282: Time Restricted Feeding In Mice On A Chronic High Fat Diet Leads To Reduced Aortic Damage And Oxidative Stress
Authors: Edell Claudia , Pati Paramita , De Miguel Carmen , Colson Jackson , Davis Gwendolyn , Madhur Meena , Bailey Shannon , Gamble Karen , Pollock David M , Pollock Jennifer
Published: August 2021

Diet-induced obesity is associated with an increased risk of developing cardiovascular disease (CVD)
.
Aortic damage and stiffness are critical risk factors for CVD progression, especially with chronic high fat diet (HFD). Mice fed HFD
ad libitum
have increased food intake during the inactive period. We previously showed that HFD leads to significantly reduced blood pressure (BP) dipping and that time restricted food availability to the active period (TRF) in the final 2 weeks of HFD restores BP dipping. Thus, we hypothesized that TRF will reduce aortic damage and stiffness in chronic HFD mice. Utilizing this same mouse model of
ad libitum
chronic HFD (20 weeks 45% fat diet, male C57Bl6/J mice) compared to normal fat diet (NFD, 10% fat) and TRF intervention (food during lights off active period only from weeks 18-20), we determined aortic fibrosis and stiffness. By histological staining and quantitative analysis of the fibrosis area, HFD+TRF mice had significantly reduced fibrosis compared to HFD mice (% fibrosis per area, NFD: 143, NFD+TRF: 132, HFD: 175, HFD+TRF: 105, 2-way ANOVA, TRF effect: p=0.02). Aortic stiffness was measured by pulse wave velocity (PWV, Vevo 3100). We found that HFD fed mice have a significant increase in PWV compared to NFD group with no significant difference in the HFD+TRF and NFD+TRF groups compared to the NFD group (PWV m/sec, NFD: 1.60, NFD+TRF: 1.5, HFD: 2.30, HFD+TRF: 1.70, 2-way ANOVA, diet effect: p=0.02). We further analyzed plasma sE-selectin (endothelial-specific damage marker) and 8-isoprostane (oxidative stress marker) in HFD and HFD+TRF mice. Plasma from HFD+TRF mice showed significantly reduced sE-selectin and 8-isoprostane compared to HFD mice (sE-selectin ng/ml, HFD: 3.50, HFD+TRF: 1.85, p=0.027; 8-isoprostane ng/ml, HFD: 159.1, HFD+TRF: 59.6, p=0.008). Thus, TRF in chronic HFD mice leads to reduced endothelial injury and oxidative stress that is correlated with reduced aortic fibrosis and stiffness compared to
ad libitum
HFD mice. This study highlights that restricting the time of food intake in a model of diet-induced obesity minimizes CVD risk by reducing aortic damage and oxidative stress.
Abstract P285: Aging In Male Mice Is Characterized By Arterial Stiffening And Diastolic Dysfunction
Authors: Ogola Benard O , Visniauskas Bruna , Kilanowski-doroh Isabella , Abshire Caleb M , Horton Alec , Diaz Zaidmara , Laradji Murad , Zimmerman Margaret , Lindsey Sarah H
Published: August 2021

Aging is a nonmodifiable risk factor for cardiovascular mortality and is associated with arterial stiffening and cardiac dysfunction. In this study, we hypothesized that aging would decrease vascular compliance and cardiac function in male mice. Tail-cuff plethysmography was used to measure blood pressure, pulse wave velocity (PWV) for arterial stiffness, echocardiography for systolic and diastolic cardiac function, and wire myography for vessel reactivity in mature adult (25 weeks) and middle-aged (57 weeks) C57Bl/6 mice. Data was analyzed by t-test or 2-way ANOVA, and P<0.05 was considered significant. While there was no difference in blood pressure, PWV was higher in middle-aged male mice (1.8 ± 0.04 m/s vs. 1.2 ± 0.05 m/s; P<0.001) and associated with increased left ventricular (LV) posterior wall thickness (1.4 ± 0.07 mm vs. 1.1 ± 0.13 mm; P=0.03), and LV mass (172 ± 8 mg vs. 158 ± 20 mg; P=0.04). The ratio of early to late filling velocities, a measure of diastolic function, was lower in middle-age (1.6 ± 0.07 vs. 2.7 ± 0.37; P<0.001). Carotid artery histological analysis indicated that middle-aged mice had a greater collagen-to-elastin ratio along with decreased amounts of smooth muscle and thin collagen (P<0.05). Mesenteric artery contraction to PGF2α (446 ± 15% vs. 378 ± 14%; P=0.02) as well as relaxation to sodium nitroprusside (55 ± 7% vs. 31 ± 7%; P<0.01) were both blunted in the middle-aged group. The current study demonstrates that aging in male mice increases arterial stiffening and LV remodeling while decreasing diastolic and vascular function, independent of increased blood pressure. Future studies will investigate whether strategies that counteract arterial stiffness in the absence of changes in blood pressure can protect from cardiovascular aging.
Abstract T5: Molecular Mechanisms Involved In The Vascular Protective Effects Of Mas1 And Et
B
R Interaction
Authors: Kuriakose Jithin , Montezano Augusto C , Lopes Rheure , Sin Angie YY , Graham Delyth , Baillie George , Touyz Rhian M
Published: August 2021

We demonstrated that Mas1 and ET
B
R physically interact in endothelial cells inducing Ang-(1-7) vascular protection. Using high throughput screening of >20,000 druggable compounds, we identified a number of molecules that enhance Mas1:ET
B
R interactions. Of these, 2 potently enhanced interaction between the receptors. These enhancers (Enh), termed Enh3 and Enh4 were used to assess Mas1:ET
B
R interaction and cellular functional responses in vascular smooth muscle cells (VSMCs) from normotensive WKY and hypertensive SHRSP rats. Cells were exposed to Enh 3 and Enh4 (10
-5
M) for short (5,15 and 30min) and long timepoints (5hours). Expression of signaling molecules was assessed by immunoblotting and Ca
2+
influx was evaluated using fluorescence microscopy. In WKY VSMCs, Enh 3 short term stimulation reduced basal ERK1/2 phosphorylation (26.8±5.9% vs veh, p<0.01), an effect absent in SHRSP VSMCs, while Enh 4 had no effect. Short term exposure to Enh 4, but not Enh3, reduced basal MLC20 phosphorylation (54.9±7.5% vs veh, p<0.001) in WKY but not in SHRSP VSMCs. In SHRSP VSMCs, Enh 3, but not Enh4, reduced basal AKT phosphorylation (63.5±8.9% vs veh, p<0.001). Long term stimulation with Enh 3 reduced expression of AKT (38.0±2.0% vs veh, p<0.001), PCNA (60.0±7.0% vs veh, p<0.001), and VCAM-1 (35.0±8.0% vs veh, p<0.001) in WKY VSMCs. Similarly, AKT (35.0±12.0% vs veh, p<0.05) expression was reduced by Enh 3, with no effect on other markers in SHRSP VSMCs. Enh 4 long-term stimulation reduced AKT expression (30.0±10.0% vs veh, p<0.05) in WKY VSMCs, without effect on SHRSP VSMCs. ET-1 induced Ca
2+
influx in WKY and SHRSP VSMCs was unaffected by Enh3 and Enh4. In conclusion, enhancing Mas1:ET
B
R interaction attenuates mitogenic and pro-inflammatory signaling pathways in WKY and SHRSP VSMCs. Enhancing interaction between these receptors does not increase Ca
2+
signaling, important in VSMC contraction. Our data suggest that Enh3 and Enh4 may have VSMC protective effects and that they do not amplify injurious signaling induced by ET-1/ETBR. These findings identify a potential new strategy in vasoprotection.
Nomenclatural changes in some sea cucumbers with the erection of a new genus and description of a Thyone ?juvenile (?n. sp.) from the Gulf of California (Echinodermata:Holothuroidea:Dendrochirotida)
Authors: THANDAR AHMED S.
Published: August 2021

This paper includes several nomenclatural changes in dendrochirotid holothuroids, mostly based on materials from the USNM. These include the erection of a new genus Pseudostolus for two Indo-Pacific Stolus species [(S. kilberti Rajpal & Thandar, 1999 and S. rapax Koehler & Vaney (1908)], re-assignment of Havelockia uniannulatus (Sluiter, 1914), Thyone pseudofusus Deichmann 1930, T. parafusus Deichmann, 1941 and T. axiologa H.L. Clark, 1938, to the genus Stolus, and re-assignment of Havelockia nozawai (Mitsukuri, 1912) and Thyone adinopoda Pawson & Miller, 1981 to the genus Sclerothyone Thandar, 1989. In addition, a lectotype is designated for (T. vilis Sluiter, 1901), based on the study of type material at the ZMUA. The Caribbean Stolus cognatus is also described and commented on and a single, perhaps juvenile specimen from the Gulf of California is described as Thyone ? n. sp.
Cation Lipid-Assisted PEG6-PLGA Polymer Nanoparticles Encapsulated Knocking Down Long ncRNAs Reverse Non-Coding RNA of Xist Through the Support Vector Machine Model to Regulate the Molecular Mechanisms of Gastric Cancer Cell Apoptosis
Authors: Sun Zhengwang , He Zirui , Liu Rujiao , Zhang Zhe
Published: August 2021

Gastric adenocarcinoma (GAC) is one kind of gastric cancer with a high incidence rate and mortality. It is essential to study the etiology of GAC and provide theoretical guidance for the prevention and treatment of GAC. Bioinformatics was used via differential expression analysis, weighted
gene co-expression network analysis, gene set enrichment analysis, and a training support vector machine (SVM) model to construct a TSIX/mir-320a/Rad51 network as the research index of GAC disease. On the basis of CRISPR/Cas9 gene editing technology, the present study utilizes the Cation lipid-assisted
PEG-6-PLGA polymer nanoparticle (CLAN) drug carrier system to prepare the target knock-out TSIX drug with CRISPR/CaS9 nucleic acid. Knocking down lncRNA TSIX restored the suppression role of miR-320a on Rad51 and inhibited the Rad51 expression. Simultaneously, this ceRNA network activated
the ATF6 signaling pathway after endoplasmic reticulum stress to promote GAC cells’ apoptosis and inhibit the disease. TSIX/miR-320a/Rad51 network may be a potential biological target of GAC disease and provides a new strategy for treating GAC disease.
Long Non-Coding RNA OIP5-AS1 Inhibits the Proliferation and Migration of Esophageal Squamous Carcinoma Cells by Targeting FOXD1/miR-30a-5p Axis and the Effect of Micro- and Nano-Particles on Targeting Transfection System
Authors: Yan Qihang , Liu Li , Yang Han , Xu Chendi , Wang Zhen , Wang Qi , Wu Zixiang , Wu Chuanqiang , Dong Lingjun , Wang Junye , Wu Ming
Published: August 2021

Esophageal cancer is one of the most common human malignancies and ranks sixth for global mortality; the major histological type is esophageal squamous cell carcinoma (ESCC). Here we assessed the effect of long non-coding (lnc) RNA OIP5-AS1 on the miR-30a-5p/Forkhead box protein D1
(FOXD1) axis in ESCC and investigated the underlying mechanism involving the ERK1/2 signaling pathway. lnc RNA OIP5-AS1 was highly expressed in human ESCC tissues and cells, targeted miR-30a-5p, and inhibited miR-30a-5p expression. Additionally, in human ESCC tissues, miR-30a-5p was poorly
expressed, whereas FOXD1 mRNA and protein were highly expressed, with a negative correlation between miR-30a-5p and FOXD1 expression. miR-30a-5p targeted and inhibited FOXD1 expression. FOXD1 promoted the proliferation and invasion of ESCC and was related to the ERK1/2 signaling pathway; ERK1/2
inhibitors (LY-3214996) reversed the biological function of FOXD1. miR-30a-5p combined with FOXD1 regulated ERK1/2 expression and inhibited tumor growth in vivo. In this study, micro- and nano-particles were used as carriers to construct Nanocapsules carrying miR-30a-5p mimics and miR-30a-5p
inhibitor through self-assembly method, so as to realize an efficient Nanocapsules delivery system of miR-30a-5p to esophageal cancer cells. It provides insights into targeted drug therapy and the development of micro- and nano-particles carriers.
A Novel Indomethacin-Tripeptide Hydrogel for Inhibiting Ocular Inflammation
Authors: Zhang Zhiyong , Ma Xiaofang , Xia Tian , Wu Yuqin , Shi Shuai , Lei Lei , Li Xingyi , Chen Hao , Lin Deqing
Published: August 2021

A highly efficient method for constructing indomethacin-peptide conjugates was developed using the natural amino acid tyrosine (Y) as the anchor for indomethacin (Idm). With pH = 6, Idm-YEE conjugate self-assembled in a low critical micelle concentration (CMC, 0.037 mg/mL) and formed
a transparent hydrogel (0.4 wt%). The formed Idm-YEE hydrogel presented sustained drug release of indomethacin with a maximum of 40% during first 24 hours, which was superior to the reported Idm-containing supramolecular hydrogel systems. As kept at 4 °C, the Idm-YEE hydrogel showed good
storage stability up to 30 days without obvious hydrolysis. As shown by MTT assay, the Idm-YEE hydrogel exhibited good cell compatibility against retinal pigment epithelial cells (ARPE-19) and Human corneal epithelial cells (HCEC). Ocular irritation test (i.e., clinical observations, fluorescein
staining and H&E histological analysis) results showed good integrity of corneal architecture and no edema after Idm-YEE hydrogel treatment, which proved its good ocular biocompatibility. Besides, the LPS-stimulated levels of key inflammatory mediators, including NO, PGE2 and
IL-6, were greatly reduced by Idm-YEE hydrogel even in a low concentration (50 μM) in Raw264.7 cells, which indicated its comparable in vitro anti-inflammatory activity to indomethacin. Furthermore, the therapeutic efficacy of Idm-YEE hydrogel was evaluated in endotoxin-induced
uveitis (EIU) rabbit model. By treating with dm-YEE hydrogel, the rabbit eyes had significantly lowered inflammation and exudation in the anterior chamber. The results of histological analysis, clinical score, inflammatory cell counts, aqueous protein concentration and immunohistochemical
staining also demonstrated its good in vivo therapeutic activity towards ocular inflammation. Therefore, with good ocular biocompatibility and comparable anti-inflammatory effect towards ocular inflammation, the novel indomethacin-tripeptide hydrogel (Idm-YEE) developed in this work
provides a potential treatment for anterior uveitis.
Characterization and Biological Evaluation of Solid Dispersed Nanoparticles of Synthetic Epoksilignan Targeting Pancreatic Cancer Cell as an Anticancer Agent
Authors: Rifai Yusnita , Nurhaidah  , Tanggulungan Weltiansy , Rahman Latifah , Sartini  , Bhuyan Deep Jyoti
Published: August 2021

MMEO (3′-methoxy-3′,4″(methylenedioxy)-2,5-epoksilignan-4′ol-6-on) is a derivative of DMEO (3′-methoxy-3″,4″(methylenedioxy)-2,5-epoksilignan-4′,6-diol) synthesized through demethylation using dimethylsulfoxide-acetic anhydride reagent.
MMEO inhibits Hedgehog signaling at a concentration of 4.1 μM. The current study aimed to formulate MMEO as solid dispersed nanoparticles and determine their physicochemical properties and inhibitory activities. XRD (X-ray diffraction) analysis showed that the crystalline particles
of the pure compound MMEO was smaller than MMEO nanoparticles. Image J software showed that at concentrations of 25 mg/mL and 50 mg/mL, the average nanoparticle sizes were 852.26 nm and 178.65 nm, respectively. Therefore, the MMEO solid dispersion system with the PEG 4000 polymer increases
the solubility of MMEO. The higher the concentration of PEG 4000 the greater the solubility of MMEO. Treating pancreatic cancer cell lines with MMEO silenced the smoothened function by downregulating mRNA Ptch expression. This study suggests that MMEO may inhibit pancreatic cancer disease.
Demystifying Drought: Strategies to Enhance the Communication of a Complex Hazard
Authors: Ward Rebecca , Lackstrom Kirsten , Davis Corey
Published: August 2021

Drought is a complex phenomenon that is difficult to characterize and monitor. Accurate and timely communication is necessary to ensure that affected sectors and the public can respond and manage associated risks and impacts. To that end, myriad drought indicators, indices, and other tools have been developed and made available, but understanding and using this information can be a challenge for end users who are unfamiliar with the information or presentation or for decision-makers with expertise in areas outside of climate and drought. This article highlights a project that aimed to improve the usability and dissemination of drought information for North Carolina (NC) audiences by addressing specific needs for a better understanding of how drought is monitored, the climatic and environmental conditions that can cause or worsen drought, and the impacts occurring in NC’s different sectors and subregions. Conducted to support NC’s official, statewide drought monitoring process, the project’s methods and results have utility for other geographies and contexts. The project team designed an iterative process to engage users in the development, evaluation, refinement, and distribution of new resources. Featured products include the Weekly Drought Update infographic, which explains the factors used to determine NC’s drought status, and the Short-Range Outlook infographic, a synthesis of National Weather Service forecasts. Effective strategies included using stakeholders’ preferred and existing channels to disseminate products, emphasizing impacts relevant to different user groups (such as agriculture, forestry, and water resources) rather than indices, and employing concise narratives and visualizations to translate technical and scientific information.
Extreme rainfall events in the Northeastern USA become more frequent with rising temperatures, but their intensity distribution remains stable
Authors: Olafsdottir Helga Kristin , Rootzén Holger , Bolin David
Published: August 2021

Both intensities of individual extreme rainfall events and the frequency of such events are important for infrastructure planning. We develop a new statistical extreme value model, the PGEV model, which makes it possible to use high quality annual maximum series data instead of lesswell checked daily data to estimate trends in intensity and frequency separately. The method is applied to annual maxima data from the NOAA Atlas 14, Volume 10, dating from approximately 1900 to 2014, showing that in the majority of 333 rain gauge stations in the Northeastern USA the frequency of extreme rainfall events increases as mean temperature increases, but that there is little evidence of trends in the distribution of the intensities of individual extreme rainfall events. The median of the frequency trends corresponds to extreme rainfalls becoming 83% more frequent for each centigrade degree of temperature increase. Naturally, increasing trends in frequency also increase the yearly or 10-yearly risks of very extreme rainfall events. Three other large areas in the contiguous USA, the Midwest, the Southeast, and Texas, are also studied, and show similar but weaker trends than those in the Northeast.
Removing the Effects of Tropical Dynamics from North Pacific Climate Variability
Authors: Zhao Yingying , Newman Matthew , Capotondi Antonietta , Di Lorenzo Emanuele , Sun Daoxun
Published: August 2021

Teleconnections from the Tropics energize variations of the North Pacific climate, but detailed diagnosis of this relationship has proven difficult. Simple univariate methods, such as regression on El Niño-Southern Oscillation (ENSO) indices, may be inadequate since the key dynamical processes involved -- including ENSO diversity in the Tropics, re-emergence of mixed layer thermal anomalies, and oceanic Rossby wave propagation in the North Pacific -- have a variety of overlapping spatial and temporal scales. Here we use a multivariate Linear Inverse Model to quantify tropical and extra-tropical multi-scale dynamical contributions to North Pacific variability, in both observations and CMIP6 models. In observations, we find that the Tropics are responsible for almost half of the seasonal variance, and almost three quarters of the decadal variance, along the North American coast and within the subtropical front region northwest of Hawaii. SST anomalies that are generated by local dynamics within the Northeast Pacific have much shorter time scales, consistent with transient weather forcing by Aleutian low anomalies. Variability within the Kuroshio-Oyashio Extension (KOE) region is considerably less impacted by the Tropics, on all time scales. Consequently, without tropical forcing the dominant pattern of North Pacific variability would be a KOE pattern, rather than the Pacific Decadal Oscillation (PDO). In contrast to observations, most CMIP6 historical simulations produce North Pacific variability that maximizes in the KOE region, with amplitude significantly higher than observed. Correspondingly, the simulated North Pacific in all CMIP6 models is shown to be relatively insensitive to the Tropics, with a dominant spatial pattern generally resembling the KOE pattern, not the PDO.
Ototoxicity and Teprotumumab
Authors: Highland Julie , Gordon Steven , Reddy Deepika , Patel Neil
Published: August 2021

Objectives:

Teprotumumab, a novel monoclonal antibody, targets the insulin-like growth factor 1 (IGF-1) receptor. IGF-1 receptors, found in muscle and fat adjacent to the eye and implicated in Graves Ophthalmopathy, are also in the cochlea. In clinical trials, 5 participants reported self-limited audiologic symptoms but there are no objective data in the literature. The aim of this report is to describe one of the first known cases of teprotumumab-induced irreversible sensorineural hearing loss.

Methods:

Case report at a tertiary referral center

Results:

A 61 year old female with Graves ophthalmopathy presented with bilateral hearing loss, sound distortion, and tinnitus following treatment with teprotumumab. Audiogram showed mild sloping to moderately-severe sensorineural hearing loss. Repeat audiometry obtained 4 months after cessation of teprotumumab and treatment with oral corticosteroids was unchanged.

Conclusions:

This is one of the first descriptive cases of ototoxicity resulting in irreversible sensorineural hearing loss in the setting of treatment with teprotumumab. Periodic audiologic evaluations should be recommended to patients on teprotumumab.
Evidence-Based Practices and Implementation Science in Special Education
Authors: Cook Bryan G. , Odom Samuel L.
Published: August 2021

Establishing a process for identifying evidence-based practices (EBPs) in special education has been a significant advance for the field because it has the potential for generating more effective educational programs and producing more positive outcomes for students with disabilities. However, the potential benefit of EBPs is bounded by the quality, reach, and maintenance of implementation. The cross-disciplinary field of implementation science has great relevance for translating the promise of EBPs into positive outcomes for children and youth with disabilities. This article examines the history, extent, and limitations of EBPs and describes the emergence and current state of implementation science as applied in special education. Subsequent articles in this special issue of Exceptional Children address a range of issues related to implementation science in special education: the research-to-practice gap, dissemination and diffusion, adherence and sustainability, scaling up, a model for state-level implementation, and fostering implementation through professional development.
Balancing Fidelity with Flexibility and Fit: What do we Really Know about Fidelity of Implementation in Schools?
Authors: Harn Beth , Parisi Danielle , Stoolmiller Mike
Published: August 2021

Treatment fidelity, or the application of an intervention as it is designed, is a critical issue for the successful implementation of evidence-based practices. Typically it is assumed that evidence-based practices implemented with high fidelity will result in improved outcomes, whereas low fidelity will lead to poorer outcomes. These assumptions presume agreement across researchers and practitioners on what fidelity is, how to measure it, and what level of fidelity optimizes outcomes; however, there is no widespread agreement on any of these issues. This article discusses the dimensions and nuances of treatment fidelity as well as the implications for measuring and analyzing it in relation to student outcomes. The authors review research demonstrating the differential relationship of fidelity across schools, program type, and impact on student outcomes that special educators should consider when designing intervention studies and implementing evidence-based practices. Special educators should prioritize practices and programs with clearly identified components that are empirically validated yet designed flexibly to match various contexts and student populations. Suggestions to support schools in implementing and sustaining evidence-based practices are provided.
Intensive Grandmothering? Exploring the Changing Nature of Grandmothering in the Context of Changes to Parenting Culture
Authors: Harman Vicki , Cappellini Benedetta , Webster Michelle
Published: August 2021

This article explores the ways in which the intensification of parenting and the notion of children at risk have influenced grandmothers’ narratives and practices. Interviews with grandmothers who regularly look after their grandchildren, reveal that their practices are framed around the notions of children to be protected, educated and entertained. Such notions reveal that aspects of grandmothers’ roles as protectors, educators, playmates and confidants involved negotiations with parents around the ideal of ‘putting the child first’. The article argues that intensive parenting has influenced grandmothering but the way this is enacted reveals resistance to certain aspects of intensive parenting.
Durable flame retardant hybrid sol–gel coating on poly(ethylene terephthalate) fabric and its flame retardant mechanism
Authors: Wei Gu , Shuo Chang
Published: August 2021

In this paper, an organic/inorganic phosphorus and silicon-containing coating was prepared by the sol–gel method and its flame retardant mechanism for poly(ethylene terephthalate) (PET) fabrics was thoroughly investigated. The influence of hybrid coating on PET fabric was investigated by the limited oxygen index (LOI), vertical flammability test (VFT) and microscale combustion calorimetry (MCC). The results revealed that the LOI of the coated PET fabric was up to 29.2% and no dripping was observed in the VFT. MCC results showed that hybrid coating reduced the peak heat release rate, heat release capacity and total heat release of PET fabric. Thermogravimetric analysis demonstrated increased thermal stability and char residue of PET fabrics due to the hybrid coating. Furthermore, the char residues were studied by X-ray photoelectron spectroscopy and scanning electron microscopy. The above results proved that the synergistic effect between the 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide group and the silicon network played a key role in the flame retardancy of PET fabrics. In addition, the durability of coated PET fabrics was interpreted by calculating the interaction energy through molecular dynamics simulation.
Predictors of Retention and Recidivism of Justice-Involved Women in a Community-Based Gender-Responsive CBT Program
Authors: Zarling Amie , Scheffert Roxann , Russell Dan
Published: August 2021

The purpose of this study was to evaluate pretreatment differences between program completers and noncompleters, as well as those who recidivated and those who did not, among a sample of 112 justice-involved women referred to a gender-responsive cognitive-behavioral program as part of supervision recommendations. Risk scores, adverse childhood experiences, emotion dysregulation, self-control, and various demographic variables were examined as predictors of program completion and 1-year recidivism. Results of logistic regression indicated that higher risk scores significantly predicted program noncompletion and 1-year recidivism, and noncompleters were 6 times more likely to recidivate than completers. These findings reveal characteristics of women as they relate to the likelihood of completing criminal justice treatment programs, and indicate a greater need for intensive support among high-risk women.
The People’s Park: Investigating Different Forms of Ownership of Victoria Park (1840-1890)
Authors: Bellamy Victoria
Published: August 2021

This paper examines the management of London’s Victoria Park over a fifty-year period from when it was laid out at the beginning of the 1840s to 1890. It investigates questions raised by other recent studies about the relationship between public and private and between the individual and the population within public parks. This is achieved by a consideration of two separate but interlinked aspects of the park: its spatiality (its relationship to the city) and its functionality (its relationship to the individual). By examining these aspects, a palimpsest of different conceptions of Victoria Park can be uncovered, which in turn directly relate to the potential field of actions in the real space of the park.
Recruitment and retention of bilingual graduate students in school psychology: Efforts and challenges in increasing professional diversity
Authors: Ding Yi , Ridgard Tamique , Cho Su-Je , Wang Jiayi
Published: August 2021

The main goal of this paper is to illustrate recruitment efforts, strategies, and challenges in the process of training bilingual school psychologists to serve diverse schools. First, we address the acute and chronic shortage of bilingual school psychologists in the United States, particularly in urban schools where student populations are increasingly diverse. Then we provide a review of strategies and efforts to recruit and retain bilingual graduate-level learners in one school psychology program in an urban university. Quantitative data regarding recruitment and retention efforts are discussed. We identify challenges and future directions to increase diversity in the field of school psychology.
A digital platform for ethical advertising and hybrid business models for news organizations: are they greening methods for ‘news deserts’?
Authors: Sparviero Sergio
Published: August 2021

This article suggests that the adoption of hybrid business models coupled with the establishment of an ethical advertising platform could help counter the emergence of news deserts. The latter are geographic areas and policy issues lacking coverage because of the crisis of the commercial model of news provision. Three clusters of characteristics are used to streamline and compare business models: (1) revenue models, (2) patrons and their motives, and (3) legal frameworks for the incorporation of the organization. Hybrid business models are designed by mixing the principles underpinning the Benefit Corporation or the Low-profit Limited Liability Company (L3C), with the basic characteristics of commercial and non-profit news organizations. The term ethical advertising refers to promotional activities that non-profits and other organizations dedicated to social goals normally undertake, including marketing, fundraising, or public-awareness campaigns. Based on data published by the Internal Revenue Services, this article argues that a digital platform for ethical advertising could face a demand worth over $1 billion a year. Additionally, this platform could effectively match non-profits’ demand for an audience with a pro-social attitude with non-profit and hybrid news organizations’ need for additional revenue streams.
Ecocritical Analysis of Manto’s ‘Toba Tek Singh’: Re-Imaging Aesthetics of Place and Person
Authors: Singh Jeet
Published: August 2021

This in-depth analysis of the aesthetics of place and person in ‘Toba Tek Singh’, a famous short story by Saadat Hassan Manto, and a masterpiece of South Asian literature in English, presents a re-reading in the light of ecotheoretical concepts of ‘place’. It theorises how material space as ‘place’ is represented in literature and brings to light the hegemony of sociocultural discourses in relation to space, belittling its connection to nature. Ecotheory raises concerns of human and non-human life within the natural ecosystem of specific indigenous places. The protagonist of the story, Bishan Singh, ultimately also the namesake of a place, Toba Tek Singh, dies a terrible death while desperately searching for his native place. The article presents the story as a powerful literary attempt to re-imagine the places and spaces where we live and our relations to them.
Communities of Judges, Protection of Tribal Cultures, and the Principle of ‘Complete Justice’
Authors: Jena Aniruddha
Published: August 2021

Samarendra Das and Felix Padel, Out of This Earth: East India Adivasis and the Aluminium Cartel (Hyderabad: Orient BlackSwan, 2020), xxxii + 776 pp.
Outcomes and measures of delirium interventional studies in palliative care to inform a core outcome set: A systematic review
Authors: Agar Meera R , Siddiqi Najma , Hosie Annmarie , Boland Jason W , Johnson Miriam J , Featherstone Imogen , Lawlor Peter G , Bush Shirley H , Page Valerie , Amgarth-Duff Ingrid , Garcia Maja , Disalvo Domenica , Rose Louise ,   The Del-COrS Group
Published: August 2021

Background:

Trials of interventions for delirium in various patient populations report disparate outcomes and measures but little is known about those used in palliative care trials. A core outcome set promotes consistency of outcome selection and measurement.

Aim:

To inform core outcome set development by examining outcomes, their definitions, measures and time-points in published palliative care studies of delirium prevention or treatment delirium interventions.

Design:

Prospectively registered systematic review adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Data sources:

We searched six electronic databases (1980–November 2020) for original studies, three for relevant reviews and the International Clinical Trials Registry Platform for unpublished studies and ongoing trials. We included randomised, quasi-randomised and non-randomised intervention studies of pharmacological and non-pharmacological delirium prevention and/or treatment interventions.

Results:

From 13/3244 studies (2863 adult participants), we identified 9 delirium-specific and 13 non-delirium specific outcome domains within eight Core Outcome Measures in Effectiveness Trials (COMET) taxonomy categories. There were multiple and varied outcomes and time points in each domain. The commonest delirium specific outcome was delirium severity ( n = 7), commonly using the Memorial Delirium Assessment Scale (6/8 studies, 75%). Four studies reported delirium incidence. Non-delirium specific outcomes included mortality, agitation, adverse events, other symptoms and quality of life.

Conclusion:

The review identified few delirium interventions with heterogeneity in outcomes, their definition and measurement, highlighting the need for a uniform approach. Findings will inform the next stage to develop consensus for a core outcome set to inform delirium interventional palliative care research.
Power in a minor key: Rethinking anthropological accounts of power alongside London’s community organisers
Authors: Samanani Farhan
Published: August 2021

Anthropological accounts of power remain characterized by an enduring tension. Social scientific theories of power allow anthropologists to situate subjects and mediate between contending perspectives. However, in doing so, such theories inevitably also end up displacing the grounded perspective of interlocutors themselves. This tension sustains a contentious debate, which positions attention to power and attention to grounded perspectives in opposition. In this article I draw on ethnography conducted with the UK’s largest community organising body, Citizens UK, to trace an alternative approach to this tension. For Citizens UK organisers this tension becomes a way of driving change by enrolling diverse actors in collective projects and by displacing hegemonic understandings from within. Good theories, for Citizens UK organisers, are characterised by the practical ability to mediate between contending positions and, in doing so, transform them. To make sense of this mode of theorisation I take up queer theorist Jack Halberstam’s notion of ‘low theory’, geographer Cindi Katz’s notion of ‘minor theory’, and I draw on the linguistic anthropology notion of ‘register’. This allows me to unpack how organisers use theory to act, but also to trouble established anthropological understandings of what theory is and what it ought to do.
Introduction: Ethnographies of power and the powerful
Authors: Archer Matthew , Souleles Daniel
Published: August 2021

This introduction suggests that anthropology often assumes that the people anthropologists work with are relatively powerless. Due to this default, anthropologists tend to design their research and theorizing to reflect a relatively powerless other. We suggest that the accumulated scholarship on studying up, that is, studying those who structure the lives of many others, offers more accurate ways to theorize power and its exercise as partial and situated, as well as more plural and productive ways to imagine anthropological practice and ethics. We also suggest that this line of thinking gives us some ground to speak to the larger direction of the discipline.