bluuebunny/crossref_metadata_2025 huggingface dataset:
Aspirin use predicts prolonged survival in patients with oropharyngeal cancer: Nationwide Veterans Affairs database study
Authors: Clark Christine M. , Newark Annemarie C. , Fokar Ali , Maxwell Jessica H.
Published: September 2020

Background

Single‐institution studies suggest that aspirin reduces the risk of death in head and neck cancer. The aim of this study was to investigate the effect of aspirin use on overall survival (OS) in veterans with oropharyngeal cancer (OPC).

Methods

A total of 23 083 veterans with OPC were identified between 2005 and 2018 from the Veterans Health Administration Corporate Data Warehouse. Records were queried for clinical‐demographic data, aspirin prescriptions, and outcomes. Three‐year OS was estimated. A Cox model was used to estimate hazard ratios (HR) for aspirin use.

Results

Among the 23 083 identified veterans, 17 206 veterans met inclusion criteria. 21.8% used aspirin. Three‐year OS was prolonged for aspirin users (66%) compared to nonaspirin users (54%; P < .001). Adjusted HR for death for nonaspirin users was 1.75 (95% confidence interval (CI) [1.60‐1.91]). The average treatment effect of aspirin on survival using inverse probability weighting was 10% (95% CI [0.08‐0.11]).

Conclusion

Aspirin use following OPC diagnosis was independently associated with improved 3‐year OS among veterans nationwide.
Twin reversed arterial perfusion sequence: A case report
Authors: Yi Jiao , Wu Xiumei
Published: September 2020

Synopsis

The present study reports a case of twin reversed arterial perfusion syndrome with spontaneous interruption of blood supply in the acardiac twin.
Application of a monitoring and evaluation method in irrigation water efficiency*
Authors: Baoqing Feng , Jing Cui , Qianming Wu , Zhenzhong Han
Published: September 2020

Water‐saving irrigation is of high priority in China for alleviation of the water resource supply–demand contradiction. Consequently, the objectives of irrigation water efficiency (IWE) are specified in policies at the macro scale such as national economic and social development programmes and national evaluation systems of water resources management. To scientifically evaluate IWE and water‐saving irrigation efficiency and to overcome the limitations of traditional IWE evaluation methods (e.g. numerous steps and not very practical), this study presents a normative and easy‐to‐use measurement and analysis method for IWE, specifically, head and end measurement. An IWE monitoring network, comprising more than 3700 irrigation districts on national and regional scales, was developed to dynamically monitor the variation in IWE of sample irrigation districts of different sizes and types from 2008 to 2018. The monitoring results provide technical support and scientific evidence for the formulation of water conservation policies and management at the macro scale of the water conservation sector. © 2020 John Wiley & Sons, Ltd.
Environmental cadmium exposure and noncancer mortality in a general Japanese population in cadmium nonpolluted regions
Authors: Suwazono Yasushi , Nogawa Kazuhiro , Sakurai Masaru , Watanabe Yuuka , Nishijo Muneko , Ishizaki Masao , Morikawa Yuko , Kido Teruhiko , Nakagawa Hideaki
Published: September 2020

The objective of this study was to assess the effect of environmental cadmium exposure according to urinary cadmium concentration (U‐Cd) on noncancer mortality in a general Japanese population. We conducted a longitudinal study for 19 years in 2804 inhabitants (1107 men and 1697 women) in some cadmium nonpolluted regions in Japan. The participants were classified into quartiles based on U‐Cd (μg/g cre) adjusted for urinary creatinine. Hazard ratio (HR) and 95% confidence interval (95% CI) for continuous U‐Cd or the quartiles of U‐Cd were calculated for noncancer mortality. By applying a Fine and Gray competing risk model, continuous U‐Cd (+1 μg/g cre) showed significant HR for cardiocerebrovascular diseases (HR 1.05, 95% CI: 1.00–1.11), cerebrovascular diseases (HR 1.08, 95% CI: 1.01–1.16), and cerebral infarction (HR 1.11, 95% CI: 1.04–1.20) in men. However, notable significant HR for continuous and quartered U‐Cd were not observed in women. In this study, U‐Cd was associated with increased cardiocerebrovascular mortality in a general Japanese population, suggesting that environmental cadmium exposure is detrimental to the life prognosis in cadmium nonpolluted regions in Japan.
Inhibition of Class IIa HDACs improves endothelial barrier function in endotoxin‐induced acute lung injury
Authors: Kovacs‐Kasa Anita , Kovacs Laszlo , Cherian‐Shaw Mary , Patel Vijay , Meadows Mary L. , Fulton David J. , Su Yunchao , Verin Alexander D.
Published: September 2020

Acute lung injury (ALI) is an acute inflammatory process arises from a wide range of lung insults. A major cause of ALI is dysfunction of the pulmonary vascular endothelial barrier but the mechanisms involved are incompletely understood. The therapeutic potential of histone deacetylase (HDAC) inhibitors for the treatment of cardiovascular and inflammatory diseases is increasingly apparent, but the mechanisms by which HDACs regulate pulmonary vascular barrier function remain to be resolved. We found that specific Class IIa HDACs inhibitor, TMP269, significantly attenuated the lipopolysaccharide (LPS)‐induced human lung microvascular endothelial cells (HLMVEC) barrier compromise in vitro and improved vascular barrier integrity and lung function in murine model of ALI in vivo. TMP269 decreased LPS‐induced myosin light chain phosphorylation suggesting the role for Class IIa HDACs in LPS‐induced cytoskeleton reorganization. TMP269 did not affect microtubule structure and tubulin acetylation in contrast to the HDAC6‐specific inhibitor, Tubastatin A suggesting that Class IIa HDACs and HDAC6 (Class IIb) regulate endothelial cytoskeleton and permeability via different mechanisms. Furthermore, LPS increased the expression of ArgBP2 which has recently been attributed to HDAC‐mediated activation of Rho. Depletion of ArgBP2 abolished the ability of LPS to disrupt barrier function in HLMVEC and both TMP269 and Tubastatin A decreased the level of ArgBP2 expression after LPS stimulation suggesting that both Class IIa and IIb HDACs regulate endothelial permeability via ArgBP2‐dependent mechanism. Collectively, our data strongly suggest that Class IIa HDACs are involved in LPS‐induced ALI in vitro and in vivo via specific mechanism which involved contractile responses, but not microtubule reorganization.
Analyzing the shear‐induced sensitization of mechanosensitive ion channel Piezo‐1 in human aortic endothelial cells
Authors: Lai Austin , Chen Yung C. , Cox Charles D. , Jaworowski Anthony , Peter Karlheinz , Baratchi Sara
Published: September 2020

Mechanosensitive ion channels mediate endothelial responses to blood flow and orchestrate their physiological function in response to hemodynamic forces. In this study, we utilized microfluidic technologies to study the shear‐induced sensitization of endothelial Piezo‐1 to its selective agonist, Yoda‐1. We demonstrated that shear stress‐induced sensitization is brief and can be impaired when exposing aortic endothelial cells to low and proatherogenic levels of shear stress. Our results suggest that shear stress‐induced sensitization of Piezo‐1 to Yoda‐1 is independent of cell–cell adhesion and is mediated by the PI3K‐AKT signaling pathway. We also found that shear stress increases the membrane density of Piezo‐1 channels in endothelial cells. To further confirm our findings, we performed experiments using a carotid artery ligation mouse model and demonstrated that transient changes in blood‐flow pattern, resulting from a high‐degree ligation of the mouse carotid artery alters the distribution of Piezo‐1 channels across the endothelial layer. These results suggest that shear stress influences the function of Piezo‐1 channels via changes in membrane density, providing a new model of shear‐stress sensitivity for Piezo‐1 ion channel.
Ten‐m/Odz3 regulates migration and differentiation of chondrogenic ATDC5 cells via RhoA‐mediated actin reorganization
Authors: Takano Ikuko , Takeshita Nobuo , Yoshida Michiko , Seki Daisuke , Oyanagi Toshihito , Kimura Seiji , Jiang Wei , Sasaki Kiyo , Sogi Chisumi , Kawatsu Masayoshi , Takano‐Yamamoto Teruko
Published: September 2020

Tenascin‐like molecule major (Ten‐m)/odd Oz (Odz), a type II transmembrane molecule, is well known to modulate neural development. We have reported that Ten‐m/Odz3 is expressed in cartilaginous tissues and cells. Actin cytoskeleton and its regulator ras homolog gene family member A (RhoA) are closely associated with chondrogenesis. The present study aimed to evaluate the function and molecular mechanism of Ten‐m/Odz3 during chondrogenesis, focusing on RhoA and the actin cytoskeleton. Ten‐m/Odz3 was expressed in precartilaginous condensing mesenchyme in mouse limb buds. Ten‐m/Odz3 knockdown in ATDC5 induced actin cytoskeleton reorganization and change of cell shape through modulation of RhoA activity and FGF2 expression. Ten‐m/Odz3 knockdown suppressed ATDC5 migration and expression of genes associated with chondrogenesis, such as Sox9 and type II collagen, via RhoA. On the other hand, Ten‐m/Odz3 knockdown inhibited proliferation of ATDC5 in a RhoA‐independent manner. These findings suggest that Ten‐m/Odz3 plays an important role in early chondrogenesis regulating RhoA‐mediated actin reorganization.
The oncogenic potential of NANOG: An important cancer induction mediator
Authors: Najafzadeh Basira , Asadzadeh Zahra , Motafakker Azad Rohollah , Mokhtarzadeh Ahad , Baghbanzadeh Amir , Alemohammad Hajar , Abdoli Shadbad Mahdi , Vasefifar Parisa , Najafi Souzan , Baradaran Behzad
Published: September 2020

Cancer stem cells (CSCs) are a unique population in the tumor, but they only comprise 2%–5% of the tumor bulk. Although CSCs share several features with embryonic stem cells, CSCs can give rise to the tumor cells. CSCs overexpress embryonic transcription factor NANOG, which is downregulated in differentiated tissues. This transcription factor confers CSC's stemness, unlimited self‐renewal, metastasis, invasiveness, angiogenesis, and drug‐resistance with the assistance of WNT, OCT4, SOX2, Hedgehog, BMI‐1, and other complexes. NANOG facilitates CSCs development via multiple pathways, like angiogenesis and lessening E‐cadherin expression levels, which paves the road for metastasis. Moreover, NANOG represses apoptosis and leads to drug‐resistance. This review aims to highlight the pivotal role of NANOG and the pertained pathways in CSCs. Also, this current study intends to demonstrate that targeting NANOG can dimmish the CSCs, sensitize the tumor to chemotherapy, and eradicate the cancer cells.
Glucagon‐like peptide 2 attenuates intestinal mucosal barrier injury through the MLCK/pMLC signaling pathway in a piglet model
Authors: Chang Yaqi , Deng Qiuhong , Zhang Zhenyu , Zhao Hua , Tang Jiayong , Chen Xiaoling , Liu Guangmang , Tian Gang , Cai Jingyi , Jia Gang
Published: September 2020

Glucagon‐like peptide‐2 (GLP‐2), an intestinotrophic hormone, has drawn considerable attention worldwide due to its potential to promote intestinal development. We investigated the effects and mechanisms of GLP‐2 against lipopolysaccharide (LPS)‐induced intestinal inflammation and injury both in vitro and in vivo. Forty healthy piglets weaned at the age of 28 days with similar body weight (BW) were assigned to four in vivo treatments with ten piglets each: (i) nonchallenged control; (ii) LPS‐challenged control; (iii) LPS + low dose GLP‐2; and (iv) LPS + high dose GLP‐2. Piglets were subcutaneously injected with phosphate‐buffered saline supplemented with GLP‐2 at doses of 0, 0, 2, and 10 nmol/kg BW per day for seven consecutive days. The piglets were challenged with an intraperitoneal injection with 100 μg/kg LPS on day 14 to induce intestinal damage. After that, the gene and protein expression levels of representative tight junction proteins and myosin light‐chain kinase (MLCK)/phosphorylated myosin light chain (pMLC), as well as proinflammatory cytokine levels were determined using quantitative reverse transcription polymerase chain reaction, western blot, and enzyme‐linked immunosorbent assay methods. A high dose of GLP‐2 pretreatment increased intestinal permeability by downregulating and redistributing tight junction proteins (p < .05), for example, zona occluden‐1 (ZO‐1) and occludin. GLP‐2 decreased the transcription of proinflammatory cytokines genes including interleukin‐1β (IL‐1β), IL‐6, IL‐8, and tumor necrosis factor‐α in small intestines (p < .05). GLP‐2 prevented the LPS‐induced increase in the expression of MLCK dose‐dependently and the increase in pMLC levels in the duodenum, jejunum, and ileum. To assess further the protective effect of GLP‐2 on LPS‐induced intestinal barrier injury after weaning and its possible mechanism, an in vitro intestinal epithelial barrier model was established with IPEC‐J2 monolayers and treated with 100 μg/ml LPS with or without 1 × 10−8 mol/L GLP‐2 pretreatment. The in vitro analysis included control, LPS, and GLP‐2 + LPS treatments. GLP‐2 treatment alleviated the destructive effect of LPS on barrier permeability by restoring the expression and ultrastructure of ZO‐1 and occludin (p < .05). In addition, GLP‐2 reversed the LPS‐induced MLCK hyperexpression and pMLC hyperphosphorylation (p < .05). Taken together, our findings revealed a mechanism by which GLP‐2 alleviated LPS‐challenged intestinal barrier injury and inflammation in weaned piglets and IPEC‐J2 cells via the MLCK/pMLC signaling pathway.
Nigerian undergraduate dental students’ knowledge, perception, and attitude to COVID‐19 and infection control practices
Authors: Umeizudike Kehinde Adesola , Isiekwe Ikenna Gerald , Fadeju Adeyemi Dada , Akinboboye Bolanle Oyeyemi , Aladenika Emmanuel Temitope
Published: September 2020

Purpose/objectives

The current coronavirus disease 19 (COVID‐19) pandemic has affected most countries. Infection, Prevention, and Control training is important in mitigating the spread of COVID‐19. The closure of universities by the Nigerian government has hampered academic activities of dental students. Our objectives were to assess the knowledge, perception, and attitude of undergraduate dental students in Nigeria to the COVID‐19 pandemic and infection control practices.

Methods

This was a cross‐sectional study of undergraduate clinical dental students from the dental schools in Nigeria. Self‐administered questionnaires were distributed to participants using an online data collection platform. Correct responses to the 45‐item questionnaire on COVID‐19 knowledge were scored to determine their knowledge level. A Likert scale of 1‐5 was used to assess the 13‐item perception and attitude questions. The level of significance was set at P values ≤ 0.05.

Results

A total of 102 undergraduate clinical dental students participated in the study. Males represented 54.9%, and mean age was 25.3 ± 2.4 years. Fifty percent of the students had adequate knowledge of COVID‐19. Final‐year students (58.1%) demonstrated more adequate knowledge of COVID‐19 than penultimate‐year students (28.6%, P = 0.008). Most (95.1%) respondents had positive attitudes towards infection control practices against COVID‐19.

Conclusion

Although the clinical dental students had a positive attitude to infection control practices against COVID‐19, the overall knowledge of COVID‐19 was barely adequate. Guidelines on COVID‐19 from reputable health authorities should be reviewed by dental school authorities and disseminated to the students to suit their clinical practice.
Intrinsic physicochemical interactions of calcium hydroxide‐based medications
Authors: Uslu Okan , Dikmen Gokhan , Orhan Ekim Onur
Published: September 2020

To investigate intrinsic physicochemical properties and interactions of three different calcium hydroxide‐based medications via means of different analytical methods. Two‐commercial premixed medications: TempCanal(TCmx) and ProCalR(PCmx) and powder‐form ProCal(PCpw) with glycerin were used. Vibrational modes were analyzed using Raman spectroscopy. Spectral mapping of samples was carried out using characteristic vibrational modes of calcium hydroxide and barium sulfate. Crystalline and amorphous phases were studied with X‐rays powder diffraction analysis. Topographic features were examined by scanning electron microscope examination and quantitative analysis was determined using energy‐dispersive X‐ray spectroscopy analysis. Strong OH stretch of in Raman spectra were observed at 3,697 and 3,615 cm−1 for TCmx and reference, respectively. However, OH mode was not observed for PCmx and PCpw. Moreover, some peaks in the fingerprint areas of TCmx and PCpw overlapped with each other. The characteristic vibration bands of barium sulfate and calcium hydroxide were observed in all samples, and no new peak was observed in the Raman spectra of samples. Calcium hydroxide‐based medications were seen as differed in their chemical composition. No new crystalline or amorphous phase peak was observed. Only calcium hydroxide and barium sulfate were matched in X‐rays powder‐diffraction analysis. Energy‐dispersive X‐ray spectroscopy analysis showed that amount of Ba and S elements in the PCpw were lower than TCmx and PCmx whereas, for Ca in the PCpw was higher than TCmx and PCmx. The present study revealed the structural difference among different forms of calcium hydroxide‐based medications. The vehicle and substrates of the tested medications altered the physicochemical properties of the compound via electrostatic interactions.
Glucocorticoids, energy metabolites, and immunity vary across allostatic states for plateau side‐blotched lizards (Uta stansburiana uniformis) residing in a heterogeneous thermal environment
Authors: Hudson Spencer B. , Lidgard Audrey D. , French Susannah S.
Published: September 2020

Reptiles rely on thermal heat exchange to achieve body temperatures (Tbody) conducive to maintaining homeostasis. Diurnal changes in the thermal environment are therefore liable to influence allostatic mediation of survival processes (e.g., immunity) during environmental challenges or stressors. However, the extent to which Tbody prompts individual variation in physiology remains largely unexplored in reptiles. Our study tested how circulating energy‐mobilizing hormone, energy metabolites, and immunity can vary across basal and stress‐induced allostatic states for plateau side‐blotched lizards (Uta stansburiana uniformis) residing in a heterogeneous thermal environment. We collected baseline and acute stress blood samples from male lizards to compare changes in plasma corticosterone (CORT), glucose, and bacterial killing ability (BKA) in relation to each other and Tbody. We hypothesized each physiological parameter differs between allostatic states, whereby stress‐induced activity increases from baseline. At basal and stress‐induced states, we also hypothesized circulating CORT, glucose, and BKA directly correspond with each other and Tbody. We found both CORT and BKA increased while glucose instead decreased from acute stress. At basal and stress‐induced allostatic states, we found CORT to be directly related to Tbody while BKA was inversely related to CORT. We also found BKA and glucose were directly related at baseline, but inversely related following acute stress. Overall, these results demonstrate allostatic outcomes from acute stress in a free‐living reptile and the role of temperature in mediating energetic state and immunity. Future research on reptilian allostasis should consider multiple environmental conditions and their implications for physiological performance and survival.
An impact of dietary intervention on blood pressures among diabetic and/or hypertensive patients with high cardiovascular disorders risk in northern Thailand by cluster randomized trial
Authors: Yokokawa Hirohide , Yuasa Motoyuki , Nedsuwan Supalert , Moolphate Saiyud , Fukuda Hiroshi , Kitajima Tsutomu , Minematsu Kazuo , Tanimura Susumu , Marui Eiji
Published: September 2020

Background

Global sodium intake remains above the recommended levels to control blood pressure (BP). We aimed to evaluate the efficacy of a dietary intervention on BP through salt reduction among community‐dwelling participants with high risk of cardiovascular disorders (CVD).

Methods

This cluster randomized trial (February 2012 to January 2013) included cooking instruction using the pocket salt meter among patients with diabetes and/or hypertension who were treated at health center in Thailand. Based on health centers, 8 clusters of eligible participants were randomly allocated to the 4 intervention and 4 control groups. Dietary intervention was performed at baseline, 1 month, and 3 months in intervention group. In both groups, systolic and diastolic BPs, and estimated 24 hours salt intake based on overnight urine samples were measured at baseline, 6 months, and 12 months.

Results

A total of 753 participants were enrolled (374 in the intervention group and 379 in the control group). In the mixed‐effects model, there were significant difference in SBP and estimated salt intake after adjusting covariates at 6 months (adjusted differences between groups [95% CI]; −7.55 [−5.61 to −9.49] mm Hg P < .01; −0.66 [−0.40 to −0.92] g/day P = .03). However, these differences were not observed at 12 months (adjusted differences between groups [95% CI]; −1.83 [0.34 to −4.00] mm Hg P = .48; −0.42 [−0.17 to −0.67] g/day P = .16). There were no differences in DBP in both follow‐ups.

Conclusions

These results may suggest the effectiveness of a visually based dietary intervention targeting salt intake reduction in short term, but the effectiveness discontinued in long term.

Clinical trial number: The International Standard Randomized Controlled Trial Number Register (ISRCTN39416277) on January 3, 2012.
Prevalence, risk factors, and healthcare‐seeking among subjects with esophageal symptoms: A community‐based study in a rural Bangladeshi population
Authors: Rahman M. Masudur , Ghoshal Uday C , Kibria Md. Golam , Sultana Nigar , Ahmed Faruque , Rowshon AHM , Hasan Mahmud
Published: September 2020

Background and Aim

As there is a scarcity of data on overall prevalence, risk factors, and health‐care utilization of esophageal symptoms using the Rome criteria in the rural population in Asia, we undertook a study with the aims to evaluate: (i) the prevalence of heartburn, chest pain, globus, and dysphagia of presumed esophageal origin; (ii) the prevalence of functional esophageal disorders by Rome III criteria; (iii) the risk factors for esophageal symptoms; and (iv) the health‐care utilization.

Methods

This door‐to‐door survey was conducted in three villages (Charcharia, Churain of Dhaka district, and Kharrah of Munshiganj district of Bangladesh) among the adult population (≥18 years) using the translated and validated Enhanced Asian Rome III questionnaire.

Results

Of 3559 individuals, 3351 (94.15%) responded (mean age 40.41 ± 16.04 years, female, 1924 [57.4%]). Heartburn was the most common symptom, 863 (25.8%), followed by chest pain, 367 (11%); globus, 285 (8.5%); and dysphagia, 146 (4.4%). At least one symptom was present in 1108 (33.1%) respondents. Based on Rome III criteria, 428 (12.8%), 41 (1.2%), 49 (1.5%), 26 (0.8%), and 524 (15.6%) had heartburn, chest pain, globus, dysphagia, and at least one functional esophageal disorder, respectively. Female gender, lower family income, presence of functional dyspepsia‐irritable bowel syndrome (FD‐IBS) overlap, FD only, and psychological distress were found to be risk factors for esophageal symptoms on multivariate analysis. Among the subjects with any esophageal disorders, 156 (14.1%) consulted any health‐care provider, and 517 (46.6%) took antisecretory medications.

Conclusion

Esophageal symptoms are common in the rural community of Bangladesh and are associated with substantial health resource utilization.
Functional morphology, diversity, and evolution of yolk processing specializations in embryonic reptiles and birds
Authors: Blackburn Daniel G.
Published: September 2020

Evolution of the terrestrial, amniotic egg of vertebrates required new mechanisms by which yolk material could be processed for embryonic use. Recent studies on each of the major extant reptile groups have revealed elaborate morphological specializations for yolk processing, features that differ dramatically from those of birds. In the avian pattern, liquid yolk is housed in a yolk sac whose endodermal lining absorbs and digests yolk material and sends resultant nutrients into the blood circulation. In snakes, lizards, turtles, and crocodilians, as documented herein, the yolk sac becomes invaded by endodermal cells that proliferate and phagocytose yolk material. Blood vessels then invade, and the endodermal cells become arranged around them, forming elongated “spaghetti‐like” strands that fill the yolk sac cavity. This pattern provides an effective means by which yolk material is cellularized, digested, and transported by vitelline vessels to the developing embryo. Phylogenetically, the (non‐avian) “reptilian” pattern was ancestral for sauropsids and was modified or replaced in ancestors to birds. This review postulates that evolution of the “avian” pattern involved increased reliance on extracellular digestion of yolk, allowing embryonic development to occur more rapidly than in typical reptiles. Comparative studies of yolk processing that draw on morphological, biochemical, molecular approaches are needed to explain how and why the “reptilian” pattern was replaced in birds or their archosaurian ancestors.
Neuroinflammatory contribution of microglia and astrocytes in fetal alcohol spectrum disorders
Authors: Kane Cynthia J. M. , Drew Paul D.
Published: September 2020

Ethanol exposure to the fetus during pregnancy can result in fetal alcohol spectrum disorders (FASD). These disorders vary in severity, can affect multiple organ systems, and can lead to lifelong disabilities. Damage to the central nervous system (CNS) is common in FASD, and can result in altered behavior and cognition. The incidence of FASD is alarmingly high, resulting in significant personal and societal costs. There are no cures for FASD. Alcohol can directly alter the function of neurons in the developing CNS. In addition, ethanol can alter the function of CNS glial cells including microglia and astrocytes which normally maintain homeostasis in the CNS. These glial cells can function as resident immune cells in the CNS to protect against pathogens and other insults. However, activation of glia can also damage CNS cells and lead to aberrant CNS function. Ethanol exposure to the developing brain can result in the activation of glia and neuroinflammation, which may contribute to the pathology associated with FASD. This suggests that anti‐inflammatory agents may be effective in the treatment of FASD.
Precipitation characteristics related to atmospheric rivers in East Asia
Authors: Kim Jinwon , Moon Hyejin , Guan Bin , Waliser Duane E. , Choi Juntae , Gu Tae‐Young , Byun Young‐Hwa
Published: September 2020

Precipitation related to atmospheric rivers (ARs) is critical in shaping climate and extreme hydrologic events in the mid‐latitude coastal regions, making it a recent topic of intense research. This study has analysed the AR climatology, AR‐precipitation characteristics and their regional variations in East Asia (EA) for 1979–2015 using an AR inventory based on vertically‐integrated water‐vapour transport and AR geometry. The AR frequency over EA varies seasonally with highest (lowest) frequency in summer (winter). The AR frequency peaks in the coastal regions of the mid‐latitude western North Pacific (WNP), then decreases rapidly away from the region towards higher/lower latitudes and inlands. ARs are related to 30–60% of the annual precipitation in EA with maximum in summer; secondary peaks occur in spring in eastern China, Korea and southern Japan, and in winter for the southern China coast. Calculating the AR precipitation on days of partial AR occurrences from daily precipitation data is a key source of uncertainties in the AR‐precipitation fraction in this study. The AR days are substantially more related to heavy precipitation than non‐AR days for all seasons and regions. Seasonal cycle of AR frequency over EA and the WNP follows the northward march of the main rainband from spring to mid‐summer, but is decoupled from it from late summer to winter as the North Pacific storm track migrates into the Eastern North Pacific. The annual cycle of AR frequency and AR precipitation varies regionally; Japan and southern China adjacent to WNP show high (low) frequency of weak‐ (heavy‐) precipitating ARs in early spring (late fall) with highly frequent heavy‐precipitating ARs in summer while the mid‐latitude coastal regions, eastern China and Korea, show low frequency of heavy‐precipitating ARs in early fall with highly frequent heavy‐precipitating ARs in mid‐summer.
Multinational enterprise—Nongovernmental organization partnerships: A case study of Accor and the Parada Foundation
Authors: Cardoso Sara , Forte Rosa
Published: September 2020

The influence of nongovernmental organizations (NGOs) has increased in recent years, pressuring both multinational enterprises (MNEs) and governments to be more conscious of social issues. For this and other reasons, partnerships between NGOs and MNEs have become common. However, most studies of this phenomenon have focused on conflict in African countries and the role they can play in promoting reconciliation and peace. This work focuses on a less explored theme, analyzing the role such partnerships can play in an economically developed country. Here we look at how a partnership between a French owned multinational hotel group—Accor—and a Romanian NGO—The Parada Foundation—helped marginalized young people living on the streets of Bucharest. The paper examines the intricacies of MNE–NGO partnerships, and indicates how both may benefit from it. It concludes with some practical guidelines on the strategies that can be used to create a win–win relationship.
Architecture of tunnel valleys in the southeastern North Sea: new insights from high‐resolution seismic imaging
Authors: Lohrberg Arne , Schwarzer Klaus , Unverricht Daniel , Omlin Andreas , Krastel Sebastian
Published: September 2020

Tunnel valleys are assumed to form near the margin of ice sheets. Hence, they can be used to reconstruct the dynamics of former ice margins. The detailed formation and infill of tunnel valleys, however, are still not well understood. Here, we present a dense grid of high‐resolution 2D multi‐channel reflection seismic data from the German sector of the southeastern North Sea imaging tunnel valleys in very great detail. Three tunnel valley systems were traced over distances ranging between 11 and 21 km. All tunnel valleys are completely filled and buried. They differ in incision depth, incision width and number of incisions. The tunnel valleys cut 130–380 m deep into Neogene, Palaeogene and Cretaceous sediments; they show a lower V‐shaped and an upper U‐shaped morphology. For individual tunnel valleys, the overall incision direction ranges from east–west to northeast–southwest. Two tunnel valleys intersect at an oblique angle without reuse of the thalweg. These valleys incise into a pre‐existing glaciotectonic complex consisting of thrust sheets in the northwest of the study area. The analysis of the glaciotectonic complex and the tunnel valleys leads us to assume that we identified several marginal positions of (pre‐)Elsterian ice lobes in the southeastern North Sea.
Holocene records of eolian dust deposition from high‐elevation lakes in the Uinta Mountains, Utah, USA
Authors: Munroe Jeffrey S. , McElroy Ryan , O'Keefe Sam , Peters Andrew , Wasson Luna
Published: September 2020

Radiocarbon‐dated sediment cores from subalpine lakes were used to investigate post‐glacial dust deposition in the Uinta Mountains (Utah, USA). Lake sediments were geochemically characterized with ICP‐OES, ICP‐MS and XRF core scanning. Collections from passive samplers constrain the properties of modern dust, and samples of regolith constrain properties of the local material within the watershed. Ca and Eu are more abundant in dust, whereas Ti and Zr are more abundant in local regolith. As a result, the Ca/Ti and Eu/Zr ratios are indices for the dust content of lake sediment. In all records, the dust index rises in the early Holocene as watersheds became stabilized with vegetation, reducing the influx of local material. After this point, values remained above average through the middle Holocene, consistent with an increased dust content in the sediment. Dust index values drop in the late Holocene in most lakes, suggesting a decrease in dust abundance. Generally synchronous shifts in dust index values in cores from lakes in different parts of this mountain range are evidence of enhanced dust deposition in this region during the middle Holocene, and are consistent with a variety of records for increased aridity in the south‐western USA at this time.
Simultaneous determination of three iridoid glycosides of Rehmannia glutinosa in rat biological samples using a validated hydrophilic interaction–UHPLC–MS/MS method in pharmacokinetic and in vitro studies
Authors: Jeong Seung‐Hyun , Jang Ji‐Hun , Cho Hea‐Young , Lee Yong‐Bok
Published: September 2020

The purpose of this study was to develop a method for simultaneous analysis of aucubin, catalpol, and geniposide, which are representative iridoid glycoside constituents of Rehmannia glutinosa, in rat plasma, urine, and feces using hydrophilic interaction ultra high‐performance liquid chromatography with tandem mass spectrometry. The three components were separated using 10 mmol/L aqueous ammonium formate containing 0.01% (v/v) formic acid and acetonitrile as a mobile phase by gradient elution at a flow rate of 0.2 mL/min, equipped with a Kinetex® HILIC column (50 × 2.1 mm, 2.6 μm). Quantitation of this analysis was performed on a triple quadrupole mass spectrometer employing electrospray ionization and operated in multiple reaction monitoring mode. The chromatograms showed high resolution, sensitivity, and selectivity with no interference with plasma constituents. In all three iridoid glycosides, both the intra‐ and interbatch precisions (coefficient of variation %) were less than 4.81%. The accuracy was 96.56–103.55% for aucubin, 95.23–106.21% for catalpol, and 94.50–104.16% for geniposide. The developed analytical method satisfied the criteria of international guidance and was successfully applied to pharmacokinetic studies including oral bioavailability of aucubin, catalpol, and geniposide, and their urinary and fecal excretion ratios after oral or intravenous administration to rats. The new method was also applied to measure plasma protein binding ratios in vitro.
An approach to the travel and tourism competitiveness index in the Caribbean region
Authors: Pérez León Victor Ernesto , Pérez Fátima , Contreras Rubio Ignacio , Guerrero Flor Mª
Published: September 2020

This study aims to propose an index for measuring tourism destination competitiveness in the Caribbean Region. The application purpose is to fill the absence of Caribbean destinations in international rankings. Thirty three destinations and 27 indicators were considered, grouped into the 4 sub‐indexes of the Travel and Tourism Competitiveness Index. The application was based on Goal Programming and Data Envelopment Analysis. Four dimensional rankings and a global rank were established as a useful tool for policy makers. The results demonstrate the proposal's explanatory power and methodological improvements in building composite indicators to measure the competitiveness of destinations.
Reaction mechanisms of a cyclic ether intermediate: Ethyloxirane
Authors: Christianson Matthew G. , Doner Anna C. , Davis Matthew M. , Koritzke Alanna L. , Turney Justin M. , Schaefer Henry F. , Sheps Leonid , Osborn David L. , Taatjes Craig A. , Rotavera Brandon
Published: September 2020

Oxiranes are a class of cyclic ethers formed in abundance during low‐temperature combustion of hydrocarbons and biofuels, either via chain‐propagating steps that occur from unimolecular decomposition of β‐hydroperoxyalkyl radicals (β‐̇QOOH) or from reactions of HOȮ with alkenes. Ethyloxirane is one of four alkyl‐substituted cyclic ether isomers produced as an intermediate from n‐butane oxidation. While rate coefficients for β‐̇QOOH → ethyloxirane + ȮH are reported extensively, subsequent reaction mechanisms of the cyclic ether are not. As a result, chemical kinetics mechanisms commonly adopt simplified chemistry to describe ethyloxirane consumption by convoluting several elementary reactions into a single step, which may introduce mechanism truncation error—uncertainty derived from missing or incomplete chemistry.

The present work provides fundamental insight on reaction mechanisms of ethyloxirane in support of ongoing efforts to minimize mechanism truncation error. Reaction mechanisms are inferred from the detection of products during chlorine atom‐initiated oxidation experiments using multiplexed photoionization mass spectrometry conducted at 10 Torr and temperatures of 650 K and 800 K. To complement the experiments, calculations of stationary point energies were conducted using the ccCA‐PS3 composite method on ̇R + O2 potential energy surfaces for the four ethyloxiranyl radical isomers, which produced barrier heights for 24 reaction pathways.

In addition to products from ̇QOOH → cyclic ether + ȮH and ̇R + O2 → conjugate alkene + HOȮ, both of which were significant pathways and are prototypical to alkane oxidation, other species were identified from ring‐opening of both ethyloxiranyl and ̇QOOH radicals. The latter occurs when the unpaired electron is localized on the ether group, causing the initial ̇QOOH structure to ring‐open and form a resonance‐stabilized ketohydroperoxide‐type radical. The present work provides the first analysis of ethyloxirane oxidation chemistry, which reveals that consumption pathways are complex and may require an expansion of submechanisms to increase the fidelity of chemical kinetics mechanisms.
Robot‐Automated Cartilage Contouring for Complex Ear Reconstruction: A Cadaveric Study
Authors: Smith Corey , van der Woerd Benjamin , Potra Robert , Ferreira Louis , Moore Corey
Published: September 2020

Objectives/Hypothesis

Auricular reconstruction requiring manual contouring of costal cartilage is complex and time consuming, which could be facilitated by a robot in a fast and precise manner. This feasibility study evaluates the accuracy and speed of robotic contouring of cadaver costal cartilage.

Methods

An augmented robot with a spherical burr was used on cadaveric rib cartilage. Using a laser scanner, each rib section was converted to a three‐dimensional model for preoperative planning. A model ear was also scanned to define a carving path for each piece of cartilage. After being contoured, each specimen was compared against the preoperative plan utilizing deviation maps to analyze topographic accuracy. Contouring times of the robot were compared with 13 retrospectively reviewed cases (2006–2017) by an experienced surgeon.

Results

Scanning the cartilage sections took 24.8 ± 6.8 seconds. Preoperative processing took an additional 29.9 ± 8.9 seconds for the preparation of the contouring path. Once the path was prepared, the robot contoured the specimens with a root mean square error of 0.54 mm and a mean absolute deviation of 0.40 mm. The average time to contour the specimens with the robot was 13 ± 2 minutes compared to 71 ± 6 minutes for the manual contouring in the reviewed cases.

Conclusions

The accuracy of the robotic system was high, with submillimeter deviations from the preoperative plan. The robot required <20% of the contouring time compared to the experienced surgeon. This represents a fast and accurate alternative to hand‐contouring costal cartilage grafts for auricular reconstruction. Laryngoscope, 131:1002–1007, 2021
Survival Outcomes in Sinonasal Poorly Differentiated Squamous Cell Carcinoma
Authors: Ackall Feras Y. , Issa Khalil , Barak Ian , Teitelbaum Jordan , Jang David W. , Jung Sin‐H , Goldstein Bradley , Carrau Ricardo , Abi Hachem Ralph
Published: September 2020

Objective

Sinonasal squamous cell carcinoma (SCC) is rare with no consensus on treatment regimen. Our goal is to analyze treatment outcomes in poorly differentiated SCC (PDSCC) using a large national database.

Study Design

Retrospective database study.

Methods

The National Cancer Database was queried for sinonasal invasive SCC, grade 3 (poorly differentiated) from 2004 to 2014. Patient demographics and tumor and treatment characteristics were tabulated. Kaplan–Meier (KM) analysis was performed to compare overall survival (OS) between histology subtype and primary site. Multivariable Cox proportional hazards regression was performed for statistical analysis of treatment regimen on OS.

Results

A total of 1,074 patients were identified. The maxillary sinus was the most common site (45%). T4 tumors were observed in 50% of patients, with most patients treated at high‐volume facilities (77%). In KM analysis, spindle cell SCC histological subtype, primary tumors of the maxillary sinus, and poorly differentiated grade had worse OS. In our Cox‐PH model, higher T stage and age were associated with worse OS. Those treated at a high‐volume facility and those who underwent surgical resection followed by adjuvant radiation had improved OS. Chemotherapy within the treatment regimen did not confer survival benefit except in surgical patients when positive margins were present, and surgery with adjuvant chemoradiation trended toward improved survival.

Conclusions

Sinonasal PDSCC appears to be best treated at high‐volume centers with surgical resection followed by adjuvant radiation. Poorly differentiated grade has worse OS compared to more differentiated tumors. Chemotherapy along with adjuvant radiation may have a role in patients with positive surgical margins.

Level of evidence

4 Laryngoscope, 131:E1040–E1048, 2021
Dimensionally Stable and Mechanically Adaptive Polyelectrolyte Hydrogel
Authors: Qian Chen , Asoh Taka‐Aki , Uyama Hiroshi
Published: September 2020

Mechanically adaptive hydrogels with reversible cross‐links can change their mechanical characteristics to adapt to the external environment. However, inevitable swelling/shrinkage occurs with the mechanical property change, which impedes the applications of these hydrogels. In this study, mechanical adaptivity with high dimensional stability is achieved in alginate‐based polyelectrolyte hydrogels by introducing an opposite swelling mechanism. The dually crosslinked alginate‐polystyrene sulfonate (Alg‐PSS) hydrogels are constructed through the copolymerization of alginate‐methacrylate (Alg‐MA) and sodium p‐styrene sulfonate (NaSS), as well as Ca2+ crosslinking. In the Alg‐PSS hydrogel network, the reversible Ca2+‐carboxylate and Ca2+‐sulfonate cross‐links can be disrupted by Na+ and soften the hydrogels. Moreover, the PSS chains crosslinked in the hydrogel network undergo the coil‐globule transition in concentrated NaCl solutions to suppress hydrogel swelling during softening. The optimized Alg‐PSS hydrogel (Alg5‐PSS0.75‐MBAA2.5) shows a dramatic tensile modulus change from 191.3 kPa in deionized water (DIW) to 15.1 kPa in 2.0 mol L−1 NaCl solution with a negligible volume increase ratio of only 0.6%. The Alg‐PSS hydrogels may find applications in artificial valves or soft robotics, where high dimensional stability and invariable volume are required for smart hydrogels.
Blinded RT‐QuIC Analysis of α‐Synuclein Biomarker in Skin Tissue From Parkinson's Disease Patients
Authors: Manne Sireesha , Kondru Naveen , Jin Huajun , Serrano Geidy E. , Anantharam Vellareddy , Kanthasamy Arthi , Adler Charles H. , Beach Thomas G. , Kanthasamy Anumantha G.
Published: September 2020

Background

An unmet clinical need in Parkinson's disease (PD) is to identify biomarkers for diagnosis, preferably in peripherally accessible tissues such as skin. Immunohistochemical studies have detected pathological α‐synuclein (αSyn) in skin biopsies from PD patients albeit sensitivity needs to be improved.

Objective

Our study provides the ultrasensitive detection of pathological αSyn present in the skin of PD patients, and thus, pathological αSyn in skin could be a potential biomarker for PD.

Methods

The real‐time quaking‐induced conversion assay was used to detect pathological αSyn present in human skin tissues. Further, we optimized this ultra‐sensitive and specific assay for both frozen and formalin‐fixed paraffin‐embedded sections of skin tissues. We determined the seeding kinetics of the αSyn present in the skin from autopsied subjects consisting of frozen skin tissues from 25 PD and 25 controls and formalin‐fixed paraffin‐embedded skin sections from 12 PD and 12 controls.

Results

In a blinded study of skin tissues from autopsied subjects, we correctly identified 24/25 PD and 24/25 controls using frozen skin tissues (96% sensitivity and 96% specificity) compared to 9/12 PD and 10/12 controls using formalin‐fixed paraffin‐embedded skin sections (75% sensitivity and 83% specificity).

Conclusions

Our blinded study results clearly demonstrate the feasibility of using skin tissues for clinical diagnosis of PD by detecting pathological αSyn. Moreover, this peripheral biomarker discovery study may have broader translational value in detecting misfolded proteins in skin samples as a longitudinal progression marker. © 2020 International Parkinson and Movement Disorder Society
Introduction of a Management Toolkit for Lewy Body Dementia: A Pilot Cluster‐Randomized Trial
Authors: O'Brien John T. , McKeith Ian G. , Thomas Alan J. , Bamford Claire , Vale Luke , Hill Sarah , Allan Louise , Finch Tracy , McNally Richard , Hayes Louise , Surendranathan Ajenthan , Kane Joseph P.M. , Dunn Sarah , Bentley Allison , Barker Sally , Mason James , Burn David , Taylor John‐Paul
Published: September 2020

Background

Lewy body dementia, comprising both dementia with Lewy bodies and Parkinson's disease dementia, is challenging to manage because of a complex symptom profile and lack of clear evidence‐based management guidelines.

Objectives

We assessed the feasibility of undertaking a cluster randomized study of the introduction of an evidence‐based management toolkit for Lewy body dementia, assessing the outcomes for patients and carers as secondary measures.

Methods

We randomized 23 memory/dementia, movement disorder, or nonspecialist secondary care services to the management toolkit or usual care. People with dementia with Lewy bodies or Parkinson's disease dementia underwent assessments of cognition, motor and neuropsychiatric symptoms, and global outcome at baseline and 3 and 6 months. Healthcare, personal and social care costs, and carer‐related outcomes of carer stress, depression, and anxiety were also examined.

Results

A total of 131 participants were recruited (target 120), for whom 6‐month data were available on 108 (83%). There was a benefit of being in the intervention arm for carers (reduced Zarit Burden Scale [P < 0.01], reduced depressive symptoms [P < 0.05]), who also reported less marked patient deterioration on the global outcome measure (P < 0.05). There were no significant differences in other outcomes or in costs between groups.

Conclusions

The introduction of an evidence‐based management toolkit for Lewy body dementia was feasible and associated with some benefits, especially for carers. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society