bluuebunny/crossref_metadata_2025 huggingface dataset:
Theoretical and Experimental Fatigue Strength Calculations of Lips Compensating Circumferential Backlash in Gear Pumps
Authors: Osiński Piotr , Chruścielski Grzegorz , Korusiewicz Leszek
Published: January 2021

This article presents theoretical and experimental calculations of the minimum thickness of a compensation lip used in external gear pumps. Pumps of this type are innovative technical solutions in which circumferential backlash (clearance) compensation is used to improve their volumetric and overall efficiency. However, constructing a prototype of such a pump requires long-lasting research, and the compensation lip is its key object, due to the fact that it is an element influenced by a notch and that it operates in unfavorable conditions of strong fatigue stresses. The theoretical calculations presented in this article are based on identifying maximum stress values in a fatigue cycle and on implementing the stress failure condition and the conditions related to the required value of the fatigue safety factor. The experimental research focuses on static bending tests of the lips as well as on the fatigue loading of the lips in series of tests at increasing stress values until lip failure due to fatigue. The tests allowed the minimum lip thickness to be found for the assumed number of fatigue cycles, which is 2.5 times the number of cycles used in wear margin tests.
Experimental Investigation of Illumination Performance of Hollow Light Pipe for Energy Consumption Reduction in Buildings
Authors: Mahawan Jiraphorn , Thongtha Atthakorn
Published: January 2021

This work investigates the light illumination intensity, light transmission performance, light distribution on the floor, and daylight factor of vertical light hollow tubes at various incident elevation angles of a light source. The light tubes were made from commercial aluminum alloy sheets and commercial zinc alloy sheets to investigate internal illuminance for buildings and reducing the demand of electrical energy from artificial lighting. The vertical light tubes with a constant length of 0.5 m and diameters of 0.20, 0.25, and 0.30 m were designed in a testing room model, with dimensions of 1 m × 1 m × 1 m. A 20-W light-emitting diode (LED) lamp was used as the light source for the lighting simulations, which was placed away from the top of the light tube. The incident elevation angle of the light source was changed between 0° and 80° with 5° increments. It was found that the elevation angle of the incidence light had an influence on the light intensity distribution on both ends of light tube. The average illuminance performance of both material types increased with an increase of the incidence angle from 0° to 80° and an increase of the tube diameter from 0.20 m to 0.30 m. The commercial aluminum alloy tube promotes greater light transmission and daylight factor when compared with the commercial zinc alloy tube in each condition. This illuminance measurement demonstrates that the light tube could be included in the lighting systems of some deeper or windowless areas of buildings to decrease the demand of energy consumption in the lighting of buildings.
An Energy Consumption Approach to Estimate Air Emission Reductions in Container Shipping
Authors: Czermański Ernest , Cirella Giuseppe T. , Oniszczuk-Jastrząbek Aneta , Pawłowska Barbara , Notteboom Theo
Published: January 2021

Container shipping is the largest producer of emissions within the maritime shipping industry. Hence, measures have been designed and implemented to reduce ship emission levels. IMO’s MARPOL Annex VI, with its future plan of applying Tier III requirements, the Energy Efficiency Design Index for new ships, and the Ship Energy Efficiency Management Plan for all ships. To assist policy formulation and follow-up, this study applies an energy consumption approach to estimate container ship emissions. The volumes of sulphur oxide (SOx), nitrous oxide (NOx), particulate matter (PM), and carbon dioxide (CO2) emitted from container ships are estimated using 2018 datasets on container shipping and average vessel speed records generated via AIS. Furthermore, the estimated reductions in SOx, NOx, PM, and CO2 are mapped for 2020. The empirical analysis demonstrates that the energy consumption approach is a valuable method to estimate ongoing emission reductions on a continuous basis and to fill data gaps where needed, as the latest worldwide container shipping emissions records date back to 2015. The presented analysis supports early-stage detection of environmental impacts in container shipping and helps to determine in which areas the greatest potential for emission reductions can be found.
Evaluation of the Effect of a Grape Seed Tannin Extract on Wine Ester Release and Perception Using In Vitro and In Vivo Instrumental and Sensory Approaches
Authors: Muñoz-González Carolina , Criado Celia , Pérez-Jiménez María , Pozo-Bayón María Ángeles
Published: January 2021

This study aimed to systematically evaluate the effect of a commercial grape seed tannin extract (GSE) fully characterized (53% monomers, 47% procyanidins) on wine ester release and perception using a global approach. The behavior of two esters (ethyl hexanoate, ethyl decanoate) was studied in a control wine or in the same wine supplemented with the GSE in preconsumption (in vitro headspace-stir bar sorptive extraction-gas chromatography mass spectrometry (HS-SBSE-GC/MS) and orthonasal perception) and consumption (intraoral-HS-SBSE-GC/MS and dynamic retronasal perception) conditions. For the compound ethyl hexanoate, no significant differences (p > 0.05) among wines were observed in the in vitro analyses while they were observed in the three in vivo experiments (p < 0.05). Thus, the wine supplemented with the GSE showed lower (35%) in vivo release and ortho (36%) and retronasal (16%) perception scores than the control wine. Overall, this suggests that components of the GSE could interact with this compound, directly and/or through complexes with oral components, affecting its release and conditioning its perception. However, perceptual interactions and effects of polyphenols on oral esterases cannot be discarded. On the contrary, the compound ethyl decanoate was not significantly affected by the addition of GSE. In conclusion, the addition of tannin extracts to wines can modulate aroma perception in a compound-dependent manner.
Insights into Drivers of Liking for Avocado Pulp (Persea americana): Integration of Descriptive Variables and Predictive Modeling
Authors: Marín-Obispo Luis Martín , Villarreal-Lara Raúl , Rodríguez-Sánchez Dariana Graciela , Del Follo-Martínez Armando , Espíndola Barquera María de la Cruz , Jaramillo-De la Garza Jesús Salvador , Díaz de la Garza Rocío I. , Hernández-Brenes Carmen
Published: January 2021

Trends in new food products focus on low-carbohydrate ingredients rich in healthy fats, proteins, and micronutrients; thus, avocado has gained worldwide attention. This study aimed to use predictive modeling to identify the potential sensory drivers of liking for avocado pulp by evaluating acceptability scores and sensory descriptive profiles of two commercial and five non-commercial cultivars. Macronutrient composition, instrumental texture, and color were also characterized. Trained panelists performed a descriptive profile of nineteen sensory attributes. Affective data from frequent avocado adult consumers (n = 116) were collected for predictive modeling of an external preference map (R2 = 0.98), which provided insight into sensory descriptors that drove preference for particular avocado pulps. The descriptive map explained 67.6% of the variance in sensory profiles. Most accepted pulps were from Hass and Colin V-33; the latter had sweet and green flavor notes. Descriptive flavor attributes related to liking were global impact, oily, and creamy. Sensory drivers of texture liking included creamy/oily, lipid residue, firmness, and cohesiveness. Instrumental stickiness was disliked and inversely correlated to dry-matter and lipids (r = −0.87 and −0.79, respectively). Color differences (∆Eab*) also contributed to dislike. Sensory-guided selection of avocado fruits and ingredients can develop products with high acceptability in breeding and industrialization strategies.
Gas Seepage-Induced Features in the Hypoxic/Anoxic, Shallow, Marine Environment of Amfilochia Bay, Amvrakikos Gulf (Western Greece)
Authors: Kordella Stavroula , Christodoulou Dimitris , Fakiris Elias , Geraga Maria , Kokkalas Sotiris , Marinaro Giuditta , Iatrou Margarita , Ferentinos George , Papatheodorou George
Published: January 2021

Amfilochia Bay (Eastern Amvrakikos Gulf, Western Greece), a complex marine area affected by tectonism, was investigated for seabed seepage manifestations and for possible inter-relationships between shallow gas accumulations and hypoxia. For this purpose, an integrated research methodology that combined geophysical, geochemical, and hydrographic surveys was applied. Marine geophysical and bathymetric surveys led to the discovery of a gas-induced pockmark group in the study area. Oceanographic surveying confirmed that the bay is hypoxic/anoxic below a depth of 15 m (dissolved oxygen from ~4 to 60 μM). Very weak CH4 seepage was detected in correspondence to the pockmark group that seemed to slightly enhance the hypoxic environment locally and close to the seabed, with no effect in shallower waters and the oxycline. Methane isotopic analysis showed variable carbon isotopic composition (from −41‰ to −86‰) which could be either related to differential CH4 oxidation or mixing between microbial and thermogenic gas. However, the pathway of degassing is clearly related to the fault-controlled pockmark group. A protrusion mound, which has erroneously been reported as a submarine “volcano” since 1876, could be the result of mud volcanism based on the geophysical data of this study.
Incidence and Clinical Impacts of COVID-19 Infection in Patients with Hemodialysis: Systematic Review and Meta-Analysis of 396,062 Hemodialysis Patients
Authors: Chen Chun-Yu , Shao Shih-Chieh , Chen Yih-Ting , Hsu Cheng-Kai , Hsu Heng-Jung , Lee Chin-Chan , Sun Chiao-Yin , Chen Yung-Chan , Hung Ming-Jui , Wu I-Wen
Published: January 2021

Hemodialysis (HD) patients are highly susceptible to COVID-19 infection. However, comprehensive assessments of current evidence regarding COVID-19 in HD patients remain incomplete. We systematically searched PUBMED and EMBASE for articles published on incidence or mortality of COVID-19 infection in HD patients until September 2020. Two independent researchers extracted data and study-level risk of bias across studies. We conducted meta-analysis of proportions for incidence and mortality rate. Study heterogeneity and publication bias were assessed. A total of 29 articles with 3261 confirmed COVID-19 cases from a pool of 396,062 HD patients were identified. Incidence of COVID-19 in these HD patients was 7.7% (95% CI: 5.0–10.9%; study heterogeneity: I2 = 99.7%, p < 0.001; risk of publication bias, Egger’s test, p < 0.001). Overall mortality rate was 22.4% (95% CI: 17.9–27.1%; study heterogeneity: I2 = 87.1%, p < 0.001; risk of publication bias, Egger’s test: p = 0.197) in HD patients with COVID-19. Reported estimates were higher in non-Asian than Asian countries. Quality of study may affect the reported incidence but not the mortality among studies. Both incidence and mortality of COVID-19 infection were higher in HD patients. Available data may underestimate the real incidence of infection. International collaboration and standardized reporting of epidemiological data should be needed for further studies.
Knowledge and Practices in Neonatal Pain Management of Nurses Employed in Hospitals with Different Levels of Referral—Multicenter Study
Authors: Popowicz Hanna , Mędrzycka-Dąbrowska Wioletta , Kwiecień-Jaguś Katarzyna , Kamedulska Agnieszka
Published: January 2021

Background: One of the key elements of patient care is the relief and prevention of pain sensations. The importance of pain prevention and treatment has been emphasized by many international organizations. Despite the recommendations and guidelines based on evidence, contemporary research shows that the problem of pain among patients in neonatal intensive care units (NICUs) in various centers is still an important and neglected problem. Aim: The aim of this study was to assess the level of knowledge of the medical personnel and their perception of the issue of pain in neonatal patients. Methods: A quantitative descriptive study carried out in 2019. The study used a nurses’ perceptions of neonatal pain questionnaire. Results: A total of 43 Polish hospitals and 558 respondents participated in the project. 60.9% (n = 340) and 39.1% (n = 218) of respondents were employed in secondary and tertiary referral departments, respectively. Conclusion: Our analyses indicate that despite the availability of pain assessment tools for neonatal patients, only a few centers use standardized tools. The introduction of strategies to promote and extend the personnel’s awareness of neonatal pain monitoring scales is necessary.
Lack of Antibodies to SARS-CoV-2 among Blood Donors during COVID-19 Lockdown: A Study from Saudi Arabia
Authors: Alandijany Thamir A. , El-Kafrawy Sherif A. , Al-Ghamdi Abrar A. , Qashqari Fadi S. , Faizo Arwa A. , Tolah Ahmed M. , Hassan Ahmed M. , Sohrab Sayed S. , Hindawi Salwa I. , Badawi Maha A. , Azhar Esam I.
Published: January 2021

In response to the coronavirus disease 2019 (COVID-19), Saudi Arabia have imposed timely restrictions to minimize the infection spread, lower the risk for vulnerable groups, and reduce the pressure on healthcare services. The effectiveness of these measures has not been assessed comprehensively and, thereby, remains uncertain. Besides monitoring the number of COVID-19 cases diagnosed by molecular assays, the seroprevalence can serve as an indicator for the incidence rate among the general population. This study aimed to evaluate seroprevalence status of all healthy blood donors who attended one of the main largest hospital located in the western region of Saudi Arabia from 1 January to 31 May 2020. The study period covered two months prior to reporting the first COVID-19 case in the country on 2 March 2020. Importantly, it covered the period when “lock-down type” measures have been enforced. Samples were subjected to in-house enzyme-linked immunosorbent assay (ELISA), chemiluminescence immunoassay (CLIA), and microneutralization (MN). The sero statuses of all samples were confirmed negative, demonstrating the lack of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among blood donors during COVID-19 lockdown period. This study supports the hypothesis that COVID-19 restrictions have potential for limiting the extent of the infection.
Validation of Clinical Characteristics and Effectiveness of Pulmonary Rehabilitation in a COPD Population with Discrepancy between Exercise Tolerance and FEV1
Authors: Horie Jun , Takahashi Koichiro , Shiranita Shuuichi , Anami Kunihiko , Hayashi Shinichiro
Published: January 2021

This study’s objective was to examine the characteristics of patients with chronic obstructive pulmonary disease (COPD) presenting with various exercise tolerance levels. A total of 235 patients with stable COPD were classified into 4 groups: (1) LoFlo + HiEx—patients with a six-minute walking distance (6MWD) ≥350 m and percentage of predicted forced expiratory volume in 1 s (%FEV1.0) <50%; (2) HiFlo + HiEx—patients with a 6MWD ≥350 m and a %FEV1.0 ≥50%; (3) LoFlo + LoEx—patients with a 6MWD < 350 m and %FEV1.0 < 50%; and (4) HiFlo + LoEx—patients with a 6MWD <350 m and %FEV1.0 ≥ 50%. Aspects of physical ability in the HiFlo + LoEx group were significantly lower than those in the HiFlo + HiEx group. The HiFlo + LoEx group was characterized by a history of hospitalization for respiratory illness within the past year, treatment with at-home oxygen therapy, and lacking daily exercise habits. Following three months of pulmonary rehabilitation, the LoFlo + HiEx group significantly improved in the modified Medical Research Council dyspnea score, maximum gait speed, and 6MWD, while the HiFlo + LoEx group significantly improved in the percentage of maximal expiratory pressure, maximum gait speed, 6MWD, incremental shuttle walking distance, and St. George’s Respiratory Questionnaire score. The HiFlo + LoEx group had the greatest effect of three-month pulmonary rehabilitation compared to other groups.
Epidemiological Analysis of the 2019 Dengue Epidemic in Bhutan
Authors: Tsheten Tsheten , Mclure Angus , Clements Archie C. A. , Gray Darren J. , Wangdi Tenzin , Wangchuk Sonam , Wangdi Kinley
Published: January 2021

Bhutan experienced its largest and first nation-wide dengue epidemic in 2019. The cases in 2019 were greater than the total number of cases in all the previous years. This study aimed to characterize the spatiotemporal patterns and effective reproduction number of this explosive epidemic. Weekly notified dengue cases were extracted from the National Early Warning, Alert, Response and Surveillance (NEWARS) database to describe the spatial and temporal patterns of the epidemic. The time-varying, temperature-adjusted cohort effective reproduction number was estimated over the course of the epidemic. The dengue epidemic occurred between 29 April and 8 December 2019 over 32 weeks, and included 5935 cases. During the epidemic, dengue expanded from six to 44 subdistricts. The effective reproduction number was <3 for most of the epidemic period, except for a ≈1 month period of explosive growth, coinciding with the monsoon season and school vacations, when the effective reproduction number peaked >30 and after which the effective reproduction number declined steadily. Interventions were only initiated 6 weeks after the end of the period of explosive growth. This finding highlights the need to reinforce the national preparedness plan for outbreak response, and to enable the early detection of cases and timely response.
Access to Health Services and Assistance Offered to the Afro-Descendant Communities in Northern Brazil: A Qualitative Study
Authors: Feitosa Marcela de Oliveira , Gomes Maria Elidiana Araújo , Fontoura Iolanda Graepp , Pereira Catilena Silva , Carneiro Ana Maria da Costa Teixeira , Oliveira Maikon Chaves de , Viana Janayna Araújo , Fontoura Volmar Morais , Silva Késia Chaves da , Ribeiro Renata de Sá , Vieira Paula Cristina de Sousa , Leite Sarah Gisele de Vasconcelos , Leal Lígia Parente de Alencar , Feitosa Ankilma do Nascimento Andrade , Fonseca Fernando Luiz Affonso
Published: January 2021

The remnants of quilombos, individuals of African descent, have faced several barriers throughout its history, either due to prejudice imposed by society, or the non-fulfillment of their rights guaranteed in the 1988 Constitution, such as access to health services. Thus, this study aims to evaluate the health care offered to quilombo communities in the northern region of Tocantins. This is an exploratory, descriptive study with a qualitative approach, including field research and focus group, carried out with 58 quilombo remnants people from communities in the northern region of Tocantins. Data collection was carried out between from October 2017 to July 2018, through semi-structured interviews. We found that these communities have limited access to health services, in addition to a negative perception of the assistance offered to the health of their population and the commitment of managers. Therefore, access to health and assistance received by the studied communities required to be prioritized since the care provided is not unique and has not met the health demands and needs of the remaining quilombos in northern Tocantins, Brazil.
Impact of COVID-19 Confinement on Physical Activity and Sedentary Behaviour in Spanish University Students: Role of Gender
Authors: Rodríguez-Larrad Ana , Mañas Asier , Labayen Idoia , González-Gross Marcela , Espin Ander , Aznar Susana , Serrano-Sánchez José Antonio , Vera-Garcia Francisco J. , González-Lamuño Domingo , Ara Ignacio , Carrasco-Páez Luis , Castro-Piñero José , Gómez-Cabrera Mari Carmen , Márquez Sara , Tur Josep A. , Gusi Narcis , Benito Pedro J. , Moliner-Urdiales Diego , Ruiz Jonatan R. , Ortega Francisco B. , Jiménez-Pavón David , Casajús José Antonio , Irazusta Jon
Published: January 2021

During the COVID-19 pandemic, entire populations were instructed to live in home-confinement to prevent the expansion of the disease. Spain was one of the countries with the strictest conditions, as outdoor physical activity was banned for nearly two months. This study aimed to analyse the changes in physical activity and sedentary behaviours in Spanish university students before and during the confinement by COVID-19 with special focus on gender. We also analysed enjoyment, the tools used and motivation and impediments for doing physical activity. An online questionnaire, which included the International Physical Activity Questionnaire Short Form and certain “ad hoc” questions, was designed. Students were recruited by distributing an invitation through the administrative channels of 16 universities and a total of 13,754 valid surveys were collected. Overall, university students reduced moderate (−29.5%) and vigorous (−18.3%) physical activity during the confinement and increased sedentary time (+52.7%). However, they spent more time on high intensity interval training (HIIT) (+18.2%) and mind-body activities (e.g., yoga) (+80.0%). Adaptation to the confinement, in terms of physical activity, was handled better by women than by men. These results will help design strategies for each gender to promote physical activity and reduce sedentary behaviour during confinement periods.
Is It Time for Sports and Health in the Era of Covid-19 Pandemic?
Authors: Nikolaidis Pantelis T. , Knechtle Beat
Published: January 2021

When we took the initiative for this Special Issue, we were uncertain about its success [...]
Migration as a Determinant in the Development of Children Emotional and Behavior Problems: A Quantitative Study for Lisbon Region, Portugal
Authors: Muggli Zélia , Mertens Thierry , -Sá Silva , Amado Regina , Teixeira Ana L. , Vaz Dora , O. Martins Maria Rosário
Published: January 2021

The role of migration as a determinant in child mental health has been demonstrated in a number of studies. However, results are not always consistent, and the research continues to be scarce, especially in Portugal. We examined the association between sociodemographic profiles and the chance for the development of emotional and behavioral difficulties in a group of 420 children, immigrant (n = 217) and born in Portugal to Portuguese born parents (n = 203). We used a structured questionnaire to obtain sociodemographic information and the Strength and Difficulties Questionnaire (SDQ). Descriptive statistics were used to characterize children and their families; variables were compared between groups using the Chi-squared, Fisher’s Exact Test, or the Mann–Whitney U test and logistic regression was used to analyze the association between socio-demographic factors and emotional and behavioral difficulties. Results showed a pattern of social and mental health inequalities with immigrant children at a disadvantage: they are more often part of families with low income and where parents had low skilled jobs. Internalizing behaviors are more frequent in immigrants than in children born in Portugal to Portuguese-born parents (p = 0.001) whereas a high total SDQ difficulties score (p = 0.039) and externalizing behaviors were more frequent in 1st generation immigrant children (p = 0.009). A low family income (aOR 4.5; 95% CI: 1.43–13.95), low parental education level (aOR 2.5; 95% CI: 1.11–5.16), and being a first-generation immigrant child (aOR 2.2; 95% CI: 1.06–4.76) increased significantly the chance of developing emotional and behavioral difficulties. This study contributes to the identification of children vulnerable to mental health problems who can benefit from monitoring, early detection and preventive interventions in order to mitigate possible negative outcomes in the future.
Understanding the Unmet Needs among Community-Dwelling Disabled Older People from a Linkage Perspective
Authors: Wu Danxian , Gao Xiaolu , Xie Zhifei , Xu Zening
Published: January 2021

One of the challenges in response to population aging is to meet needs for elderly care among older people especially for those who want to age in their homes or communities. However, disabled older people have more challenges due to their restricted mobility to access care resources than non-disabled ones. We propose a new framework based on the changing relationship between older people and their environment, in which resource linkage in elderly care utilization is emphasized. We conducted a survey with 139 participants (i.e., older people age 60 years or over with different level of disabilities) in three types of neighborhoods in Beijing, China. By conducting a decision tree analysis under the Person-Environment Link (P-E Link) model, we (1) characterized unmet needs for elderly care (activities of daily living (ADL) and instrumental activities of daily living (IADL) assistance) among community-dwelling disabled older people; (2) found disabled older people had more unmet needs for both ADL and IADL assistance because of a lack in linkages to care resources than non-disabled ones; and (3) characterized the linkages to care resources for better supporting disabled older people to age in place, including family support, social connection, and spatial environment. Our findings help improve the Anderson behavioral model by characterizing enabling environments, which highlights that not only the availability of enabling resources but also linkages to these enabling resources play an important role in meeting needs for care among disabled older people. Our findings can also inform improvements in policy design that are targeted to reduce elderly care inequalities.
Effects of Hurricane Michael on Access to Care for Pregnant Women and Associated Pregnancy Outcomes
Authors: Pan Ke , Beitsch Leslie , Gonsoroski Elaina , Sherchan Samendra P. , Uejio Christopher K. , Lichtveld Maureen Y. , Harville Emily W.
Published: January 2021

Background: Disasters are associated with worse perinatal outcomes, perhaps due to inadequate prenatal care (PNC). Methods: Using 2017–2019 Florida vital statistics, we compared PNC use before and after Hurricane Michael. We categorized counties as most affected (Area A) or less affected (Area B and C). We examined whether Michael’s effects on perinatal outcomes varied by maternity care availability and used the Baron and Kenny method to assess whether delayed PNC initiation mediated perinatal outcomes. Log-binomial regression and semi-parametric linear regression were used, controlling for maternal and ZIP code tabulation area characteristics. Results: Compared to the one-year period pre-Michael, the week of the first PNC was later in all areas in the one-year period post-Michael, with the largest change in Area A (adjusted difference 0.112, 95% CI: 0.055–0.169), where women were less likely to receive PNC overall (aRR = 0.994, 95% CI = 0.990–0.998) and more likely to have inadequate PNC (aRR = 1.193, 95% CI = 1.127–1.264). Michael’s effects on perinatal outcomes did not vary significantly by maternity care availability within Area A. Delayed PNC initiation appeared to mediate an increased risk in small for gestational age (SGA) births after Michael. Conclusion: Women in Area A initiated PNC later and had a higher likelihood of inadequate PNC. Delayed PNC initiation may partially explain increased risk of SGA.
Prion-Associated Neurodegeneration Causes Both Endoplasmic Reticulum Stress and Proteasome Impairment in a Murine Model of Spontaneous Disease
Authors: Otero Alicia , Betancor Marina , Eraña Hasier , Fernández Borges Natalia , Lucas José J. , Badiola Juan José , Castilla Joaquín , Bolea Rosa
Published: January 2021

Prion diseases are a group of neurodegenerative disorders that can be spontaneous, familial or acquired by infection. The conversion of the prion protein PrPC to its abnormal and misfolded isoform PrPSc is the main event in the pathogenesis of prion diseases of all origins. In spontaneous prion diseases, the mechanisms that trigger the formation of PrPSc in the central nervous system remain unknown. Several reports have demonstrated that the accumulation of PrPSc can induce endoplasmic reticulum (ER) stress and proteasome impairment from the early stages of the prion disease. Both mechanisms lead to an increment of PrP aggregates in the secretory pathway, which could explain the pathogenesis of spontaneous prion diseases. Here, we investigate the role of ER stress and proteasome impairment during prion disorders in a murine model of spontaneous prion disease (TgVole) co-expressing the UbG76V-GFP reporter, which allows measuring the proteasome activity in vivo. Spontaneously prion-affected mice showed a significantly higher accumulation of the PKR-like ER kinase (PERK), the ER chaperone binding immunoglobulin protein (BiP/Grp78), the ER protein disulfide isomerase (PDI) and the UbG76V-GFP reporter than age-matched controls in certain brain areas. The upregulation of PERK, BiP, PDI and ubiquitin was detected from the preclinical stage of the disease, indicating that ER stress and proteasome impairment begin at early stages of the spontaneous disease. Strong correlations were found between the deposition of these markers and neuropathological markers of prion disease in both preclinical and clinical mice. Our results suggest that both ER stress and proteasome impairment occur during the pathogenesis of spontaneous prion diseases.
AtPiezo Plays an Important Role in Root Cap Mechanotransduction
Authors: Fang Xianming , Liu Beibei , Shao Qianshuo , Huang Xuemei , Li Jia , Luan Sheng , He Kai
Published: January 2021

Plants encounter a variety of mechanical stimuli during their growth and development. It is currently believed that mechanosensitive ion channels play an essential role in the initial perception of mechanical force in plants. Over the past decade, the study of Piezo, a mechanosensitive ion channel in animals, has made significant progress. It has been proved that the perception of mechanical force in various physiological processes of animals is indispensable. However, little is still known about the function of its homologs in plants. In this study, by investigating the function of the AtPiezo gene in the model plant Arabidopsis thaliana, we found that AtPiezo plays a role in the perception of mechanical force in plant root cap and the flow of Ca2+ is involved in this process. These findings allow us to understand the function of AtPiezo from the perspective of plants and provide new insights into the mechanism of plant root cap in response to mechanical stimuli.
Alternative Splicing Increases Sirtuin Gene Family Diversity and Modulates Their Subcellular Localization and Function
Authors: Zhang Xiaomin , Ameer Fathima S. , Azhar Gohar , Wei Jeanne Y.
Published: January 2021

Alternative splicing generates multiple distinct isoforms that increase transcriptome and proteome diversity. There are seven sirtuin genes in humans, each consists of multiple exons that are likely to undergo alternative splicing. Our aim was to characterize the effect of alternative splicing on the sirtuin genes. Here, we report the identification of 23 human sirtuin isoforms, most of which were not previously reported. Five of the sirtuin genes had more than one isoform, whereas sirtuin-6 had nine isoforms. Exon skipping was the main event. Most of the sirtuin isoforms were deficient in parts of the protein domains, including the catalytic domain, the N- or C-terminus, nuclear localization signal or mitochondrial targeting signal. The domain loss caused potential structural changes. Three SIRT1 isoforms had a differential effect on the mitochondrial oxygen consumption rate. Age-related changes in the expression of SIRT1 isoforms were observed in the human heart in fetus, adults, and very old individuals. We also identified 15 sirtuin isoforms in mice. Our data indicate that alternative splicing increases sirtuin gene diversity and may modulate subcellular localization and function, thereby adding complexity to the gene regulation of mitochondrial respiration, metabolism, and cardiac function during maturation and aging.
Osteogenic Properties of 3D-Printed Silica-Carbon-Calcite Composite Scaffolds: Novel Approach for Personalized Bone Tissue Regeneration
Authors: Memarian Parastoo , Sartor Francesco , Bernardo Enrico , Elsayed Hamada , Ercan Batur , Delogu Lucia Gemma , Zavan Barbara , Isola Maurizio
Published: January 2021

Carbon enriched bioceramic (C-Bio) scaffolds have recently shown exceptional results in terms of their biological and mechanical properties. The present study aims at assessing the ability of the C-Bio scaffolds to affect the commitment of canine adipose-derived mesenchymal stem cells (cAD-MSCs) and investigating the influence of carbon on cell proliferation and osteogenic differentiation of cAD-MSCs in vitro. The commitment of cAD-MSCs to an osteoblastic phenotype has been evaluated by expression of several osteogenic markers using real-time PCR. Biocompatibility analyses through 3-(4,5-dimethyl- thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), lactate dehydrogenase (LDH) activity, hemolysis assay, and Ames test demonstrated excellent biocompatibility of both materials. A significant increase in the extracellular alkaline phosphatase (ALP) activity and expression of runt-related transcription factor (RUNX), ALP, osterix (OSX), and receptor activator of nuclear factor kappa-Β ligand (RANKL) genes was observed in C-Bio scaffolds compared to those without carbon (Bio). Scanning electron microscopy (SEM) demonstrated excellent cell attachment on both material surfaces; however, the cellular layer on C-Bio fibers exhibited an apparent secretome activity. Based on our findings, graphene can improve cell adhesion, growth, and osteogenic differentiation of cAD-MSCs in vitro. This study proposed carbon as an additive for a novel three-dimensional (3D)-printable biocompatible scaffold which could become the key structural material for bone tissue reconstruction.
Generation of a Novel Mesothelin-Targeted Oncolytic Herpes Virus and Implemented Strategies for Manufacturing
Authors: Froechlich Guendalina , Gentile Chiara , Infante Luigia , Caiazza Carmen , Pagano Pasqualina , Scatigna Sarah , Cotugno Gabriella , D’Alise Anna Morena , Lahm Armin , Scarselli Elisa , Nicosia Alfredo , Mallardo Massimo , Sasso Emanuele , Zambrano Nicola
Published: January 2021

Background: HER2-based retargeted viruses are in advanced phases of preclinical development of breast cancer models. Mesothelin (MSLN) is a cell-surface tumor antigen expressed in different subtypes of breast and non-breast cancer. Its recent identification as a marker of some triple-negative breast tumors renders it an attractive target, presently investigated in clinical trials employing antibody drug conjugates and CAR-T cells. The availability of MSLN-retargeted oncolytic viruses may complement the current immunotherapeutic panel of biological drugs against HER2-negative breast and non-breast tumors. Methods: A fully virulent, tumor-targeted oncolytic Herpes simplex virus-1 (MSLN-THV) with a selectivity for mesothelin-expressing cancer cells was generated. Recombineering technology was used to replace an essential moiety of the viral glycoprotein D with antibody fragments derived from clinically validated MSLN monoclonal antibodies, and to allow IL12 cargo expression in infected cells. Panels of breast and female reproductive system cell lines were used to verify the oncolytic potential of the viral constructs. A platform for production of the retargeted viruses was developed in HEK 293 cells, providing stable expression of a suitable chimeric receptor. Results: We demonstrated the selectivity of viral infection and cytotoxicity by MSLN-retargeted viruses in a panel of mesothelin-positive cancer cells, originating from breast and female reproductive system tumors. We also developed a second-generation oncolytic MSLN-THV, encoding IL12, to enhance the immunotherapeutic potential of the viral backbone. A non-tumor cell line expressing a chimeric MSLN/Nectin-1 receptor, de-sensitized from antiviral responses by genetic inactivation of the Stimulator of Interferon Genes (STING)-dependent pathway was engineered, to optimize viral yields. Conclusions: Our proof-of-concept study proposes MSLN-retargeted herpesviruses as potential cancer immunotherapeutics for assessments in preclinical models of MSLN-positive tumors, complementing the available panel of oncolytic viruses to HER2-negative breast tumors.
Camphor and Eucalyptol—Anticandidal Spectrum, Antivirulence Effect, Efflux Pumps Interference and Cytotoxicity
Authors: Ivanov Marija , Kannan Abhilash , Stojković Dejan S. , Glamočlija Jasmina , Calhelha Ricardo C. , Ferreira Isabel C. F. R. , Sanglard Dominique , Soković Marina
Published: January 2021

Candidaalbicans represents one of the most common fungal pathogens. Due to its increasing incidence and the poor efficacy of available antifungals, finding novel antifungal molecules is of great importance. Camphor and eucalyptol are bioactive terpenoid plant constituents and their antifungal properties have been explored previously. In this study, we examined their ability to inhibit the growth of different Candida species in suspension and biofilm, to block hyphal transition along with their impact on genes encoding for efflux pumps (CDR1 and CDR2), ergosterol biosynthesis (ERG11), and cytotoxicity to primary liver cells. Camphor showed excellent antifungal activity with a minimal inhibitory concentration of 0.125–0.35 mg/mL while eucalyptol was active in the range of 2–23 mg/mL. The results showed camphor’s potential to reduce fungal virulence traits, that is, biofilm establishment and hyphae formation. On the other hand, camphor and eucalyptol treatments upregulated CDR1;CDR2 was positively regulated after eucalyptol application while camphor downregulated it. Neither had an impact on ERG11 expression. The beneficial antifungal activities of camphor were achieved with an amount that was non-toxic to porcine liver cells, making it a promising antifungal compound for future development. The antifungal concentration of eucalyptol caused cytotoxic effects and increased expression of efflux pump genes, which suggests that it is an unsuitable antifungal candidate.
Left Axis Deviation in Brugada Syndrome: Vectorcardiographic Evaluation during Ajmaline Provocation Testing Reveals Additional Depolarization Abnormalities
Authors: van der Ree Martijn H. , Vendrik Jeroen , Kors Jan A. , Amin Ahmad S. , Wilde Arthur A. M. , Tan Hanno L. , Postema Pieter G.
Published: January 2021

Patients with Brugada syndrome (BrS) can show a leftward deviation of the frontal QRS-axis upon provocation with sodium channel blockers. The cause of this axis change is unclear. In this study, we aimed to determine (1) the prevalence of this left axis deviation and (2) to evaluate its cause, using the insights that could be derived from vectorcardiograms. Hence, from a large cohort of patients who underwent ajmaline provocation testing (n = 1430), we selected patients in whom a type-1 BrS-ECG was evoked (n = 345). Depolarization and repolarization parameters were analyzed for reconstructed vectorcardiograms and were compared between patients with and without a >30° leftward axis shift. We found (1) that the prevalence of a left axis deviation during provocation testing was 18% and (2) that this left axis deviation was not explained by terminal conduction slowing in the right ventricular outflow tract (4th QRS-loop quartile: +17 ± 14 ms versus +13 ± 15 ms, nonsignificant) but was associated with a more proximal conduction slowing (1st QRS-loop quartile: +12[8;18] ms versus +8[4;12] ms, p < 0.001 and 3rd QRS-loop quartile: +12 ± 10 ms versus +5 ± 7 ms, p < 0.001). There was no important heterogeneity of the action potential morphology (no difference in the ventricular gradient), but a left axis deviation did result in a discordant repolarization (spatial QRS-T angle: 122[59;147]° versus 44[25;91]°, p < 0.001). Thus, although the development of the type-1 BrS-ECG is characterized by a terminal conduction delay in the right ventricle, BrS-patients with a left axis deviation upon sodium channel blocker provocation have an additional proximal conduction slowing, which is associated with a subsequent discordant repolarization. Whether this has implications for risk stratification is still undetermined.
Tetraoctylammonium, a Long Chain Quaternary Ammonium Blocker, Promotes a Noncollapsed, Resting-Like Inactivated State in KcsA
Authors: Giudici Ana Marcela , Díaz-García Clara , Renart Maria Lourdes , Coutinho Ana , Prieto Manuel , González-Ros José M. , Poveda José Antonio
Published: January 2021

Alkylammonium salts have been used extensively to study the structure and function of potassium channels. Here, we use the hydrophobic tetraoctylammonium (TOA+) to shed light on the structure of the inactivated state of KcsA, a tetrameric prokaryotic potassium channel that serves as a model to its homologous eukaryotic counterparts. By the combined use of a thermal denaturation assay and the analysis of homo-Förster resonance energy transfer in a mutant channel containing a single tryptophan (W67) per subunit, we found that TOA+ binds the channel cavity with high affinity, either with the inner gate open or closed. Moreover, TOA+ bound at the cavity allosterically shifts the equilibrium of the channel’s selectivity filter conformation from conductive to an inactivated-like form. The inactivated TOA+–KcsA complex exhibits a loss in the affinity towards permeant K+ at pH 7.0, when the channel is in its closed state, but maintains the two sets of K+ binding sites and the W67–W67 intersubunit distances characteristic of the selectivity filter in the channel resting state. Thus, the TOA+–bound state differs clearly from the collapsed channel state described by X-ray crystallography and claimed to represent the inactivated form of KcsA.
Down-Regulation of Claudin-2 Expression by Cyanidin-3-Glucoside Enhances Sensitivity to Anticancer Drugs in the Spheroid of Human Lung Adenocarcinoma A549 Cells
Authors: Eguchi Hiroaki , Matsunaga Haruka , Onuma Saki , Yoshino Yuta , Matsunaga Toshiyuki , Ikari Akira
Published: January 2021

Claudin-2 (CLDN2), an integral membrane protein located at tight junctions, is abnormally expressed in human lung adenocarcinoma tissues, and is linked to drug resistance in human lung adenocarcinoma A549 cells. CLDN2 may be a target for the prevention of lung adenocarcinoma, but there are few compounds which can reduce CLDN2 expression. We found that cyanidin-3-glucoside (C3G), the anthocyanin with two hydroxyl groups on the B-ring, and cyanidin significantly reduce the protein level of CLDN2 in A549 cells. In contrast, pelargonidin-3-glucoside (P3G), the anthocyanin with one hydroxyl group on the B-ring, had no effect. These results suggest that cyanidin and the hydroxyl group at the 3-position on the B-ring play an important role in the reduction of CLDN2 expression. The phosphorylation of Akt, an activator of CLDN2 expression at the transcriptional level, was inhibited by C3G, but not by P3G. The endocytosis and lysosomal degradation are suggested to be involved in the C3G-induced decrease in CLDN2 protein expression. C3G increased the phosphorylation of p38 and the p38 inhibitor SB203580 rescued the C3G-induced decrease in CLDN2 expression. In addition, SB203580 rescued the protein stability of CLDN2. C3G may reduce CLDN2 expression at the transcriptional and post-translational steps mediated by inhibiting Akt and activating p38, respectively. C3G enhanced the accumulation and cytotoxicity of doxorubicin (DXR) in the spheroid models. The percentages of apoptotic and necrotic cells induced by DXR were increased by C3G. Our data suggest that C3G-rich foods can prevent the chemoresistance of lung adenocarcinoma A549 cells through the reduction of CLDN2 expression.
Interaction between Pain, Disability, Mechanosensitivity and Cranio-Cervical Angle in Subjects with Cervicogenic Headache: A Cross-Sectional Study
Authors: Martínez-Merinero Patricia , Aneiros Tarancón Fernando , Montañez-Aguilera Javier , Nuñez-Nagy Susana , Pecos-Martín Daniel , Fernández-Matías Rubén , Achalandabaso-Ochoa Alexander , Fernández-Carnero Samuel , Gallego-Izquierdo Tomás
Published: January 2021

The relationship between the forward head posture and mechanosensitivity in subjects with a cervicogenic headache (CGH) remains uncertain. The aim of the study was to evaluate if there was a relationship between the tissue mechanosensitivity and cranio-cervical angle (CCA) that was moderated by pain intensity and/or disability in subjects with CGH. A convenience sample of 102 subjects was recruited. The CCA was measured with photographs, using a postural assessment software. The pain intensity was measured with a visual analogue scale (VAS), and the disability was measured with the Northwick Park Questionnaire. The pressure pain threshold (PPT) was measured at the spinous process of C2, the upper trapezius and splenius capitis muscles, and the median nerve. Simple moderation multiple regression analyses were constructed. There was a positive relationship between PPT at C2 and CCA, but a nonsignificant relationship for the PPT measured at the muscles and median nerve. The effect of PPT at C2 over CCA was moderated by pain intensity (R2 = 0.17; R2 change = 0.06; p < 0.05) but not disability. The Johnson–Neyman analysis revealed a cut-off point for the statistical significance of 4.66 cm in VAS. There seems to be a positive relationship between PPT at C2 and CCA, which is positively moderated by pain intensity in subjects with CGH.
Acute Care and Medication Management in Older Adults
Authors: Manckoundia Patrick , Putot Alain
Published: January 2021

The number of healthy and frail older adults is increasing worldwide, especially in industrialized countries, as a result of the increase in life expectancy [...]
Comparison of Methods for Estimating Retinal Shape: Peripheral Refraction vs. Optical Coherence Tomography
Authors: Breher Katharina , Calabuig Alejandro , Kühlewein Laura , Ziemssen Focke , Ohlendorf Arne , Wahl Siegfried
Published: January 2021

Retinal shape presents a clinical parameter of interest for myopia, and has commonly been inferred indirectly from peripheral refraction (PRX) profiles. Distortion-corrected optical coherence tomography (OCT) scans offer a new and direct possibility for retinal shape estimation. The current study compared retinal curvatures derived from OCT scans vs. PRX measurements in three refractive profiles (0° and 90° meridians, plus spherical equivalent) for 25 participants via Bland–Altman analysis. The radial differences between both procedures were correlated to axial length using Pearson correlation. In general, PRX- and OCT-based retinal radii showed low correlation (all intraclass correlation coefficients < 0.21). PRX found flatter retinal curvatures compared to OCT, with the highest absolute agreement found with the 90° meridian (mean difference +0.08 mm) and lowest in the 0° meridian (mean difference +0.89 mm). Moreover, a negative relation between axial length and the agreement of both methods was detected especially in the 90° meridian (R = −0.38, p = 0.06). PRX measurements tend to underestimate the retinal radius with increasing myopia when compared to OCT measurements. Therefore, future conclusions from PRX on retinal shape should be made cautiously. Rather, faster and more clinically feasible OCT imaging should be performed for this purpose.