bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of Combined Turbulators on the Hydraulic-Thermal Performance and Exergy Efficiency of MWCNT-Cu/Water Nanofluid in a Parabolic Solar Collector: A Numerical Approach
Authors: Khetib Yacine , Melaibari Ammar , Alsulami Radi
Published: July 2021

The present research benefits from the finite volume method in investigating the influence of combined turbulators on the thermal and hydraulic exergy of a parabolic solar collector with two-phase hybrid MWCNT-Cu/water nanofluid. All parabolic geometries are produced using DesignModeler software. Furthermore, FLUENT software, equipped with a SIMPLER algorithm, is applied for analyzing the performance of thermal and hydraulic, and exergy efficiency. The Eulerian–Eulerian multiphase model and k-ε were opted for simulating the two-phase hybrid MWCNT-Cu/water nanofluid and turbulence model in the collector. The research was analyzed in torsion ratios from 1 to 4, Re numbers from 6,000 to 18,000 (turbulent flow), and the nanofluid volume fraction of 3%. The numerical outcomes confirm that the heat transfer and lowest pressure drop are relevant to the Re number of 18,000, nanofluid volume fraction of 3%, and torsion ratio of 4. Furthermore, in all torsion ratios, rising Re numbers and volume fraction lead to more exergy efficiency. The maximum value of 26.32% in the exergy efficiency was obtained at a volume fraction of 3% and a torsion ratio of 3, as the Re number goes from 60,000 to 18,000.
Economic Aspects of Introducing Artificial Intelligence Solutions in Logistics and Port Sectors: The Data Entry Case
Authors: Carlan Valentin , Vanelslander Thierry
Published: July 2021

The development and implementation of digital solutions are new in contemporary businesses in logistics. As a next step, the potential of advanced solutions that make use of an AI or ML algorithm and which leverage on data is highly promoted. Yet, the implementation on a large scale of these types of solutions is happening at a slow pace. Recent studies show that a considerable amount of data in the maritime supply chain (MarSC) is still transferred through traditional communication channels (e.g., via e-mails or attached xls, pdf, csv, xml, etc. documents). Human intervention is thus needed to fetch this information and type it over in internal ERP systems. This type of practice opens the scene for extra labor, misinterpretation, or faults. This research puts forward the port users’ perspective on the implementation of AI and ML-based applications for the automatic handling of data. To achieve this goal, a structured survey is launched. The survey results show that, while AI and ML technologies have a high potential to take over repetitive and fault-sensitive tasks, human operators are still needed to maintain customer relations or carry out other planning-related tasks. This initial inquiry shows that, although there are operational costs that are avoided by AI-based technologies, the logistics sector shows low willingness to pay or join development tracks for this type of solutions.
RESIC: A Tool for Comprehensive Adenosine to Inosine RNA Editing Site Identification and Classification
Authors: Light Dean , Haas Roni , Yazbak Mahmoud , Elfand Tal , Blau Tal , Lamm Ayelet T.
Published: July 2021

Adenosine to inosine (A-to-I) RNA editing, the most prevalent type of RNA editing in metazoans, is carried out by adenosine deaminases (ADARs) in double-stranded RNA regions. Several computational approaches have been recently developed to identify A-to-I RNA editing sites from sequencing data, each addressing a particular issue. Here, we present RNA Editing Sites Identification and Classification (RESIC), an efficient pipeline that combines several approaches for the detection and classification of RNA editing sites. The pipeline can be used for all organisms and can use any number of RNA-sequencing datasets as input. RESIC provides (1) the detection of editing sites in both repetitive and non-repetitive genomic regions; (2) the identification of hyper-edited regions; and (3) optional exclusion of polymorphism sites to increase reliability, based on DNA, and ADAR-mutant RNA sequencing datasets, or SNP databases. We demonstrate the utility of RESIC by applying it to human, successfully overlapping and extending the list of known putative editing sites. We further tested changes in the patterns of A-to-I RNA editing, and RNA abundance of ADAR enzymes, following SARS-CoV-2 infection in human cell lines. Our results suggest that upon SARS-CoV-2 infection, compared to mock, the number of hyper editing sites is increased, and in agreement, the activity of ADAR1, which catalyzes hyper-editing, is enhanced. These results imply the involvement of A-to-I RNA editing in conceiving the unpredicted phenotype of COVID-19 disease. RESIC code is open-source and is easily extendable.
Evolution of Human Memory B Cells From Childhood to Old Age
Authors: Ciocca Michela , Zaffina Salvatore , Fernandez Salinas Ane , Bocci Chiara , Palomba Patrizia , Conti Maria Giulia , Terreri Sara , Frisullo Giuseppe , Giorda Ezio , Scarsella Marco , Brugaletta Rita , Vinci Maria Rosaria , Magnavita Nicola , Carsetti Rita , Piano Mortari Eva
Published: July 2021

High quality medical assistance and preventive strategies, including pursuing a healthy lifestyle, result in a progressively growing percentage of older people. The population and workforce is aging in all countries of the world. It is widely recognized that older individuals show an increased susceptibility to infections and a reduced response to vaccination suggesting that the aged immune system is less able to react and consequently protect the organism. The SARS-CoV-2 pandemic is dramatically showing us that the organism reacts to novel pathogens in an age-dependent manner. The decline of the immune system observed in aging remains unclear. We aimed to understand the role of B cells. We analyzed peripheral blood from children (4-18 years); young people (23-60 years) and elderly people (65-91 years) by flow cytometry. We also measured antibody secretion by ELISA following a T-independent stimulation. Here we show that the elderly have a significant reduction of CD27dull memory B cells, a population that bridges innate and adaptive immune functions. In older people, memory B cells are mostly high specialized antigen-selected CD27bright. Moreover, after in vitro stimulation with CpG, B cells from older individuals produced significantly fewer IgM and IgA antibodies compared to younger individuals. Aging is a complex process characterized by a functional decline in multiple physiological systems. The immune system of older people is well equipped to react to often encountered antigens but has a low ability to respond to new pathogens.
Adenovirus Armed With TNFa and IL2 Added to aPD-1 Regimen Mediates Antitumor Efficacy in Tumors Refractory to aPD-1
Authors: Cervera-Carrascon Victor , Quixabeira Dafne C. A. , Santos Joao M. , Havunen Riikka , Milenova Ioanna , Verhoeff Jan , Heiniö Camilla , Zafar Sadia , Garcia-Vallejo Juan J. , van Beusechem Victor W. , de Gruijl Tanja D. , Kalervo Aino , Sorsa Suvi , Kanerva Anna , Hemminki Akseli
Published: July 2021

Immune checkpoint inhibitors such as anti-PD-1 have revolutionized the field of oncology over the past decade. Nevertheless, the majority of patients do not benefit from them. Virotherapy is a flexible tool that can be used to stimulate and/or recruit different immune populations. T-cell enabling virotherapy could enhance the efficacy of immune checkpoint inhibitors, even in tumors resistant to these inhibitors. The T-cell potentiating virotherapy used here consisted of adenoviruses engineered to express tumor necrosis factor alpha and interleukin-2 in the tumor microenvironment. To study virus efficacy in checkpoint-inhibitor resistant tumors, we developed an anti-PD-1 resistant melanoma model in vivo. In resistant tumors, adding virotherapy to an anti-PD-1 regimen resulted in increased survival (p=0.0009), when compared to anti-PD-1 monotherapy. Some of the animals receiving virotherapy displayed complete responses, which did not occur in the immune checkpoint-inhibitor monotherapy group. When adenoviruses were delivered into resistant tumors, there were signs of increased CD8 T-cell infiltration and activation, which - together with a reduced presence of M2 macrophages and myeloid-derived suppressor cells - could explain those results. T-cell enabling virotherapy appeared as a valuable tool to counter resistance to immune checkpoint inhibitors. The clinical translation of this approach could increase the number of cancer patients benefiting from immunotherapies.
Modeling Whale Deaths From Vessel Strikes to Reduce the Risk of Fatality to Endangered Whales
Authors: Rockwood R. Cotton , Adams Jeffrey D. , Hastings Sean , Morten Jessica , Jahncke Jaime
Published: July 2021

Vessel strikes have been documented around the world and frequently figure as a top human cause of large whale mortality. The shipping lanes in the Santa Barbara Channel, California and nearby waters have some of the highest predicted whale mortality from vessel strikes in the United States waters of the eastern Pacific. Beginning in 2007, National Oceanographic and Atmospheric Administration requested voluntary vessel speed reductions (VSRs) for vessels greater than 300 GT traveling in the Santa Barbara Channel shipping routes to decrease whale mortality from ship strikes. We employed a ship strike model using whale density data and automatic identification system (AIS) vessel data to estimate mortality under several management scenarios. To assess the effect of the VSR on strike mortality, we bootstrapped speeds from vessels greater than 19 m long that transited when no VSR was in place. Finally, we calculated the predicted mortality for hypothetical cooperation scenarios by artificially adding speed caps post-hoc to real vessel transits. For 2012–2018, we estimated that in our study area on average during summer/fall (June–November) 8.9 blue, 4.6 humpback, and 9.7 fin whales were killed from ship strikes each year (13–26% greater than previously estimated). We evaluated winter/spring (January–April) humpback mortality for the first time, resulting in an estimate of 5.7 deaths on average per year. Poor cooperation with the VSR led to low (5% maximum) to no reductions in the estimated number of strike mortalities. Evaluating potential scenarios showed that if 95% cooperation occurred in the lanes, whale deaths there would decrease by 22–26%. Adding VSRs with similar cooperation levels at the northern end of the Santa Barbara Channel and south of Channel Islands National Marine Sanctuary could decrease estimated strike mortalities in those areas by 30%. If VSRs were added and cooperation reached 95% there and in the lanes, we estimate a 21–29% decrease in vessel strike mortalities could be attained relative to estimated mortality in the entire study area. To decrease the vessel strike related whale mortalities in this region, we recommend expanding the VSR areas and increasing cooperation voluntarily, or considering mandatory speed limits if desired cooperation levels cannot otherwise be met.
A Novel Orthoreovirus Isolated From Dead Stranded Harbor Seals From Puget Sound, Washington State, United States
Authors: Nielsen Ole , Rodrigues Thaís C. S. , Popov Vsevolod L. , Subramaniam Kuttichantran , Waltzek Thomas B. , Lambourn Dyanna M. , Raverty Stephen
Published: July 2021

As part of an ongoing investigation of harbor seal (Phoca vitulina) mortalities within Puget Sound, Washington State, United States, between October 2007 and July 2008, 25 seal cases were submitted for histopathology and ancillary diagnostic testing, including additional attempted virus isolation. In vitro granular and refractile cytopathic effects (CPE) were consistently observed in Vero.DogSLAMtag cells inoculated with tissue homogenates from three seals. Transmission electron microscopy of infected Vero.DogSLAMtag cells revealed cytoplasmic clusters of icosahedral viral particles morphologically consistent with members of the family Reoviridae. The complete genome of a novel species within the genus Orthoreovirus, tentatively named phocid orthoreovirus 1 (PhRV1), was determined by next-generation sequencing and confirmed by rt-PCR in isolates from the three harbor seals. This is the first report of an orthoreovirus infection associated with dead stranded harbor seals. Aside from the CPE and ultrastructural findings, no consistent signalment, gross pathology, histopathology, or ancillary diagnostic findings were identified with PhRV1 infection. Further research is needed to determine the prevalence, tissue tropism, transmission, pathogenicity, zoonotic potential, and host range of orthoreoviruses in pinnipeds. This study demonstrates the value of thorough necropsy investigations and a multidisciplinary team approach to advance our understanding of marine mammal health.
Environmental Reconstruction and Tracking as Methods to Explore Social Interactions in Marine Environments: A Test Case With the Mediterranean Rainbow Wrasse Coris julis
Authors: Goverts Zoë , Nührenberg Paul , Jordan Alex
Published: July 2021

A key aspect of understanding social interactions in marine animals is determining whether individuals freely interact in fission-fusion groups, or have spatially structured interactions, for example territories or home ranges. Territoriality can influence access to mates, food resources, or shelter sites, and may also impact conservation efforts, as the delineation of marine protected areas relies on knowledge of home ranges and movement patterns. However, accurately determining distribution and movement is challenging for many marine species, especially small and medium species, which cannot carry beacons or tags to automatically measure movement, and are also difficult for human observers to accurately follow. Yet these smaller species comprise the bulk of near-shore assemblages, and are essential conservation targets. As such, novel solutions for monitoring movement and behavior are required. Here we use a combination of tracking and environmental reconstruction to explore territoriality, aggression, and navigation in a small marine fish, explicitly applying this technique to questions of sociality in the marine environment. We use the Mediterranean Rainbow Wrasse, Coris julis, as a test case, but this approach can be extended to many other species and contexts. In contrast with previous reports for this species, we find that during our observation period, female C. julis occupy consistent territories over sand patches, and that they defend these territories against same-sex conspecifics. Displacement experiments revealed two further important social behavioral traits – first that displaced individuals were able to navigate back to their territory, avoiding almost all other female territories as they returned. Second that when displaced fish approached the territories of others, residents of these territories were often aggressive to the non-neighboring fish, in contrast with our observations of low aggression counts toward their natural neighbors. Resident fish therefore appear to show differing levels of aggressiveness depending on their social relationship with same-sex conspecifics. Overall, these results suggest a sophisticated degree of social behavior in this marine wrasse, dependent on social and structural environment, but which can only effectively be revealed by state-of-the-art tracking and environment reconstruction techniques.
Feeding Protocol Modulates the Digestive Process in Senegalese Sole (Solea senegalensis) Juveniles
Authors: Gilannejad Neda , Moyano Francisco J. , Martínez-Rodríguez Gonzalo , Yúfera Manuel
Published: July 2021

Understanding the daily digestive function could lead to more efficient feeding practices in the farmed fish species. In this work, the effect of several daily feeding protocols was assessed on the daily expression of the genes related to the circadian system (arntl1, clock, per1, and cry1), appetite (cck), nutrients hydrolysis (try1, ctrb1, pga, atp4a, cel, and amy2a), peptides transport (slc15a1), pH, and activity of key digestive (trypsin, chymotrypsin, amylase, 4C- and 7C-like lipases) and absorptive (alkaline phosphatase) enzymes in the gastrointestinal tract (GIT) of Senegalese sole (Solea senegalensis) juveniles. Some of the tested feeding protocols demonstrated a significant influence on the entrainment of the peripheral oscillator. The synchrony of slc15a1 and some digestive proenzymes with per1 in some of the experimental treatments could underline the role of clock genes in the regulation of these biological functions. Unlike gene expression of the digestive proenzymes wherein feeding protocol occasionally affected the temporal organization, the influence of this factor was determinant on the daily average production and/or circadian pattern of their activities. Daily pH was maintained at approximately neutral levels in all the GIT segments, and no pepsin activity was detected. Fish fed a single diurnal meal showed the lowest activity for all the studied enzymes, except for amylase, suggesting an insufficient utilization of the ingested nutrients. Higher amylase activity in this group, on the other hand, implies the possible activation of alternative compensatory metabolic pathways. Overall, our results pointed to the suitability of higher feeding frequencies, especially during dark hours, for the aquaculture production of this species.
Evaluating Impacts of Trophic Interactions on the Effectiveness of Single-Species Fisheries Management
Authors: Xing Lei , Chen Yong , Li Bai , Tanaka Kisei R. , Boenish Robert , Ren Yiping , Xu Binduo
Published: July 2021

Single-species fisheries management (SSFM) is applied to many fisheries ecosystems around the world. The associated ecological impacts are usually not well understood due to the lack of considering trophic interactions among species in the ecosystem. This impedes the implementation of SSFM in an ecosystem context and reduces our ability to understand the possible ecological impacts of fishing activities. This study focuses on two economically important species in the Jiaozhou Bay, China: the short-lived, fast-growing, and relatively abundant Japanese mantis shrimp (Oratosquilla oratoria) and the long-lived, slow-growing, and less abundant Korean rockfish (Sebastes schlegelii). We evaluated how varying trophic interactions influenced O. oratoria and S. schlegelii (i.e., target-species) who were managed under constant fishing pressure. The increase of fishing pressure to other species (i.e., non-target species) was beneficial to O. oratoria and S. schlegelii. O. oratoria was more sensitive to the decrease of fishing pressure to other species. The predation mortality of age-0 O. oratoria increased with the increased fishing pressure to other species. The predation mortality of age-1 O. oratoria and age-0 S. schlegelii had negative relationships with the fishing pressure to other species. Age-1 S. schlegelii seemed not to be sensitive to the changes in trophic interactions. The predation mortality of O. oratoria and S. schlegelii had bigger changes than the starvation mortality after fishing changed. It suggested the prey-predator relationship had a bigger impact than the food competition. The increase of high-trophic-level fish Johnius belangerii fishery positively impacted O. oratoria, but negatively impacted S. schlegelii. S. schlegelii was more sensitive to the changes of the low-trophic-level fish Pholis fangi fishery. Given the complex dynamics of ecosystems, this study highlights the importance of species-specific responses of fishes to shifting trophic interactions in fisheries management.
Case Report: Infection With SARS-CoV-2 in the Presence of High Levels of Vaccine-Induced Neutralizing Antibody Responses
Authors: Schulte Bianca , Marx Benjamin , Korencak Marek , Emmert Dorian , Aldabbagh Souhaib , Eis-Hübinger Anna Maria , Streeck Hendrik
Published: July 2021

We present a case of SARS-CoV-2 B.1. 525 infection in a healthcare worker despite the presence of highly neutralizing, multivariant-specific antibodies 7 weeks after full vaccination with the mRNA vaccine BNT162b2. We show that the virus replicated to high levels in the upper respiratory tract over the course of several days in the presence of strong antibody responses. The virus was readily propagatablein vitro, demonstrating the potential to transmit to others, bolstered by the fact that several household members were equally infected. This highlights the importance of protective measures even in vaccinated individuals.
Whole Genome Analysis of Three Multi-Drug Resistant Listeria innocua and Genomic Insights Into Their Relatedness With Resistant Listeria monocytogenes
Authors: Li Menghan , Yan Shaofei , Fanning Séamus , Li Fengqin , Xu Jin
Published: July 2021

Listeria innocua are Gram-positive rod-shaped bacteria, which are not generally infectious as opposed to Listeria monocytogenes. However, the comparatively high genomic similarity between both along with on occasion, their coexistence in similar ecological niches may present the opportunity for resistance or virulence gene transfer. In this study, three multi-drug resistant L. innocua originally cultured from food were put forward for long-read genome sequencing. Chromosome and plasmid genomes were assembled and annotated. Analysis demonstrated that the resistant phenotypes correlated well with genotypes. Three plasmids pLI42, pLI203, and pLI47-1 were identified which harbor resistance islands. Sequence alignments suggested that plasmids pLI42 and pLI203 were highly similar to a previously sequenced L. monocytogenes plasmid pLR1. Similarly, another three types of resistance gene islands were observed on chromosome, including tet(M) gene islands (transposon Tn916 orthologs), dfrG gene islands and optrA-erm(A) gene islands. All three L. innocua isolates possessed listeria pathogenicity island-4 (LIPI-4) which is linked to cases of mengitis. Further genome environment and phylogenic analysis of regions flanking LIPI-4 of L. innocua and L. monocytogenes showed that these may have common origins and with the potential to transmit from the former. Our findings raise the possible need to include both L. monocytogenes and L. innocua in food surveillance programs so as to further understand of the origins of antimicrobial resistance and virulence markers of public health importance in L. monocytogenes.
Specific White Matter Tracts and Diffusion Properties Predict Conversion From Mild Cognitive Impairment to Alzheimer’s Disease
Authors: Stone David B. , Ryman Sephira G. , Hartman Alexandra P. , Wertz Christopher J. , Vakhtin Andrei A. ,   Alzheimer’s Disease Neuroimaging Initiative
Published: July 2021

Identifying biomarkers that can assess the risk of developing Alzheimer’s Disease (AD) remains a significant challenge. In this study, we investigated the integrity levels of brain white matter in 34 patients with mild cognitive impairment (MCI) who later converted to AD and 53 stable MCI patients. We used diffusion tensor imaging (DTI) and automated fiber quantification to obtain the diffusion properties of 20 major white matter tracts. To identify which tracts and diffusion measures are most relevant to AD conversion, we used support vector machines (SVMs) to classify the AD conversion and non-conversion MCI patients based on the diffusion properties of each tract individually. We found that diffusivity measures from seven white matter tracts were predictive of AD conversion with axial diffusivity being the most predictive diffusion measure. Additional analyses revealed that white matter changes in the central and parahippocampal terminal regions of the right cingulate hippocampal bundle, central regions of the right inferior frontal occipital fasciculus, and posterior and anterior regions of the left inferior longitudinal fasciculus were the best predictors of conversion from MCI to AD. An SVM based on these white matter tract regions achieved an accuracy of 0.75. These findings provide additional potential biomarkers of AD risk in MCI patients.
The Impact of High-Fat Diet and Restrictive Feeding on Natural Killer Cells in Obese-Resistant BALB/c Mice
Authors: Spielmann Julia , Naujoks Wiebke , Emde Matthias , Allweyer Martin , Fänder Johannes , Kielstein Heike , Quandt Dagmar , Bähr Ina
Published: July 2021

Background: The association of obesity and an increased risk for severe infections and various cancer types is well-described. Natural killer (NK) cells are circulating lymphoid cells and promoters of the immune response toward viruses and malignant cells. As demonstrated in previous studies the phenotype and functionality of NK cells is impaired in obesity. So far, the majority of animal studies were exclusively performed using ad libitum feeding regimes and it remained unclear whether NK cell alterations are mediated by obesity-associated immunological changes or by direct effects of the dietary composition. Therefore, the aim of the present study was to characterize NK cells in the peripheral blood of obese-resistant BALB/c mice supplied a normal-fat diet (NFD) or high-fat diet (HFD), ad libitum or in a restrictive manner.

Methods: Twenty-eight BALB/c-mice were fed a NFD or HFD either ad libitum or in a restrictive feeding regime with 90% of the mean daily diet supply of the corresponding ad libitum group (each group n = 7). Blood and visceral adipose tissue were collected for flow cytometric analysis, analysis of plasma cytokine concentrations by multiplex immunoassay and real-time RT-PCR analyses. For statistical analyses two-way ANOVA with the factors “feeding regime” and “diet” was performed followed by a post-hoc Tukey's multiple comparison test and to compare means of the four mouse groups.

Results:Ad libitum-feeding of a HFD in BALB/c mice has no influence on body weight gain, visceral fat mass, plasma cytokine concentrations, immune cell populations as well as the number, frequency and phenotype of NK cells. In contrast, restrictive feeding of a HFD compared to NFD led to significantly higher body weights, visceral fat mass and plasma interferon-γ concentrations which was associated with changes in the frequencies of granulocytes and NK cell subsets as well as in the surface expression of NK cell maturation markers.

Conclusion: Results demonstrate for the first time that HFD-induced alterations in NK cells are consequences of the obese associated immunological profile rather than a direct effect of the dietary composition. These data can help to clarify the increased risk for cancer and severe infections in obesity.
PSMB7 Is a Key Gene Involved in the Development of Multiple Myeloma and Resistance to Bortezomib
Authors: Wu Dong , Miao Jiyu , Hu Jinsong , Li Fangmei , Gao Dandan , Chen Hongli , Feng Yuandong , Shen Ying , He Aili
Published: July 2021

Multiple myeloma (MM), the second most commonly diagnosed hematologic neoplasm, is the most significant clinical manifestation in a series of plasma cell (PC) dyscrasia. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM), approximately 1% or 10% of which, respectively, can progress to MM per year, are the premalignant stages of MM. The overall survival (OS) of MM is significantly improved by the introduction of proteasome inhibitors (PIs), but almost all MM patients eventually relapse and resist anti-MM drugs. Therefore, it is crucial to explore the progression of MM and the mechanisms related to MM drug resistance. In this study, we used weighted gene co-expression network analysis (WGCNA) to analyze the gene expression of the dynamic process from normal plasma cells (NPC) to malignant profiling PC, and found that the abnormal gene expression was mainly concentrated in the proteasome. We also found that the expression of one of the proteasomal subunits PSMB7 was capable of distinguishing the different stages of PC dyscrasia and was the highest in ISS III. In the bortezomib (BTZ) treated NDMM patients, higher PSMB7 expression was associated with shorter survival time, and the expression of PSMB7 in the BTZ treatment group was significantly higher than in the thalidomide (Thai) treatment group. In summary, we found that PSMB7 is the key gene associated with MM disease progression and drug resistance.
Overview of Cardiomyopathies in Childhood
Authors: Rath Anika , Weintraub Robert
Published: July 2021

Paediatric cardiomyopathies are a heterogenous group of rare disorders, characterised by mechanical and electrical abnormalities of the heart muscle. The overall annual incidence of childhood cardiomyopathies is estimated at about 1 per 100,000 children and is significantly higher during the first 2 years of life. Dilated cardiomyopathies account for approximately half of the cases. Hypertrophic cardiomyopathies form the second largest group, followed by the less common left ventricular non-compaction and restrictive phenotypes. Infectious, metabolic, genetic, and syndromic conditions account for the majority of cases. Congestive heart failure is the typical manifestation in children with dilated cardiomyopathy, whereas presenting symptoms are more variable in other phenotypes. The natural history is largely influenced by the type of cardiomyopathy and its underlying aetiology. Results from a national population-based study revealed 10-year transplant-free survival rates of 80, 62, and 48% for hypertrophic, dilated and left ventricular non-compaction cardiomyopathies, respectively. Long-term survival rates of children with a restrictive phenotype have largely been obscured by early listing for heart transplantation. In general, the majority of adverse events, including death and heart transplantation, occur during the first 2 years after the initial presentation. This review provides an overview of childhood cardiomyopathies with a focus on epidemiology, natural history, and outcomes.
Mechanistic Modeling of a Novel Oncolytic Virus, V937, to Describe Viral Kinetic and Dynamic Processes Following Intratumoral and Intravenous Administration
Authors: Parra-Guillen Zinnia P. , Freshwater Tomoko , Cao Youfang , Mayawala Kapil , Zalba Sara , Garrido Maria J. , de Alwis Dinesh , Troconiz Iñaki F.
Published: July 2021

V937 is an investigational novel oncolytic non-genetically modified Kuykendall strain of Coxsackievirus A21 which is in clinical development for the treatment of advanced solid tumor malignancies. V937 infects and lyses tumor cells expressing the intercellular adhesion molecule I (ICAM-I) receptor. We integrated in vitro and in vivo data from six different preclinical studies to build a mechanistic model that allowed a quantitative analysis of the biological processes of V937 viral kinetics and dynamics, viral distribution to tumor, and anti-tumor response elicited by V937 in human xenograft models in immunodeficient mice following intratumoral and intravenous administration. Estimates of viral infection and replication which were calculated from in vitro experiments were successfully used to describe the tumor response in vivo under various experimental conditions. Despite the predicted high clearance rate of V937 in systemic circulation (t1/2 = 4.3 min), high viral replication was observed in immunodeficient mice which resulted in tumor shrinkage with both intratumoral and intravenous administration. The described framework represents a step towards the quantitative characterization of viral distribution, replication, and oncolytic effect of a novel oncolytic virus following intratumoral and intravenous administrations in the absence of an immune response. This model may further be expanded to integrate the role of the immune system on viral and tumor dynamics to support the clinical development of oncolytic viruses.
Autophagy Modulators From Chinese Herbal Medicines: Mechanisms and Therapeutic Potentials for Asthma
Authors: Zhang Yun , Wang Xing , Zhang He , Tang Hongmei , Hu Hang , Wang Songping , Wong Vincent Kam Wai , Li Yuying , Deng Jun
Published: July 2021

Asthma has become a global health issue, suffering more than 300 million people in the world, which is a heterogeneous disease, usually characterized by chronic airway inflammation and airway hyperreactivity. Combination of inhaled corticosteroids (ICS) and long acting β-agonists (LABA) can relieve asthma symptoms and reduce the frequency of exacerbations, especially for patients with refractory asthma, but there are limited treatment options for people who do not gain control on combination ICS/LABA. The increase in ICS dose generally provides little additional benefit, and there is an increased risk of side effects. Therefore, therapeutic interventions integrating the use of different agents that focus on different targets are needed to overcome this set of diseases. Some findings suggest autophagy is closely correlated with the severity of asthma through eosinophilic inflammation, and its modulation may provide novel therapeutic approaches for severe allergic asthma. The chinese herbal medicine (CHM) have been demonstrated clinically as potent therapeutic interventions for asthma. Moreover some reports have found that the bioactive components isolated from CHM could modulate autophagy, and exhibit potent Anti-inflammatory activity. These findings have implied the potential for CHMs in asthma or allergic inflammation therapy via the modulation of autophagy. In this review, we discuss the basic pathomechanisms underpinning asthma, and the potential role of CHMs in treating asthma with modulating autophagy.
Microvolt T-Wave Alternans Is Modulated by Acute Low-Level Tragus Stimulation in Patients With Ischemic Cardiomyopathy and Heart Failure
Authors: Kulkarni Kanchan , Stavrakis Stavros , Elkholey Khaled , Singh Jagmeet P. , Parks Kimberly A. , Armoundas Antonis A.
Published: July 2021

Aims: Microvolt T-wave alternans (TWA), an oscillation in T-wave morphology of the electrocardiogram (ECG), has been associated with increased susceptibility to ventricular tachy-arrhythmias, while vagus nerve stimulation has shown promising anti-arrhythmic effects in in vivo and ex vivo animal studies. We aimed to examine the effect of non-invasive, acute low-level tragus stimulation (LLTS) on TWA in patients with ischemic cardiomyopathy and heart failure.

Methods: 26 patients with ischemic cardiomyopathy (left ventricular ejection fraction <35%) and chronic stable heart failure, previously implanted with an automatic implantable cardioverter defibrillator (ICD) device with an atrial lead (dual chamber ICD or cardiac resynchronization therapy defibrillator), were enrolled in the study. Each patient sequentially received, (1) Sham LLTS (electrode on tragus, but no stimulation delivered) for 5 min; (2) Active LLTS at two different frequencies (5 and 20 Hz, 15 min each); and (3) Active LLTS, during concomitant atrial pacing at 100 bpm at two different frequencies (5 and 20 Hz, 15 min each). LLTS was delivered through a transcutaneous electrical nerve stimulation device (pulse width 200 μs, frequency 5/20 Hz, amplitude 1 mA lower than the discomfort threshold). TWA burden was assessed using continuous ECG monitoring during sham and active LLTS in sinus rhythm, as well as during atrial pacing.

Results: Right atrial pacing at 100 bpm led to significantly heightened TWA burden compared to sinus rhythm, with or without LLTS. Acute LLTS at both 5 and 20 Hz, during sinus rhythm led to a significant rise in TWA burden in the precordial leads (p < 0.05).

Conclusion: Acute LLTS results in a heart-rate dependent increase in TWA burden.
ZmACY-1 Antagonistically Regulates Growth and Stress Responses in Nicotiana benthamiana
Authors: Chen Dongbin , Li Junhua , Jiao Fuchao , Wang Qianqian , Li Jun , Pei Yuhe , Zhao Meiai , Song Xiyun , Guo Xinmei
Published: July 2021

Aminoacylase-1 is a zinc-binding enzyme that is important in urea cycling, ammonia scavenging, and oxidative stress responses in animals. Aminoacylase-1 (ACY-1) has been reported to play a role in resistance to pathogen infection in the model plant Nicotiana benthamiana. However, little is known about its function in plant growth and abiotic stress responses. In this study, we cloned and analyzed expression patterns of ZmACY-1 in Zea mays under different conditions. We also functionally characterized ZmACY-1 in N. benthamiana. We found that ZmACY-1 is expressed specifically in mature shoots compared with other tissues. ZmACY-1 is repressed by salt, drought, jasmonic acid, and salicylic acid, but is induced by abscisic acid and ethylene, indicating a potential role in stress responses and plant growth. The overexpression of ZmACY-1 in N. benthamiana promoted growth rate by promoting growth-related genes, such as NbEXPA1 and NbEIN2. At the same time, the overexpression of ZmACY-1 in N. benthamiana reduced tolerance to drought and salt stress. With drought and salt stress, the activity of protective enzymes, such as peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) from micrococcus lysodeikticus was lower; while the content of malondialdehyde (MDA) and relative electrolytic leakage was higher in ZmACY-1 overexpression lines than that in wild-type lines. The results indicate that ZmACY-1 plays an important role in the balance of plant growth and defense and can be used to assist plant breeding under abiotic stress conditions.
Genome-Wide SNPs Provide Insights on the Cryptic Genetic Structure and Signatures of Climate Adaption in Amorphophallus albus Germplasms
Authors: Gao Yong , Yin Si , Chu Honglong , Zhang Yanan , Wang Haibo , Chen Huanhuan , Liu Chao , Dai Dongqin , Tang Lizhou
Published: July 2021

Domesticated species represent unique systems in which the evolutionary genomic consequences of intensive selective breeding and adaptation can be thoroughly investigated. Amorphophallus albus occurs naturally and is in cultivation throughout the downstream region of the Jinshajiang River in Southwest China. This species is characterised by high konjac glucomannan content, and has been cultivated in China for nearly 2,000 years. To study genetic differentiation and local adaption of A. albus, we sampled 13 distinct local cultivated populations of this species. Restriction site-associated DNA sequencing was conducted with 87 samples, resulting in 24,225 SNPs. The population structure analyses suggest two main genetic groups: one in the relatively upstream region, and one downstream. We found evidence of additional sub-structure within the upstream group, demonstrating the statistical power of genomic SNPs in discovering subtle genetic structure. The environmental and geographic factors were all identified as significant in shaping the genetic differentiation of this species. Notably, the proportion of environmental factors was larger than geographic factors in influencing the population genetic patterns of A. albus. We also discovered loci that were associated with local adaptation. These findings will help us understand the genetic differentiation of this newly domesticated species, thereby informing future breeding programs of A. albus.
Nighttime Temperatures and Sunlight Intensities Interact to Influence Anthocyanin Biosynthesis and Photooxidative Sunburn in “Fuji” Apple
Authors: Xue Xiaomin , Duan Ying , Wang Jinzheng , Ma Fengwang , Li Pengmin
Published: July 2021

Light and low temperatures induce anthocyanin accumulation, but intense sunlight causes photooxidative sunburn. Nonetheless, there have been few studies of anthocyanin synthesis under different sunlight intensities and low nighttime temperatures. Here, low nighttime temperatures followed by low light intensity were associated with greater anthocyanin accumulation and the expression of anthocyanin biosynthesis genes in “Fuji” apple peel. UDP-glucose flavonoid-3-O-glucosyltransferase (UFGT) activity was positively associated with anthocyanin enrichment. Ascorbic acid can be used as an electron donor of APX to scavenge H2O2 in plants, which makes it play an important role in oxidative defense. Exogenous ascorbate altered the anthocyanin accumulation and reduced the occurrence of high light–induced photooxidative sunburn by removing hydrogen peroxide from the peel. Overall, low light intensity was beneficial for the accumulation of anthocyanin and did not cause photooxidative sunburn, whereas natural light had the opposite effect on the apple peel at low nighttime temperatures. This study provides an insight into the mechanisms by which low temperatures induce apple coloration and high light intensity causes photooxidative sunburn.
OsNAC2 Is Involved in Multiple Hormonal Pathways to Mediate Germination of Rice Seeds and Establishment of Seedling
Authors: Yu Jiangtao , Mao Chanjuan , Zhong Qun , Yao Xuefeng , Li Peng , Liu Chunming , Ming Feng
Published: July 2021

The germination of seeds and establishment of seedling are the preconditions of plant growth and are antagonistically regulated by multiple phytohormones, e.g., ethylene, abscisic acid (ABA), and gibberellic acid (GA). However, the interactions between these phytohormones and their upstream transcriptional regulation during the seed and seedling growth in rice remain poorly understood. Here, we demonstrated a rice NAC (NAM-ATAF-CUC) transcription factor, OsNAC2, the overexpression of which increases the ethylene sensitivity in rice roots during the seedling period. Further study proved that OsNAC2 directly activates the expressions of OsACO and OsACO3, enhancing ethylene synthesis, and then retards seedling establishment. Moreover, OsNAC2 delays the germination of seeds and coleoptile growth through the ABA pathway instead of the ethylene and GA pathway, by targeting the promoters of OsNCED3, OsZEP1, and OsABA8ox1. We also found that OsNAC2 regulates downstream targets in a time-dependent manner by binding to the promoter of OsKO2 in the seedling period but not in the germination stage. Our finding enriched the regulatory network of ethylene, ABA, and GA in the germination of rice seeds and seedling growth, and uncovered new insights into the difference of transcription factors in targeting their downstream components.
Creation and Validation of the First French Scale for Measuring Bore-Out in the Workplace
Authors: Poirier Clément , Gelin Margaux , Mikolajczak Moïra
Published: July 2021

The aim of this study was to create and validate a scale of bore-out at work: a measure for bore-out that could be used in French-speaking workplaces. Bore-out is a recently defined phenomenon, and few studies have been conducted to evaluate it- particularly in a French context. We investigated the dimensional structure of bore-out in a sample of French-speaking workers by distributing an online survey. Exploratory and confirmatory factor analysis indicated four dimensions with high internal consistency. Through a measurement invariance analysis, a factorial structure was confirmed for men and women as well as for Gen-X and Gen-Y workers. Criterion validity was verified in regard to the relation between the scores on the WBOS dimensions and those obtained for self-esteem, depression, perceived self-efficacy, and perceived helplessness. The overall results of the analysis performed in this study show satisfactory psychometric qualities for the Work Bore-Out Scale (WBOS).
Knowledge, Attitude, and Practices Associated With COVID-19 Among Healthcare Workers in Hospitals: A Cross-Sectional Study in Saudi Arabia
Authors: Almohammed Omar A. , Aldwihi Leen A. , Alragas Adel M. , Almoteer Ali I. , Gopalakrishnan Shivkumar , Alqahtani Nasser M.
Published: July 2021

Lack of knowledge among healthcare workers (HCWs) about infectious diseases leads to delayed diagnosis of new cases, spread of infection, and poor infection control practices. Therefore, HCWs based in hospitals must be equipped with good knowledge about the pathogen and disease to put up a robust fight against the virus. The aim of this study was to assess knowledge, attitude, and practices (KAP) of HCWs about coronavirus disease 2019 (COVID-19) at multiple public and private hospitals in Riyadh, Saudi Arabia. A cross-sectional, online questionnaire-based study was conducted between July and August of 2020. Logistic regression was used to investigate differences in the level of KAP among different participants. A total of 510 HCWs in hospitals completed the questionnaire. Only two-thirds of the participants (67.8%) had adequate knowledge about COVID-19, 72.2% of the participants had a positive attitude toward COVID-19, and 80.2% of the participants were practicing appropriately most of the time. Poor KAP was associated with a low education level. The females had better knowledge and attitude, whereas the males were more likely to practice appropriately most of the time. Notably, the participants from the nursing profession demonstrated a less favorable attitude compared with medical staff from other professions, but that did not prevent them from being the best when it comes to applying appropriate practices. The inadequate level of KAP among HCWs with the continuation of the pandemic and the possibility of a second wave demonstrates the need for continuous COVID-19-specific infection control training and emotional well-being supporting programs, especially for HCWs with a low education level.
Priorities and Instruments of Local Elderly Care Policies in China: Text Mining and Comparative Analysis
Authors: Li Xiuqi , Yang Aoyi , Yan Han
Published: July 2021

Health care for the elderly is one of the key issues in the field of public health. In the context of global aging, the government's policy framework for elderly care affects the development of local elderly care. The priorities and instruments of the elderly care policy are important windows for understanding the local development planning system. This paper uses a quantitative text analysis method based on text mining to analyze 3,618 provincial policies in China. Considering the pilot demonstration projects for elderly care selected by the Chinese government in recent years, this paper finds that local elderly care policies have a three-phase evolution, and the priorities in each phase are solving the legacy of transition, expanding private sector participation, and realizing the well-being of the elderly. Moreover, mature regions use more environmental policy instruments, and the most effective are financial services, regulatory systems, and strategic guidance. For immature regions, it is necessary to use more core instruments on the premise of using basic instruments so that public policies can serve local development and realize the well-being of the elderly.