bluuebunny/crossref_metadata_2025 huggingface dataset:
Pass-Through of Crude-oil Price Shocks to Consumer Prices in Nigeria: Pre and Post 2008 Global Financial Crisis
Authors: I. Otoakhia Eric
Published: April 2021

This study investigates the responses of consumer price index (CPI) to crude oil price shocks in the pre- and post-2008 global financial crisis. The study used the Structural Vector Autoregressive model to analyse monthly data from 2000M01 to 2019M12. The impulse response analysis showed that for pre and post-crisis periods, oil price shocks have a positive impact on CPI. This impact was an insignificant direct momentary increase in pre-crisis CPI before dissipating. Conversely, the impact on post crisis CPI response tends to be stable and long-lasting starting from the third month. The confidence bands for the post crisis CPI are large, indicating the long-lasting positive response in the CPI pose no significant threat to price stability in the long run horizon. In conclusion, CPI response varies in terms of intensity for pre and post crisis periods. In terms of level of significance, the effect of the shocks on CPI is transient and insignificant in both periods. The post crisis oil price shock is not a significant channel that created price instability in Nigeria after the crisis and this study recommend partial deregulation of energy price should be maintained. Establishing oil price –inflation pass-through, external shocks like financial crisis should be accounted for.
As the Tree Greens: Deleuze's Form-Event Assemblage and Chinese Ideograms in a Biosemiotic Ecosystem
Authors: Wong Kin-yuen
Published: April 2021

This paper takes Deleuze's idea ‘to green’ as a qualitative predicate which becomes a rhizomatic event where Jesper Hoffmeyer's ‘plant being’ contemplates through waves and rhythms (refrains), hence affects and percepts. The article then brings forward an intertwined group of Chinese ideograms which are designed with plant-radicals, making up an ecosystem towards the establishment of a new Chinese ecocriticism under the banner of biosemiotics. Such an effort will, hopefully, widen the scope and dimension of the new field of environmental humanities, with an emphasis on the scenario of affective attuning to the agency of vegetal life. The main purpose is to put Deleuze and Guattari's form-event assemblage within the stratification of regimes of signs in A Thousand Plateaus, in order to establish a ‘natureculture’ continuity not only between science and art, but also between a Western rethinking of language/culture and a Chinese ecosystem/ecocriticism.
Cuidados de la Salud Centrado en la Persona
Authors: Payet-Meza Eduardo
Published: April 2021

Hacer salud pública hoy, exige muchos cambios en la visión que hemos tenido sobre los enfoques en la salud. Estos hacen necesario  que tengamos una visión y un enfoque transformado para actuar diferente.
Remdesivir para el tratamiento del COVID-19
Authors: Calderón-Velasco Rolando
Published: April 2021

El Remdesivir es un profármaco (una sustancia inócua que se transforma en fármaco dentro del organismo cuando es metabolizada) antiviral. Pertenece a la familia de los análogos de los nucleótidos y actúa inhibiendo una enzima del virus indispensable para su multiplicación. Ha demostrado tener actividad contra el SARS COVID-19.
Simposio sobre Abdomen Agudo - Segunda Parte
Authors: Herrera-Matta Juan Jaime
Published: April 2021

Entre las causas de abdomen agudo de origen vascular, la isquemia mesentérica aguda (IMA) permanece como un desafío diagnóstico y terapéutico. La variable presentación de síntomas y signos no evidentes en la fase inicial, exámenes auxiliares que pueden desviar la atención a otras patologías y su baja frecuencia pueden ser algunos factores responsables de un retardo en el diagnóstico con consecuencias en el pronóstico de la enfermedad llegando a tener una mortalidad de 50 a 100%(1, 2). En países de primer mundo puede ser el hallazgo en 2.1% de exploraciones quirúrgicas por abdomen agudo o ser causa del 0.1% de hospitalizaciones(3). En todo caso aumenta con la edad(4) y en nuestro país la población adulta mayor de 60 años constituía el 5.7% en 1950 pero el 2019 representa el 12.4% de la población(5), tendencia que continuará progresando cada año, por lo que se espera aumente su frecuencia como causa de abdomen agudo quirúrgico en nuestro población.
Prevalence of Endodontically Treated Teeth in an Adult Malaysian Population Attending a Dental School Clinic
Authors: Rathi Rahul , Saroha Priti , Shin Ling Teck , Khye Lim Sher , Yee Lim Ren
Published: April 2021

Introduction: The study of endodontic epidemiology may help in prediction of future needs for dental treatment in a dentate population. The prevalence of endodontically treated teeth in the Malaysian population has never been investigated and their estimates have been based on studies from other countries. This study evaluated the prevalence of endodontically treated teeth in an adult Malaysian population attending a dental school clinic in northern Malaysia. Methods: The sample of this cross-sectional study examined the orthopantograms of 1663 patients in age group 18 to 75 years old, visiting the clinics of AIMST dental institute. A total of 33462 teeth were examined by four calibrated professionals. Any radiographic evidence of presence of radio-opaque material in pulp space was considered as endodontic treatment for the particular tooth. Third molars, supernumerary teeth and faulty radiographs were excluded from the study. Data was recorded with respect to gender, age and ethnicity of the patient and also the type of tooth. It was statistically analysed using Odds ratio, logistic regression and chi-square test. Results: There was a greater prevalence of endodontic treatment in females than males and 31 to 40 years age group. Malay population had higher number of cases of overall endodontically treated teeth, while Indian population showed highest percentage of cases within any ethnic group. Maxillary molars and mandibular molars were most frequently treated teeth, whereas canines showed the lowest prevalence. Findings were more significantly higher for maxillary teeth than mandibular teeth and for left side than right side. Conclusion: The prevalence of endodontically treated teeth in the Malaysian adult population was higher than that observed in epidemiological studies from other countries. This might is considered due to the higher incidence of caries and awareness emerging among the sub-population for preserving natural teeth. The results also concluded the necessity of more educational programs in Endodontics.
Seed Biology of Witchgrass (Panicum capillare L.) Ensures Its Success Under Different Environmental Conditions
Authors: Wu Hanwen , Asaduzzaman Md , Shephard Adam , Ma Xiaoyan
Published: April 2021

Witchgrass (PanicumcapillareL.) is a summer growing grass weed species and is increasing its prevalence in southern Australia. A better understanding of the seed biology is needed to effectively manage this weed. A series of field and laboratory studies were conducted to determine seed germination factors, field emergence patterns, and soil seedbank longevity. Witchgrass germination was stimulated by light and it germinated better at temperature over 20°C, with 93–100% germination at the two constant temperatures of 20 and 30°C, and the two alternating day/night temperatures of 30/25 and 35/25°C. It is highly tolerant to moisture stress at germination, with 2–7% germination even at −0.48 Mpa. Witchgrass seed lost 47–68% viability after 12 months of burial in the soil, however the seed persisted for more than 4 years if buried at 10 cm in the soil. Witchgrass emergence in southern New South Wales (NSW) commenced in mid spring (early October), with peak emergence of 63–83% in November and then significantly reduced to 16–37% emergence in December. Little emergence (<1%) occurred in the summer months from January to February. These results provide useful information for designing effective management strategies and the optimum timing of control. Climate change could favor the phenological development and the further spread of this weed, which present new challenges for its effective management. Further study is needed to investigate the impact of climate change on the biology, spread, and management of witchgrass.
One-Pot Synthesis of (Z)-β-Halovinyl Ketones via the Cascade of Sonogashira Coupling and Hydrohalogenation
Authors: Chen Fa-Jie , Hua Zhenguo , Chen Jianhui , Chen Jiajia , Lee Daesung , Xia Yuanzhi
Published: April 2021

Herein, we report an efficient method for the synthesis of (Z)-β-halovinyl ketones through a one-pot Sonogashira coupling and hydrohalogenation reaction promoted by palladium-copper catalyst and Brønsted acid. The ynone intermediates are generated in situ from readily available acid chlorides and terminal alkynes at room temperature, which are directly converted to (Z)-β-halovinyl ketones by treating with triflic acid. This method avoids the use of an external halogen source and features broad substrate scope, high yield, and good to excellent stereoselectivity.
The Human Bone Marrow Is Host to the DNAs of Several Viruses
Authors: Toppinen Mari , Sajantila Antti , Pratas Diogo , Hedman Klaus , Perdomo Maria F.
Published: April 2021

The long-term impact of viruses residing in the human bone marrow (BM) remains unexplored. However, chronic inflammatory processes driven by single or multiple viruses could significantly alter hematopoiesis and immune function. We performed a systematic analysis of the DNAs of 38 viruses in the BM. We detected, by quantitative PCRs and next-generation sequencing, viral DNA in 88.9% of the samples, up to five viruses in one individual. Included were, among others, several herpesviruses, hepatitis B virus, Merkel cell polyomavirus and, unprecedentedly, human papillomavirus 31. Given the reactivation and/or oncogenic potential of these viruses, their repercussion on hematopoietic and malignant disorders calls for careful examination. Furthermore, the implications of persistent infections on the engraftment, regenerative capacity, and outcomes of bone marrow transplantation deserve in-depth evaluation.
Clonal Candidemia Outbreak by Candida parapsilosis Carrying Y132F in Turkey: Evolution of a Persisting Challenge
Authors: Arastehfar Amir , Hilmioğlu-Polat Suleyha , Daneshnia Farnaz , Pan Weihua , Hafez Ahmed , Fang Wenjie , Liao Wanqing , Şahbudak-Bal Zümrüt , Metin Dilek Yeşim , Júnior João N. de Almeida , Ilkit Macit , Perlin David S. , Lass-Flörl Cornelia
Published: April 2021

As the second leading etiological agent of candidemia in Turkey and the cause of severe fluconazole-non-susceptible (FNS) clonal outbreaks, Candida parapsilosis emerged as a major health threat at Ege University Hospital (EUH). Evaluation of microbiological and pertinent clinical profiles of candidemia patients due to C. parapsilosis in EUH in 2019–2020. Candida parapsilosis isolates were collected from blood samples and identified by sequencing internal transcribed spacer ribosomal DNA. Antifungal susceptibility testing was performed in accordance with CLSI M60 protocol and ERG11 and HS1/HS2-FKS1 were sequenced to explore the fluconazole and echinocandin resistance, respectively. Isolates were typed using a multilocus microsatellite typing assay. Relevant clinical data were obtained for patients recruited in the current study. FNS C. parapsilosis isolates were recovered from 53% of the patients admitted to EUH in 2019–2020. Y132F was the most frequent mutation in Erg11. All patients infected with C. parapsilosis isolates carrying Y132F, who received fluconazole showed therapeutic failure and significantly had a higher mortality than those infected with other FNS and susceptible isolates (50% vs. 16.1%). All isolates carrying Y132F grouped into one major cluster and mainly recovered from patients admitted to chest diseases and pediatric surgery wards. The unprecedented increase in the number of Y132F C. parapsilosis, which corresponded with increased rates of fluconazole therapeutic failure and mortality, is worrisome and highlights the urgency for strict infection control strategies, antifungal stewardship, and environmental screening in EUH.
GLOBE Observer and the GO on a Trail Data Challenge: A Citizen Science Approach to Generating a Global Land Cover Land Use Reference Dataset
Authors: Kohl Holli A. , Nelson Peder V. , Pring John , Weaver Kristen L. , Wiley Daniel M. , Danielson Ashley B. , Cooper Ryan M. , Mortimer Heather , Overoye David , Burdick Autumn , Taylor Suzanne , Haley Mitchell , Haley Samual , Lange Josh , Lindblad Morgan E.
Published: April 2021

Land cover and land use are highly visible indicators of climate change and human disruption to natural processes. While land cover is frequently monitored over a large area using satellite data, ground-based reference data is valuable as a comparison point. The NASA-funded GLOBE Observer (GO) program provides volunteer-collected land cover photos tagged with location, date and time, and, in some cases, land cover type. When making a full land cover observation, volunteers take six photos of the site, one facing north, south, east, and west (N-S-E-W), respectively, one pointing straight up to capture canopy and sky, and one pointing down to document ground cover. Together, the photos document a 100-meter square of land. Volunteers may then optionally tag each N-S-E-W photo with the land cover types present. Volunteers collect the data through a smartphone app, also called GLOBE Observer, resulting in consistent data. While land cover data collected through GLOBE Observer is ongoing, this paper presents the results of a data challenge held between June 1 and October 15, 2019. Called “GO on a Trail,” the challenge resulted in more than 3,300 land cover data points from around the world with concentrated data collection in the United States and Australia. GLOBE Observer collections can serve as reference data, complementing satellite imagery for the improvement and verification of broad land cover maps. Continued collection using this protocol will build a database documenting climate-related land cover and land use change into the future.
Experimental Aqueous Alteration of Cortical Bone Microarchitecture Analyzed by Quantitative Micro-Computed Tomography
Authors: Kral Anna G. , Ziegler Alexander , Tütken Thomas , Geisler Thorsten
Published: April 2021

Bones are one of the most common vertebrate fossil remains and are widely used as proxy archives in palaeontology and archaeology. Previous histological analyses have shown that bone microarchitecture is mostly well-preserved in fossil remains, but partially or even entirely lost in most archaeological specimens. As a consequence, processes occurring during early diagenesis are pivotal for the preservation of bones and a better understanding of these processes would be required to assess the significance of information stored in fossilized bones. Although much of the changes occur at the nanometer scale, determining the resistance of bone microarchitecture to diagenetic alteration on a microscopic scale constitutes a prerequisite for more detailed studies. Here, results from the first comparative in vitro taphonomy study of cortical bone simulating conditions potentially encountered in early diagenetic settings are presented. In order to accelerate anticipated early diagenetic changes and to facilitate their study in a practical framework, cortical bone samples were exposed to aqueous solutions with temperature, time, and composition of the experimental solutions as controlled parameters. Before and after the experiments, all samples were characterized quantitatively using micro-computed tomography to document structural changes. The results show that the overall change in cortical porosity predominantly occurred in canals with diameters ≤9 µm (∆Ct.Po = ±30%). Furthermore, the data also show that the solution composition had a stronger impact on changes observed than either temperature or time. It was also found that samples from the two experimental series with a freshwater-like solution composition showed a characteristic reaction rim. However, it remains unclear at present if the observed changes have an impact on reactions occurring at the nanometer scale. Nonetheless, the results clearly demonstrate that on a micrometer scale down to 3 μm, bone microarchitecture is largely resistant to aqueous alteration, even under very different physicochemical conditions. In addition, the data illustrate the complexity of the interaction of different diagenetic factors. The results presented here provide a solid framework for future investigations on reaction and transport mechanisms occurring during the early diagenesis of fossil bones.
The Effect of Diagenetic Evolution on Shale Gas Exploration and Development of the Longmaxi Formation Shale, Sichuan Basin, China
Authors: Wang Jia , Tan Xianfeng , Tian Jingchun , Luo Long , Gao Xuanbo , Luo Chao , Zeng Chunlin , Zhang Lei , Xue Weiwei
Published: April 2021

Diagenetic evolution is an important controlling factor of shale gas reservoirs. In this study, based on field outcrop and drilling core data, analytical techniques including X-ray diffraction (XRD), field emission scanning electron microscope combined with a focused ion beam (FIB-FESEM), and energy-dispersive spectroscopy (EDS) analyses were performed to determine the diagenetic evolution of the Longmaxi Formation shale and reveal the effect of diagenetic evolution on the shale gas exploration and development in the Sichuan Basin, Southwest China. The eodiagenesis phase was subdivided into two evolution stages, and the mesodiagenesis phase was subdivided into three evolution stages in the basin margin and center. Absorbed capacity and artificial fracturing effect of the Longmaxi Formation shale gas were related to mineral composition, which was influenced by sedimentary characteristics and diagenetic evolution. The diagenetic system in the basin margin was more open than that in the basin center due to a different burial history. The more open diagenetic system, with more micro-fractures and soluble constitute (e.g., feldspar), was in favor for the formation and preservation of secondary dissolved pores and organic pores in the basin margin. The relatively closed diagenetic system with stronger compaction resulted in deformation of pore space in the central basin.
A Resource and Policy Driven Assessment of the Geothermal Energy Potential Across the Islands of St. Vincent and the Grenadines
Authors: Koon Koon Randy , Shah Kalim , Ashtine Masaō , Lewis Santana
Published: April 2021

The energy security of each Caribbean Community (CARICOM) member state is a key issue specifically addressed based on the energy demands of each nation. St. Vincent and the Grenadines (SVG) has the potential to strengthen its energy sector through the exploitation of immense untapped natural geothermal resources. Currently, SVG is planning to integrate base load power through a 10 Megawatt-electric (MWe) geothermal power plant (GPP1). The paper aims to highlight a detailed resource assessment profile of the renewables across SVG and the projected benefits of the proposed 10 MWe geothermal power potential, such as the positive economic development (displacing 149,000 bbls of crude oil), and the transition to a more climate-sensitive nation (displacing an estimated 0.172 million tCO2e/year). In addition, a volumetric method (Monte Carlo simulations) has been applied to reveal that the geothermal reservoir can sustain a minimum of 31 MWe, 34 MWe and 92 MWe over the lifespan of 25–30 years, for well 1 (SVG01), well 2 (SVG02) and well 3 (SVG03) respectively. Given the findings of the assessment and simulations, several policy approaches are identified as potential means of enhancing geothermal resource development and leveraging the resource for the islands’ sustainable energy demands. These include incentivization for public-private partnerships, information certainty, regulatory processes, and strengthened institutions.
Exploring the Kairomone-Based Foraging Behaviour of Natural Enemies to Enhance Biological Control: A Review
Authors: Ayelo Pascal M. , Pirk Christian W. W. , Yusuf Abdullahi A. , Chailleux Anaïs , Mohamed Samira A. , Deletre Emilie
Published: April 2021

Kairomones are chemical signals that mediate interspecific interactions beneficial to organisms that detect the cues. These attractants can be individual compounds or mixtures of herbivore-induced plant volatiles (HIPVs) or herbivore chemicals such as pheromones, i.e., chemicals mediating intraspecific communication between herbivores. Natural enemies eavesdrop on kairomones during their foraging behaviour, i.e., location of oviposition sites and feeding resources in nature. Kairomone mixtures are likely to elicit stronger olfactory responses in natural enemies than single kairomones. Kairomone-based lures are used to enhance biological control strategies via the attraction and retention of natural enemies to reduce insect pest populations and crop damage in an environmentally friendly way. In this review, we focus on ways to improve the efficiency of kairomone use in crop fields. First, we highlight kairomone sources in tri-trophic systems and discuss how these attractants are used by natural enemies searching for hosts or prey. Then we summarise examples of field application of kairomones (pheromones vs. HIPVs) in recruiting natural enemies. We highlight the need for future field studies to focus on the application of kairomone blends rather than single kairomones which currently dominate the literature on field attractants for natural enemies. We further discuss ways for improving kairomone use through attract and reward technique, olfactory associative learning, and optimisation of kairomone lure formulations. Finally, we discuss why the effectiveness of kairomone use for enhancing biological control strategies should move from demonstration of increase in the number of attracted natural enemies, to reducing pest populations and crop damage below economic threshold levels and increasing crop yield.
Association of CD40 Gene Polymorphisms With Systemic Lupus Erythematosus and Rheumatoid Arthritis in a Chinese Han Population
Authors: Huang Qi , Xu Wang-Dong , Su Lin-Chong , Liu Xiao-Yan , Huang An-Fang
Published: April 2021

Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are complex autoimmune diseases. CD40 participates in inflammatory response, and promotes fibroblast proliferation, leading to occurrence and progression of SLE, RA. This study explores CD40 gene polymorphisms in SLE and RA patients from a Chinese Han population. Two hundred SLE patients, 340 RA patients, and 900 healthy controls were enrolled. Genomic DNA was extracted from peripheral blood, and six polymorphisms of CD40 gene (rs3765456, rs1569723, rs73115010, rs13040307, rs1883832, and rs4810485) were detected by KASP method. Frequencies of rs1569723 genotypes AA, AC, AA+AC were significantly higher in RA patients as compared to those in healthy controls (P = 0.049, P = 0.024, P = 0.022). Frequencies of genotypes CT, CC+CT of rs1883832, and GT, GG+GT of rs4810485 were significantly higher in RA patients as compared to those in healthy controls (P = 0.012, P = 0.018, P = 0.009, P = 0.015). RA patients carrying rs13040307 C allele and rs73115010 T allele showed increased number of swollen joints. Moreover, frequency of allele T of rs13040307 was lower in SLE patients with positive anti-dsDNA and hematuria as compared to that in patients without these parameters (P = 0.038, P = 0.045). There were increased frequencies of genotype TT, allele T for rs13040307 and lower frequencies of genotype TT, allele T for rs73115010 in lupus patients with myositis (all P<0.05). Interestingly, frequencies of rs1569723 A allele, rs4810485 T allele were higher in SLE patients with myositis, and frequencies of rs3765456 A allele, rs1883832 T allele were lower in SLE patients with myositis (All P<0.05). In conclusion, CD40 gene polymorphisms may associate with susceptibility to SLE and RA.
Inclusion of Intra- and Interspecific Facilitation Expands the Theoretical Framework for Seagrass Restoration
Authors: Zhang Y. Stacy , Gittman Rachel K. , Donaher Sarah E. , Trackenberg Stacy N. , van der Heide T. , Silliman Brian R.
Published: April 2021

Restoration is increasingly utilized as a strategy to stymie the loss of coastal habitats. Coastal habitat restoration has predominantly emphasized designs that minimize physical stress and competition. As evidence of the pervasiveness of this approach, we conducted a global survey of seagrass restorationers and found a strong affinity for stress-avoidant designs with adult shoots in dispersed rather than aggregated configurations. To test the alternative hypothesis that including positive interactions can enhance restoration success, we experimentally incorporated: (i) interspecific facilitation (clam additions) into seed sowing, and (ii) both intra- and interspecific facilitation (planting a single-large versus multiple-small patches and adding clams) into shoot planting. Clam additions to seeds significantly enhanced plant biomass and patch size; and nutrient analysis suggested the causative mechanism was clam enhancement of available nitrogen. In contrast, adult outplant growth was enhanced by intra- but not inter-specific facilitation. Dispersed configurations consistently declined, whereas large-intact patches, which had the same initial biomass as dispersed plots, increased in patch area and doubled in shoot density. These results demonstrate that expanding restoration strategies to include positive interactions with respect to seagrass ontogeny has the capability to switch the trajectory of restoration from failure to success.
Time or Space? Relative Importance of Geographic Distribution and Interannual Variation in Three Lineages of the Ascidian Pyura chilensis in the Southeast Pacific Coast
Authors: Haye Pilar A. , Turon Xavier , Segovia Nicolás I.
Published: April 2021

Spatial and temporal variation of environmental parameters can affect dispersal, recruitment and population persistence of marine benthic species. Studies including inter-annual comparisons of genetic structure often indicate high/moderate temporal heterogeneity in marine invertebrates, which may be a prevailing pattern. This suggests that temporal studies are necessary to understand the dynamics of marine metapopulations. In this study, we analyzed the spatio-temporal genetic structure of the ascidianPyura chilensis, a low dispersal sessile marine species endemic from the Southeast Pacific coast and highly demanded for human consumption. We sequenced a fragment of the mitochondrial gene Cytochrome Oxidase I (COI) from 1,005 individuals of six locations (30–40 individuals per site and year) spanning a wide latitudinal range (24°–42°S) and sampled over 5 years (2012, 2014, 2015, 2016, and 2017). The genetic structure of COI indicates the presence of three monophyletic lineages (haplogroups 1–3) previously described for the species, being one of them highly divergent and geographically restricted (~39°S, Los Molinos). Considering the whole dataset, a picture of strong spatial differentiation but temporal stability emerged inPyura chilensis.However, detailed studies of the two main lineages revealed important differences in the extent of spatio-temporal variation. Analyses using haplotype frequencies sorted by site and year showed that, for haplogroup 1, genetic variation was explained mainly by differences between sites, while for haplogroup 2 differences between years were prevailing. Haplogroup 3 was restricted to the most southern sites, and also showed inter-annual variability in its frequency. These results point to disparate patterns of genetic differentiation, which may reflect different adaptive scope or variation in reproductive and dispersal features and could be a response to extreme events such as El Niño (2015–2016). This work calls for caution when obtaining general trends in species clearly differentiated in lineages, and prompts instead for separate analyses of sub-specific genetic lineages whenever possible.
Wave Climate Variability and Occurrence of Mudbanks Along the Southwest Coast of India
Authors: Saprykina Yana V. , Samiksha S. V. , Kuznetsov Sergey Yu.
Published: April 2021

Mudbanks (MBs) are a natural phenomenon, forming along the southwest coast of India during southwest monsoon (SWM), almost every year. High waves initiate these formations. The temporal variability (both intra-annual and multi-decadal) of wave climate of the southeastern Arabian Sea (AS) is related to main climate indices which determine climate fluctuations in this region, and based on that, occurrence of MBs is illustrated. Voluntary Observing Ships data and climate indices such as El Niño phenomenon index for the site 5N-5S and 170W-120W (NINO3.4), El Niño/Southern Oscillation (ENSO), Southern Oscillation Index (SOI), Pacific Decadal Oscillation (PDO), AAO, Atlantic Multi-decadal Oscillation (AMO), and IO Dipole (IOD) have been analyzed. Using wavelet correlation method, high correlations with positive and negative phase of climatic indices (IOD, SOI, NINO3.4, ENSO, AMO, PDO, and AAO) fluctuations in heights of wind waves and swell and time lags between them on monthly, yearly, decadal, and multi-decadal time scales are identified. For the first time, high correlation between the annual fluctuations of AMO and monthly average wave heights is shown. It has been found that the El Niño phenomenon plays a major role in the variability of wave climate of the southeastern AS for all time scales. A strong variability in wave climate at short time scales, such as 0.5, 1, 3.0–3.5, 4–5, and 7–8 years, is evident from the analyses. Decadal changes correspond to 10, 12–13, and 16 years. The influence of El Niño is manifested with a delay of several months (3–6) on annual time scales and about 1–2 years on a decadal and multi-decadal time scales. Possible connection between the occurrence of MBs and variability in wave climate in the southeastern AS is shown for the periods 7, 10–12, 18–20, and about 40 years correlating with fluctuation in the climate indices—IOD, ENSO, NINO3.4, and SOI. It is shown that intra-annual fluctuations in occurrence and duration of existence of MBs depend on the distribution of highest monthly averaged significant wave heights (SWHs) in the summer monsoon cycle.
Valproic Acid Protects Chondrocytes from LPS-Stimulated Damage via Regulating miR-302d-3p/ITGB4 Axis and Mediating the PI3K-AKT Signaling Pathway
Authors: Sun Long , Zheng Wei , Liu Qian-Dong , Ge Lei
Published: April 2021

Background: Osteoarthritis (OA) is one of the most common degenerative joint diseases characterized by increased apoptosis and autophagy deficiency. The investigation was performed to examine the effect of valproic acid (VPA) and molecular mechanism related to miR-302d-3p/ITGB4 axis in OA.

Methods: The OA clinical samples were obtained from the GEO database to analyze differentially expressed genes. An in vitro OA model was mimicked by LPS in CHON-001 cells. Autophagy-related genes were downloaded from the HADb website, and potential drugs were mined using the CTD website. The upstream factors of ITGB4 were predicted with bioinformatics analysis, which was validated by luciferase activity assay and RIP assay. Cell viability and apoptosis were evaluated using CCK-8 and flow cytometry. The expression levels, including ITGB4, miR-302d-3p, and autophagy-/PI3K-AKT pathway-related markers, were measured by qRT-PCR or/and western blot.

Results: Our results showed that miR-302d-3p inhibited cell viability and promoted apoptosis of LPS-treated CHON-001 cells by targeting ITGB4. VPA treatment remarkably alleviated LPS-stimulated injury in CHON-001 cells. The inhibitory effect of VPA on LPS-stimulated damage in CHON-001 cells was weakened by miR-302d-3p overexpression, while it was intensified because of ITGB4 upregulation. Mechanistically, VPA treatment induced a significant decrease in the levels of p-PI3K and p-AKT in LPS-stimulated CHON-001 cells through regulating miR-302d-3p/ITGB4 axis.

Conclusion: Overall, VPA treatment may ameliorate LPS-induced injury on chondrocytes via the regulation of miR-302d-3p/ITGB4 pair and the inactivation of the PI3K-AKT pathway.
The Emerging World of Membrane Vesicles: Functional Relevance, Theranostic Avenues and Tools for Investigating Membrane Function
Authors: Srivatsav Aswin T. , Kapoor Shobhna
Published: April 2021

Lipids are essential components of cell membranes and govern various membrane functions. Lipid organization within membrane plane dictates recruitment of specific proteins and lipids into distinct nanoclusters that initiate cellular signaling while modulating protein and lipid functions. In addition, one of the most versatile function of lipids is the formation of diverse lipid membrane vesicles for regulating various cellular processes including intracellular trafficking of molecular cargo. In this review, we focus on the various kinds of membrane vesicles in eukaryotes and bacteria, their biogenesis, and their multifaceted functional roles in cellular communication, host-pathogen interactions and biotechnological applications. We elaborate on how their distinct lipid composition of membrane vesicles compared to parent cells enables early and non-invasive diagnosis of cancer andtuberculosis, while inspiring vaccine development and drug delivery platforms. Finally, we discuss the use of membrane vesicles as excellent tools for investigating membrane lateral organization and protein sorting, which is otherwise challenging but extremely crucial for normal cellular functioning. We present current limitations in this field and how the same could be addressed to propel a fundamental and technology-oriented future for extracellular membrane vesicles.
Refinement of α-Synuclein Ensembles Against SAXS Data: Comparison of Force Fields and Methods
Authors: Ahmed Mustapha Carab , Skaanning Line K. , Jussupow Alexander , Newcombe Estella A. , Kragelund Birthe B. , Camilloni Carlo , Langkilde Annette E. , Lindorff-Larsen Kresten
Published: April 2021

The inherent flexibility of intrinsically disordered proteins (IDPs) makes it difficult to interpret experimental data using structural models. On the other hand, molecular dynamics simulations of IDPs often suffer from force-field inaccuracies, and long simulation times or enhanced sampling methods are needed to obtain converged ensembles. Here, we apply metainference and Bayesian/Maximum Entropy reweighting approaches to integrate prior knowledge of the system with experimental data, while also dealing with various sources of errors and the inherent conformational heterogeneity of IDPs. We have measured new SAXS data on the protein α-synuclein, and integrate this with simulations performed using different force fields. We find that if the force field gives rise to ensembles that are much more compact than what is implied by the SAXS data it is difficult to recover a reasonable ensemble. On the other hand, we show that when the simulated ensemble is reasonable, we can obtain an ensemble that is consistent with the SAXS data, but also with NMR diffusion and paramagnetic relaxation enhancement data.
The Effect of Cholesterol on Membrane-Bound Islet Amyloid Polypeptide
Authors: Christensen Mikkel , Berglund Nils A. , Schiøtt Birgit
Published: April 2021

Islet amyloid polypeptide (IAPP) is a proposed cause of the decreased beta-cell mass in patients with type-II diabetes. The molecular composition of the cell-membrane is important for regulating IAPP cytotoxicity and aggregation. Cholesterol is present at high concentrations in the pancreatic beta-cells, and in-vitro experiments have indicated that it affects the amyloid formation of IAPP either by direct interactions or by changing the properties of the membrane. In this study we apply atomistic, unbiased molecular dynamics simulations at a microsecond timescale to investigate the effect of cholesterol on membrane bound IAPP. Simulations were performed with various combinations of cholesterol, phosphatidylcholine (PC) and phosphatidylserine (PS) lipids. In all simulations, the helical structure of monomer IAPP was stabilized by the membrane. We found that cholesterol decreased the insertion depth of IAPP compared to pure phospholipid membranes, while PS lipids counteract the effect of cholesterol. The aggregation propensity has previously been proposed to correlate with the insertion depth of IAPP, which we found to decrease with the increased ordering of the lipids induced by cholesterol. Cholesterol is depleted in the vicinity of IAPP, and thus our results suggest that the effect of cholesterol is indirect.
Development and Validation of a Nomogram for Preoperative Prediction of Lymph Node Metastasis in Lung Adenocarcinoma Based on Radiomics Signature and Deep Learning Signature
Authors: Ran Jia , Cao Ran , Cai Jiumei , Yu Tao , Zhao Dan , Wang Zhongliang
Published: April 2021

Background and Purpose

The preoperative LN (lymph node) status of patients with LUAD (lung adenocarcinoma) is a key factor for determining if systemic nodal dissection is required, which is usually confirmed after surgery. This study aimed to develop and validate a nomogram for preoperative prediction of LN metastasis in LUAD based on a radiomics signature and deep learning signature.

Materials and Methods

This retrospective study included a training cohort of 200 patients, an internal validation cohort of 40 patients, and an external validation cohort of 60 patients. Radiomics features were extracted from conventional CT (computed tomography) images. T-test and Extra-trees were performed for feature selection, and the selected features were combined using logistic regression to build the radiomics signature. The features and weights of the last fully connected layer of a CNN (convolutional neural network) were combined to obtain a deep learning signature. By incorporating clinical risk factors, the prediction model was developed using a multivariable logistic regression analysis, based on which the nomogram was developed. The calibration, discrimination and clinical values of the nomogram were evaluated.

Results

Multivariate logistic regression analysis showed that the radiomics signature, deep learning signature, and CT-reported LN status were independent predictors. The prediction model developed by all the independent predictors showed good discrimination (C-index, 0.820; 95% CI, 0.762 to 0.879) and calibration (Hosmer-Lemeshow test, P=0.193) capabilities for the training cohort. Additionally, the model achieved satisfactory discrimination (C-index, 0.861; 95% CI, 0.769 to 0.954) and calibration (Hosmer-Lemeshow test, P=0.775) when applied to the external validation cohort. An analysis of the decision curve showed that the nomogram had potential for clinical application.

Conclusions

This study presents a prediction model based on radiomics signature, deep learning signature, and CT-reported LN status that can be used to predict preoperative LN metastasis in patients with LUAD.
Delirium in Children Undergoing Hematopoietic Cell Transplantation: A Multi-Institutional Point Prevalence Study
Authors: Traube Chani , Gerber Linda M. , Mauer Elizabeth A. , Small Keshia , Broglie Larisa , Chopra Yogi Raj , Duncan Christine N. , Ebens Christen L. , Fitzgerald Julie C. , Freedman Jason L. , Hudspeth Michelle P. , Hurley Caitlin , Mahadeo Kris M. , McArthur Jennifer , Shapiro Miriam C. , Sharron Matthew P. , Wall Donna A. , Zinter Matt S. , Greenwald Bruce M. , Silver Gabrielle , Boulad Farid
Published: April 2021

Introduction: Delirium occurs frequently in adults undergoing hematopoietic cell transplantation, with significant associated morbidity. Little is known about the burden of delirium in children in the peri-transplant period. This study was designed to determine delirium rates, define risk factors (demographic and treatment related), and establish feasibility of multi-institutional bedside screening for delirium in children undergoing hematopoietic cell transplant.

Methods: This is a multi-institutional point prevalence study. All subjects were prospectively screened for delirium twice daily using the Cornell Assessment of Pediatric Delirium over a 10-day period. De-identified data, including basic demographics and daily characteristics, were extracted from the electronic medical record.

Results: Eleven North American institutions were included, 106 children were enrolled, and 883 hospital days were captured. Delirium screening was successfully completed on more than 98% of the study days. Forty-eight children (45%) developed delirium over the course of the 10-day study. Children were diagnosed with delirium on 161/883 study days, for an overall delirium rate of 18% per day. Higher delirium rates were noted in children <5 years old (aOR 0.41 for children over 5 years), and in association with specific medications (melatonin, steroids, and tacrolimus).

Conclusion: Delirium was a frequent occurrence in our study cohort, with identifiable risk factors. Delirium screening is highly feasible in the pediatric hematopoietic cell transplant patient population. A large-scale prospective longitudinal study following children throughout their transplant course is urgently needed to fully describe the epidemiology of pediatric delirium, explore the effects of delirium on patient outcomes, and establish guidelines to prevent and treat delirium in the peri-transplant period.
Case Report: Outcome of Osimertinib Treatment in Lung Adenocarcinoma Patients With Acquired KRAS Mutations
Authors: Xiu Weigang , Zhang Qianqian , Yu Min , Huang Yin , Huang Meijuan
Published: April 2021

Background

Osimertinib belongs to the third-generation epidermal growth factor receptor tyrosine kinase inhibitor that has shown positive effects in treating lung adenocarcinoma cancer. However, the subsequent resistance to Osimertinib has become a clinical challenge.

Case Presentation

We present two lung adenocarcinoma cases that developed a resistance to Osimertinib. Among them, one patient attained both KRAS exon 2 and exon 3 mutations and was given paclitaxel (albumin-bound) plus carboplatin. The other patient exhibited a KRAS exon 3 mutation, so the paclitaxel (albumin-bound) plus nivolumab was administered. Eventually, the second patient manifested a better clinical outcome than the first.

Conclusion

These results provide supporting evidence that KRAS exon 3 (R68S) mutations may be associated with Osimertinib resistance in lung adenocarcinoma patients. This further reveals the relationship between subtypes of acquired KRAS mutations and the effect of therapeutic approaches. Moreover, the combination of chemotherapy and immune checkpoint inhibitors may generate a satisfying disease control.
Analysis of Adenoviral p53 Gene Therapy Clinical Trials in Recurrent Head and Neck Squamous Cell Carcinoma
Authors: Sobol Robert E. , Menander Kerstin B. , Chada Sunil , Wiederhold Dora , Sellman Beatha , Talbott Max , Nemunaitis John J.
Published: April 2021

Background

We conducted an analysis of previous adenoviral p53 (Ad-p53) treatment data in recurrent head and neck squamous cell carcinoma (HNSCC) patients to identify optimal Ad-p53 treatment methods for future clinical trials.

Methods

The analysis involved recurrent HNSCC patients treated with Ad-p53 for whom p53 genotyping and immunohistochemistry tumor biomarker studies had been performed (n = 70). Ad-p53 tumor treatment responses defined by RECIST 1.1 criteria were correlated with Ad-p53 dose and tumor p53 biomarkers. Gene expression profiles induced by Ad-p53 treatment were evaluated using the Nanostring IO 360 panel.

Results

Ad-p53 dose based upon the injected tumor volume had a critical effect on tumor responses. All responders had received Ad-p53 doses greater than 7 × 1010 viral particles/cm3 of tumor volume. There was a statistically significant difference in tumor responses between patients treated with greater than 7 × 1010 viral particles/cm3 compared to patients treated at lower Ad-p53 doses (Tumor Response 31% (9/29) for Ad-p53 > 7 × 1010 viral particles/cm3 versus 0% (0/25) for Ad-p53 < 7 × 1010 viral particles/cm3; p = 0.0023). All responders were found to have favorable p53 biomarker profiles defined by less than 20% p53 positive tumor cells by immunohistochemistry (IHC), wild type p53 gene sequence or p53 deletions, truncations, or frame-shift mutations without functional p53 tetramerization domains. Preliminary gene expression profiling results revealed that Ad-p53 treatment increased interferon signaling, decreased TGF-beta and beta-catenin signaling resulting in an increased CD8+ T cell signature which are associated with increased responses to immune checkpoint blockade.

Conclusions

Our findings have important implications for future p53 targeted cancer treatments and identify fundamental principles to guide Ad-p53 gene therapy. We discovered that previous Ad-p53 clinical trials were negatively impacted by the inclusion of patients with unfavorable p53 biomarker profiles and by under dosing of Ad-p53 treatment. Future Ad-p53 clinical trials should have favorable p53 biomarker profiles inclusion criteria and Ad-p53 dosing above 7 × 1010 viral particles/cm3 of injected tumor volume. Preliminary gene expression profiling identified p53 mechanisms of action associated with responses to immune checkpoint blockade supporting evaluation of Ad-p53 in combination with immune checkpoint inhibitors.
p53 Expression, Programmed Death Ligand 1, and Risk Factors in Urinary Tract Small Cell Carcinoma
Authors: Golijanin Borivoj , Gershman Boris , De Souza Andre , Kott Ohad , Carneiro Benedito A. , Mega Anthony , Golijanin Dragan J. , Amin Ali
Published: April 2021

Introduction: Small cell carcinoma of the urinary tract (SCCUT) is a rare finding with poor clinical course. This study sheds light on the molecular subtype and identifies risk factors in patients diagnosed with SCCUT.

Methods: Immunohistochemical expression of immunotherapy target programmed death ligand 1 (PD-L1) and luminal (GATA3), basal (p63), and p53 markers are assessed in patients diagnosed with SCCUT. Univariate analysis identified risk factors. Overall survival (OS) is computed using the Kaplan–Meier method.

Results: Tissue was available for 70.2% (33/47). All showed a high PD-L1 expression phenotype. p53 is seen in 93.9% (31/33), mostly as overexpression, GATA3 in 45.5% (15/33), and p63 in 57.6% (19/33). For the entire cohort (n = 47), 1-year survival was 59.6%, and the median OS was 17 months. Univariate analysis shows that chemotherapy [hazard ratio (HR) = 0.29, 95% confidence interval (CI) = 0.14–0.61, p = 0.001], radical surgery (HR = 0.37, 95% CI = 0.18–0.76, p = 0.007), and diagnosis of non-pure SCCUT (HR = 0.44, 95% CI = 0.22–0.86, p = 0.02) are favorable prognostic features. Metastasis had negative associations with survival (HR = 2.1, 95% CI = 1.1–4.2, p = 0.03).

Conclusions: In this series, pure and mixed SCCUT are characterized by p53 overexpression and a high PD-L1 phenotype. Histology of non-pure SCCUT is a positive prognosticator, and radical cystectomy or chemotherapy can improve OS. These findings demonstrate that SCCUT may be eligible for PD-L1 immunotherapy.
Coiled-Coil Domain-Containing 68 Downregulation Promotes Colorectal Cancer Cell Growth by Inhibiting ITCH-Mediated CDK4 Degradation
Authors: Wang Cong , Li Hongyan , Wu Lei , Jiao Xueli , Jin Zihui , Zhu Yujie , Fang Ziling , Zhang Xiaodong , Huang Haishan , Zhao Lingling
Published: April 2021

Coiled-coil domain-containing 68 (CCDC68) plays different roles in cancer and is predicted as a tumor suppressor in human colorectal cancer (CRC). However, the specific role of CCDC68 in CRC and the underlying mechanisms remain unknown. Here, we showed that CCDC68 expression was lower in CRC than that in corresponding normal tissues, and CCDC68 level was positively correlated with disease-free survival. Ectopic expression of CCDC68 decreased CRC cell proliferation in vitro and suppressed the growth of CRC xenograft tumors in vivo. CCDC68 caused G0/G1 cell cycle arrest, downregulated CDK4, and upregulated ITCH, the E3 ubiquitin ligase responsible for CDK4 protein degradation. This increased CDK4 degradation, which decreased CDK4 protein levels and inhibited CRC tumor growth. Collectively, the present results identify a novel CDK4 regulatory axis consisting of CCDC68 and ITCH, which suggest that CCDC68 is a promising target for the treatment of CRC.