bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drivers of Phytoplankton Blooms in Hawaii: A Regional Model Study
Authors: Friedrich T. , Powell B. S. , Stock C. A. , Hahn‐Woernle L. , Dussin R. , Curchitser E. N. 
Published: May 2021

AbstractThe region around the main Hawaiian Islands (MHI) is characterized by a permanent thermocline, and numerous processes have been proposed to facilitate phytoplankton blooms in this oligotrophic province. Here, we use a coupled physical‐biogeochemical model of the MHI to elucidate some of the different dynamics behind phytoplankton blooms. The model permits submesoscale processes and is integrated for the years 2010–2017 embedded in a physical state‐estimate reanalysis using nearly 50 million observations. Model results exhibit good agreement between simulated values and observations at Station ALOHA for physical and biogeochemical parameters. The overall levels and the amplitude of the seasonal cycles are well captured for many variables. We show that variations in net primary production are mainly driven by domain‐wide seasonal cycles of light and nitrogen fixers, respectively, as well as short‐lived, stochastic bloom events resulting from the formation of eddies to the west of the island of Hawaii. Furthermore, sporadic wind‐ and current‐driven upwelling is resulting in ephemeral enhancements of nearshore phytoplankton blooms mainly on the northeastern side of the islands.
Cadherin-13 is a critical regulator of GABAergic modulation in human stem-cell-derived neuronal networks
Authors: Mossink Britt , van Rhijn Jon-Ruben , Wang Shan , Linda Katrin , Vitale Maria R. , Zöller Johanna E. M. , van Hugte Eline J. H. , Bak Jitske , Verboven Anouk H. A. , Selten Martijn , Negwer Moritz , Latour Brooke L. , van der Werf Ilse , Keller Jason M. , Klein Gunnewiek Teun M. , Schoenmaker Chantal , Oudakker Astrid , Anania Alessia , Jansen Sophie , Lesch Klaus-Peter , Frega Monica , van Bokhoven Hans , Schubert Dirk , Nadif Kasri Nael 
Published: May 2021

AbstractActivity in the healthy brain relies on a concerted interplay of excitation (E) and inhibition (I) via balanced synaptic communication between glutamatergic and GABAergic neurons. A growing number of studies imply that disruption of this E/I balance is a commonality in many brain disorders; however, obtaining mechanistic insight into these disruptions, with translational value for the patient, has typically been hampered by methodological limitations.Cadherin-13(CDH13) has been associated with autism and attention-deficit/hyperactivity disorder. CDH13 localizes at inhibitory presynapses, specifically of parvalbumin (PV) and somatostatin (SST) expressing GABAergic neurons. However, the mechanism by which CDH13 regulates the function of inhibitory synapses in human neurons remains unknown. Starting from human-induced pluripotent stem cells, we established a robust method to generate a homogenous population of SST and MEF2C (PV-precursor marker protein) expressing GABAergic neurons (iGABA) in vitro, and co-cultured these with glutamatergic neurons at defined E/I ratios on micro-electrode arrays. We identified functional network parameters that are most reliably affected by GABAergic modulation as such, and through alterations of E/I balance by reduced expression of CDH13 in iGABAs. We found that CDH13 deficiency in iGABAs decreased E/I balance by means of increased inhibition. Moreover, CDH13 interacts with Integrin-β1 and Integrin-β3, which play opposite roles in the regulation of inhibitory synaptic strength via this interaction. Taken together, this model allows for standardized investigation of the E/I balance in a human neuronal background and can be deployed to dissect the cell-type-specific contribution of disease genes to the E/I balance.
The viral hypothesis: how herpesviruses may contribute to Alzheimer’s disease
Authors: Wainberg Michael , Luquez Tain , Koelle David M. , Readhead Ben , Johnston Christine , Darvas Martin , Funk Cory C. 
Published: May 2021

AbstractThe hypothesis that infectious agents, particularly herpesviruses, contribute to Alzheimer’s disease (AD) pathogenesis has been investigated for decades but has long engendered controversy. In the past 3 years, several studies in mouse models, human tissue models, and population cohorts have reignited interest in this hypothesis. Collectively, these studies suggest that many of the hallmarks of AD, like amyloid beta production and neuroinflammation, can arise as a protective response to acute infection that becomes maladaptive in the case of chronic infection. We place this work in its historical context and explore its etiological implications.
Extended real-world experience with the ILUVIEN® (fluocinolone acetonide) implant in the United Kingdom: 3-year results from the Medisoft® audit study
Authors: Bailey Clare , Chakravarthy Usha , Lotery Andrew , Menon Geeta , Talks James ,   for the Medisoft Audit Group
Published: May 2021

Abstract
Background
This study aimed to assess the long-term effectiveness of the 0.2 μg/day fluocinolone acetonide (FAc) implant over ≥3 years for patients with diabetic macular oedema.

Methods
A retrospective audit of pseudo-anonymised data from patients with chronic diabetic macular oedema (cDMO) and treated with the FAc implant across 14 UK clinical sites. Safety and clinical effectiveness were measured.

Results
Two-hundred and fifty-six eyes had ≥3 years of follow-up (mean 4.28 years), during which a mean of 1.14 FAc implants were used per eye. Mean best-recorded visual acuity (BRVA) increased from 52.6 to 56.7 letters at month 3 and remained stable thereafter; this trend was also seen in pseudophakic eyes. The proportion of patients attaining a BRVA ≥6/12 increased from 17% at baseline to 27% 1 month after FAc implant and remained stable above 30% from month 12 onwards. Eyes with no prior history of intraocular pressure (IOP)-related events required significantly less treatment-emergent IOP-lowering medication than those with a prior history of IOP events (17.9% vs. 50.0% of eyes; p < 0.001). The incidence of an IOP increase of ≥10 mmHg, use of IOP-lowering medication, laser trabeculoplasty and IOP-lowering surgery was 28.9%, 29.7%, 0.8% and 2.7%, respectively, for the whole cohort. There were significant reductions in mean central foveal thickness and macular volume (p < 0.001).

Conclusions
The FAc implant was well tolerated, with predictable and manageable IOP-related events while delivering a continuous microdose of corticosteroid to eyes with cDMO, providing prolonged vision preservation and a reduced number of treatments.
Capturing the clinical decision-making processes of expert and novice diabetic retinal graders using a ‘think-aloud’ approach
Authors: Curran Katie , Congdon Nathan , Peto Tunde , Dardis Catherine , Nguyen Quan Nhu , Hoang Tung Thanh , Bannon Finian , Luu An , Mai Tung Quoc , Nguyen Van Thu , Thi Nguyen Hue , Tran Huong , Tran Hoang Huy , Lohfeld Lynne 
Published: May 2021

Abstract
Background
Diabetic eye screening programmes have been developed worldwide based on evidence that early detection and treatment of diabetic retinopathy are crucial to preventing sight loss. However, little is known about the decision-making processes and training needs of diabetic retinal graders, particularly in low- and middle-income countries.

Objectives
To provide data for improving evidence-based diabetic retinopathy training to help novice graders process fundus images more like experts.

Subjects/methods
This is a mixed-methods qualitative study conducted in southern Vietnam and Northern Ireland. Novice diabetic retinal graders in Vietnam (n = 18) and expert graders in Northern Ireland (n = 5) were selected through a purposive sampling technique. Data were collected from 21st February to 3rd September 2019. The interviewer used neutral prompts during think-aloud sessions to encourage participants to verbalise their thought processes while grading fundus images from anonymised patients, followed by semi-structured interviews. Thematic framework analysis was used to identify themes, supported by illustrative quotes from interviews. Mann–Whitney U tests were used to compare graders’ performance.

Results
Expert graders used a more systematic approach when grading images, considered all four images per patient and used available software tools such as red-free filters prior to making a decision on management. The most challenging features for novice graders were intra-retinal microvascular abnormalities and new vessels, which were more accurately identified by experts.

Conclusion
Taking more time to grade fundus images and adopting a protocol-driven “checklist” approach may help novice graders to function more like experts.
Automatic wavelet-based 3D nuclei segmentation and analysis for multicellular embryo quantification
Authors: Wu Tzu-Ching , Wang Xu , Li Linlin , Bu Ye , Umulis David M. 
Published: May 2021

AbstractIdentification of individual cells in tissues, organs, and in various developing systems is a well-studied problem because it is an essential part of objectively analyzing quantitative images in numerous biological contexts. We developed a size-dependent wavelet-based segmentation method that provides robust segmentation without any preprocessing, filtering or fine-tuning steps, and is robust to the signal-to-noise ratio. The wavelet-based method achieves robust segmentation results with respect to True Positive rate, Precision, and segmentation accuracy compared with other commonly used methods. We applied the segmentation program to zebrafish embryonic development IN TOTO for nuclei segmentation, image registration, and nuclei shape analysis. These new approaches to segmentation provide a means to carry out quantitative patterning analysis with single-cell precision throughout three dimensional tissues and embryos and they have a high tolerance for non-uniform and noisy image data sets.
The effects of the exposure to neurotoxic elements on Italian schoolchildren behavior
Authors: Renzetti Stefano , Cagna Giuseppa , Calza Stefano , Conversano Michele , Fedrighi Chiara , Forte Giovanni , Giorgino Augusto , Guazzetti Stefano , Majorani Costanza , Oppini Manuela , Peli Marco , Petrucci Francesco , Pino Anna , Placidi Donatella , Senofonte Oreste , Zoni Silvia , Alimonti Alessandro , Lucchini Roberto G. 
Published: May 2021

AbstractNeurodevelopmental disorders are constantly increasing on a global scale. Some elements like heavy metals are known to be neurotoxic. In this cross-sectional study we assessed the neurobehavioral effect of the exposure to trace elements including lead, mercury, cadmium, manganese, arsenic and selenium and their interactions among 299 schoolchildren residing in the heavily polluted Taranto area in Italy. Whole blood, urine and hair were collected for metal analyses, while the Child Behavior Checklist and the Social Responsiveness Scale, administered to the main teacher and the mothers were considered to identify behavioral problems in children. Blood lead mainly influenced social problems, aggressive behavior, externalizing and total problems. Urinary arsenic showed an impact on anxiety and depression, somatic problems, attention problems and rule breaking behavior. A significant interaction between lead and arsenic was observed, with a synergistic effect of the two metals increasing the risk of attention problems, aggressive behavior, externalizing problems and total problems. Overall, we were able to test that higher blood lead, urinary arsenic concentrations and their interaction increase the risk of neurobehavioral problems. This is in line with the U.S. Environmental Protection Agency’s priority list of hazardous substances where arsenic and lead are ranked as first and second respectively.
Selection and validation of appropriate reference genes for RT-qPCR analysis of flowering stages and different genotypes of Iris germanica L
Authors: Wang Yinjie , Zhang Yongxia , Liu Qingquan , Tong Haiying , Zhang Ting , Gu Chunsun , Liu Liangqin , Huang Suzhen , Yuan Haiyan 
Published: May 2021

AbstractIris germanica L. is a perennial herbaceous plant that has been widely cultivated worldwide and is popular for its elegant and vibrantly colorful flowers. Selection of appropriate reference genes is the prerequisite for accurate normalization of target gene expression by quantitative real-time PCR. However, to date, the most suitable reference genes for flowering stages have not been elucidated in I. germanica. In this study, eight candidate reference genes were examined for the normalization of RT-qPCR in three I. germanica cultivars, and their stability were evaluated by four different algorithms (GeNorm, NormFinder, BestKeeper, and Ref-finder). The results revealed that IgUBC and IgGAPDH were the most stable reference genes in ‘00246’ and ‘Elizabeth’, and IgTUB and IgUBC showed stable expression in ‘2010200’. IgUBC and IgGAPDH were the most stable in all samples, while IgUBQ showed the least stability. Finally, to validate the reliability of the selected reference genes, the expression patterns of IgFT (Flowering Locus T gene) was analyzed and emphasized the importance of appropriate reference gene selection. This work presented the first systematic study of reference genes selection during flower bud development and provided guidance to research of the molecular mechanisms of flowering stages in I. germanica.
Bortezomib induces methylation changes in neuroblastoma cells that appear to play a significant role in resistance development to this compound
Authors: Łuczkowska Karolina , Sokolowska Katarzyna Ewa , Taryma-Lesniak Olga , Pastuszak Krzysztof , Supernat Anna , Bybjerg-Grauholm Jonas , Hansen Lise Lotte , Paczkowska Edyta , Wojdacz Tomasz K. , Machaliński Bogusław 
Published: May 2021

AbstractThe anticancer activity of bortezomib (BTZ) has been increasingly studied in a number of indications and promising results for the use of this treatment have been shown in neuroblastoma. As BTZ treatment is usually administered in cycles, the development of resistance and side effects in patients undergoing therapy with BTZ remains a major challenge for the clinical usage of this compound. Common resistance development also means that certain cells are able to survive BTZ treatment and bypass molecular mechanisms that render BTZ anticancer activity. We studied the methylome of neuroblastoma cells that survived BTZ treatment. Our results indicate that BTZ induces pronounced genome wide methylation changes in cells which recovered from the treatment. Functional analyses of identified methylation changes demonstrated they were involved in key cancer pathology pathways. These changes may allow the cells to bypass the primary anticancer activity of BTZ and develop a treatment resistant and proliferative phenotype. To study whether cells surviving BTZ treatment acquire a proliferative phenotype, we repeatedly treated cells which recovered from the first round of BTZ treatment. The repetitive treatment led to induction of the extraordinary proliferative potential of the cells, that increased with subsequent treatments. As we did not observe similar effects in cells that survived treatment with lenalidomide, and non-treated cells cultured under the same experimental conditions, this phenomenon seems to be BTZ specific. Overall, our results indicate that methylation changes may play major role in the development of BTZ resistance.
Searching for pneumothorax in x-ray images using autoencoded deep features
Authors: Sze-To Antonio , Riasatian Abtin , Tizhoosh H. R. 
Published: May 2021

AbstractFast diagnosis and treatment of pneumothorax, a collapsed or dropped lung, is crucial to avoid fatalities. Pneumothorax is typically detected on a chest X-ray image through visual inspection by experienced radiologists. However, the detection rate is quite low due to the complexity of visual inspection for small lung collapses. Therefore, there is an urgent need for automated detection systems to assist radiologists. Although deep learning classifiers generally deliver high accuracy levels in many applications, they may not be useful in clinical practice due to the lack of high-quality and representative labeled image sets. Alternatively, searching in the archive of past cases to find matching images may serve as a “virtual second opinion” through accessing the metadata of matched evidently diagnosed cases. To use image search as a triaging or diagnosis assistant, we must first tag all chest X-ray images with expressive identifiers, i.e., deep features. Then, given a query chest X-ray image, the majority vote among the top k retrieved images can provide a more explainable output. In this study, we searched in a repository with more than 550,000 chest X-ray images. We developed the Autoencoding Thorax Net (short AutoThorax -Net) for image search in chest radiographs. Experimental results show that image search based on AutoThorax -Net features can achieve high identification performance providing a path towards real-world deployment. We achieved 92% AUC accuracy for a semi-automated search in 194,608 images (pneumothorax and normal) and 82% AUC accuracy for fully automated search in 551,383 images (normal, pneumothorax and many other chest diseases).
Southward growth of Mauna Loa’s dike-like magma body driven by topographic stress
Authors: Varugu Bhuvan , Amelung Falk 
Published: May 2021

AbstractSpace-geodetic observations of a new period of inflation at Mauna Loa volcano, Hawaii, recorded an influx of 0.11 km3 of new magma into it’s dike-like magma body during 2014–2020. The intrusion started after at least 4 years of decollement slip under the eastern flank creating > 0.15 MPa opening stresses in the rift zone favorable for magma intrusion. Volcanoes commonly respond to magma pressure increase with the injection of a dike, but Mauna Loa responded with lateral growth of its magma body in the direction of decreasing topographic stress. In 2017, deformation migrated back, and inflation continued at the pre-2015 location. Geodetic inversions reveal a 8 × 8.5, 10 × 3 and 9 × 4 km2 dike-like magma body during the 2014–2015, 2015–2018 and 2018–2020 periods, respectively, and an average decollement slip of ~ 23 cm/year along a 10 × 5 km2 fault. The evolution of the dike-like magma body including the reduction in vertical extent is consistent with a slowly ascending dike propagating laterally when encountering a stress barrier and freezing its tip when magma influx waned. Overall, the magma body widened about 4.5 m during 2002–2020.
Environmental determinants of COVID-19 transmission across a wide climatic gradient in Chile
Authors: Correa-Araneda Francisco , Ulloa-Yáñez Alfredo , Núñez Daniela , Boyero Luz , Tonin Alan M. , Cornejo Aydeé , Urbina Mauricio A. , Díaz María Elisa , Figueroa-Muñoz Guillermo , Esse Carlos 
Published: May 2021

AbstractSeveral studies have examined the transmission dynamics of the novel COVID-19 disease in different parts of the world. Some have reported relationships with various environmental variables, suggesting that spread of the disease is enhanced in colder and drier climates. However, evidence is still scarce and mostly limited to a few countries, particularly from Asia. We examined the potential role of multiple environmental variables in COVID-19 infection rate [measured as mean relative infection rate = (number of infected inhabitants per week / total population) × 100.000) from February 23 to August 16, 2020 across 360 cities of Chile. Chile has a large climatic gradient (≈ 40º of latitude, ≈ 4000 m of altitude and 5 climatic zones, from desert to tundra), but all cities share their social behaviour patterns and regulations. Our results indicated that COVID-19 transmission in Chile was mostly related to three main climatic factors (minimum temperature, atmospheric pressure and relative humidity). Transmission was greater in colder and drier cities and when atmospheric pressure was lower. The results of this study support some previous findings about the main climatic determinants of COVID-19 transmission, which may be useful for decision-making and management of the disease.
Cyclooxygenase-2 induces neoplastic transformation by inhibiting p53-dependent oncogene-induced senescence
Authors: Lee Hyeon Ju , Kim So Ra , Jung Yu-Jin , Han Jeong A. 
Published: May 2021

AbstractMuch in vivo evidence indicates that cyclooxygenase-2 (COX-2) is deeply involved in tumorigenesis. Although it has been proposed that COX-2-derived pro-inflammatory prostanoids mediate the tumorigenic activity of COX-2, the tumorigenic mechanisms of COX-2 are not yet fully understood. Here, we investigated the mechanism by which COX-2 causes transformation from normal cells to malignant cells by using normal murine or human cells. We found that COX-2 inhibits the pro-senescent function of p53 under oncogenic RAS activation, by which it prevents oncogene-induced senescence (OIS) and induces neoplastic transformation. We also found that COX-2 physically interacts with p53 in the nucleus under oncogenic RAS activation, and that this COX-2-p53 interaction rather than the catalytic activity is involved in the COX-2-mediated inhibition of the pro-senescent function of p53 and OIS, and induction of neoplastic transformation. These findings strongly suggest that the oncogenic property of COX-2 is closely related to its ability to inactivate p53 under strong mitogenic signals, and that aberrant activation of the COX-2/a mitogenic oncogene combination can be a potent driving force for tumorigenesis. This study might contribute to our understanding of the molecular basis for the tumorigenic activity of COX-2 and the development of novel anti-tumor drugs targeting COX-2-p53 interactions.
Atherogenic index of plasma as predictors for metabolic syndrome, hypertension and diabetes mellitus in Taiwan citizens: a 9-year longitudinal study
Authors: Li Yen-Wei , Kao Tung-Wei , Chang Pi-Kai , Chen Wei-Liang , Wu Li-Wei 
Published: May 2021

AbstractDeeply involved with dyslipidemia, cardiovascular disease has becoming the leading cause of mortality since the early twentieth century in the modern world. Whose correlation with metabolic syndrome (MetS), hypertension and type 2 diabetes mellitus (T2DM) has been well established. We conducted a 9-year longitudinal study to identify the association between easily measured lipid parameters, future MetS, hypertension and T2DM by gender and age distribution. Divided into three groups by age (young age: < 40, middle age: ≥ 40 and < 65 and old age: ≥ 65), 7670 participants, receiving standard medical inspection at Tri-Service General Hospital (TSGH) in Taiwan, had been enrolled in this study. Atherogenic index of plasma (AIP) was a logarithmically transformed ratio of triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C). Through multivariate regression analyses, the hazard ratio (HR) of AIP for MetS, hypertension and T2DM were illustrated. AIP revealed significant association with all the aforementioned diseases through the entire three models for both genders. Additionally, AIP revealed significant correlation which remained still after fully adjustment in MetS, hypertension, and T2DM groups for subjects aged 40–64-year-old. Nevertheless, for participants aged above 65-year-old, AIP only demonstrated significant association in MetS group. Our results explore the promising value of AIP to determine the high-risk subjects, especially meddle-aged ones, having MetS, hypertension, and T2DM in the present and the future.