bluuebunny/crossref_metadata_2025 huggingface dataset:
Utility of Red Tide (Karenia brevis) Monitoring Data as a Predictive Tool to Estimate Brevetoxin Accumulation in Live, Free-Ranging Marine Mammals
Authors: Fire Spencer E. , Miller Glenn A. , Sabater Edna R. , Wells Randall S.
Published: March 2021

Exposure of common bottlenose dolphins (Tursiops truncatus) to brevetoxins (PbTx) produced by blooms of the toxic phytoplanktonKarenia brevisfrequently results in severe health impacts, including illness and large-scale mortality events. Although PbTx accumulation in dead-stranded dolphins is well documented, there are limited data for corresponding brevetoxin exposure in live dolphins. In addition, the severity of impacts on living survivors of such toxic blooms is difficult to assess due to a lack of data on the relationship betweenK. brevisbloom severity and corresponding PbTx concentrations in exposed animals. Here we present results of PbTx analysis of urine, serum, milk, gastric fluid, and feces samples collected from live, free-ranging dolphins (n= 253) from Sarasota Bay, Florida during 2000–2018, and investigate the relationship between PbTx concentrations detected and correspondingK. breviscell abundances that are temporally (within 30 days) and spatially (within 16 km) associated with each individual. We found that 28% of dolphins were associated with elevatedK. brevisabundances (10,000–60,000,000 cells/L), with 41% (n= 104) of dolphins testing positive for PbTx in at least one sample type. The proportion of PbTx-positive animals was significantly greater in animals exposed to elevated cell abundances vs. those exposed to background cell abundances (<10,000 cells/L), with 60 and 34% testing positive, respectively (p< 0.001). PbTx was detected most frequently in feces (57%,n= 38), followed by gastric (35%,n= 37), urine (32%,n= 55), and blood (7%,n= 17). PbTx concentrations by sample type were highest in feces (2–231 ng/g; mean 46), followed by urine (0.8–90 ng/g; mean 7.2), gastric (0.8–61 ng/g; mean 12), and blood (0.3–5 ng/g; mean 1.3). Regression analyses ofK. breviscell abundance as an index of exposure vs. corresponding PbTx concentration found no statistically significant relationship for feces (p= 0.120), gastric (p= 0.349), urine (p= 0.053), or blood (p= 0.729) samples. PbTx concentrations typically ranged over two orders of magnitude between minimum and maximum values and did not scale with corresponding indices of exposure, which ranged over three orders of magnitude or more. Our results indicate thatK. breviscell abundance alone is a poor predictor of brevetoxin accumulation in bottlenose dolphins, and suggest that alternative methods (e.g., endocrine or immunological biomarkers) should be investigated as more appropriate methods for determining the severity of health impacts due to red tides.
Deformation Texture Evolution in Flat Profile AlMgSi Extrusions: Experiments, FEM, and Crystal Plasticity Modeling
Authors: Manik Tomas , Marthinsen Knut , Zhang Kai , Aria Arash Imani , Holmedal Bjørn
Published: March 2021

In the present work, the deformation textures during flat profile extrusion from round billets of an AA6063 and an AA6082 aluminium alloy have been numerically modeled by coupling FEM flow simulations and crystal plasticity simulations and compared to experimentally measured textures obtained by electron back-scatter diffraction (EBSD). The AA6063 alloy was extruded at a relatively low temperature (350°C), while the AA6082 alloy, containing dispersoids that prevent recrystallization, was extruded at a higher temperature (500°C). Both alloys were water quenched at the exit of the die, to maintain the deformation texture after extrusion. In the center of the profiles, both alloys exhibit a conventional β-fiber texture and the Cube component, which was significantly stronger at the highest extrusion temperature. The classical full-constraint (FC)-Taylor and the Alamel grain cluster model were employed for the texture predictions. Both models were implemented using the regularized single crystal yield surface. This approach enables activation of any number and type of slip systems, as well as accounting for strain rate sensitivity, which are important at 350°C and 500°C. The strength of the nonoctahedral slips and the strain-rate sensitivity were varied by a global optimization algorithm. At 350°C, a good fit could be obtained both with the FC Taylor and the Alamel model, although the Alamel model clearly performs the best. However, even with rate sensitivity and nonoctahedral slip systems invoked, none of the models are capable of predicting the strong Cube component observed experimentally at 500°C.
Evolution of Pathology Patterns in Persons Who Died From COVID-19 in Italy: A National Study Based on Death Certificates
Authors: Grippo Francesco , Grande Enrico , Maraschini Alice , Navarra Simone , Pappagallo Marilena , Marchetti Stefano , Crialesi Roberta , Frova Luisa , Orsi Chiara , Simeoni Silvia , Carinci Annamaria , Loreto Giuseppe , Donfrancesco Chiara , Lo Noce Cinzia , Palmieri Luigi , Andrianou Xanthi , Urdiales Alberto Mateo , Onder Graziano , Minelli Giada ,   Italian National Institute of Health COVID-19 Mortality Group
Published: March 2021

Background: In Italy, during the first epidemic wave of 2020, the peak of coronavirus disease 2019 (COVID-19) mortality was reached at the end of March. Afterward, a progressive reduction was observed until much lower figures were reached during the summer, resulting from the contained circulation of SARS-CoV-2. This study aimed to determine if and how the pathological patterns of the individuals deceased from COVID-19 changed during the phases of epidemic waves in terms of: (i) main cause of death, (ii) comorbidities, and (iii) complications related to death.

Methods: Death certificates of persons who died and tested positive for SARS-CoV-2, provided by the National Surveillance system, were coded according to ICD rev10. Deaths due to COVID-19 were defined as those in which COVID-19 was the underlying cause of death.

Results: The percentage of COVID-19 deaths varied over time. It decreased in the downward phase of the epidemic curve (76.6 vs. 88.7%). In February–April 2020, hypertensive heart disease was mentioned as a comorbidity in 18.5% of death certificates, followed by diabetes (15.9% of cases), ischemic heart disease (13.1%), and neoplasms (12.1%). In May–September, the most frequent comorbidity was neoplasms (17.3% of cases), followed by hypertensive heart disease (14.9%), diabetes (14.8%), and dementia/Alzheimer's disease (11.9%). The most mentioned complications in both periods were pneumonia and respiratory failure with a frequency far higher than any other condition (78.4% in February–April 2020 and 63.7% in May–September 2020).

Discussion: The age of patients dying from COVID-19 and their disease burden increased in the May–September 2020 period. A more serious disease burden was observed in this period, with a significantly higher frequency of chronic pathologies. Our study suggests better control of the virus' lethality in the second phase of the epidemic, when the health system was less burdened. Moreover, COVID-19 care protocols had been created in hospitals, and knowledge about the diagnosis and treatment of COVID-19 had improved, potentially leading to more accurate diagnosis and better treatment. All these factors may have improved survival in patients with COVID-19 and led to a shift in mortality to older, more vulnerable, and complex patients.
Examining the Evidence for Regulated and Programmed Cell Death in Cyanobacteria. How Significant Are Different Forms of Cell Death in Cyanobacteria Population Dynamics?
Authors: Franklin Daniel J.
Published: March 2021

Cyanobacteria are ancient and versatile members of almost all aquatic food webs. In freshwater ecosystems some cyanobacteria form “bloom” populations containing potent toxins and such blooms are therefore a key focus of study. Bloom populations can be ephemeral, with rapid population declines possible, though the factors causing such declines are generally poorly understood. Cell death could be a significant factor linked to population decline. Broadly, three forms of cell death are currently recognized – accidental, regulated and programmed – and efforts are underway to identify these and standardize the use of cell death terminology, guided by work on better-studied cells. For cyanobacteria, the study of such differing forms of cell death has received little attention, and classifying cell death across the group, and within complex natural populations, is therefore hard and experimentally difficult. The population dynamics of photosynthetic microbes have, in the past, been principally explained through reference to abiotic (“bottom-up”) factors. However, it has become clearer that in general, only a partial linkage exists between abiotic conditions and cyanobacteria population fluctuations in many situations. Instead, a range of biotic interactions both within and between cyanobacteria, and their competitors, pathogens and consumers, can be seen as the major drivers of the observed population fluctuations. Whilst some evolutionary processes may theoretically account for the existence of an intrinsic form of cell death in cyanobacteria, a range of biotic interactions are also likely to frequently cause the ecological incidence of cell death. New theoretical models and single-cell techniques are being developed to illuminate this area. The importance of such work is underlined by both (a) predictions of increasing cyanobacteria dominance due to anthropogenic factors and (b) the realization that influential ecosystem modeling work includes mortality terms with scant foundation, even though such terms can have a very large impact on model predictions. These ideas are explored and a prioritization of research needs is proposed.
Doxycycline Interferes With Tau Aggregation and Reduces Its Neuronal Toxicity
Authors: Medina Luciana , González-Lizárraga Florencia , Dominguez-Meijide Antonio , Ploper Diego , Parrales Valeria , Sequeira Sabrina , Cima-Omori Maria-Sol , Zweckstetter Markus , Del Bel Elaine , Michel Patrick P. , Outeiro Tiago Fleming , Raisman-Vozari Rita , Chehín Rosana , Socias Sergio B.
Published: March 2021

Tauopathies are neurodegenerative disorders with increasing incidence and still without cure. The extensive time required for development and approval of novel therapeutics highlights the need for testing and repurposing known safe molecules. Since doxycycline impacts α-synuclein aggregation and toxicity, herein we tested its effect on tau. We found that doxycycline reduces amyloid aggregation of the 2N4R and K18 isoforms of tau protein in a dose-dependent manner. Furthermore, in a cell free system doxycycline also prevents tau seeding and in cell culture reduces toxicity of tau aggregates. Overall, our results expand the spectrum of action of doxycycline against aggregation-prone proteins, opening novel perspectives for its repurposing as a disease-modifying drug for tauopathies.
Human Lateralization, Maternal Effects and Neurodevelopmental Disorders
Authors: Malatesta Gianluca , Marzoli Daniele , Prete Giulia , Tommasi Luca
Published: March 2021

In humans, behavioral laterality and hemispheric asymmetries are part of a complex biobehavioral system in which genetic factors have been repeatedly proposed as developmental determinants of both phenomena. However, no model solely based on genetic factors has proven conclusive, pushing towards the inclusion of environmental and epigenetic factors into the system. Moreover, it should be pointed out that epigenetic modulation might also account for why certain genes are expressed differently in parents and offspring. Here, we suggest the existence of a sensitive period in early postnatal development, during which the exposure to postural and motor lateral biases, expressed in interactive sensorimotor coordination with the caregiver, canalizes hemispheric lateralization in the “typical” direction. Despite newborns and infants showing their own inherent asymmetries, the canalizing effect of the interactive context owes most to adult caregivers (usually the mother), whose infant-directed lateralized behavior might have been specifically selected for as a population-level trait, functional to confer fitness to offspring. In particular, the case of the left-cradling bias (LCB; i.e., the population-level predisposition of mothers to hold their infants on the left side) represents an instance of behavioral trait exhibiting heritability along the maternal line, although no genetic investigation has been carried out so far. Recent evidence, moreover, seems to suggest that the reduction of this asymmetry is related to several unfavorable conditions, including neurodevelopmental disorders. Future studies are warranted to understand whether and how genetic and epigenetic factors affect the lateralization of early mother-infant interaction and the proneness of the offspring to neurodevelopmental disorders.
Comparison of the Impact of Zika and Dengue Virus Infection, and Other Acute Illnesses of Unidentified Origin on Cognitive Functions in a Prospective Cohort in Chiapas Mexico
Authors: Belaunzarán-Zamudio Pablo F. , Ortega-Villa Ana M. , Mimenza-Alvarado Alberto J. , Guerra-De-Blas Paola Del Carmen , Aguilar-Navarro Sara G. , Sepúlveda-Delgado Jesús , Hunsberger Sally , Salgado Raydel Valdés , Ramos-Castañeda José , Rincón León Héctor Armando , Rodríguez de La Rosa Paul , Nájera Cancino José Gabriel , Beigel John , Caballero Sosa Sandra , Ruiz Hernández Emilia , Powers John H. , Ruiz-Palacios Guillermo M. , Lane Clifford
Published: March 2021

Zika has been associated with a variety of severe neurologic manifestations including meningitis and encephalitis. We hypothesized that it may also cause mild to subclinical neurocognitive alterations during acute infection or over the long term. In this observational cohort study, we explored whether Zika cause subclinical or mild neurocognitive alterations, estimate its frequency and duration, and compare it to other acute illnesses in a cohort of people with suspected Zika infection, in the region of Tapachula in Chiapas, Mexico during 2016–2018. We enrolled patients who were at least 12 years old with suspected Zika virus infection and followed them up for 6 months. During each visit participants underwent a complete clinical exam, including a screening test for neurocognitive dysfunction (Montreal Cognitive Assessment score). We enrolled 406 patients [37 with Zika, 73 with dengue and 296 with other acute illnesses of unidentified origin (AIUO)]. We observed a mild and transient impact over cognitive functions in patients with Zika, dengue and with other AIUO. The probability of having an abnormal MoCA score (<26 points) was significantly higher in patients with Zika and AIUO than in those with dengue. Patients with Zika and AIUO had lower memory scores than patients with dengue (Zika vs. Dengue: −0.378, 95% CI−0.678 to −0.078; p = 0.014: Zika vs. AIUO 0.264, 95% CI 0.059, 0.469; p = 0.012). The low memory performance in patients with Zika and AIUO accounts for most of the differences in the overall MoCA score when compared with patients with dengue. Our results show a decrease in cognitive function during acute illness and provides no evidence to support the hypothesis that Zika might cause neurocognitive alterations longer than the period of acute infection or different to other infectious diseases. While effects on memory or perhaps other cognitive functions over the long term are possible, larger studies using more refined tools for neurocognitive functioning assessment are needed to identify these.

Trial Registration: NCT02831699.
Combination of Quantitative MRI Fat Fraction and Texture Analysis to Evaluate Spastic Muscles of Children With Cerebral Palsy
Authors: Akinci D'Antonoli Tugba , Santini Francesco , Deligianni Xeni , Garcia Alzamora Meritxell , Rutz Erich , Bieri Oliver , Brunner Reinald , Weidensteiner Claudia
Published: March 2021

Background: Cerebral palsy (CP) is the most common cause of physical disability in childhood. Muscle pathologies occur due to spasticity and contractures; therefore, diagnostic imaging to detect pathologies is often required. Imaging has been used to assess torsion or estimate muscle volume, but additional methods for characterizing muscle composition have not thoroughly been investigated. MRI fat fraction (FF) measurement can quantify muscle fat and is often a part of standard imaging in neuromuscular dystrophies. To date, FF has been used to quantify muscle fat and assess function in CP. In this study, we aimed to utilize a radiomics and FF analysis along with the combination of both methods to differentiate affected muscles from healthy ones.

Materials and Methods: A total of 9 patients (age range 8–15 years) with CP and 12 healthy controls (age range 9–16 years) were prospectively enrolled (2018–2020) after ethics committee approval. Multi-echo Dixon acquisition of the calf muscles was used for FF calculation. The images of the second echo (TE = 2.87 ms) were used for feature extraction from the soleus, gastrocnemius medialis, and gastrocnemius lateralis muscles. The least absolute shrinkage and selection operator (LASSO) regression was employed for feature selection. RM, FF model (FFM), and combined model (CM) were built for each calf muscle. The receiver operating characteristic (ROC) curve and their respective area under the curve (AUC) values were used to evaluate model performance.

Results: In total, the affected legs of 9 CP patients and the dominant legs of 12 healthy controls were analyzed. The performance of RM for soleus, gastrocnemius medialis, and gastrocnemius lateralis (AUC 0.92, 0.92, 0.82, respectively) was better than the FFM (AUC 0.88, 0.85, 0.69, respectively). The combination of both models always had a better performance than RM or FFM (AUC 0.95, 0.93, 0.83). FF was higher in the patient group (FFS 9.1%, FFGM 8.5%, and FFGL 10.2%) than control group (FFS 3.3%, FFGM 4.1%, FFGL 6.6%).

Conclusion: The combination of MRI quantitative fat fraction analysis and texture analysis of muscles is a promising tool to evaluate muscle pathologies due to CP in a non-invasive manner.
The Impact of COVID-19 on Patients With Neuromyelitis Optica Spectrum Disorder Beyond Infection Risk
Authors: Yin Hexiang , Zhang Yao , Xu Yan , Peng Bin , Cui Liying , Zhang Shuyang
Published: March 2021

There is an increasing need for better understanding of the impact of coronavirus disease 2019 (COVID-19) on patients with neuromyelitis optica spectrum disorder (NMOSD). A few pilot studies have investigated COVID-19 infections in NMOSD, but few studies have addressed disease activity and immune status of these patients during the pandemic. We carried out a cross-sectional study to examine immune status, relapses, and COVID-19 infections in a cohort of NMOSD patients using an electronic patient registry (MSNMOBase) for multiple sclerosis and related disorders. An online questionnaire was administered to all NMOSD patients in the registry from January 1, 2011, to June 1, 2020. Clinical demographic characteristics, immune status, relapses, treatments, COVID-19 infections, and preventive measures were evaluated. Of the 752 registered patients, 535 (71.1%) with qualified data were included. A total of 486 used preventive therapies during the pandemic, including mycophenolate mofetil (71.2%), azathioprine (13.3%), and other immunosuppressants (6.4%). Neither median immune cell counts nor immunoglobulin levels (p > 0.05) were significantly different between patients with or without immunosuppression. During the pandemic, no patients were diagnosed with COVID-19, and the majority (>95%) took one or more effective protective measures (e.g., wearing a mask and social distancing). However, a significantly higher annualized relapse rate (ARR) was observed in the 33 patients with treatment interruptions due to the pandemic compared to before it (p < 0.05), whereas ARR changes were not found in patients with continuous treatments or those without treatments (p > 0.05). Interruption frequency was significantly higher in patients with relapses compared to those without (34.9 vs. 15.7%, p < 0.01). For stable NMOSD patients during the pandemic, the risk of relapse due to treatment interruption may be higher than the risk of COVID-19 infection when protective measures are used, and continuous relapse-prevention treatments may be necessary.
Transcriptomic Analysis of Mouse Brain After Traumatic Brain Injury Reveals That the Angiotensin Receptor Blocker Candesartan Acts Through Novel Pathways
Authors: Attilio Peter J. , Snapper Dustin M. , Rusnak Milan , Isaac Akira , Soltis Anthony R. , Wilkerson Matthew D. , Dalgard Clifton L. , Symes Aviva J.
Published: March 2021

Traumatic brain injury (TBI) results in complex pathological reactions, where the initial lesion is followed by secondary inflammation and edema. Our laboratory and others have reported that angiotensin receptor blockers (ARBs) have efficacy in improving recovery from traumatic brain injury in mice. Treatment of mice with a subhypotensive dose of the ARB candesartan results in improved functional recovery, and reduced pathology (lesion volume, inflammation and gliosis). In order to gain a better understanding of the molecular mechanisms through which candesartan improves recovery after controlled cortical impact injury (CCI), we performed transcriptomic profiling on brain regions after injury and drug treatment. We examined RNA expression in the ipsilateral hippocampus, thalamus and hypothalamus at 3 or 29 days post injury (dpi) treated with either candesartan (0.1 mg/kg) or vehicle. RNA was isolated and analyzed by bulk mRNA-seq. Gene expression in injured and/or candesartan treated brain region was compared to that in sham vehicle treated mice in the same brain region to identify genes that were differentially expressed (DEGs) between groups. The most DEGs were expressed in the hippocampus at 3 dpi, and the number of DEGs reduced with distance and time from the lesion. Among pathways that were differentially expressed at 3 dpi after CCI, candesartan treatment altered genes involved in angiogenesis, interferon signaling, extracellular matrix regulation including integrins and chromosome maintenance and DNA replication. At 29 dpi, candesartan treatment reduced the expression of genes involved in the inflammatory response. Some changes in gene expression were confirmed in a separate cohort of animals by qPCR. Fewer DEGs were found in the thalamus, and only one in the hypothalamus at 3 dpi. Additionally, in the hippocampi of sham injured mice, 3 days of candesartan treatment led to the differential expression of 384 genes showing that candesartan in the absence of injury had a powerful impact on gene expression specifically in the hippocampus. Our results suggest that candesartan has broad actions in the brain after injury and affects different processes at acute and chronic times after injury. These data should assist in elucidating the beneficial effect of candesartan on recovery from TBI.
Alterations of Regional Homogeneity in Preschool Boys With Autism Spectrum Disorders
Authors: Lan Zhihong , Xu Shoujun , Wu Yunfan , Xia Likun , Hua Kelei , Li Meng , Liu Mengchen , Yin Yi , Li Chunlong , Huang Shumei , Feng Ying , Jiang Guihua , Wang Tianyue
Published: March 2021

Objectives

The study was aimed at investigating the alterations of local spontaneous brain activity in preschool boys with autism spectrum disorders (ASD).

Methods

Based on regional homogeneity (ReHo), the acquired resting state functional magnetic resonance imaging (fMRI) data sets, which included 86 boys with ASD and 54 typically developing (TD) boys, were used to detect regional brain activity. Pearson correlation analysis was used to study the relationship between abnormal ReHo value and the Childhood Autism Rating Scale (CARS), Autism Behavior Checklist (ABC), developmental quotient, and age.

Results

In the ASD group, we found increased ReHo in the right calcarine as well as decreased ReHo in the opercular part of the left inferior frontal gyrus, the left middle temporal gyrus, the left angular gyrus, and the right medial orbital frontal cortex (p < 0.05, false discovery rate correction). We did not find a correlation between the results of brain regions and the CARS, ABC, and age.

Conclusions

Our study found spontaneous activity changes in multiple brain regions, especially the visual and language-related areas of ASD, that may help to further understand the clinical characteristics of boys with ASD.
Mapping Network Activity in Sleep
Authors: Shiromani Priyattam J. , Blanco-Centurion Carlos , Vidal-Ortiz Aurelio
Published: March 2021

It was in the influenza pandemic of 1918 that von Economo identified specific brain regions regulating sleep and wake. Since then researchers have used a variety of tools to determine how the brain shifts between states of consciousness. In every enterprise new tools have validated existing data, corrected errors and made new discoveries to advance science. The brain is a challenge but new tools can disentangle the brain network. We summarize the newest tool, a miniature microscope, that provides unprecedented view of activity of glia and neurons in freely behaving mice. With this tool we have observed that the activity of a majority of GABA and MCH neurons in the lateral hypothalamus is heavily biased toward sleep. We suggest that miniscope data identifies activity at the cellular level in normal versus diseased brains, and also in response to specific hypnotics. Shifts in activity in small networks across the brain will help identify point of criticality that switches the brain from wake to sleep.
Therapeutic Potential of Vagus Nerve Stimulation for Inflammatory Bowel Diseases
Authors: Bonaz Bruno , Sinniger Valérie , Pellissier Sonia
Published: March 2021

The vagus nerve is a mixed nerve, comprising 80% afferent fibers and 20% efferent fibers. It allows a bidirectional communication between the central nervous system and the digestive tract. It has a dual anti-inflammatory properties via activation of the hypothalamic pituitary adrenal axis, by its afferents, but also through a vago-vagal inflammatory reflex involving an afferent (vagal) and an efferent (vagal) arm, called the cholinergic anti-inflammatory pathway. Indeed, the release of acetylcholine at the end of its efferent fibers is able to inhibit the release of tumor necrosis factor (TNF) alpha by macrophages via an interneuron of the enteric nervous system synapsing between the efferent vagal endings and the macrophages and releasing acetylcholine. The vagus nerve also synapses with the splenic sympathetic nerve to inhibit the release of TNF-alpha by splenic macrophages. It can also activate the spinal sympathetic system after central integration of its afferents. This anti-TNF-alpha effect of the vagus nerve can be used in the treatment of chronic inflammatory bowel diseases, represented by Crohn’s disease and ulcerative colitis where this cytokine plays a key role. Bioelectronic medicine, via vagus nerve stimulation, may have an interest in this non-drug therapeutic approach as an alternative to conventional anti-TNF-alpha drugs, which are not devoid of side effects feared by patients.
Comparing Explicit and Implicit Measures for Assessing Cross-Cultural Food Experience
Authors: Kaneko Daisuke , Stuldreher Ivo , Reuten Anne J. C. , Toet Alexander , van Erp Jan B. F. , Brouwer Anne-Marie
Published: March 2021

The present study investigated the potential of implicit physiological measures to provide objective measures of affective food experience in contrast to explicit self-report ratings in a cross-cultural context. Dutch and Thai participants viewed 120 food images portraying universal food image categories (regular and molded food) and cultural food image categories (typically Dutch and Thai food). The universal food images were taken as ground truth high and low valence stimuli, where we assumed no genuine difference in affective experience between nationalities. In contrast, for the cultural food images, we did expect a genuine difference between nationalities. Participants were asked to rate valence, arousal and liking of each food image. In addition, heart rate (HR) and phasic electrodermal activity (EDA) responses to the images were recorded. Typically Asian and Western response biases were found for explicit ratings of regular and molded food with an extreme response style for Dutch, and a middle response style for Thai participants. However, such bias was not observed in HR. For cultural food image categories, HR showed the hypothesized interaction between participant nationality and food image category, reflecting the expected genuine difference between nationalities in affective food experience. Besides presenting participants with images, we also asked participants to taste typically Thai and Dutch drinks. Similar to images, a significant interaction between participant nationality and cultural food category was found for HR. An interaction was also found for sip size, while this was not seen in explicit measures. We attribute this to differences in the moment that these measures were taken. In this study, phasic EDA did not appear to be a sensitive measure of affective food experience, possibly since stimuli mostly differed in valence rather than arousal. To conclude, our study constitutes an example where cultural bias negatively affected the accuracy of self-reports, and only the implicit physiological measures followed the prior expectations of genuine food experience, indicating the potential of these measures to study cross-cultural food experience.
Multispectral Imaging for Metallic Biopsy Marker Detection During MRI-Guided Breast Biopsy: A Feasibility Study for Clinical Translation
Authors: Eskreis-Winkler Sarah , Simon Katherine , Reichman Melissa , Spincemaille Pascal , Nguyen Thanh D. , Christos Paul J. , Drotman Michele , Prince Martin R. , Pinker Katja , Sutton Elizabeth J. , Morris Elizabeth A. , Wang Yi
Published: March 2021

Purpose

To assess the feasibility and diagnostic accuracy of multispectral MRI (MSI) in the detection and localization of biopsy markers during MRI-guided breast biopsy.

Methods

This prospective study included 20 patients undergoing MR-guided breast biopsy. In 10 patients (Group 1), MSI was acquired following tissue sampling and biopsy marker deployment. In the other 10 patients (Group 2), MSI was acquired following tissue sampling but before biopsy marker deployment (to simulate deployment failure). All patients received post-procedure mammograms. Group 1 and Group 2 designations, in combination with the post-procedure mammogram, served as the reference standard. The diagnostic performance of MSI for biopsy marker identification was independently evaluated by two readers using two-spectral-bin MR and one-spectral-bin MR. The κ statistic was used to assess inter-rater agreement for biopsy marker identification.

Results

The sensitivity, specificity, and accuracy of biopsy marker detection for readers 1 and 2 using 2-bin MSI were 90.0% (9/10) and 90.0% (9/10), 100.0% (10/10) and 100.0% (10/10), 95.0% (19/20) and 95.0% (19/20); and using 1-bin MSI were 70.0% (7/10) and 80.0% (8/10), 100.0% (8/8) and 100.0% (10/10), 85.0% (17/20) and 90.0% (18/20). Positive predictive value was 100% for both readers for all numbers of bins. Inter-rater agreement was excellent: κ was 1.0 for 2-bin MSI and 0.81 for 1-bin MSI.

Conclusion

MSI is a feasible, diagnostically accurate technique for identifying metallic biopsy markers during MRI-guided breast biopsy and may eliminate the need for a post-procedure mammogram.
The Value of Anlotinib in the Treatment of Intractable Brain Edema: Two Case Reports
Authors: Yang Song , Sun Jian , Xu Mingna , Wang Yuru , Liu Guihong , Jiang Aijun
Published: March 2021

About 20-30 percent of patients with cancer, such as non-small cell lung cancer, breast cancer, melanoma and renal cell carcinoma, will develop brain metastases (BM). Primary and secondary brain tumors are often accompanied by peritumoral edema. Due to the limited intracranial space, peritumoral edema will further increase the intracranial pressure and aggravate clinical symptoms. Radiotherapy, as a basic component of the treatment of intracranial tumors, induces blood vessel damage and aggravates brain edema. The combination of edema caused by the tumor itself and radiotherapy is collectively referred to as intractable brain edema. Edema can increase intracranial pressure and cause associated neurologic symptoms, which seriously affects the quality of life of patients. Steroids, specifically dexamethasone, have become the gold standard for the management of tumor-associated edema. However, steroids can lead to variety of adverse effects, including moon face, high blood pressure, high blood sugar, increased risk of infection, bone thinning (osteoporosis), and fractures, especially with prolonged use. The investigation of other types of drugs is urgently needed to address this problem.Compared to other anti-angiogenic agents, anlotinib acts on vascular endothelial growth factor receptors (VEGFR1, VEGFR2/KDR, and VEGFR3), fibroblast growth factor receptors (FGFR1, FGFR2, FGFR3 and FGFR4), platelet derived growth factor receptor (PDGFR) and stem cell factor receptor (c-kit) simultaneously. However, according to the literature retrieval, there are no studies on anlotinib for the treatment of intractable brain edema. We describe here two cases of brain edema and review the literature available and hope to discover new agents that are safer and more effective.
Improving the Prediction of Benign or Malignant Breast Masses Using a Combination of Image Biomarkers and Clinical Parameters
Authors: Cui Yanhua , Li Yun , Xing Dong , Bai Tong , Dong Jiwen , Zhu Jian
Published: March 2021

Background: Breast cancer is one of the leading causes of death in female cancer patients. The disease can be detected early using Mammography, an effective X-ray imaging technology. The most important step in mammography is the classification of mammogram patches as benign or malignant. Classically, benign or malignant breast tumors are diagnosed by radiologists' interpretation of mammograms based on clinical parameters. However, because masses are heterogeneous, clinical parameters supply limited information on mammography mass. Therefore, this study aimed to predict benign or malignant breast masses using a combination of image biomarkers and clinical parameters.

Methods: We trained a deep learning (DL) fusion network of VGG16 and Inception-V3 network in 5,996 mammography images from the training cohort; DL features were extracted from the second fully connected layer of the DL fusion network. We then developed a combined model incorporating DL features, hand-crafted features, and clinical parameters to predict benign or malignant breast masses. The prediction performance was compared between clinical parameters and the combination of the above features. The strengths of the clinical model and the combined model were subsequently validated in a test cohort (n = 244) and an external validation cohort (n = 100), respectively.

Results: Extracted features comprised 30 hand-crafted features, 27 DL features, and 5 clinical features (shape, margin type, breast composition, age, mass size). The model combining the three feature types yielded the best performance in predicting benign or malignant masses (AUC = 0.961) in the test cohort. A significant difference in the predictive performance between the combined model and the clinical model was observed in an independent external validation cohort (AUC: 0.973 vs. 0.911, p = 0.019).

Conclusion: The prediction of benign or malignant breast masses improves when image biomarkers and clinical parameters are combined; the combined model was more robust than clinical parameters alone.
The Dual-Role of Methylglyoxal in Tumor Progression – Novel Therapeutic Approaches
Authors: Leone Alessia , Nigro Cecilia , Nicolò Antonella , Prevenzano Immacolata , Formisano Pietro , Beguinot Francesco , Miele Claudia
Published: March 2021

One of the hallmarks of cancer cells is their metabolic reprogramming, which includes the preference for the use of anaerobic glycolysis to produce energy, even in presence of normal oxygen levels. This phenomenon, known as “Warburg effect”, leads to the increased production of reactive intermediates. Among these Methylglyoxal (MGO), a reactive dicarbonyl known as the major precursor of the advanced glycated end products (AGEs), is attracting great attention. It has been well established that endogenous MGO levels are increased in several types of cancer, however the MGO contribution in tumor progression is still debated. Although an anti-cancer role was initially attributed to MGO due to its cytotoxicity, emerging evidence has highlighted its pro-tumorigenic role in several types of cancer. These apparently conflicting results are explained by the hormetic potential of MGO, in which lower doses of MGO are able to establish an adaptive response in cancer cells while higher doses cause cellular apoptosis. Therefore, the extent of MGO accumulation and the tumor context are crucial to establish MGO contribution to cancer progression. Several therapeutic approaches have been proposed and are currently under investigation to inhibit the pro-tumorigenic action of MGO. In this review, we provide an overview of the early and latest evidence regarding the role of MGO in cancer, in order to define its contribution in tumor progression, and the therapeutic strategies aimed to counteract the tumor growth.
Antifibrotic Effect of a Novel Selective 11β-HSD2 Inhibitor (WZ51) in a rat Model of Myocardial Fibrosis
Authors: Zhuang Fei , Ge Qin , Qian Jianchang , Wang Zhe , Dong Yaoyao , Chen Mengchun , Zhang Xiaodan , Sun Wei
Published: March 2021

Myocardial fibrosis (MF) is one of the leading causes of end-stage heart disease. Many studies have confirmed that inflammation caused by aldosterone may play an important role in the process of MF. A selective 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) enzyme inhibitor can reduce the inactivation of cortisol, allowing cortisol to compete for mineralocorticoid receptors. This study investigated the protective effect of a novel selective 11βHSD2 inhibitor (WZ51) on MF and described its underlying mechanism. The administration of WZ51 in rats with MF significantly alleviated myocardial injury, accompanied by a decrease in lactate dehydrogenase and the creatine kinase myocardial band. Furthermore, WZ51 significantly inhibited the development of MF and increased the protein level of 11β-HSD2. The results of this study demonstrate that 11β-HSD2 plays an important pathological role in MF. Thus, WZ51 may be a potential therapeutic agent for the treatment of this condition.
Single-Element Reflective Digital Holographic Microscopy
Authors: Picazo-Bueno José Ángel , García Javier , Micó Vicente
Published: March 2021

Digital holographic microscopy (DHM) is a well-known microscopy technique using an interferometric architecture for quantitative phase imaging (QPI) and it has been already implemented utilizing a large number of interferometers. Among them, single-element interferometers are of particular interest due to its simplicity, stability, and low cost. Here, we present an extremely simple common-path interferometric layout based on the use of a single one-dimensional diffraction grating for both illuminating the sample in reflection and generating the digital holograms. The technique, named single-element reflective digital holographic microscopy (SER-DHM), enables QPI and topography analysis of reflective/opaque objects using a single-shot operation principle. SER-DHM is experimentally validated involving different reflective samples.
Advances on Post-translational Modifications Involved in Seed Germination
Authors: Yu Feng , Li Ming , He Dongli , Yang Pingfang
Published: March 2021

Seed germination and subsequent seedling establishment are important developmental processes that undergo extremely complex changes of physiological status and are precisely regulated at transcriptional and translational levels. Phytohormones including abscisic acid (ABA) and gibberellin (GA) are the critical signaling molecules that modulate the alteration from relative quiescent to a highly active state in seeds. Transcription factors such as ABA insensitive5 (ABI5) and DELLA domain-containing proteins play the central roles in response to ABA and GA, respectively, which antagonize each other during seed germination. Recent investigations have demonstrated that the regulations at translational and post-translational levels, especially post-translational modifications (PTMs), play a decisive role in seed germination. Specifically, phosphorylation and ubiquitination were shown to be involved in regulating the function of ABI5. In this review, we summarized the latest advancement on the function of PTMs involved in the regulation of seed germination, in which the PTMs for ABI5- and DELLA-containing proteins play the key roles. Meanwhile, the studies on PTM-based proteomics during seed germination and the crosstalk of different PTMs are also discussed. Hopefully, it will facilitate in obtaining a comprehensive understanding of the physiological functions of different PTMs in seed germination.
Grape Berry Secondary Metabolites and Their Modulation by Abiotic Factors in a Climate Change Scenario–A Review
Authors: Rienth Markus , Vigneron Nicolas , Darriet Philippe , Sweetman Crystal , Burbidge Crista , Bonghi Claudio , Walker Robert Peter , Famiani Franco , Castellarin Simone Diego
Published: March 2021

Temperature, water, solar radiation, and atmospheric CO2concentration are the main abiotic factors that are changing in the course of global warming. These abiotic factors govern the synthesis and degradation of primary (sugars, amino acids, organic acids, etc.) and secondary (phenolic and volatile flavor compounds and their precursors) metabolites directly, via the regulation of their biosynthetic pathways, or indirectly, via their effects on vine physiology and phenology. Several hundred secondary metabolites have been identified in the grape berry. Their biosynthesis and degradation have been characterized and have been shown to occur during different developmental stages of the berry. The understanding of how the different abiotic factors modulate secondary metabolism and thus berry quality is of crucial importance for breeders and growers to develop plant material and viticultural practices to maintain high-quality fruit and wine production in the context of global warming. Here, we review the main secondary metabolites of the grape berry, their biosynthesis, and how their accumulation and degradation is influenced by abiotic factors. The first part of the review provides an update on structure, biosynthesis, and degradation of phenolic compounds (flavonoids and non-flavonoids) and major aroma compounds (terpenes, thiols, methoxypyrazines, and C13 norisoprenoids). The second part gives an update on the influence of abiotic factors, such as water availability, temperature, radiation, and CO2concentration, on berry secondary metabolism. At the end of the paper, we raise some critical questions regarding intracluster berry heterogeneity and dilution effects and how the sampling strategy can impact the outcome of studies on the grapevine berry response to abiotic factors.
Binding Mechanisms in Visual Perception and Their Link With Neural Oscillations: A Review of Evidence From tACS
Authors: Ghiani Andrea , Maniglia Marcello , Battaglini Luca , Melcher David , Ronconi Luca
Published: March 2021

Neurophysiological studies in humans employing magneto- (MEG) and electro- (EEG) encephalography increasingly suggest that oscillatory rhythmic activity of the brain may be a core mechanism for binding sensory information across space, time, and object features to generate a unified perceptual representation. To distinguish whether oscillatory activity is causally related to binding processes or whether, on the contrary, it is a mere epiphenomenon, one possibility is to employ neuromodulatory techniques such as transcranial alternating current stimulation (tACS). tACS has seen a rising interest due to its ability to modulate brain oscillations in a frequency-dependent manner. In the present review, we critically summarize current tACS evidence for a causal role of oscillatory activity in spatial, temporal, and feature binding in the context of visual perception. For temporal binding, the emerging picture supports a causal link with the power and the frequency of occipital alpha rhythms (8–12 Hz); however, there is no consistent evidence on the causal role of the phase of occipital tACS. For feature binding, the only study available showed a modulation by occipital alpha tACS. The majority of studies that successfully modulated oscillatory activity and behavioral performance in spatial binding targeted parietal areas, with the main rhythms causally linked being the theta (~7 Hz) and beta (~18 Hz) frequency bands. On the other hand, spatio-temporal binding has been directly modulated by parieto-occipital gamma (~40–60 Hz) and alpha (10 Hz) tACS, suggesting a potential role of cross-frequency coupling when binding across space and time. Nonetheless, negative or partial results have also been observed, suggesting methodological limitations that should be addressed in future research. Overall, the emerging picture seems to support a causal role of brain oscillations in binding processes and, consequently, a certain degree of plasticity for shaping binding mechanisms in visual perception, which, if proved to have long lasting effects, can find applications in different clinical populations.
Examining the Psychological State Analysis Relationship Between Bitcoin Prices and COVID-19
Authors: Hou JianPing , Liu Jingyi , Jie YingJiang
Published: March 2021

The rapid worldwide spread of COVID-19 forced many countries to enforce complete lockdown and strict quarantine policies. The strict lockdown and quarantine affect the psychological state of people toward cryptocurrency. The current research aims to examine the effect of COVID-19 on Bitcoin prices concerning cumulative deaths and confirmed cases. The research comprises daily data from January 20, 2020, to April 30, 2020, during the initial worldwide breakout of COVID-19. This research employed the augmented Dickey-Fuller test to check the stationarity of data, the co-integration test for the interdependency of variables, and the vector error correction model for identifying the direction and long or short-run relationship between Bitcoin prices and COVID-19. The research results show that Bitcoin prices are negatively significant and related to COVID-19 in the short-run. A unidirectional relationship between Bitcoin prices and cumulative deaths is also observed. Investors and the public’s psychological state were positively significant to Bitcoin prices in the long-term because of cashless transactions, unbanked, and less risky virus traveling. The second reason behind the positive psychological relation is un-centralization and easy-to-make payments by Bitcoin. This study’s finding provides timely evidence to decision-makers on Bitcoin price volatility and its impacts on the public’s psychological states regarding COVID-19.