bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating Neuroimaging Correlates of Early Frailty in Patients With Behavioral Variant Frontotemporal Dementia: A MRI and FDG-PET Study
Authors: Amanzio Martina , Palermo Sara , Stanziano Mario , D'Agata Federico , Galati Antonello , Gentile Salvatore , Castellano Giancarlo , Bartoli Massimo , Cipriani Giuseppina Elena , Rubino Elisa , Fonio Paolo , Rainero Innocenzo
Published: April 2021

Frailty is a dynamic clinical condition characterized by the reduction of interconnections among different psychobiological domains, which leads to a homeostatic vulnerability. The association between physical frailty and cognitive dysfunctions is a possible predictor of poor prognosis in patients with neurodegenerative disorders. However, this construct has not been fully analyzed by a multidimensional neuropsychogeriatric assessment matched with multimodal neuroimaging methods in patients with behavioral variant frontotemporal dementia (bvFTD). We have investigated cognitive dysfunctions and frailty status, assessed by both a neuropsychological evaluation and the Multidimensional Prognostic Index (MPI), in a sample of 18 bvFTD patients and compared to matched healthy controls. Gray matter (GM) volume (as assessed by voxel-based morphometry) and metabolism (on 18fluorodeoxyglucose positron emission tomography) were first separately compared between groups, then voxelwise compared and correlated to each other within patients. Linear regression of the MPI was performed on those voxels presenting a significant correlation between altered GM volume and metabolism. The neuropsychological assessment reflected the diagnoses and the functional–anatomical alterations documented by neuroimaging analyses. In particular, the majority of patients presented significant executive dysfunction and mood changes in terms of apathy, depression, and anxiety. In the overall MPI score, the patients fell in the lower range (indicating an early frailty status). On imaging, they exhibited a bilateral decrease of GM density and hypometabolism involving the frontal pole, the anterior opercular region, and the anterior cingulate cortex. Greater atrophy than hypometabolism was observed in the bilateral orbitofrontal cortex, the triangular part of the inferior frontal gyrus, and the ventral striatum, whereas the contrary was detected in the bilateral dorsal anterior cingulate cortex and pre-supplementary motor area. MPI scores significantly correlated only with the co-occurrence of a decrease of GM density and hypometabolism in the right anterior insular cortex, but not with the separate pathological phenomena. Our results show a correlation between a specific pattern of co-occurring GM atrophy and hypometabolism with early frailty in bvFTD patients. These aspects, combined with executive dysfunction and mood changes, may lead to an increased risk of poor prognosis, highlighting a potentially critical and precocious role of the insula in the pathogenesis of frailty.
Myelin Repair: From Animal Models to Humans
Authors: Cayre Myriam , Falque Marie , Mercier Océane , Magalon Karine , Durbec Pascale
Published: April 2021

It is widely thought that brain repair does not occur, but myelin regeneration provides clear evidence to the contrary. Spontaneous remyelination may occur after injury or in multiple sclerosis (MS). However, the efficiency of remyelination varies considerably between MS patients and between the lesions of each patient. Myelin repair is essential for optimal functional recovery, so a profound understanding of the cells and mechanisms involved in this process is required for the development of new therapeutic strategies. In this review, we describe how animal models and modern cell tracing and imaging methods have helped to identify the cell types involved in myelin regeneration. In addition to the oligodendrocyte progenitor cells identified in the 1990s as the principal source of remyelinating cells in the central nervous system (CNS), other cell populations, including subventricular zone-derived neural progenitors, Schwann cells, and even spared mature oligodendrocytes, have more recently emerged as potential contributors to CNS remyelination. We will also highlight the conditions known to limit endogenous repair, such as aging, chronic inflammation, and the production of extracellular matrix proteins, and the role of astrocytes and microglia in these processes. Finally, we will present the discrepancies between observations in humans and in rodents, discussing the relationship of findings in experimental models to myelin repair in humans. These considerations are particularly important from a therapeutic standpoint.
Examining the Research Criteria for Traumatic Encephalopathy Syndrome in Middle-Aged Men From the General Population Who Played Contact Sports in High School
Authors: Iverson Grant L. , Merz Zachary C. , Terry Douglas P.
Published: April 2021

Objective: There are no validated or agreed upon diagnostic clinical criteria for chronic traumatic encephalopathy or traumatic encephalopathy syndrome. This study examines the leading research criteria for traumatic encephalopathy syndrome (TES) in middle-aged men in the general population.

Method: Participants were 409 men between the ages of 35 and 55 recruited through an online crowdsourcing platform. Participants provided demographic information, medication history, concussion history, contact sport history, current medication use, and current symptoms. Research criteria for TES were applied to the sample.

Results: Over half of the total sample met TES symptom criteria (56.2%), without applying the neurotrauma exposure criteria. Those with 4+ prior concussions had higher rates of meeting TES criteria compared to those with 0–3 prior concussions, but the results were not statistically significant (69.8 vs. 54.6%; χ2 = 3.58, p = 0.06). Exposure to contact sports was not related to higher rates of TES (ps ≥ 0.55). In a binary logistic regression predicting the presence of mild or greater TES, significant predictors were sleep difficulties [Odds ratio (OR) = 6.68], chronic pain (OR = 3.29), and age (OR = 1.04). Neurotrauma exposure was not a significant predictor (p = 0.66). When analyzing those with no prior concussions or contact sport histories (n = 126), 45.2% met symptom criteria for mild or greater TES; chronic pain and sleep difficulties were associated with a higher prevalence of meeting criteria for TES in this subgroup (ps < 0.001).

Conclusions: Men who participated in contact sports in high school or college were not more likely to meet criteria for TES than men who participated in non-contact sports or no sports. In a multivariable model, sleep problems and chronic pain were predictive of meeting the symptom criteria for TES, but the repetitive neurotrauma exposure criterion was not a significant predictor of meeting the TES symptom criteria.
A Precision Medicine Approach to Biomarker Utilization in Pediatric Sepsis-Associated Acute Kidney Injury
Authors: Odum James D. , Wong Hector R. , Stanski Natalja L.
Published: April 2021

Sepsis is a leading cause of morbidity and mortality in critically ill children, and acute kidney injury (AKI) is a frequent complication that confers an increased risk for poor outcomes. Despite the documented consequences of sepsis-associated AKI (SA-AKI), no effective disease-modifying therapies have been identified to date. As such, the only treatment options for these patients remain prevention and supportive care, both of which rely on the ability to promptly and accurately identify at risk and affected individuals. To achieve these goals, a variety of biomarkers have been investigated to help augment our currently limited predictive and diagnostic strategies for SA-AKI, however, these have had variable success in pediatric sepsis. In this mini-review, we will briefly outline the current use of biomarkers for SA-AKI, and propose a new framework for biomarker discovery and utilization that considers the individual patient's sepsis inflammatory response. Now recognized to be a key driver in the complex pathophysiology of SA-AKI, understanding the dysregulated host immune response to sepsis is a growing area of research that can and should be leveraged to improve the prediction and diagnosis of SA-AKI, while also potentially identifying novel therapeutic targets. Reframing SA-AKI in this manner – as a direct consequence of the individual patient's sepsis inflammatory response – will facilitate a precision medicine approach to its management, something that is required to move the care of this consequential disorder forward.
Guardians at the Gate: Early Adversity, Neurocognitive Development, and the Role of the Pediatrician in the Era of COVID-19
Authors: Berken Jonathan A. , Heard-Garris Nia , Wakschlag Lauren S.
Published: April 2021

Adverse childhood experiences (ACEs) profoundly impact neurocognitive development. Specifically, when these events occur during critical periods of brain plasticity, a time of significant synaptogenesis, neural pruning, and myelination, typical neurodevelopment can become derailed. Adverse childhood experiences promote morphological changes in neuronal microcircuitry which may lead to diminished cognitive flexibility, inattention, increased impulsivity, decreased school readiness, and disruptive behaviors. In this regard, the current COVID-19 pandemic represents an especially complex adverse experience that disturbs a child's social milieu and support network, likely interfering with brain maturation and executive function. Here, we take a neurodevelopmental approach to argue for the critical role that pediatricians must fulfill in mitigating the potentially detrimental consequences of COVID-19. We call for ACE screening and anticipatory guidance in the primary care setting, and the use of validated interventions and skills to bolster resilience, when ACEs are identified. We present a clinical workflow for the physician to proactively assess, identify, stratify, and address the severity of ACEs worsened by COVID-19. We discuss home-based activities and resources for children and adolescents to promote stress reduction, connectiveness, and self-awareness and create a more positive environment to maximize neurodevelopmental potential in the face of the ongoing pandemic.
Immune Axonal Neuropathies Associated With Systemic Autoimmune Rheumatic Diseases
Authors: Tulbă Delia , Popescu Bogdan Ovidiu , Manole Emilia , Băicuș Cristian
Published: April 2021

Immune axonal neuropathies are a particular group of immune-mediated neuropathies that occasionally accompany systemic autoimmune rheumatic diseases such as connective tissue dissorders and primary systemic vasculitides. Apart from vasculitis of vasa nervorum, various other mechanisms are involved in their pathogenesis, with possible therapeutic implications. Immune axonal neuropathies have highly heterogeneous clinical presentation and course, ranging from mild chronic distal sensorimotor polyneuropathy to severe subacute mononeuritis multiplex with rapid progression and constitutional symptoms such as fever, malaise, weight loss and night sweats, underpinning a vasculitic process. Sensory neuronopathy (ganglionopathy), small fiber neuropathy (sensory and/or autonomic), axonal variants of Guillain-Barré syndrome and cranial neuropathies have also been reported. In contrast to demyelinating neuropathies, immune axonal neuropathies show absent or reduced nerve amplitudes with normal latencies and conduction velocities on nerve conduction studies. Diagnosis and initiation of treatment are often delayed, leading to accumulating disability. Considering the lack of validated diagnostic criteria and evidence-based treatment protocols for immune axonal neuropathies, this review offers a comprehensive perspective on etiopathogenesis, clinical and paraclinical findings as well as therapy guidance for assisting the clinician in approaching these patients. High quality clinical research is required in order to provide indications and follow up rules for treatment in immune axonal neuropathies related to systemic autoimmune rheumatic diseases.
Novel and Emerging Therapies for Inflammatory Bowel Disease
Authors: Al-Bawardy Badr , Shivashankar Raina , Proctor Deborah D.
Published: April 2021

Inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn’s disease are chronic, relapsing and remitting disorders of intestinal inflammation with potential systemic manifestations. Despite the availability of current biologics, such as anti-tumor necrosis factor (anti-TNF), anti-integrins, anti-interleukins and small molecules such as tofacitinib, the rates of primary and secondary treatment failure remain high in IBD. This highlights the importance of continued development of new therapeutic targets and modifications of existing ones to improve the treatment response rates and to also improve the safety profile and tolerability of these medications. In this review we will discuss novel treatment target agents including selective janus kinase (JAK) inhibitors, anti-interleukin (IL) (IL-12/IL-23), leukocyte trafficking/migrating inhibitors (such as sphingosine-1-phosphate receptor modulator) and other small molecules currently in development.
Detection of EGFR Mutations From Plasma of NSCLC Patients Using an Automatic Cartridge-Based PCR System
Authors: Heeke Simon , Hofman Véronique , Benzaquen Jonathan , Otto Josiane , Tanga Virginie , Zahaf Katia , Allegra Maryline , Long-Mira Elodie , Lassalle Sandra , Marquette Charles-Hugo , Ilie Marius , Hofman Paul
Published: April 2021

The introduction of liquid biopsies for the detection of EGFR mutations in non-small cell lung cancer patients (NSCLC) has revolutionized the clinical care. However, liquid biopsies are technically challenging and require specifically trained personnel. To facilitate the implementation of liquid biopsies for the detection of EGFR mutations from plasma, we have assessed a fully automated cartridge-based qPCR test that allows the automatic detection of EGFR mutations directly from plasma. We have analyzed 54 NSCLC patients and compared the results of the cartridge-base device to an FDA-approved assay. Detection of EGFR mutations was comparable but slightly lower in the cartridge-based device for L858R mutations (14/15 detected, 93%) and exon 19 deletions (18/20 detected, 90%). Unfortunately, 8/54 (15%) tests failed but increasing the proteinase K volume helped to recover 3/4 (75%) unsuccessful samples. In summary, the fully automated cartridge-based device allowed the detection of EGFR mutations directly from plasma in NSCLC patients with promising accuracy. However, protocol adjustments are necessary to reduce a high test failure rate.
Hepatic Oxidative Stress, Apoptosis, and Inflammation in Broiler Chickens With Wooden Breast Myopathy
Authors: Xing Tong , Pan Xiaona , Zhang Lin , Gao Feng
Published: April 2021

Wooden breast (WB) syndrome has emerged as a global myopathy in modern commercial broiler chickens, mainly affecting the pectoralis major muscle. Recent evidence suggests that WB myopathy is a systemic disease, which might be accompanied by other physiological disparities and metabolic changes. This study was conducted to systemically investigate the potential physiological changes in liver tissues as well as the possible mechanisms involved to enhance the understanding of the etiology. A total of 93 market-age Arbor Acres male broiler chickens were sampled and categorized into control (CON) and WB groups based on the evaluation of myopathic lesions. Liver samples were collected (n = 10 in each group) for histopathological evaluation and biochemical analyses. Results indicated that WB birds exhibited significantly higher plasma aspartate amino transferase, alkaline phosphatase, and gamma glutamyl transpeptidase activities. Histopathological changes in hydropic/fatty degeneration, inflammatory cell infiltration, intrahepatic hemorrhages, elevated myeloperoxidase activity, and overproduction of nitric oxide were observed in WB liver compared with CON, suggesting the occurrence of liver injury in birds affected by WB myopathy. The WB group showed increased levels of reactive oxygen species, oxidative products, as well as enhanced antioxidant capacities in the liver. These changes were associated with impaired mitochondria morphology and mitochondrial dysfunction. WB myopathy also induced mitochondria-mediated hepatic apoptosis by upregulating levels of caspases 3 and 9, altering the expressions of apoptotic B-cell lymphoma-2 family regulators, as well as increasing the release of cytochrome c. The activation of nuclear factor kappa-light-chain-enhancer of activated B cell signaling enhanced the mRNA expression of downstream inflammatory mediators, contributing to the production of inflammatory cytokines in WB liver. Combined, these findings suggest that hepatic disorders may be conjoined with WB myopathy in broiler chickens and indicating systemic physiological disparities, and other metabolic changes accompanying this myopathy need further assessment.
Arabidopsis thaliana EARLY RESPONSIVE TO DEHYDRATION 7 Localizes to Lipid Droplets via Its Senescence Domain
Authors: Doner Nathan M. , Seay Damien , Mehling Marina , Sun Siqi , Gidda Satinder K. , Schmitt Kerstin , Braus Gerhard H. , Ischebeck Till , Chapman Kent D. , Dyer John M. , Mullen Robert T.
Published: April 2021

Lipid droplets (LDs) are neutral-lipid-containing organelles found in all kingdoms of life and are coated with proteins that carry out a vast array of functions. Compared to mammals and yeast, relatively few LD proteins have been identified in plants, particularly those associated with LDs in vegetative (non-seed) cell types. Thus, to better understand the cellular roles of LDs in plants, a more comprehensive inventory and characterization of LD proteins is required. Here, we performed a proteomics analysis of LDs isolated from drought-stressed Arabidopsis leaves and identified EARLY RESPONSIVE TO DEHYDRATION 7 (ERD7) as a putative LD protein. mCherry-tagged ERD7 localized to both LDs and the cytosol when ectopically expressed in plant cells, and the protein’s C-terminal senescence domain (SD) was both necessary and sufficient for LD targeting. Phylogenetic analysis revealed that ERD7 belongs to a six-member family in Arabidopsis that, along with homologs in other plant species, is separated into two distinct subfamilies. Notably, the SDs of proteins from each subfamily conferred targeting to either LDs or mitochondria. Further, the SD from the ERD7 homolog in humans, spartin, localized to LDs in plant cells, similar to its localization in mammals; although, in mammalian cells, spartin also conditionally localizes to other subcellular compartments, including mitochondria. Disruption of ERD7 gene expression in Arabidopsis revealed no obvious changes in LD numbers or morphology under normal growth conditions, although this does not preclude a role for ERD7 in stress-induced LD dynamics. Consistent with this possibility, a yeast two-hybrid screen using ERD7 as bait identified numerous proteins involved in stress responses, including some that have been identified in other LD proteomes. Collectively, these observations provide new insight to ERD7 and the SD-containing family of proteins in plants and suggest that ERD7 may be involved in functional aspects of plant stress response that also include localization to the LD surface.
Arithmetic Errors in Financial Contexts in Parkinson’s Disease
Authors: Loenneker Hannah D. , Becker Sara , Nussbaum Susanne , Nuerk Hans-Christoph , Liepelt-Scarfone Inga
Published: April 2021

Research on dyscalculia in neurodegenerative diseases is still scarce, despite high impact on patients’ independence and activities of daily living function. Most studies address Alzheimer’s Disease; however, patients with Parkinson’s Disease (PD) also have a higher risk for cognitive impairment while the relation to arithmetic deficits in financial contexts has rarely been studied. Therefore, the current exploratory study investigates deficits in two simple arithmetic tasks in financial contexts administered within the Clinical Dementia Rating in a sample of 100 PD patients. Patients were classified as cognitively normal (PD-NC) or mildly impaired (PD-MCI) according to Level I consensus criteria, and assessed using a comprehensive neuropsychological test battery, neurological motor examination, and sociodemographic and clinical questionnaires. In total, 18% showed arithmetic deficits: they were predominately female, had longer disease duration, more impaired global cognition, but minor signs of depression compared to PD patients without arithmetic deficits. When correcting for clinical and sociodemographic confounders, greater impairments in attention and visuo-spatial/constructional domains predicted occurrence of arithmetic deficits. The type of deficit did not seem to be arbitrary but seemed to involve impaired place × value processing frequently. Our results argue for the importance of further systematic investigations of arithmetic deficits in PD with sensitive tests to confirm the results of our exploratory study that a specific subgroup of PD patients present themselves with dyscalculia.
Association of Birth Order With Mental Health Problems, Self-Esteem, Resilience, and Happiness Among Children: Results From A-CHILD Study
Authors: Fukuya Yoshifumi , Fujiwara Takeo , Isumi Aya , Doi Satomi , Ochi Manami
Published: April 2021

Objective: This study aimed to investigate the association of birth order with mental health problems, self-esteem, resilience, and happiness among children aged 9–10 years.

Methods: This was a cross-sectional study using data from the Adachi Child Health Impact of Living Difficulty (A-CHILD) study, which was a population-based study of children in fourth grade in public schools in Adachi City, Tokyo, Japan in 2018 (N = 3,744). Parent-rated Strengths and Difficulties Questionnaire (SDQ) and self-rated resilience, happiness, and self-esteem score were used to assess child mental health. Multiple regression analysis for continuous outcomes and logistic regression for dichotomous outcomes were used to examine the association of birth order with mental health problems, resilience, happiness, and self-esteem. The analysis was controlled for child sex, mother's age, mother's education, caregiver's depressive symptoms, household income, and living with grandparents.

Results: Last-borns showed the lowest total difficulties score in the SDQ, while only children showed the highest (p < 0.001). The highest prosocial behaviors score was found among last-borns (p < 0.001). Resilience score was also highest among last-borns, followed by first-borns, middle-borns, and only children. The lowest happiness score was found among middle-borns. Self-esteem score did not differ by sibling types. These associations were similar in the adjusted model and dichotomized outcomes model.

Conclusions: Differential impacts of birth order on child mental health, for both positive and negative sides, were found. Further research is warranted to elucidate the mechanism of the association between birth order and the development of behavior problems and the positive aspects such as resilience, happiness, and self-esteem among children.
India's COVID-19 Burdens, 2020
Authors: Joshi Ashish , Mewani Apeksha H. , Arora Srishti , Grover Ashoo
Published: April 2021

The purpose of this article is two pronged; first, to identify and report public health implications of the ongoing coronavirus (COVID-19) pandemic, and second, to report challenges uniquely faced by the citizens of India from a population health perspective. We have done both while closely examining epidemiological data that is accessible via SMAART's RAPID Tracker. This policy informatics platform is a live database aimed to track the geospatial spread of the COVID-19 outbreak and policy actions globally and is administered collaboratively by CUNY's Graduate School of Public Health and Health Policy and a global, non-profit public health incubator. Infectivity, incidence, and recovery rates were computed and graphical representations of epidemiological datasets were studied. We have discussed a plausible conceptual framework based on the principles of population health informatics for countries with similar characteristics to build a stronger public and community health foundation in order to safeguard populations during a health emergency in the future.
AI-Based Estimation of End-Systolic Elastance From Arm-Pressure and Systolic Time Intervals
Authors: Bikia Vasiliki , Adamopoulos Dionysios , Pagoulatou Stamatia , Rovas Georgios , Stergiopulos Nikolaos
Published: April 2021

Left ventricular end-systolic elastance (Ees) is a major determinant of cardiac systolic function and ventricular-arterial interaction. Previous methods for the Ees estimation require the use of the echocardiographic ejection fraction (EF). However, given that EF expresses the stroke volume as a fraction of end-diastolic volume (EDV), accurate interpretation of EF is attainable only with the additional measurement of EDV. Hence, there is still need for a simple, reliable, noninvasive method to estimate Ees. This study proposes a novel artificial intelligence—based approach to estimate Ees using the information embedded in clinically relevant systolic time intervals, namely the pre-ejection period (PEP) and ejection time (ET). We developed a training/testing scheme using virtual subjects (n = 4,645) from a previously validated in-silico model. Extreme Gradient Boosting regressor was employed to model Ees using as inputs arm cuff pressure, PEP, and ET. Results showed that Ees can be predicted with high accuracy achieving a normalized RMSE equal to 9.15% (r = 0.92) for a wide range of Ees values from 1.2 to 4.5 mmHg/ml. The proposed model was found to be less sensitive to measurement errors (±10–30% of the actual value) in blood pressure, presenting low test errors for the different levels of noise (RMSE did not exceed 0.32 mmHg/ml). In contrast, a high sensitivity was reported for measurements errors in the systolic timing features. It was demonstrated that Ees can be reliably estimated from the traditional arm-pressure and echocardiographic PEP and ET. This approach constitutes a step towards the development of an easy and clinically applicable method for assessing left ventricular systolic function.
Automatic Supplement Weighing Units for Monitoring the Time of Accessing Mineral Block Supplements by Rangeland Cattle in Northern Queensland, Australia
Authors: Simanungkalit Gamaliel , Bremner Graeme , Cowley Frances , Barwick Jamie , Dawson Bradley , Dobos Robin , Hegarty Roger
Published: April 2021

Time spent feeding by grazing cattle is an important predictor of intake and feed efficiency. This study examined the use of automatic supplement weighing (ASW) units for monitoring voluntary access of breeding cows (n = 430) to mineral block supplements in an extensive rangeland of northern Australia. The ASW units (n = 10) were located within each of experimental sites (5 units per site; Bore and Eldons). Over the 62 days of data collection, 85%, 13%, and 2% of cows spent <600, 600–1200, >1200 min accessing supplements, respectively, with between-animal variation (CV) of 107%. A total of 133 cows visited both sites while 142 and 155 cows visited only Bore and Eldons, respectively. Most visits (80–90%) were recorded during the day (800–1700 h), 7–17% during the night (1800–2300 h), and 3% during the dawn (0–700 h). Time spent accessing supplements differed between ASW units across the two sites (p < 0.001) and varied according to the day of visits (p < 0.001). There was a significant relationship between time spent at the ASW units and supplement intake on a herd basis (p < 0.001; R2adj = 0.70). The results showed that the ASW units were capable of monitoring access to mineral block supplements that may reflect the supplement intake of rangeland cattle.
Quantification of the Starling Population, Estimation and Mapping of the Damage to Olive Crops in the Apulia Region
Authors: Bozzo Francesco , Tarricone Simona , Petrontino Alessandro , Cagnetta Prospero , Maringelli Giacomo , La Gioia Giuseppe , Fucilli Vincenzo , Ragni Marco
Published: April 2021

The presence of wildlife in areas with a high concentration of farming activities can create a conflict between conservation objectives and productive purposes. Near Brindisi (Apulia, S-E Italy), a substantial amount of cash compensation claims for damages reported by local farmers and attributed to starlings (Sturnus vulgaris) has been registered. The aim of this study was to quantify the starling population wintering in the Apulia region, in order to assess the potential damage to crop production caused by this species. Our analysis was conducted over three years and included three main activities: a study of starling abundance and movements, the identification of areas and crops affected by damages, and a determination of the damage to the agricultural system in terms of quantity and concentration (heatmap). The study showed a loss of expected production that was coherent with the eating capacity of starlings wintering in the region. This means a loss, in terms of gross profitable production, of around 550,000 euros concentrated in a few narrow areas close to the roosts. Results on species behavior, damage quantification, and mapping are useful elements aimed to activate trade-off measures to preserve production and protection objectives, and to allow policymakers to address enforcement interventions and to establish parameters for financial compensation.
Oxidative Stress and Inflammatory Markers in Abdominal Aortic Aneurysm
Authors: Sánchez-Infantes David , Nus Meritxell , Navas-Madroñal Miquel , Fité Joan , Pérez Belén , Barros-Membrilla Antonio J. , Soto Begoña , Martínez-González José , Camacho Mercedes , Rodriguez Cristina , Mallat Ziad , Galán María
Published: April 2021

Abdominal aortic aneurysm (AAA) is increasing due to aging of the population and is a major cause of death among the elderly. Ultrasound screening programs are useful in early diagnosis, but aneurysm size is not always a good predictor of rupture. Our aim was to analyze the value of circulating molecules related to oxidative stress and inflammation as new biomarkers to assist the management of AAA. The markers were quantified by ELISA, and their expression in the aneurysmal wall was studied by real-time PCR and by immunostaining. Correlation analysis of the studied markers with aneurysm diameter and peak wall stress (PWS), obtained by finite element analysis, and multivariate regression analysis to assess potential confounding factors were performed. Our study shows an extensive inflammatory infiltration in the aneurysmal wall, mainly composed by T-cells, macrophages and B-cells and altered levels of reactive oxygen species (ROS), IgM, IgG, CD38, GDF15, S100A4 and CD36 in plasma and in the aneurysmal tissue of AAA patients compared with controls. Circulating levels of IgG, CD38 and GDF15 positively correlated with abdominal aortic diameter, and CD38 was correlated with PWS. Our data show that altered levels of IgG, CD38 and GDF15 have potential diagnostic value in the assessment of AAA.
Pre- and Post-Operative Limb Symmetry Indexes and Estimated Preinjury Capacity Index of Muscle Strength as Predictive Factors for the Risk of ACL Reinjury: A Retrospective Cohort Study of Athletes after ACLR
Authors: Zore Martin Rudolf , Kregar Velikonja Nevenka , Hussein Mohsen
Published: April 2021

Long-term muscle weakness may increase the risk of knee reinjury after anterior cruciate ligament reconstruction (ACLR) and of osteoarthritis. The incidence of secondary injuries after ACLR and the predictive value of preoperative and postoperative limb symmetry index (LSI) and estimated preinjury capacity (EPIC) index were studied for predicting the risk of reinjury in a retrospective study. Sixty-three recreational and professional athletes after ACLR with hamstring autograft were followed for secondary injury in the period from 2012 to 2014, 5 years after ACLR. Peak torque values of knee extensor and flexor muscle strength of the involved and uninvolved limb were measured with an isokinetic dynamometer at 60 degrees per second before ACLR and 6 months after ACLR and were used to calculate LSI and EPIC index. The results suggest that the preoperative LSI and EPIC indexes predict a secondary ACL injury better than the postoperative LSI for extensor muscles which is often used as a criterion to determine the time for returning to normal sports activities. Individuals with secondary ACL injuries suffer greater loss of knee extensor muscle strength of the uninvolved limb between preoperative and postoperative ACLR testing compared to the individuals without secondary injury.
Franken-CT: Head and Neck MR-Based Pseudo-CT Synthesis Using Diverse Anatomical Overlapping MR-CT Scans
Authors: Martinez-Girones Pedro Miguel , Vera-Olmos Javier , Gil-Correa Mario , Ramos Ana , Garcia-Cañamaque Lina , Izquierdo-Garcia David , Malpica Norberto , Torrado-Carvajal Angel
Published: April 2021

Typically, pseudo-Computerized Tomography (CT) synthesis schemes proposed in the literature rely on complete atlases acquired with the same field of view (FOV) as the input volume. However, clinical CTs are usually acquired in a reduced FOV to decrease patient ionization. In this work, we present the Franken-CT approach, showing how the use of a non-parametric atlas composed of diverse anatomical overlapping Magnetic Resonance (MR)-CT scans and deep learning methods based on the U-net architecture enable synthesizing extended head and neck pseudo-CTs. Visual inspection of the results shows the high quality of the pseudo-CT and the robustness of the method, which is able to capture the details of the bone contours despite synthesizing the resulting image from knowledge obtained from images acquired with a completely different FOV. The experimental Zero-Normalized Cross-Correlation (ZNCC) reports 0.9367 ± 0.0138 (mean ± SD) and 95% confidence interval (0.9221, 0.9512); the experimental Mean Absolute Error (MAE) reports 73.9149 ± 9.2101 HU and 95% confidence interval (66.3383, 81.4915); the Structural Similarity Index Measure (SSIM) reports 0.9943 ± 0.0009 and 95% confidence interval (0.9935, 0.9951); and the experimental Dice coefficient for bone tissue reports 0.7051 ± 0.1126 and 95% confidence interval (0.6125, 0.7977). The voxel-by-voxel correlation plot shows an excellent correlation between pseudo-CT and ground-truth CT Hounsfield Units (m = 0.87; adjusted R2 = 0.91; p < 0.001). The Bland–Altman plot shows that the average of the differences is low (−38.6471 ± 199.6100; 95% CI (−429.8827, 352.5884)). This work serves as a proof of concept to demonstrate the great potential of deep learning methods for pseudo-CT synthesis and their great potential using real clinical datasets.
Consistent Implicit Time Integration for Viscoplastic Modelingof Subsidence above Hydrocarbon Reservoirs
Authors: Ghisi Aldo , Cremonesi Massimiliano , Perego Umberto , Corradi Anna , Gemelli Fabrizio , Mantica Stefano
Published: April 2021

The viscoplastic model proposed by Vermeer and Neher in 1999 is still currently used in the oil and gas industry for subsidence modeling, to predict the deformation of the ground surface induced by hydrocarbon withdrawal from underground reservoirs. Even though several different implementations of this model have been proposed in the literature, also very recently, a consistent fully implicit implementation is still missing, probably due to the technical difficulties involved in the rigorous derivation of the analytical tangent matrix. To fill this gap and to provide an effective tool to the engineering community, a fully implicit backward Euler integration is proposed and validated in this work. The consistent expression of the tangent stiffness matrix is also derived analytically, and its validation strategy is described in detail. The model was implemented in a commercial finite element code through a user-defined material subroutine. The advantages of the proposed implicit formulation in terms of stability with respect to an explicit formulation were assessed and validated. The examples include studies at material point level and at field scale for a case study of subsidence in a synthetic reservoir.
At the Core of the Workshop: Novel Aspects of the Use of Blue Smalt in Two Paintings by Cristóbal de Villalpando
Authors: Insaurralde Caballero Mirta , Castañeda-Delgado María
Published: April 2021

During the seventeenth century, the use of smalt and indigo became increasingly common among painters’ workshops in New Spain. The unprecedented importance of these two blue pigments in oil painting may be explained by artistic and geopolitical circumstances. This article expands on the use of blue smalt—a byproduct of glass production and a material that lacks in-depth study in viceregal painting—by focusing on the technical analysis of El Triunfo de la Eucaristía and La Asunción painted by Cristóbal de Villalpando (ca. 1649–1714), which are part of the collection of the Museo Regional de Guadalajara (Mexico). The technological and material study of both paintings, situated within the trade and circulation of painting materials at the turn of the eighteenth century, shows how the painter deployed techniques rooted in his predecessors while incorporating particular technical adaptations. The authors examine cross-section samples of Villalpando’s paintings with optical microscopy, Scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX), and Fourier-transformed infrared spectroscopy (FT-IR), and were able to identify different qualities of smalt as well to suggest a possible provenance. These analyses evidence novel aspects in the painting tradition of workshops in New Spain that ultimately reverberated in practices of the long eighteenth century.
Are Grimmia Mosses Good Biomonitors for Urban Atmospheric Metallic Pollution? Preliminary Evidence from a French Case Study on Cadmium
Authors: Vieille Bartholomé , Albert Isabelle , Leblond Sébastien , Couvidat Florian , Parent Éric , Meyer Caroline
Published: April 2021

Assessment of human exposure to atmospheric metals is a challenge, and mosses seem to be good biomonitors to help this purpose. Lacking roots, they are easy to collect and analyze. However, to our knowledge, no formal comparison was made between cadmium (Cd) measurements in Grimmia mosses and alternative forecasts of atmospheric Cd pollution as those produced by the CHIMERE chemistry transport model. This work aims at studying this link to improve further biomonitoring. We compare 128 Cd measurements in the cemetery mosses of Paris and Lyon metropolitan areas (France) to CHIMERE Cd atmospheric forecasts. The area to consider around the cemetery for the CHIMERE forecasts has been defined by Kendall rank correlations between both information sources—Cd in mosses and CHIMERE Cd forecasts—from different area sizes. Then, we fit linear models to those two data sets including step-by-step different sources of uncertainty. Finally, we calculate moss predictions to compare predictions and measurements in the two cities. The results show an apparent link between the Cd concentrations in mosses and CHIMERE Cd forecasts including in addition the same unique covariate, the moss support (grave or wall), in the two cities. However, this model cannot be directly transposed from region to region because the strength of the link appears to be regional.
Haslea silbo, A Novel Cosmopolitan Species of Blue Diatoms
Authors: Gastineau Romain , Hansen Gert , Poulin Michel , Lemieux Claude , Turmel Monique , Bardeau Jean-François , Leignel Vincent , Hardivillier Yann , Morançais Michèle , Fleurence Joël , Gaudin Pierre , Méléder Vona , Cox Eileen J. , Davidovich Nikolaï A. , Davidovich Olga I. , Witkowski Andrzej , Kaczmarska Irena , Ehrman James M. , Soler Onís Emilio , Quintana Antera Martel , Mucko Maja , Mordret Solenn , Sarno Diana , Jacquette Boris , Falaise Charlotte , Séveno Julie , Lindquist Niels L. , Kemp Philip S. , Eker-Develi Elif , Konucu Merve , Mouget Jean-Luc
Published: April 2021

Specimens of a new species of blue diatoms from the genus Haslea Simonsen were discovered in geographically distant sampling sites, first in the Canary Archipelago, then North Carolina, Gulf of Naples, the Croatian South Adriatic Sea, and Turkish coast of the Eastern Mediterranean Sea. An exhaustive characterization of these specimens, using a combined morphological and genomic approach led to the conclusion that they belong to a single new to science cosmopolitan species, Haslea silbo sp. nov. A preliminary characterization of its blue pigment shows similarities to marennine produced by Haslea ostrearia, as evidenced by UV–visible spectrophotometry and Raman spectrometry. Life cycle stages including auxosporulation were also observed, providing data on the cardinal points of this species. For the two most geographically distant populations (North Carolina and East Mediterranean), complete mitochondrial and plastid genomes were sequenced. The mitogenomes of both strains share a rare atp6 pseudogene, but the number, nature, and positions of the group II introns inside its cox1 gene differ between the two populations. There are also two pairs of genes fused in single ORFs. The plastid genomes are characterized by large regions of recombination with plasmid DNA, which are in both cases located between the ycf35 and psbA genes, but whose content differs between the strains. The two sequenced strains hosts three plasmids coding for putative serine recombinase protein whose sequences are compared, and four out of six of these plasmids were highly conserved.
Agent Based Modelling of a Local Energy Market: A Study of the Economic Interactions between Autonomous PV Owners within a Micro-Grid
Authors: Lovati Marco , Huang Pei , Olsmats Carl , Yan Da , Zhang Xingxing
Published: April 2021

Urban Photovoltaic (PV) systems can provide large fractions of the residential electric demand at socket parity (i.e., a cost below the household consumer price). This is obtained without necessarily installing electric storage or exploiting tax funded incentives. The benefits of aggregating the electric demand and renewable output of multiple households are known and established; in fact, regulations and pilot energy communities are being implemented worldwide. Financing and managing a shared urban PV system remains an unsolved issue, even when the profitability of the system as a whole is demonstrable. For this reason, an agent-based modelling environment has been developed and is presented in this study. It is assumed that an optimal system (optimized for self-sufficiency) is shared between 48 households in a local grid of a positive energy district. Different scenarios are explored and discussed, each varying in number of owners (agents who own a PV system) and their pricing behaviour. It has been found that a smaller number of investors (i.e., someone refuse to join) provokes an increase of the earnings for the remaining investors (from 8 to 74% of the baseline). Furthermore, the pricing strategy of an agent shows improvement potential without knowledge of the demand of others, and thus it has no privacy violations.
Liquid Biopsies in Solid Cancers: Implementation in a Nordic Healthcare System
Authors: Nordgård Oddmund , Brendsdal Forthun Rakel , Lapin Morten , Grønberg Bjørn Henning , Kalland Karl Henning , Kopperud Reidun Kristin , Thomsen Liv Cecilie Vestrheim , Tjensvoll Kjersti , Gilje Bjørnar , Gjertsen Bjørn Tore , Hovland Randi
Published: April 2021

Liquid biopsies have emerged as a potential new diagnostic tool, providing detailed information relevant for characterization and treatment of solid cancers. We here present an overview of current evidence supporting the clinical relevance of liquid biopsy assessments. We also discuss the implementation of liquid biopsies in clinical studies and their current and future clinical role, with a special reference to the Nordic healthcare systems. Our considerations are restricted to the most established liquid biopsy specimens: circulating tumor DNA (ctDNA) and circulating tumor cells (CTC). Both ctDNA and CTCs have been used for prognostic stratification, treatment choices, and treatment monitoring in solid cancers. Several recent publications also support the role of ctDNA in early cancer detection. ctDNA seems to provide more robust clinically relevant information in general, whereas CTCs have the potential to answer more basic questions related to cancer biology and metastasis. Epidermal growth factor receptor-directed treatment of non-small-cell lung cancer represents a clinical setting where ctDNA already has entered the clinic. The role of liquid biopsies in treatment decisions, standardization of methods, diagnostic performance and the need for further research, as well as cost and regulatory issues were identified as factors that influence further integration in the clinic. In conclusion, substantial evidence supports the clinical utility of liquid biopsies in cancer diagnostics, but further research is still required for a more general application in clinical practice.
FEN1 Blockade for Platinum Chemo-Sensitization and Synthetic Lethality in Epithelial Ovarian Cancers
Authors: Mesquita Katia A. , Ali Reem , Doherty Rachel , Toss Michael S. , Miligy Islam , Alblihy Adel , Dorjsuren Dorjbal , Simeonov Anton , Jadhav Ajit , Wilson David M. , Hickson Ian , Tatum Natalie J. , Rakha Emad A. , Madhusudan Srinivasan
Published: April 2021

FEN1 plays critical roles in long patch base excision repair (LP-BER), Okazaki fragment maturation, and rescue of stalled replication forks. In a clinical cohort, FEN1 overexpression is associated with aggressive phenotype and poor progression-free survival after platinum chemotherapy. Pre-clinically, FEN1 is induced upon cisplatin treatment, and nuclear translocation of FEN1 is dependent on physical interaction with importin β. FEN1 depletion, gene inactivation, or inhibition re-sensitizes platinum-resistant ovarian cancer cells to cisplatin. BRCA2 deficient cells exhibited synthetic lethality upon treatment with a FEN1 inhibitor. FEN1 inhibitor-resistant PEO1R cells were generated, and these reactivated BRCA2 and overexpressed the key repair proteins, POLβ and XRCC1. FEN1i treatment was selectively toxic to POLβ deficient but not XRCC1 deficient ovarian cancer cells. High throughput screening of 391,275 compounds identified several FEN1 inhibitor hits that are suitable for further drug development. We conclude that FEN1 is a valid target for ovarian cancer therapy.
Inhibiting FAK–Paxillin Interaction Reduces Migration and Invadopodia-Mediated Matrix Degradation in Metastatic Melanoma Cells
Authors: Mousson Antoine , Legrand Marlène , Steffan Tania , Vauchelles Romain , Carl Philippe , Gies Jean-Pierre , Lehmann Maxime , Zuber Guy , De Mey Jan , Dujardin Denis , Sick Emilie , Rondé Philippe
Published: April 2021

The nonreceptor tyrosine kinase FAK is a promising target for solid tumor treatment because it promotes invasion, tumor progression, and drug resistance when overexpressed. Investigating the role of FAK in human melanoma cells, we found that both in situ and metastatic melanoma cells strongly express FAK, where it controls tumor cells’ invasiveness by regulating focal adhesion-mediated cell motility. Inhibiting FAK in human metastatic melanoma cells with either siRNA or a small inhibitor targeting the kinase domain impaired migration but led to increased invadopodia formation and extracellular matrix degradation. Using FAK mutated at Y397, we found that this unexpected increase in invadopodia activity is due to the lack of phosphorylation at this residue. To preserve FAK–Src interaction while inhibiting pro-migratory functions of FAK, we found that altering FAK–paxillin interaction, with either FAK mutation in the focal adhesion targeting (FAT) domain or a competitive inhibitor peptide mimicking paxillin LD domains drastically reduces cell migration and matrix degradation by preserving FAK activity in the cytoplasm. In conclusion, our data show that targeting FAK–paxillin interactions could be a potential therapeutic strategy to prevent metastasis formation, and molecules targeting this interface could be alternative to inhibitors of FAK kinase activity which display unexpected effects.