bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fetal whole heart blood flow imaging using 4D cine MRI
Authors: Roberts Thomas A. , van Amerom Joshua F. P. , Uus Alena , Lloyd David F. A. , van Poppel Milou P. M. , Price Anthony N. , Tournier Jacques-Donald , Mohanadass Chloe A. , Jackson Laurence H. , Malik Shaihan J. , Pushparajah Kuberan , Rutherford Mary A. , Razavi Reza , Deprez Maria , Hajnal Joseph V. 
Published: October 2020

AbstractPrenatal detection of congenital heart disease facilitates the opportunity for potentially life-saving care immediately after the baby is born. Echocardiography is routinely used for screening of morphological malformations, but functional measurements of blood flow are scarcely used in fetal echocardiography due to technical assumptions and issues of reliability. Magnetic resonance imaging (MRI) is readily used for quantification of abnormal blood flow in adult hearts, however, existing in utero approaches are compromised by spontaneous fetal motion. Here, we present and validate a novel method of MRI velocity-encoding combined with a motion-robust reconstruction framework for four-dimensional visualization and quantification of blood flow in the human fetal heart and major vessels. We demonstrate simultaneous 4D visualization of the anatomy and circulation, which we use to quantify flow rates through various major vessels. The framework introduced here could enable new clinical opportunities for assessment of the fetal cardiovascular system in both health and disease.
Immunological fingerprint of 4CMenB recombinant antigens via protein microarray reveals key immunosignatures correlating with bactericidal activity
Authors: Bartolini E. , Borgogni E. , Bruttini M. , Muzzi A. , Giuliani M. , Iozzi S. , Petracca R. , Martinelli M. , Bonacci S. , Marchi S. , Brettoni C. , Donati C. , Torricelli G. , Guidotti S. , Domina M. , Beninati C. , Teti G. , Felici F. , Rappuoli R. , Castellino F. , Del Giudice G. , Masignani V. , Pizza M. , Maione D. 
Published: October 2020

AbstractSerogroup B meningococcus (MenB) is a leading cause of meningitis and sepsis across the world and vaccination is the most effective way to protect against this disease. 4CMenB is a multi-component vaccine against MenB, which is now licensed for use in subjects >2 months of age in several countries. In this study, we describe the development and use of an ad hoc protein microarray to study the immune response induced by the three major 4CMenB antigenic components (fHbp, NHBA and NadA) in individual sera from vaccinated infants, adolescents and adults. The resulting 4CMenB protein antigen fingerprinting allowed the identification of specific human antibody repertoire correlating with the bactericidal response elicited in each subject. This work represents an example of epitope mapping of the immune response induced by a multicomponent vaccine in different age groups with the identification of protective signatures. It shows the high flexibility of this microarray based methodology in terms of high-throughput information and minimal volume of biological samples needed.
Molecular phenotyping of oxidative stress in diabetes mellitus with point-of-care NMR system
Authors: Peng Weng Kung , Chen Lan , Boehm Bernhard O. , Han Jongyoon , Loh Tze Ping 
Published: October 2020

AbstractDiabetes mellitus is one of the fastest-growing health burdens globally. Oxidative stress, which has been implicated in the pathogenesis of diabetes complication (e.g., cardiovascular event), remains poorly understood. We report a new approach to rapidly manipulate and evaluate the redox states of blood using a point-of-care NMR system. Various redox states of the hemoglobin were mapped out using the newly proposed (pseudo) two-dimensional map known as T1–T2 magnetic state diagram. We exploit the fact that oxidative stress changes the subtle molecular motion of water proton in the blood, and thus inducing a measurable shift in magnetic resonance relaxation properties. We demonstrated the clinical utilities of this technique to rapidly stratify diabetes subjects based on their oxidative status in conjunction to the traditional glycemic level to improve the patient stratification and thus the overall outcome of clinical diabetes care and management.
Genomic testing in 1019 individuals from 349 Pakistani families results in high diagnostic yield and clinical utility
Authors: Cheema Huma , Bertoli-Avella Aida M. , Skrahina Volha , Anjum Muhammad Nadeem , Waheed Nadia , Saeed Anjum , Beetz Christian , Perez-Lopez Jordi , Rocha Maria Eugenia , Alawbathani Salem , Pereira Catarina , Hovakimyan Marina , Patric Irene Rosita Pia , Paknia Omid , Ameziane Najim , Cozma Claudia , Bauer Peter , Rolfs Arndt 
Published: October 2020

AbstractWe implemented a collaborative diagnostic program in Lahore (Pakistan) aiming to establish the genetic diagnosis, and to asses diagnostic yield and clinical impact in patients with suspected genetic diseases. Local physicians ascertained pediatric patients who had no previous access to genetic testing. More than 1586 genetic tests were performed in 1019 individuals (349 index cases, 670 relatives). Most frequently performed tests were exome/genome sequencing (ES/GS, 284/78 index cases) and specific gene panels (55 index cases). In 61.3% of the patients (n = 214) a genetic diagnosis was established based on pathogenic and likely pathogenic variants. Diagnostic yield was higher in consanguineous families (60.1 vs. 39.5%). In 27 patients, genetic diagnosis relied on additional biochemical testing, allowing rapid assessment of the functional effect of the variants. Remarkably, the genetic diagnosis had a direct impact on clinical management. Most relevant consequences were therapy related such as initiation of the appropriated treatment in a timely manner in 51.9% of the patients (n = 111). Finally, we report 12 candidate genes among 66 cases with no genetic diagnosis. Importantly, three of these genes were validated as ‘diagnostic’ genes given the strong evidence supporting causality derived from our data repository (CAP2-dilated cardiomyopathy, ITFG2-intellectual disability and USP53-liver cholestasis). The high diagnostic yield, clinical impact, and research findings demonstrate the utility of genomic testing, especially when used as first-line genetic test. For patients with suspected genetic diseases from resource-limited regions, ES can be considered as the test of choice to achieve genetic diagnosis.
Data for training and testing radiation detection algorithms in an urban environment
Authors: Ghawaly James M. , Nicholson Andrew D. , Peplow Douglas E. , Anderson-Cook Christine M. , Myers Kary L. , Archer Daniel E. , Willis Michael J. , Quiter Brian J. 
Published: October 2020

AbstractThe detection, identification, and localization of illicit nuclear materials in urban environments is of utmost importance for national security. Most often, the process of performing these operations consists of a team of trained individuals equipped with radiation detection devices that have built-in algorithms to alert the user to the presence nuclear material and, if possible, to identify the type of nuclear material present. To encourage the development of new detection, radioisotope identification, and source localization algorithms, a dataset consisting of realistic Monte Carlo–simulated radiation detection data from a 2 in. × 4 in. × 16 in. NaI(Tl) scintillation detector moving through a simulated urban environment based on Knoxville, Tennessee, was developed and made public in the form of a Topcoder competition. The methodology used to create this dataset has been verified using experimental data collected at the Fort Indiantown Gap National Guard facility. Realistic signals from special nuclear material and industrial and medical sources are included in the data for developing and testing algorithms in a dynamic real-world background.
Birth control knowledge among freshmen of four Italian universities
Authors: Cegolon L. , Bortolotto M. , Bellizzi S. , Cegolon A. , Mastrangelo G. , Xodo C. 
Published: October 2020

AbstractSince sexual health education (SHE) is not mandatory in Italian schools, we conducted a survey on freshmen of four Italian university campuses in 2012 to investigate the respective level of sexual health knowledge (SHK) in relation to birth control, with the aim to inform public health policy makers. A convenience strategy was employed to sample 4,552 freshmen registered with various undergraduate courses at four Italian universities: Padua university (Veneto Region); university of Milan (Lombardy Region); university of Bergamo (Lombardy Region); university of Palermo (Sicily Region). We investigated the level of SHK on birth control using 6 proxy indicators: (1) the average length of a woman’s period [outcome with 3 levels: wrong (base) vs. acceptable vs. correct]; (2) the most fertile interval within a woman’s period (binary outcome: correct vs. wrong answer); (3) the event between the end of a period and the beginning of the next cycle (binary outcome: correct vs. wrong answer); (4) the average survival of spermatozoa in the womb (binary outcome: correct vs. wrong answer); (5) the concept of contraception (binary outcome: correct vs. wrong answer); (6) the efficacy of various contraceptives to prevent unintended pregnancies (linear score: 0–17). We fitted 6 separate models of multiple regression: multinomial for outcome 1; logistic for outcomes 2, 3, 4, 6; linear for outcome 6. Statistical estimates were adjusted for a number of socio-demographic factors. Results were expressed as odds ratios (OR) for the 4 multiple logistic regression models, linear coefficients (RC) for the linear regression model and relative risk ratio (RRR) for the multinomial logistic regression model. The level of significance of each risk estimate was set at 0.05. The level of SHK of freshmen sampled was rather low, as 60% interviewees did not know the average length of a woman’s period, the average survival of spermatozoa in the womb and the concept of contraception, whilst the most fertile interval within a woman’s period was known only to 55% of interviewees. The mean score of SHK on the efficacy of various contraceptive methods was only 5 (scale 0–17). Some categories of students were consistently and significantly less knowledgeable on birth control at multivariable analysis: males; students from the university of Palermo; those with vocational secondary school education and those not in a romantic relationship at the time the survey was conducted. The results of this survey clearly call for the introduction of SHE programs in Italian schools, as already done in several European countries. School SHE should start as early as possible, ideally even before secondary school. SHE should be holistic and delivered with a multiple agency coordinated approach involving the Ministry of Health, the Ministry of Education, University and Scientific Research (MIUR), families, schools, public health departments, primary health care providers, pharmacists, media, other.
Effects of Alzheimer’s disease and formalin fixation on the different mineralised-iron forms in the human brain
Authors: van der Weerd Louise , Lefering Anton , Webb Andrew , Egli Ramon , Bossoni Lucia 
Published: October 2020

AbstractIron accumulation in the brain is a phenomenon common to many neurodegenerative diseases, perhaps most notably Alzheimer’s disease (AD). We present here magnetic analyses of post-mortem brain tissue of patients who had severe Alzheimer’s disease, and compare the results with those from healthy controls. Isothermal remanent magnetization experiments were performed to assess the extent to which different magnetic carriers are affected by AD pathology and formalin fixation. While Alzheimer’s brain material did not show higher levels of magnetite/maghemite nanoparticles than corresponding controls, the ferrihydrite mineral, known to be found within the core of ferritin proteins and hemosiderin aggregates, almost doubled in concentration in patients with Alzheimer’s pathology, strengthening the conclusions of our previous studies. As part of this study, we also investigated the effects of sample preparation, by performing experiments on frozen tissue as well as tissue which had been fixed in formalin for a period of 5 months. Our results showed that the two different preparations did not critically affect the concentration of magnetic carriers in brain tissue, as observable by SQUID magnetometry.
Development of a novel molecular probe for the detection of liver mitochondrial redox metabolism
Authors: Hosain Md. Zahangir , Hyodo Fuminori , Mori Takeshi , Takahashi Koyo , Nagao Yusuke , Eto Hinako , Murata Masaharu , Akahoshi Tomohiko , Matsuo Masayuki , Katayama Yoshiki 
Published: October 2020

AbstractRedox status influences the course of the inflammatory, metabolic, and proliferative liver diseases. Oxidative stress is thought to play a crucial and sustained role in the pathological progression of early steatosis to severe hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Oxidative stress induced by reactive oxygen species which are generated in the mitochondria can lead to chronic organelle damage in hepatocytes. Currently, the diagnosis of liver disease requires liver biopsy, which is invasive and associated with complications. The present report describes the development of a novel molecular probe, EDA-PROXYL, with higher reactivity and mitochondrial selectivity than standard carboxyl-PROXYL and carbamoyl-PROXYL probes. The membrane permeability of our probe improved in aqueous environments which led to increased accumulation in the liver and interaction of EDA-PROXYL with the carnitine transporter via the amine (NH3+) group further increased accumulation. This increased mitochondrial sensitivity and enhanced accumulation highlight the potential of EDA-PROXYL as a molecular probe for determining metabolic reactions of the mitochondria. Thus, this novel probe could be a tool for the evaluation of redox status of the mitochondria to assess the degree of liver injury and, ultimately, the response to pharmacological therapy.
Fast and antibiotic free genome integration into Escherichia coli chromosome
Authors: Egger Esther , Tauer Christopher , Cserjan-Puschmann Monika , Grabherr Reingard , Striedner Gerald 
Published: October 2020

AbstractGenome-based Escherichia coli expression systems are superior to conventional plasmid-based systems as the metabolic load triggered by recombinant compounds is significantly reduced. The efficiency of T7-based transcription compensates for low gene dosage (single copy) and facilitates high product formation rates. While common Gene Bridges’ λ-red mediated recombination technique for site directed integration of genes into the host genome is very efficient, selection for positive clones is based on antibiotic resistance markers and removal thereof is often time consuming. For the generation of industrial production strains, flexibility in terms of integration site is not required, yet time from gene design to a stable clone is a quite relevant parameter. In this study, we developed a fast, efficient and antibiotic-free integration method for E. coli as production strain. We combined the λ-red recombination system with the site-directed homing endonuclease I from Saccharaomyces cerevisiae (I-SceI) for selection. In a first step, λ-red proteins are performing genome integration of a linear, antibiotic marker-free integration cassette. The engineered host strain carries the I-SceI restriction sequence at the attTn7 site, where the integration event happens. After homologous recombination and integration at the target site, site-specific genome cleavage by endonuclease I-SceI is induced, thereby killing all cells still containing an intact I-SceI site. In case of positive recombination events, the genomic I-SceI site is deleted and cleavage is no longer possible. Since plasmids are designed to contain another I-SceI restriction site they are destroyed by self-cleavage, a procedure replacing the time-consuming plasmid curing. The new plasmid-based “All-In-One” genome integration method facilitates significantly accelerated generation of genome-integrated production strains in 4 steps.
Germline BRCA 1-2 status prediction through ovarian ultrasound images radiogenomics: a hypothesis generating study (PROBE study)
Authors: Nero Camilla , Ciccarone Francesca , Boldrini Luca , Lenkowicz Jacopo , Paris Ida , Capoluongo Ettore Domenico , Testa Antonia Carla , Fagotti Anna , Valentini Vincenzo , Scambia Giovanni 
Published: October 2020

AbstractRadiogenomics is a specific application of radiomics where imaging features are linked to genomic profiles. We aim to develop a radiogenomics model based on ovarian US images for predicting germline BRCA1/2 gene status in women with healthy ovaries. From January 2013 to December 2017 a total of 255 patients addressed to germline BRCA1/2 testing and pelvic US documenting normal ovaries, were retrospectively included. Feature selection for univariate analysis was carried out via correlation analysis. Multivariable analysis for classification of germline BRCA1/2 status was then carried out via logistic regression, support vector machine, ensemble of decision trees and automated machine learning pipelines. Data were split into a training (75%) and a testing (25%) set. The four strategies obtained a similar performance in terms of accuracy on the testing set (from 0.54 of logistic regression to 0.64 of the auto-machine learning pipeline). Data coming from one of the tested US machine showed generally higher performances, particularly with the auto-machine learning pipeline (testing set specificity 0.87, negative predictive value 0.73, accuracy value 0.72 and 0.79 on training set). The study shows that a radiogenomics model on machine learning techniques is feasible and potentially useful for predicting gBRCA1/2 status in women with healthy ovaries.
A novel, low cost, and accessible method for rapid fabrication of the modifiable microfluidic devices
Authors: Annabestani Mohsen , Esmaeili-Dokht Pouria , Fardmanesh Mehdi 
Published: October 2020

AbstractAs microfluidic chips are evolving to become a significant analysis tool toward POCT devices, it is crucial to make the cost and the time required for the fabrication process of these chips as low as possible. Because of the multidisciplinary nature of these systems and the collaboration of many different laboratories and organizations from vastly various fields with unequal types of equipment, it is essential to develop new techniques and materials to make the integration of disparate systems together more straightforward, accessible, and economical. In this paper, we present ethylene–vinyl acetate (EVA) as a new polymer-based material for the fabrication of different microfluidic chips, which brings new features and tools in fabrication, integration, and functionality of microfluidic systems. We put this material next to PDMS for comparison between various aspects of these materials. We have shown that besides the low-cost ability, ubiquitousness, geometrical modifiability, and ease of fabrication of EVA chips, due the lower hydrophobicity and lower terahertz (THz) absorption of EVA than PDMS, EVA chips, in comparison to PDMS counterparts, can work faster, have less number of channel blocking and can be used in THz biosensing application like metamaterial-based cancer detection. Finally, several devices are made using EVA to demonstrate the functionality and versatility of this material for the fabrication of microfluidic chips.
Evaluation of real-world early response of DMO to aflibercept therapy to inform future clinical trial design of novel investigational agents
Authors: Halim Sandra , Gurudas Sarega , Chandra Shruti , Greenwood John , Sivaprasad Sobha 
Published: October 2020

AbstractNew clinical trials for diabetic macular oedema (DMO) are being designed to prove superiority over aflibercept when this agent is already very effective in improving visual acuity (VA) and DMO. The aim of this study was to determine the optimal inclusion–exclusion criteria for trials to aim for superiority in visual outcomes with newer agents. As Phase 1 studies are short duration, we aimed to evaluate the early response of aflibercept in a real-world cohort initiated on monthly aflibercept for 3 consecutive injections and observed the effects at 4 months. The sub-optimal responders were pre-defined based on different cut-offs for VA and central sub-field thickness (CST). 200 patients with treatment naïve DMO treated with 3 loading doses of aflibercept were included in the study. We found that those presenting with baseline VA of 35–54 ETDRS letters (n = 43) had higher proportion of sub-optimal responders compared to other categories (p < 0.001). Patients with baseline CST of less than 400 µm (n = 96) responded less well functionally and anatomically to loading dose than eyes with baseline CST of 400 µm or more (n = 104, p = 0.02), indicating that eyes with CST ≥ 400 µm is another inclusion criteria. There was minimal correlation between change in CST and change in VA at 4 months (r = − 0.27), suggesting that both these inclusion criteria are non-exclusive. However, for maximal efficacy, patients that meet both these inclusion criteria are more likely to show benefit from an alternative intervention. New trials should aim to include patients with treatment naïve DMO with VA between 35–54 letters and CST of 400 µm or more when aflibercept is used as the comparator.
Bovine sperm-oviduct interactions are characterized by specific sperm behaviour, ultrastructure and tubal reactions which are impacted by sex sorting
Authors: Camara Pirez Miguel , Steele Heather , Reese Sven , Kölle Sabine 
Published: October 2020

AbstractTo date sperm-oviduct interactions have largely been investigated under in vitro conditions. Therefore we set out to characterize the behaviour of bovine spermatozoa within the sperm reservoir under near in vivo conditions and in real-time using a novel live cell imaging technology and a newly established fluorescent sperm binding assay. Sperm structure and tubal reactions after sperm binding were analysed using scanning and transmission electron microscopy and histochemistry. As a model to specify the impact of stress on sperm-oviduct interactions, frozen-thawed conventional and sex-sorted spermatozoa from the same bulls (n = 7) were co-incubated with oviducts obtained from cows immediately after slaughter. Our studies revealed that within the oviductal sperm reservoir agile (bound at a tangential angle of about 30°, actively beating undulating tail), lagging (bound at a lower angle, reduced tail movement), immotile (absence of tail movement) and hyperactivated (whip-like movement of tail) spermatozoa occur, the prevalence of which changes in a time-dependent pattern. After formation of the sperm reservoir, tubal ciliary beat frequency is significantly increased (p = 0.022) and the epithelial cells show increased activity of endoplasmic reticula. After sex sorting, spermatozoa occasionally display abnormal movement patterns characterized by a 360° rotating head and tail. Sperm binding in the oviduct is significantly reduced (p = 0.008) following sexing. Sex-sorted spermatozoa reveal deformations in the head, sharp bends in the tail and a significantly increased prevalence of damaged mitochondria (p < 0.001). Our results imply that the oviductal cells specifically react to the binding of spermatozoa, maintaining sperm survival within the tubal reservoir. The sex-sorting process, which is associated with mechanical, chemical and time stress, impacts sperm binding to the oviduct and mitochondrial integrity affecting sperm motility and function.