bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigations of an inducible intact dystrophin gene excision system in cardiac and skeletal muscle in vivo
Authors: Bez Batti Angulski Addeli , Bauer John , Cohen Houda , Kobuke Kazuhiro , Campbell Kevin P. , Metzger Joseph M. 
Published: July 2020

AbstractWe sought here to induce the excision of a large intragenic segment within the intact dystrophin gene locus, with the ultimate goal to elucidate dystrophin protein function and stability in striated muscles in vivo. To this end, we implemented an inducible-gene excision methodology using a floxed allele approach, demarcated by dystrophin exons 2–79, in complementation with a cardiac and skeletal muscle directed gene deletion system for spatial–temporal control of dystrophin gene excision in vivo. Main findings of this study include evidence of significant intact dystrophin gene excision, ranging from ~ 25% in heart muscle to ~ 30–35% in skeletal muscles in vivo. Results show that despite evidence of significant dystrophin gene excision, no significant decrease in dystrophin protein content was evident by Western blot analysis, at three months post excision in skeletal muscles or by 6 months post gene excision in heart muscle. Challenges of in vivo dystrophin gene excision revealed acute deleterious effects of tamoxifen on striated muscles, including a transient down regulation in dystrophin gene transcription in the absence of dystrophin gene excision. In addition, technical limitations of incomplete dystrophin gene excision became apparent that, in turn, tempered interpretation. Collectively, these findings are in keeping with earlier studies suggesting the dystrophin protein to be long-lived in striated muscles in vivo; however, more rigorous quantitative analysis of dystrophin stability in vivo will require future works in which more complete gene excision can be demonstrated, and without significant off-target effects of the gene deletion experimental platform per se.
Realistic simulation of virtual multi-scale, multi-modal patient trajectories using Bayesian networks and sparse auto-encoders
Authors: Sood Meemansa , Sahay Akrishta , Karki Reagon , Emon Mohammad Asif , Vrooman Henri , Hofmann-Apitius Martin , Fröhlich Holger 
Published: July 2020

AbstractTranslational research of many disease areas requires a longitudinal understanding of disease development and progression across all biologically relevant scales. Several corresponding studies are now available. However, to compile a comprehensive picture of a specific disease, multiple studies need to be analyzed and compared. A large number of clinical studies is nowadays conducted in the context of drug development in pharmaceutical research. However, legal and ethical constraints typically do not allow for sharing sensitive patient data. In consequence there exist data “silos”, which slow down the overall scientific progress in translational research. In this paper, we suggest the idea of a virtual cohort (VC) to address this limitation. Our key idea is to describe a longitudinal patient cohort with the help of a generative statistical model, namely a modular Bayesian Network, in which individual modules are represented as sparse autoencoder networks. We show that with the help of such a model we can simulate subjects that are highly similar to real ones. Our approach allows for incorporating arbitrary multi-scale, multi-modal data without making specific distribution assumptions. Moreover, we demonstrate the possibility to simulate interventions (e.g. via a treatment) in the VC. Overall, our proposed approach opens the possibility to build sufficiently realistic VCs for multiple disease areas in the future.
Prediction accuracy of L- and M-cone based human pupil light models
Authors: Zandi Babak , Klabes Julian , Khanh Tran Quoc 
Published: July 2020

AbstractMulti-channel LED luminaires offer a powerful tool to vary retinal receptor signals while keeping visual parameters such as color or brightness perception constant. This technology could provide new fields of application in indoor lighting since the spectrum can be enhanced individually to the users’ favor or task. One possible application would be to optimize a light spectrum by using the pupil diameter as a parameter to increase the visual acuity. A spectral- and time-dependent pupil model is the key requirement for this aim. We benchmarked in our work selected L- and M-cone based pupil models to find the estimation error in predicting the pupil diameter for chromatic and polychromatic spectra at 100 cd/m2. We report an increased estimation error up to 1.21 mm for 450 nm at 60–300 s exposure time. At short exposure times, the pupil diameter was approximately independent of the used spectrum, allowing to use the luminance for a pupil model. Polychromatic spectra along the Planckian locus showed at 60–300 s exposure time, a prediction error within a tolerance range of ± 0.5 mm. The time dependency seems to be more essential than the spectral dependency when using polychromatic spectra.
Diagnosis of cytomegalovirus infection from clinical whole genome sequencing
Authors: Ramchandar Nanda , Ding Yan , Farnaes Lauge , Dimmock David , Hobbs Charlotte , Kingsmore Stephen F. , Bainbridge Matthew 
Published: July 2020

AbstractRapid whole genome sequencing (rWGS) of peripheral blood has been used to detect microbial DNA in acute infections. Cytomegalovirus (CMV) is a herpesvirus capable of causing severe disease in neonates and immunocompromised patients. We identified CMV in patients undergoing diagnostic rWGS by matching reads that did not align to the human reference genome to a database of microbial genomes. rWGS was conducted on peripheral blood obtained from ill pediatric patients (age 1 day to 18 years). Reads not aligning to the human genome were analyzed using an in-house pipeline to identify DNA consistent with CMV infection. Of 669 patients who received rWGS from July 2016 through July 2019, we identified 28 patients (4.2%) with reads that aligned to the CMV reference genome. Six of these patients had clinical findings consistent with symptomatic CMV infection. Positive results were highly correlated (R2 > 0.99, p < 0.001) to a CMV-qPCR assay conducted on DNA isolated from whole blood samples. In acutely ill children receiving rWGS for diagnosis of genetic disease, we propose analysis of patient genetic data to identify CMV, which could impact treatment of up to 4% of children in the intensive care unit.
Data-derived metrics describing the behaviour of field-based citizen scientists provide insights for project design and modelling bias
Authors: August Tom , Fox Richard , Roy David B. , Pocock Michael J. O. 
Published: July 2020

AbstractAround the world volunteers and non-professionals collect data as part of environmental citizen science projects, collecting wildlife observations, measures of water quality and much more. However, where projects allow flexibility in how, where, and when data are collected there will be variation in the behaviour of participants which results in biases in the datasets collected. We develop a method to quantify this behavioural variation, describing the key drivers and providing a tool to account for biases in models that use these data. We used a suite of metrics to describe the temporal and spatial behaviour of participants, as well as variation in the data they collected. These were applied to 5,268 users of the iRecord Butterflies mobile phone app, a multi-species environmental citizen science project. In contrast to previous studies, after removing transient participants (those active on few days and who contribute few records), we do not find evidence of clustering of participants; instead, participants fall along four continuous axes that describe variation in participants’ behaviour: recording intensity, spatial extent, recording potential and rarity recording. Our results support a move away from labelling participants as belonging to one behavioural group or another in favour of placing them along axes of participant behaviour that better represent the continuous variation between individuals. Understanding participant behaviour could support better use of the data, by accounting for biases in the data collection process.
Noninvasive and safe cell viability assay for Paramecium using natural pigment extracted from food
Authors: Yamashita Kyohei , Tokunaga Eiji 
Published: July 2020

AbstractNoninvasive, safe and cost-effective cell viability assay is important in many fields of biological research such as cell culture and counting. We examined ten typical natural pigments extracted from food to find that Monascus pigment (MP) or anthocyanin pigment (AP: purple sweet potato and purple cabbage) with Tris (Trimethylolaminomethane) works as a good indicator of viability assay for dye exclusion test (DET) of Paramecium. This was confirmed spectrally by scan-free, non-invasive absorbance spectral imaging A (x, y, λ) microscopy. We developed a new method of cell capture using a metal mesh to confine live Paramecium in a restricted space. This has the advantage that a low-cost and robust capture can be fabricated without using special equipment, compared to a conventional lab-on-a-chip. As a result, MP and AP stained dead cells as quick as methylene blue (MB), a synthetic dye conventionally used in DET within 1 min when treated with microwave and benzalkonium chloride. The natural pigments with Tris had little effect on inhibiting the growth of Paramecium, but MB killed all the cells within 1 h. MP is most useful because it allows non-invasive DET without Tris. This approach provides less invasive and safe DET.
Rare variant of the epigenetic regulator SMCHD1 in a patient with pituitary hormone deficiency
Authors: Kinjo Kenichi , Nagasaki Keisuke , Muroya Koji , Suzuki Erina , Ishiwata Keisuke , Nakabayashi Kazuhiko , Hattori Atsushi , Nagao Koji , Nozawa Ryu-Suke , Obuse Chikashi , Miyado Kenji , Ogata Tsutomu , Fukami Maki , Miyado Mami 
Published: July 2020

AbstractIsolated hypogonadotropic hypogonadism (IHH), combined pituitary hormone deficiency (CPHD), and septo-optic dysplasia (SOD) constitute a disease spectrum whose etiology remains largely unknown. This study aimed to clarify whether mutations in SMCHD1, an epigenetic regulator gene, might underlie this disease spectrum. SMCHD1 is a causative gene for Bosma arhinia microphthalmia syndrome characterized by arhinia, microphthalmia and IHH. We performed mutation screening of SMCHD1 in patients with etiology-unknown IHH (n = 31) or CPHD (n = 43, 19 of whom also satisfied the SOD diagnostic criteria). Rare variants were subjected to in silico analyses and classified according to the American College of Medical Genetics and Genomics guidelines. Consequently, a rare likely pathogenic variant, p.Asp398Asn, was identified in one patient. The patient with p.Asp398Asn exhibited CPHD, optic nerve hypoplasia, and a thin retinal nerve fiber layer, and therefore satisfied the criteria of SOD. This patient showed a relatively low DNA methylation level of the 52 SMCHD1-target CpG sites at the D4Z4 locus. Exome sequencing for the patient excluded additional variants in other IHH/CPHD-causative genes. In vitro assays suggested functional impairment of the p.Asp398Asn variant. These results provide the first indication that SMCHD1 mutations represent a rare genetic cause of the HH-related disease spectrum.
Novel thymoquinone lipidic core nanocapsules with anisamide-polymethacrylate shell for colon cancer cells overexpressing sigma receptors
Authors: Ramzy Lydia , Metwally Abdelkader A. , Nasr Maha , Awad Gehanne A. S. 
Published: July 2020

AbstractThe biggest challenge in colorectal cancer therapy is to avoid intestinal drug absorption before reaching the colon, while focusing on tumor specific delivery with high local concentration and minimal toxicity. In our work, thymoquinone (TQ)-loaded polymeric nanocapsules were prepared using the nanoprecipitation technique using Eudragit S100 as polymeric shell. Conjugation of anisamide as a targeting ligand for sigma receptors overexpressed by colon cancer cells to Eudragit S100 was carried out via carbodiimide coupling reaction, and was confirmed by thin layer chromatography and 1H-NMR. TQ nanocapsules were characterized for particle size, surface morphology, zeta potential, entrapment efficiency % (EE%), in vitro drug release and physical stability. A cytotoxicity study on three colon cancer cell lines (HT-29, HCT-116, Caco-2) was performed. Results revealed that the polymeric nanocapsules were successfully prepared, and the in vitro characterization showed a suitable size, zeta potential, EE% and physical stability. TQ exhibited a delayed release pattern from the nanocapsules in vitro. Anisamide-targeted TQ nanocapsules showed higher cytotoxicity against HT-29 cells overexpressing sigma receptors compared to their non-targeted counterparts and free TQ after incubation for 48 h, hence delineating anisamide as a promising ligand for active colon cancer targeting.
Validity of traditional physical activity intensity calibration methods and the feasibility of self-paced walking and running on individualised calibration of physical activity intensity in children
Authors: Haapala Eero A. , Gao Ying , Vanhala Anssi , Rantalainen Timo , Finni Taija 
Published: July 2020

AbstractThere are no practical and valid methods for the assessment of individualised physical activity (PA) intensity in observational studies. Therefore, we investigated the validity of commonly used metabolic equivalent of tasks (METs) and pre-determined PA intensity classification methods against individualised PA intensity classification in 35 children 7–11-years-of-age. Then, we studied validity of mean amplitude deviation (MAD) measured by accelerometry during self-paced walking and running in assessment of individualised PA intensity. Individualised moderate PA (MPA) was defined as V̇O2 ≥ 40% of V̇O2reserveand V̇O2 < ventilatory threshold (VT) and vigorous PA (VPA) as V̇O2 ≥ VT. We classified > 3–6 (or alternatively > 4–7) METs as MPA and > 6 (> 7) METs as VPA. Task intensities were classified according to previous calibration studies. MET-categories correctly identified 25.9–83.3% of light PA, 85.9–90.3% of MPA, and 56.7–82.2% of VPA. Task-specific categories correctly classified 53.7% of light PA, 90.6% of MPA, and 57.8% of VPA. MAD during self-paced walking discriminated MVPA from light PA (sensitivity = 67.4, specificity = 88.0) and MAD during self-paced running discriminated VPA from MPA (sensitivity = 78.8, specificity = 79.3). In conclusion, commonly used methods may misclassify PA intensity in children. MAD during self-paced running may provide a novel and practical method for determining individualised VPA intensity in children.
Iron and manganese migration in “soil–plant” system in Scots pine stands in conditions of contamination by the steel plant’s emissions
Authors: Zaitsev Gleb A. , Dubrovina Olga A. , Shainurov Ruslan I. 
Published: July 2020

AbstractIn this paper, Scots pine (Pinus sylvestris L.) roots grown in soils with and without contamination from emission of a plant steel were analyzed for Fe and Mn, as well as the shoots and needles with and lacking pollution. The aim was to assess the content of Fe and Mn in soils under given conditions, and the interaction between pine plant and soil in terms of metal accumulation in the fine roots, annual shoots, and annual needles. The iron content in the soil of polluted areas does not contrast with its control amount. Conversely, the iron content in fine pine roots under contamination conditions is 2.1–4.4 times higher than the control values. There were no significant excesses of the manganese content in the soil in polluted conditions compared to the control, but its content in the 0–20 cm soil layer is 27–32 times higher than the background concentrations. The iron contentment in belowground (fine roots) and aboveground (annual shoots and needles) parts of pine trees in a context of contamination is higher than the control values (2.1–4.4 and 1.50–1.54 times, respectively). The manganese content in fine pine roots under contamination conditions is 2.8–10.7 times less than in control, while its content in shoots and needles is higher (2.23–2.76 times) in comparison with the control. Based on the values of the biological accumulation and migration coefficients, what in each case slighter than one, for Scots pine the iron represent not an element that actively accumulates. Nevertheless, for manganese, this stock model is valid only for fine roots, whereas under the contaminated environment, the metal mobility steepen, and the migration pattern shifts towards increased manganese accumulation in the aboveground part of pine trees.
Ctcf is required for renin expression and maintenance of the structural integrity of the kidney
Authors: Martinez Maria Florencia , Martini Alexandre G. , Sequeira-Lopez Maria Luisa S. , Gomez R. Ariel 
Published: July 2020

Abstract
Renin cells are crucial for the regulation of blood pressure and fluid electrolyte homeostasis. We have recently shown that renin cells possess unique chromatin features at regulatory regions throughout the genome that may determine the identity and memory of the renin phenotype. The 3-D structure of chromatin may be equally important in the determination of cell identity and fate. CCCTC-binding factor (Ctcf) is a highly conserved chromatin organizer that may regulate the renin phenotype by controlling chromatin structure. We found that Ctcf binds at several conserved DNA sites surrounding and within the renin locus, suggesting that Ctcf may regulate the transcriptional activity of renin cells. In fact, deletion of Ctcf in cells of the renin lineage led to decreased endowment of renin-expressing cells accompanied by decreased circulating renin, hypotension, and severe morphological abnormalities of the kidney, including defects in arteriolar branching, and ultimately renal failure. We conclude that control of chromatin architecture by Ctcf is necessary for the appropriate expression of renin, control of renin cell number and structural integrity of the kidney.
Assoziationen von Tumorpatienten und deren Behandelnden zu den Themen Ernährung und Appetit
Authors: Appelmann Iris , Halfmann Zarah , Elsner Frank 
Published: July 2020

Zusammenfassung
Ziel der Studie Die vorliegende Studie zielt auf ein besseres Verständnis für hypothetisch unterschiedliche Perspektiven zu dem Themenkomplex „Ernährung und Appetit“ von kurativ gegenüber palliativ behandelten Tumorpatienten und deren Behandelnden ab, um so möglichen Schwierigkeiten in der Therapie zugunsten einer guten Compliance des Patienten besser entgegenwirken zu können.
Methodik Für die Untersuchungen wurde primär die Technik der Freien Assoziation genutzt und deren Ergebnisse unter Berücksichtigung soziodemografischer Informationen in den Kontext der Therapieabsichten gestellt.
Ergebnisse Es wurden insgesamt 100 Probanden rekrutiert, 60 Patienten und 40 Behandelnde jeweils in gleichem Verhältnis aus den Kliniken für Palliativmedizin und Hämatologie, Onkologie und Stammzelltransplantation. Für die Probanden wurden soziodemografische Daten wie Alter, Ausbildungsniveau und zusätzlich zeitliche Berufserfahrung bei den Behandelnden erfasst. Nach Anwendung von Freier Assoziation wurde eine qualitative Analyse der assoziierten Begriffe zu den Themen „Nahrung, Ernährung und Appetit“ durchgeführt. Hier zeigten sich in der Bewertung von insgesamt 11 mit diesem Thema verbundenen Begriffen eine große Schnittmenge zwischen palliativen gegenüber kurativ behandelten Patienten als auch eine deutliche Überlappung bezüglich der Behandelnden der verschiedenen Abteilungen, aber auch eine wesentliche Überlappung in der Wahrnehmung bei Patienten und Behandelnden. Dennoch zeigten sich kleine Unterschiede, beispielsweise Wahrnehmung des Begriffs „Appetit“, der von Patienten häufiger mit negativen Assoziationen versehen war und bei Behandelnden durchweg positive Assoziationen hervorrief.
Schlussfolgerung Die große Schnittmenge der hervorgerufenen Assoziationen unter den verschiedenen Vergleichsgruppen spricht insbesondere bei Betrachtung von Patienten und den Behandelnden im Vergleich für eine hohe Wahrnehmungsübereinstimmung bezüglich der Themen „Ernährung und Appetit“. Die Studie leistet somit einen Beitrag zu einem verbesserten Verständnis der Patientenperspektive im Rahmen der Ernährungsoptimierung bei Tumorpatienten allgemein und in fortgeschrittenen Krankheitsstadien. Die in einigen Punkten divergierenden Aussagen und Einstellungen gegenüber den Themen dieser Studie zeigen, wie wichtig Kommunikation zwischen Patienten und Behandelnden ist, um gegenseitiges Unverständnis zu vermeiden und Compliance zu stärken.
Aicardi Syndrome: Key Fetal MRI Features and Prenatal Differential Diagnosis
Authors: Chiara Doneda , Giana Izzo , Masnada Silvia , Manuela Formica , Marco Scarabello , Andrea Accogli , Patrizia Accorsi , Nadia Bahi-Buisson , Valeria Capra , Mara Cavallin , Bernardo Dalla Bernardina , Francesca Darra , Valentina De Giorgis , Elisa Fazzi , Miguel Fontanillas R. L. , Carlo Fusco , Lucio Giordano , Simona Orcesi , Lorenzo Pinelli , Erika Rebessi , Antonino Romeo , Mariasavina Severino , Carlotta Spagnoli , Pierangelo Veggiotti , Anna Pichiecchio , Andrea Righini , Cecilia Parazzini 
Published: July 2020

Abstract
Objective This study was aimed to investigate the prenatal findings in Aicardi syndrome (AIC) by intrauterine magnetic resonance imaging (iuMRI) suggesting possible diagnostic criteria and differential diagnosis.
Methods The iuMRI features of nine AIC confirmed cases were described and then compared with those of postnatal MRI. Furthermore, all iuMRI cases with both corpus callosum (CC) agenesis–dysgenesis and cortical malformation (AIC mimickers) were retrospectively reviewed and compared with iuMRI AIC cases, in order to identify possible neuroradiological predictors of AIC syndrome. For this purpose, Chi-square statistic and binary logistic regression analysis were performed.
Results In all AIC cases, iuMRI was able to detect CC agenesis–dysgenesis and cortical development anomalies. Postnatal MRI revealed some additional findings mainly including further cystic lesions and in two cases small coloboma. A statistically significant difference between AIC and AIC mimicker were found regarding sex, nodular heterotopias, posterior fossa abnormalities, coloboma, and cortical gyration abnormalities. The most predictive variables in the logistic regression model were cortical gyration abnormalities, coloboma, and sex.
Conclusion The iuMRI findings may suggest prenatal diagnosis of AIC syndrome with significant impact on parental counseling. Among possible differential diagnoses, tubulinopathies emerged.