bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment pathways and disease journeys differ before and after introduction of novel agents in newly diagnosed multiple myeloma in Taiwan
Authors: Liu Yanfang , Tang Chao-Hsiun , Qiu Hong , Siggins Sarah , Hou Hsin-An 
Published: January 2021

AbstractLimited real-world data are available regarding treatment practices and outcomes of multiple myeloma (MM) in Asia. We conducted a retrospective cohort study using the Taiwan National Healthcare Insurance Research database and Taiwan Death Registry and used a Markov model to describe disease progression and outcomes in 4092 patients newly diagnosed with MM from 01-Jan-2007 to 31-Dec-2015. We observed marked differences in the characteristics, length and outcome of the clinical journey between patients who did/did not receive autologous stem cell transplant, and between patients initiated on novel agents versus other treatment regimens. In transplant recipients, initiation with combined thalidomide + bortezomib increased over time (12.2–77.5%). Progression-free survival after first-line treatment improved and a lower percentage of patients died. Lenalidomide in second and third-line regimens increased (15.5–31.5%). In non-transplanted patients, initiation with novel agents increased (17.5–54.6%), but death rates remained high (60.3%). The treatment landscape of MM in Taiwan has evolved, with increased use of combined bortezomib + thalidomide for first-line and lenalidomide for second/third-line but many patients die before receiving second-line treatment. Novel agents with different modes of action should be used as early as possible to maximize their benefits. Improved MM treatments remains a critical medical need.
LEDs driven by AC without transformers or rectifiers
Authors: Hughes Robin W. , Warner Mark 
Published: January 2021

AbstractWe explore the driving of LEDs by untransformed AC. An extreme case is driving 1.9 V threshold (red) LEDs with UK mains, peak voltage 325 V. Commonly, driving is by transformed, rectified (DC) supply with a series resistor (where a significant fraction of the power is wasted) to limit current in the LED. With AC, one can instead reactively limit to a maximum current safe for an LED by employing a series capacitive impedance. Cheaper and simpler supplies can thus be employed in some cases. We analyse such non-linear circuits, and also explore questions of duty cycle and power experimentally.
Alterations in B cell subsets correlate with body composition parameters in female adolescents with anorexia nervosa
Authors: Freff Jana , Schwarte Kathrin , Bröker Lisa , Bühlmeier Judith , Kraft Isabelle , Öztürk Dana , Hinney Anke , Arolt Volker , Dannlowski Udo , Romer Georg , Baune Bernhard T. , Hebebrand Johannes , Föcker Manuel , Alferink Judith 
Published: January 2021

AbstractAnorexia nervosa (AN) is a severe eating disorder and often associated with altered humoral immune responses. However, distinct B cell maturation stages in peripheral blood in adolescents with AN have not been characterized. Treatment effects and the relationship between clinical and B cell parameters are also not fully understood. Here we investigated the phenotype of circulating B cell subsets and the relationship with body composition in adolescents with AN before (T0, n = 24) and after 6 weeks (T1, n = 20) of treatment. Using multi-parameter flow cytometry, we found increased percentages of antigen-experienced B cells and plasmablasts in patients with AN compared to healthy controls (n = 20). In contrast, percentages of CD1d+CD5+ B cells and transitional B cells with immunoregulatory roles were reduced at T0 and T1. These B cell frequencies correlated positively with fat mass, fat mass index (FMI), free fat mass index, and body mass index standard deviation score. In addition, scavenger-like receptor CD5 expression levels were downregulated on transitional B cells and correlated with fat mass and FMI in AN. Our findings that regulatory B cell subgroups were reduced in AN and their strong relationship with body composition parameters point toward an impact of immunoregulatory B cells in the pathogenesis of AN.
MicroRNA-494-3p inhibits formation of fast oxidative muscle fibres by targeting E1A-binding protein p300 in human-induced pluripotent stem cells
Authors: Iwasaki Hirotaka , Ichihara Yoshinori , Morino Katsutaro , Lemecha Mengistu , Sugawara Lucia , Sawano Tatsuya , Miake Junichiro , Sakurai Hidetoshi , Nishi Eiichiro , Maegawa Hiroshi , Imamura Takeshi 
Published: January 2021

AbstractMYOD-induced microRNA-494-3p expression inhibits fast oxidative myotube formation by downregulating myosin heavy chain 2 (MYH2) in human induced pluripotent stem cells (hiPSCs) during skeletal myogenesis. However, the molecular mechanisms regulating MYH2 expression via miR-494-3p remain unknown. Here, using bioinformatic analyses, we show that miR-494-3p potentially targets the transcript of the E1A-binding protein p300 at its 3′-untranslated region (UTR). Myogenesis in hiPSCs with the Tet/ON-myogenic differentiation 1 (MYOD1) gene (MyoD-hiPSCs) was induced by culturing them in doxycycline-supplemented differentiation medium for 7 days. p300 protein expression decreased after transient induction of miR-494-3p during myogenesis. miR-494-3p mimics decreased the levels of p300 and its downstream targets MYOD and MYH2 and myotube formation efficiency. p300 knockdown decreased myotube formation efficiency, MYH2 expression, and basal oxygen consumption rate. The binding of miR-494-3p to the wild type p300 3′-UTR, but not the mutated site, was confirmed using luciferase assay. Overexpression of p300 rescued the miR-494-3p mimic-induced phenotype in MyoD-hiPSCs. Moreover, miR-494-3p mimic reduced the levels of p300, MYOD, and MYH2 in skeletal muscles in mice. Thus, miR-494-3p might modulate MYH2 expression and fast oxidative myotube formation by directly regulating p300 levels during skeletal myogenesis in MyoD-hiPSCs and murine skeletal muscle tissues.
Cone-beam CT image quality improvement using Cycle-Deblur consistent adversarial networks (Cycle-Deblur GAN) for chest CT imaging in breast cancer patients
Authors: Tien Hui-Ju , Yang Hsin-Chih , Shueng Pei-Wei , Chen Jyh-Cheng 
Published: January 2021

AbstractCone-beam computed tomography (CBCT) integrated with a linear accelerator is widely used to increase the accuracy of radiotherapy and plays an important role in image-guided radiotherapy (IGRT). For comparison with fan-beam computed tomography (FBCT), the image quality of CBCT is indistinct due to X-ray scattering, noise, and artefacts. We proposed a deep learning model, “Cycle-Deblur GAN”, combined with CycleGAN and Deblur-GAN models to improve the image quality of chest CBCT images. The 8706 CBCT and FBCT image pairs were used for training, and 1150 image pairs were used for testing in deep learning. The generated CBCT images from the Cycle-Deblur GAN model demonstrated closer CT values to FBCT in the lung, breast, mediastinum, and sternum compared to the CycleGAN and RED-CNN models. The quantitative evaluations of MAE, PSNR, and SSIM for CBCT generated from the Cycle-Deblur GAN model demonstrated better results than the CycleGAN and RED-CNN models. The Cycle-Deblur GAN model improved image quality and CT-value accuracy and preserved structural details for chest CBCT images.
Prediction of lithium response using genomic data
Authors: Stone William , Nunes Abraham , Akiyama Kazufumi , Akula Nirmala , Ardau Raffaella , Aubry Jean-Michel , Backlund Lena , Bauer Michael , Bellivier Frank , Cervantes Pablo , Chen Hsi-Chung , Chillotti Caterina , Cruceanu Cristiana , Dayer Alexandre , Degenhardt Franziska , Del Zompo Maria , Forstner Andreas J. , Frye Mark , Fullerton Janice M. , Grigoroiu-Serbanescu Maria , Grof Paul , Hashimoto Ryota , Hou Liping , Jiménez Esther , Kato Tadafumi , Kelsoe John , Kittel-Schneider Sarah , Kuo Po-Hsiu , Kusumi Ichiro , Lavebratt Catharina , Manchia Mirko , Martinsson Lina , Mattheisen Manuel , McMahon Francis J. , Millischer Vincent , Mitchell Philip B. , Nöthen Markus M. , O’Donovan Claire , Ozaki Norio , Pisanu Claudia , Reif Andreas , Rietschel Marcella , Rouleau Guy , Rybakowski Janusz , Schalling Martin , Schofield Peter R. , Schulze Thomas G. , Severino Giovanni , Squassina Alessio , Veeh Julia , Vieta Eduard , Trappenberg Thomas , Alda Martin 
Published: January 2021

AbstractPredicting lithium response prior to treatment could both expedite therapy and avoid exposure to side effects. Since lithium responsiveness may be heritable, its predictability based on genomic data is of interest. We thus evaluate the degree to which lithium response can be predicted with a machine learning (ML) approach using genomic data. Using the largest existing genomic dataset in the lithium response literature (n = 2210 across 14 international sites; 29% responders), we evaluated the degree to which lithium response could be predicted based on 47,465 genotyped single nucleotide polymorphisms using a supervised ML approach. Under appropriate cross-validation procedures, lithium response could be predicted to above-chance levels in two constituent sites (Halifax, Cohen’s kappa 0.15, 95% confidence interval, CI [0.07, 0.24]; and Würzburg, kappa 0.2 [0.1, 0.3]). Variants with shared importance in these models showed over-representation of postsynaptic membrane related genes. Lithium response was not predictable in the pooled dataset (kappa 0.02 [− 0.01, 0.04]), although non-trivial performance was achieved within a restricted dataset including only those patients followed prospectively (kappa 0.09 [0.04, 0.14]). Genomic classification of lithium response remains a promising but difficult task. Classification performance could potentially be improved by further harmonization of data collection procedures.
Fast 3 T nigral hyperintensity magnetic resonance imaging in Parkinson’s disease
Authors: Hernadi Gabriella , Pinter David , Nagy Szilvia Anett , Orsi Gergely , Komoly Samuel , Janszky Jozsef , Kovacs Norbert , Perlaki Gabor 
Published: January 2021

AbstractThe absence of nigral hyperintensity is a promising MR marker for Parkinson’s disease (PD), but its small size imposes limitations on its routine use. Our aim was to compare Multi Echo Data Image Combination (MEDIC), segmented echo-planar imaging (EPISEG) and fluid-attenuated inversion recovery (FLAIR) sequences, as well as both magnitude (MAG) and susceptibility-weighted imaging (SWI) reconstructions of single-echo gradient echo for nigral hyperintensity imaging. Twenty-five healthy and twenty PD subjects were included. Sensitivity to motion artefacts, confidence of the radiologist in interpretation, rate of nondiagnostic scans and diagnostic accuracy were assessed. EPISEG was less motion-sensitive than MEDIC, MAG, and SWI, while FLAIR was less motion-sensitive than MAG and SWI. The reviewers were more confident when using EPISEG compared to any other techniques and MEDIC was superior to FLAIR. The proportions of nondiagnostic scans were lower for EPISEG than for other sequences. The best diagnostic performance was achieved for EPISEG (sensitivity = 65%, specificity = 96%). Using EPISEG, the absence of nigral hyperintensity in PD was associated with higher Hoehn-Yahr stage and MDS-UPDRS II + III. Nigral hyperintensity may be intact at the very early stages of PD. The promising properties of EPISEG may help the transfer of nigral hyperintensity imaging into daily clinical practice.
Computational fluid dynamics for enhanced tracheal bioreactor design and long-segment graft recellularization
Authors: Lee Hankyu , Marin-Araujo Alba E. , Aoki Fabio G. , Haykal Siba , Waddell Thomas K. , Amon Cristina H. , Romero David A. , Karoubi Golnaz 
Published: January 2021

AbstractSuccessful re-epithelialization of de-epithelialized tracheal scaffolds remains a challenge for tracheal graft success. Currently, the lack of understanding of the bioreactor hydrodynamic environment, and its relation to cell seeding outcomes, serve as major obstacles to obtaining viable tracheal grafts. In this work, we used computational fluid dynamics to (a) re-design the fluid delivery system of a trachea bioreactor to promote a spatially uniform hydrodynamic environment, and (b) improve the perfusion cell seeding protocol to promote homogeneous cell deposition. Lagrangian particle-tracking simulations showed that low rates of rotation provide more uniform circumferential and longitudinal patterns of cell deposition, while higher rates of rotation only improve circumferential uniformity but bias cell deposition proximally. Validation experiments with human bronchial epithelial cells confirm that the model accurately predicts cell deposition in low shear stress environments. We used the acquired knowledge from our particle tracking model, as a guide for long-term tracheal repopulation studies. Cell repopulation using conditions resulting in low wall shear stress enabled enhanced re-epithelialization of long segment tracheal grafts. While our work focuses on tracheal regeneration, lessons learned in this study, can be applied to culturing of any tissue engineered tubular scaffold.
Novel Iodine nanoparticles target vascular mimicry in intracerebral triple negative human MDA-MB-231 breast tumors
Authors: Ridwan Sharif M. , Hainfeld James F. , Ross Vanessa , Stanishevskiy Yaroslav , Smilowitz Henry M. 
Published: January 2021

AbstractTriple negative breast cancer (TNBC), ~ 10–20% of diagnosed breast cancers, metastasizes to brain, lungs, liver. Iodine nanoparticle (INP) radioenhancers specifically localize to human TNBC MDA-MB-231 tumors growing in mouse brains after iv injection, significantly extending survival of mice after radiation therapy (RT). A prominent rim of INP contrast (MicroCT) previously seen in subcutaneous tumors but not intracerebral gliomas, provide calculated X-ray dose-enhancements up to > eightfold. Here, MDA-MB-231-cells, INPs, CD31 were examined by fluorescence confocal microscopy. Most INP staining co-localized with CD31 in the tumor center and periphery. Greatest INP/CD31 staining was in the tumor periphery, the region of increased MicroCT contrast. Tumor cells are seen to line irregularly-shaped spaces (ISS) with INP, CD31 staining very close to or on the tumor cell surface and PAS stain on their boundary and may represent a unique form of CD31-expressing vascular mimicry in intracerebral 231-tumors. INP/CD31 co-staining is also seen around ISS formed around tumor cells migrating on CD31+ blood-vessels. The significant radiation dose enhancement to the prolific collagen I containing, INP-binding ISS found throughout the tumor but concentrated in the tumor rim, may contribute significantly to the life extensions observed after INP-RT; VM could represent a new drug/NP, particularly INP, tumor-homing target.
Odontogenesis-associated phosphoprotein truncation blocks ameloblast transition into maturation in OdaphC41*/C41* mice
Authors: Liang Tian , Hu Yuanyuan , Kawasaki Kazuhiko , Zhang Hong , Zhang Chuhua , Saunders Thomas L. , Simmer James P. , Hu Jan C.-C. 
Published: January 2021

AbstractMutations of Odontogenesis-Associated Phosphoprotein (ODAPH, OMIM *614829) cause autosomal recessive amelogenesis imperfecta, however, the function of ODAPH during amelogenesis is unknown. Here we characterized normal Odaph expression by in situ hybridization, generated Odaph truncation mice using CRISPR/Cas9 to replace the TGC codon encoding Cys41 into a TGA translation termination codon, and characterized and compared molar and incisor tooth formation in Odaph+/+, Odaph+/C41*, and OdaphC41*/C41* mice. We also searched genomes to determine when Odaph first appeared phylogenetically. We determined that tooth development in Odaph+/+ and Odaph+/C41* mice was indistinguishable in all respects, so the condition in mice is inherited in a recessive pattern, as it is in humans. Odaph is specifically expressed by ameloblasts starting with the onset of post-secretory transition and continues until mid-maturation. Based upon histological and ultrastructural analyses, we determined that the secretory stage of amelogenesis is not affected in OdaphC41*/C41* mice. The enamel layer achieves a normal shape and contour, normal thickness, and normal rod decussation. The fundamental problem in OdaphC41*/C41* mice starts during post-secretory transition, which fails to generate maturation stage ameloblasts. At the onset of what should be enamel maturation, a cyst forms that separates flattened ameloblasts from the enamel surface. The maturation stage fails completely.
The impact of smoking different tobacco types on the subgingival microbiome and periodontal health: a pilot study
Authors: Al Kawas Sausan , Al-Marzooq Farah , Rahman Betul , Shearston Jenni A. , Saad Hiba , Benzina Dalenda , Weitzman Michael 
Published: January 2021

AbstractSmoking is a risk factor for periodontal disease, and a cause of oral microbiome dysbiosis. While this has been evaluated for traditional cigarette smoking, there is limited research on the effect of other tobacco types on the oral microbiome. This study investigates subgingival microbiome composition in smokers of different tobacco types and their effect on periodontal health. Subgingival plaques were collected from 40 individuals, including smokers of either cigarettes, medwakh, or shisha, and non-smokers seeking dental treatment at the University Dental Hospital in Sharjah, United Arab Emirates. The entire (~ 1500 bp) 16S rRNA bacterial gene was fully amplified and sequenced using Oxford Nanopore technology. Subjects were compared for the relative abundance and diversity of subgingival microbiota, considering smoking and periodontal condition. The relative abundances of several pathogens were significantly higher among smokers, such as Prevotella denticola and Treponema sp. OMZ 838 in medwakh smokers, Streptococcus mutans and Veillonella dispar in cigarette smokers, Streptococcus sanguinis and Tannerella forsythia in shisha smokers. Subgingival microbiome of smokers was altered even in subjects with no or mild periodontitis, probably making them more prone to severe periodontal diseases. Microbiome profiling can be a useful tool for periodontal risk assessment. Further studies are recommended to investigate the impact of tobacco cessation on periodontal disease progression and oral microbiome.
Connecting complex networks to nonadditive entropies
Authors: de Oliveira R. M. , Brito Samuraí , da Silva L. R. , Tsallis Constantino 
Published: January 2021

AbstractBoltzmann–Gibbs statistical mechanics applies satisfactorily to a plethora of systems. It fails however for complex systems generically involving nonlocal space–time entanglement. Its generalization based on nonadditive q-entropies adequately handles a wide class of such systems. We show here that scale-invariant networks belong to this class. We numerically study a d-dimensional geographically located network with weighted links and exhibit its ‘energy’ distribution per site at its quasi-stationary state. Our results strongly suggest a correspondence between the random geometric problem and a class of thermal problems within the generalised thermostatistics. The Boltzmann–Gibbs exponential factor is generically substituted by its q-generalisation, and is recovered in the $$q=1$$

q
=
1

limit when the nonlocal effects fade away. The present connection should cross-fertilise experiments in both research areas.
Safety assessment of genetically modified rice expressing Cry1Ab protein in Sprague–Dawley rats
Authors: Hajimohammadi Bahador , Eslami Gilda , Zandi Hengameh , Ehrampoush Mohammad Hassan , Naimi Azar , Derakhshan Maryam , Hedayat Pegah , Fallahi Roozbeh , Fallahzadeh Hossein , Rezvani Mohammad Ebrahim , Vakili Mahmoud , Moshtaghioun Seyed Mohammad , Athari Seyyed Shamsadin , Asadi-Yousefabad Seyedeh Leili , Hosseini Saeedeh Sadat , Shirdeli Mehrnoush , Ahmadian Salman , Mortazavi Shirin , Loni Elahe , Ajamein Vahid , Ahmadi Amin , Askari Vahideh 
Published: January 2021

AbstractRice is considered one of the most important staple food crops. Genetically modified (GM) Bt rice, harbored cry1Ab gene expressing the insect-resistance protein has been developed to resistance to the insects. In this study, we assessed the safety of the GM Bt rice on Sprague–Dawley rats for 90 days. Totally, 120 rats in both sexes were used for three different diets, including 50% GM Bt rice, feeding with 50% rice, and standard feeding. Each 40 SD rats including 20 males and 20 females were considered as each diet. The clinical variables such as body weight and food consumption were measured and a range of clinical tests was examined, including hematology, serum chemistry parameters, urinalysis profile, thyroid, and sex hormone levels. Pathological assessments were also done. The results showed that the mean weekly feed utilization (%) had no significant difference among the studied groups. Also, blood biochemistry, hematological parameters, urine analysis, and hormonal levels had no significant differences among the groups. However, alanine aminotransferase was less in males versus female feeding with GM Bt rice. No histopathological changes were observed among the groups. In conclusion, this study demonstrated that GM Bt rice had no obvious adverse effects on rats' health.
Color and contrast vision in mouse models of aging and Alzheimer’s disease using a novel visual-stimuli four-arm maze
Authors: Vit Jean-Philippe , Fuchs Dieu-Trang , Angel Ariel , Levy Aharon , Lamensdorf Itschak , Black Keith L. , Koronyo Yosef , Koronyo-Hamaoui Maya 
Published: January 2021

AbstractWe introduce a novel visual-stimuli four-arm maze (ViS4M) equipped with spectrally- and intensity-controlled LED emitters and dynamic grayscale objects that relies on innate exploratory behavior to assess color and contrast vision in mice. Its application to detect visual impairments during normal aging and over the course of Alzheimer’s disease (AD) is evaluated in wild-type (WT) and transgenic APPSWE/PS1∆E9 murine models of AD (AD+) across an array of irradiance, chromaticity, and contrast conditions. Substantial color and contrast-mode alternation deficits appear in AD+ mice at an age when hippocampal-based memory and learning is still intact. Profiling of timespan, entries and transition patterns between the different arms uncovers variable AD-associated impairments in contrast sensitivity and color discrimination, reminiscent of tritanomalous defects documented in AD patients. Transition deficits are found in aged WT mice in the absence of alternation decline. Overall, ViS4M is a versatile, controlled device to measure color and contrast-related vision in aged and diseased mice.