bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paraffin-embedding for large volume bio-tissue
Authors: Zhanmu Ouyang , Yang Xiaoying , Gong Hui , Li Xiangning 
Published: July 2020

AbstractAcquiring ultrahigh-resolution three-dimensional images of large-volume tissues non-human primate tissues was an enormous challenge. Given the preservation of structure and excellent sectioning property, formalin-fixed paraffin-embedding method had an enormous potential for three-dimensional reconstruction of fine structures, based on the very thin histological sections and optical images. However, maintaining the structure uniformly in large-volume tissues was difficult during the complex processes. In this study, we presented a detailed protocol for the whole mouse, rat, rabbit brains, and even for the macaque hemisphere. The entire protocol took about 2–30 days to complete for a large sample, including fixation, dehydration, clearing, wax immersion and embedding. In addition, it could be applied to other species and organs, while the embedding processes depended on the size and the type of organs. This method had wide applicability to serve as a baseline for further technique development.
Comparative clinical and genomic analysis of neurofibromatosis type 2-associated cranial and spinal meningiomas
Authors: Pemov Alexander , Dewan Ramita , Hansen Nancy F. , Chandrasekharappa Settara C. , Ray-Chaudhury Abhik , Jones Kristine , Luo Wen , Heiss John D. , Mullikin James C. , Chittiboina Prashant , Stewart Douglas R. , Asthagiri Ashok R. 
Published: July 2020

AbstractNeurofibromatosis type 2 (NF2) is an autosomal dominant Mendelian tumor predisposition disorder caused by germline pathogenic variants in the tumor suppressor NF2. Meningiomas are the second most common neoplasm in NF2, often occurring in multiple intracranial and spinal locations within the same patient. In this prospective longitudinal study, we assessed volumes and growth rates of ten spinal and ten cranial benign meningiomas in seven NF2 patients that concluded with surgical resection and performed whole-exome sequencing and copy-number variant (CNV) analysis of the tumors. Our comparison of the volume and the growth rate of NF2-associated spinal and cranial meningiomas point to the differences in timing of tumor initiation and/or to the differences in tumor progression (e.g., non-linear, saltatory growth) at these two anatomical locations. Genomic investigation of these tumors revealed that somatic inactivation of NF2 is the principal and perhaps the only driver of tumor initiation; and that tumor progression likely occurs via accumulation of CNVs, rather than point mutations. Results of this study contribute to a better understanding of NF2-associated meningiomas clinical behavior and their genetic underpinnings.
Neuronal correlates of spider phobia in a combined fNIRS-EEG study
Authors: Rosenbaum David , Leehr Elisabeth J. , Kroczek Agnes , Rubel Julian A. , Int-Veen Isabell , Deutsch Kira , Maier Moritz J. , Hudak Justin , Fallgatter Andreas J. , Ehlis Ann-Christine 
Published: July 2020

AbstractSpecific phobia is associated with aberrant brain activation in confrontation paradigms with phobic stimuli. In previous EEG research enhanced event-related potentials (ERPs) in the late-positive potential (LPP) window have been observed. Further, studies with functional near-infrared spectroscopy (fNIRS) and fMRI suggest that spider phobia is associated with enhanced activation within cortical and subcortical areas. In the current study we investigated the neuronal correlates of spider phobia in a combined fNIRS–EEG study. To this end, 37 spider phobic patients (PP) and 32 healthy controls (HC) underwent a symptom provocation paradigm during which subjects watched video clips of spiders and domestic animals (confrontation phase) after being primed on the content of the video (anticipation phase). Simultaneously, fNIRS, EEG, electromyography (EMG), electrocardiography and behavioral measures were assessed. Results showed increased LPP amplitudes, increased hemodynamic responses in the cognitive control network, and increased EMG activity and heart rate during spider conditions in PP in comparison to HC. Furthermore, in behavioral ratings PP showed higher emotional distress and avoidance. Behavioral ratings, fNIRS and EEG data showed positive correlations on a between-subject as well as on a within-subject level. Our results merge the existing data on neurophysiological correlates of phobic stimulus processing in hemodynamic and electrophysiological research and extend those of static visual material (pictures) to dynamic visual material (videos).
Federated learning in medicine: facilitating multi-institutional collaborations without sharing patient data
Authors: Sheller Micah J. , Edwards Brandon , Reina G. Anthony , Martin Jason , Pati Sarthak , Kotrotsou Aikaterini , Milchenko Mikhail , Xu Weilin , Marcus Daniel , Colen Rivka R. , Bakas Spyridon 
Published: July 2020

AbstractSeveral studies underscore the potential of deep learning in identifying complex patterns, leading to diagnostic and prognostic biomarkers. Identifying sufficiently large and diverse datasets, required for training, is a significant challenge in medicine and can rarely be found in individual institutions. Multi-institutional collaborations based on centrally-shared patient data face privacy and ownership challenges. Federated learning is a novel paradigm for data-private multi-institutional collaborations, where model-learning leverages all available data without sharing data between institutions, by distributing the model-training to the data-owners and aggregating their results. We show that federated learning among 10 institutions results in models reaching 99% of the model quality achieved with centralized data, and evaluate generalizability on data from institutions outside the federation. We further investigate the effects of data distribution across collaborating institutions on model quality and learning patterns, indicating that increased access to data through data private multi-institutional collaborations can benefit model quality more than the errors introduced by the collaborative method. Finally, we compare with other collaborative-learning approaches demonstrating the superiority of federated learning, and discuss practical implementation considerations. Clinical adoption of federated learning is expected to lead to models trained on datasets of unprecedented size, hence have a catalytic impact towards precision/personalized medicine.
β1 integrin, ILK and mTOR regulate collagen synthesis in mechanically loaded tendon cells
Authors: Mousavizadeh Rouhollah , Hojabrpour Payman , Eltit Felipe , McDonald Paul C. , Dedhar Shoukat , McCormack Robert G. , Duronio Vincent , Jafarnejad Seyed Mehdi , Scott Alex 
Published: July 2020

AbstractTendons are specialized tissues composed primarily of load-responsive fibroblasts (tenocytes) embedded in a collagen-rich extracellular matrix. Habitual mechanical loading or targeted exercise causes tendon cells to increase the stiffness of the extracellular matrix; this adaptation may occur in part through collagen synthesis or remodeling. Integrins are likely to play an important role in transmitting mechanical stimuli from the extracellular matrix to tendon cells, thereby triggering cell signaling pathways which lead to adaptive regulation of mRNA translation and protein synthesis. In this study, we discovered that mechanical stimulation of integrin β1 leads to the phosphorylation of AKT, an event which required the presence of integrin-linked kinase (ILK). Repetitive stretching of tendon cells activates the AKT and mTOR pathways, which in turn regulates mRNA translation and collagen expression. These results support a model in which integrins are an upstream component of the mechanosensory cellular apparatus, regulating fundamental tendon cell functions relevant to exercise-induced adaptation and mechanotherapy.
An unbiased stereological method for corneal confocal microscopy in patients with diabetic polyneuropathy
Authors: Schaldemose Ellen L. , Hammer Rasmus E. , Ferdousi Maryam , Malik Rayaz A. , Nyengaard Jens R. , Karlsson Páll 
Published: July 2020

AbstractCorneal confocal microscopy (CCM) derived corneal nerve measures are lower in diabetic sensorimotor polyneuropathy (DSPN). There are, however, methodological challenges in relation to adequate and unbiased sampling of images with objective corneal nerve quantification. Here we compare a new sampling method and adjusted area calculation with established methods of corneal nerve quantification in patients with and without DSPN and healthy controls. CCM images from 26 control subjects and 62 patients with type 1 diabetes with (n = 17) and without (n = 45) DSPN were analyzed. The images were randomly selected and corneal nerve fiber length (CNFL), corneal nerve fiber branch density (CNBD) and corneal nerve fiber density (CNFD) were determined in both a manual and automated manner. The new method generated 8–40% larger corneal nerve parameters compared to the standard procedure (p < 0.05). CNFL was significantly reduced using the new method for both manual and automated analysis; whilst CNFD and CNBD were significantly reduced using the automated method in both diabetic groups compared with controls. The new, objective method showed a reduction in corneal nerve parameters in diabetic patients with and without DSPN. We recommend using a randomized sampling method and area-dependent analysis to enable objective unbiased corneal nerve quantification.
Learning to see the Ebbinghaus illusion in the periphery reveals a top-down stabilization of size perception across the visual field
Authors: Eymond Cécile , Seidel Malkinson Tal , Naccache Lionel 
Published: July 2020

AbstractOur conscious visual perception relies on predictive signals, notably in the periphery where sensory uncertainty is high. We investigated how such signals could support perceptual stability of objects’ size across the visual field. When attended carefully, the same object appears slightly smaller in the periphery compared to the fovea. Could this perceptual difference be encoded as a strong prior to predict the peripheral perceived size relative to the fovea? Recent studies emphasized the role of foveal information in defining peripheral size percepts. However, they could not disentangle bottom-up from top-down mechanisms. Here, we revealed a pure top-down contribution to the perceptual size difference between periphery and fovea. First, we discovered a novel Ebbinghaus illusion effect, inducing a typical reduction of foveal perceived size, but a reversed increase effect in the periphery. The resulting illusory size percept was similar at both locations, deviating from the classic perceptual difference. Then through an updating process of successive peripheral-foveal viewing, the unusual peripheral perceived size decreased. The classic perceptual eccentricity difference was restored and the peripheral illusion effect changed into a fovea-like reduction. Therefore, we report the existence of a prior that actively shapes peripheral size perception and stabilizes it relative to the fovea.
Leprosy piRnome: exploring new possibilities for an old disease
Authors: Pinto Pablo , da Silva Moisés Batista , Moreira Fabiano Cordeiro , Bouth Raquel Carvalho , Gobbo Angélica Rita , Sandoval Tatiana Vinasco , Ribeiro-dos-Santos André Mauricio , Vidal Amanda Ferreira , Barreto Josafá Gonçalves , Santos Sidney , Spencer John Stewart , Salgado Claudio Guedes , Ribeiro-dos-Santos Ândrea 
Published: July 2020

AbstractLeprosy, which is caused by the human pathogen Mycobacterium leprae, causes nerve damage, deformity and disability in over 200,000 people every year. Because of the long doubling time of M. leprae (13 days) and the delayed onset of detectable symptoms, which is estimated to be approximately 3–7 years after infection, there is always a large percentage of subclinically infected individuals in the population who will eventually develop the disease, mainly in endemic countries. piRNAs comprise the largest group of small noncoding RNAs found in humans, and they are distinct from microRNAs (miRNAs) and small interfering RNAs (siRNAs). piRNAs function in transposon silencing, epigenetic regulation, and germline development. The functional role of piRNAs and their associated PIWI proteins have started to emerge in the development of human cancers and viral infections, but their relevance to bacterial diseases has not been investigated. The present study reports the piRNome of human skin, revealing that all but one of the piRNAs examined are downregulated in leprosy skin lesions. Considering that one of the best characterized functions of piRNAs in humans is posttranscriptional mRNA silencing, their functions are similar to what we have described for miRNAs, including acting on apoptosis, M. leprae recognition and engulfment, Schwann cell (SC) demyelination, epithelial–mesenchymal transition (EMT), loss of sensation and neuropathic pain. In addition to new findings on leprosy physiopathology, the discovery of relevant piRNAs involved in disease processes in human skin may provide new clues for therapeutic targets, specifically to control nerve damage, a prominent feature of leprosy that has no currently available pharmaceutical treatment.
Single-cell mass cytometry on peripheral blood identifies immune cell subsets associated with primary biliary cholangitis
Authors: Jang Jin Sung , Juran Brian D. , Cunningham Kevin Y. , Gupta Vinod K. , Son Young Min , Yang Ju Dong , Ali Ahmad H. , Enninga Elizabeth Ann L. , Sung Jaeyun , Lazaridis Konstantinos N. 
Published: July 2020

AbstractThe relationship between primary biliary cholangitis (PBC), a chronic cholestatic autoimmune liver disease, and the peripheral immune system remains to be fully understood. Herein, we performed the first mass cytometry (CyTOF)-based, immunophenotyping analysis of the peripheral immune system in PBC at single-cell resolution. CyTOF was performed on peripheral blood mononuclear cells (PBMCs) from PBC patients (n = 33) and age-/sex-matched healthy controls (n = 33) to obtain immune cell abundance and marker expression profiles. Hierarchical clustering methods were applied to identify immune cell types and subsets significantly associated with PBC. Subsets of gamma-delta T cells (CD3+TCRgd+), CD8+T cells (CD3+CD8+CD161+PD1+), and memory B cells (CD3−CD19+CD20+CD24+CD27+) were found to have lower abundance in PBC than in control. In contrast, higher abundance of subsets of monocytes and naïve B cells were observed in PBC compared to control. Furthermore, several naïve B cell (CD3−CD19+CD20+CD24−CD27−) subsets were significantly higher in PBC patients with cirrhosis (indicative of late-stage disease) than in those without cirrhosis. Alternatively, subsets of memory B cells were lower in abundance in cirrhotic relative to non-cirrhotic PBC patients. Future immunophenotyping investigations could lead to better understanding of PBC pathogenesis and progression, and also to the discovery of novel biomarkers and treatment strategies.
Pessimism is associated with greater all-cause and cardiovascular mortality, but optimism is not protective
Authors: Whitfield John B. , Zhu Gu , Landers J. George , Martin Nicholas G. 
Published: July 2020

AbstractScores on an optimistic-pessimistic personality scale have been associated with mortality, but optimism and pessimism scores are separable traits and it is unclear which has effects on health or longevity. The Life Orientation Test (LOT), containing items for optimism and pessimism, was included in a twin study on health of Australians aged over 50 in 1993–1995. After a mean of 20 years, participants were matched against death information from the Australian National Death Index. 1,068 out of 2,978 participants with useable LOT scores had died. Survival analysis tested for associations between separate optimism and pessimism scores and mortality from any cause, and from cancers, cardiovascular diseases or other known causes. Age-adjusted scores on the pessimism scale were associated with all-cause and cardiovascular mortality (Hazard Ratios per 1 standard deviation unit, 95% confidence intervals and p-values 1.134, 1.065–1.207, 8.85 × 10–5 and 1.196, 1.045–1.368, 0.0093, respectively) but not with cancer deaths. Optimism scores, which were only weakly correlated with pessimism scores (age-adjusted rank correlation = − 0.176), did not show significant associations with overall or cause-specific mortality. Reverse causation (disease causing pessimism) is unlikely because in that case both cardiovascular diseases and cancers would be expected to lead to pessimism.
Cover crops and chicken grazing in a winter fallow field improve soil carbon and nitrogen contents and decrease methane emissions
Authors: Zheng Huabin , Zhou Linhong , Wei Jiabing , Tang Qiyuan , Zou Yingbin , Tang Jianwu , Xu Huaqin 
Published: July 2020

AbstractUsing symbiotic farming methods [cover crops and chicken grazing (+ C)] in a winter fallow field, we found that the soil organic matter and total nitrogen of the + C treatment were 5.2% and 26.6% higher, respectively, than those of a treatment with cover crops and no chicken grazing (− C). The annual rice grain yield of the + C treatment was 3.8% higher than that of the − C treatment and 12.3% higher than that of the bare fallow field (CK), while the annual CH4 emissions of the + C treatment were 26.9% lower than those of the − C treatment and 10.6% lower than those of the CK treatment. The 100-year global warming potential of the + C treatment was 6.2% lower than that of the − C treatment. Therefore, the use of winter cover crops and chicken grazing in a winter fallow field was effective at reducing CH4 emissions and significantly improving soil nutrients and rice yield.
C22 podovirus infectivity is associated with intermediate stiffness
Authors: Sae-Ueng Udom , Bhunchoth Anjana , Phironrit Namthip , Treetong Alongkot , Sapcharoenkun Chaweewan , Chatchawankanphanich Orawan , Leartsakulpanich Ubolsree , Chitnumsub Penchit 
Published: July 2020

AbstractBacteriophages have potential for use as biological control agents (biocontrols) of pathogenic bacteria, but their low stability is limiting for their utilization as biocontrols. Understanding of the conditions conducive to storage of phages in which infectivity is maintained over long periods will be useful for their application as biocontrols. We employed a nanomechanical approach to study how external environmental factors affect surface properties and infectivity of the podovirus C22 phage, a candidate for biocontrol of Ralstonia solanacearum, the agent of bacterial wilt in crops. We performed atomic force microscopy (AFM)-based nano-indentation on the C22 phage in buffers with varying pH and ionic strength. The infectivity data from plaque assay in the same conditions revealed that an intermediate range of stiffness was associated with phage titer that remained consistently high, even after prolonged storage up to 182 days. The data are consistent with the model that C22 phage must adopt a metastable state for maximal infectivity, and external factors that alter the stiffness of the phage capsid lead to perturbation of this infective state.
Evaluating the quantity, quality and size distribution of cell-free DNA by multiplex droplet digital PCR
Authors: Alcaide Miguel , Cheung Matthew , Hillman Jack , Rassekh S. Rod , Deyell Rebecca J. , Batist Gerald , Karsan Aly , Wyatt Alexander W. , Johnson Nathalie , Scott David W. , Morin Ryan D. 
Published: July 2020

AbstractCell-free DNA (cfDNA) has become a comprehensive biomarker in the fields of non-invasive cancer detection and monitoring, organ transplantation, prenatal genetic testing and pathogen detection. While cfDNA samples can be obtained using a broad variety of approaches, there is an urgent need to standardize analytical tools aimed at assessing its basic properties. Typical methods to determine the yield and fragment size distribution of cfDNA samples are usually either blind to genomic DNA contamination or the presence of enzymatic inhibitors, which can confound and undermine downstream analyses. Here, we present a novel droplet digital PCR assay to identify suboptimal samples and aberrant cfDNA size distributions, the latter typically associated with high levels of circulating tumour DNA (ctDNA). Our assay was designed to promiscuously cross-amplify members of the human olfactory receptor (OR) gene family and includes a customizable diploid locus for the determination of absolute cfDNA concentrations. We demonstrate here the utility of our assay to estimate the yield and quality of cfDNA extracts and deduce fragment size distributions that correlate well with those inferred by capillary electrophoresis and high throughput sequencing. The assay described herein is a powerful tool to establish quality controls and stratify cfDNA samples based on presumed ctDNA levels, then facilitating the implementation of robust, cost-effective and standardized analytical workflows into clinical practice.
The associations of BMI with mean diffusivity of basal ganglia among young adults with mild obesity and without obesity
Authors: Takeuchi Hikarua , Taki Yasuyuki , Nouchi Rui , Yokoyama Ryoichi , Nakagawa Seishu , Iizuka Kunio , Sakaki Kohei , Araki Tsuyoshi , Nozawa Takayuki , Ikeda Shigeyuki , Yokota Susumu , Hanawa Sugiko , Magistro Daniele , Kotozaki Yuka , Sasaki Yukako , dos S. Kawata Kelssy H. , Kawashima Ryuta 
Published: July 2020

AbstractObesity causes a wide range of systemic diseases and is associated with mood and anxiety disorders. It is also associated with dopaminergic reward system function. However, the relationships between microstructural properties of the dopaminergic system and body mass index (BMI) have not been investigated. In this study, we investigated the associations of BMI with mean diffusivity (MD), diffusion tensor imaging measure in areas of the dopaminergic system (MDDS) in 435 healthy young adults with mild obesity and without obesity (BMI < 40). We detected the association between greater BMI and lower MD of the right globus pallidus and the right putamen. These results suggest that the property of the dopaminergic system is associated with BMI among young adults with mild obesity and without obesity.
Cholesterol modulates presynaptic and postsynaptic properties of excitatory synaptic transmission
Authors: Korinek Miloslav , Gonzalez-Gonzalez Inmaculada M. , Smejkalova Tereza , Hajdukovic Dragana , Skrenkova Kristyna , Krusek Jan , Horak Martin , Vyklicky Ladislav 
Published: July 2020

AbstractCholesterol is a structural component of cellular membranes particularly enriched in synapses but its role in synaptic transmission remains poorly understood. We used rat hippocampal cultures and their acute cholesterol depletion by methyl-β-cyclodextrin as a tool to describe the physiological role of cholesterol in glutamatergic synaptic transmission. Cholesterol proved to be a key molecule for the function of synapses as its depletion resulted in a significant reduction of both NMDA receptor (NMDAR) and AMPA/kainate receptor-mediated evoked excitatory postsynaptic currents (eEPSCs), by 94% and 72%, respectively. We identified two presynaptic and two postsynaptic steps of synaptic transmission which are modulated by cholesterol and explain together the above-mentioned reduction of eEPSCs. In the postsynapse, we show that physiological levels of cholesterol are important for maintaining the normal probability of opening of NMDARs and for keeping NMDARs localized in synapses. In the presynapse, our results favour the hypothesis of a role of cholesterol in the propagation of axonal action potentials. Finally, cholesterol is a negative modulator of spontaneous presynaptic glutamate release. Our study identifies cholesterol as an important endogenous regulator of synaptic transmission and provides insight into molecular mechanisms underlying the neurological manifestation of diseases associated with impaired cholesterol synthesis or decomposition.