bluuebunny/crossref_metadata_2025_split huggingface dataset:
Locomotion in virtual environments predicts cardiovascular responsiveness to subsequent stressful challenges
Authors: Rodrigues João , Studer Erik , Streuber Stephan , Meyer Nathalie , Sandi Carmen 
Published: November 2020

AbstractIndividuals differ in their physiological responsiveness to stressful challenges, and stress potentiates the development of many diseases. Heart rate variability (HRV), a measure of cardiac vagal break, is emerging as a strong index of physiological stress vulnerability. Thus, it is important to develop tools that identify predictive markers of individual differences in HRV responsiveness without exposing subjects to high stress. Here, using machine learning approaches, we show the strong predictive power of high-dimensional locomotor responses during novelty exploration to predict HRV responsiveness during stress exposure. Locomotor responses are collected in two ecologically valid virtual reality scenarios inspired by the animal literature and stress is elicited and measured in a third threatening virtual scenario. Our model’s predictions generalize to other stressful challenges and outperforms other stress prediction instruments, such as anxiety questionnaires. Our study paves the way for the development of behavioral digital phenotyping tools for early detection of stress-vulnerable individuals.
Functional characterisation guides classification of novel BAP1 germline variants
Authors: Hong Jing Han , Chong Siao Ting , Lee Po-Hsien , Tan Jing , Heng Hong Lee , Ishak Nur Diana Binte , Chan Sock Hoai , Teh Bin Tean , Ngeow Joanne 
Published: November 2020

AbstractWe have identified six patients harbouring distinct germline BAP1 mutations. In this study, we functionally characterise known BAP1 pathogenic and likely benign germline variants out of these six patients to aid in the evaluation and classification of unknown BAP1 germline variants. We found that pathogenic germline variants tend to encode truncated proteins, show diminished expression of epithelial-mesenchymal transition (EMT) markers, are localised in the cytosol and have reduced deubiquitinase capabilities. We show that these functional assays are useful for BAP1 variant curation and may be added in the American College of Medical Genetics and Genomics (ACMG) criteria for BAP1 variant classification. This will allow clinicians to distinguish between BAP1 pathogenic and likely benign variants reliably and may aid to quickly benchmark newly identified BAP1 germline variants. Classification of novel BAP1 germline variants allows clinicians to inform predisposed patients and relevant family members regarding potential cancer risks, with appropriate clinical interventions implemented if required.
Stroke promotes the development of brain atrophy and delayed cell death in hypertensive rats
Authors: Sayed Mohammed A. , Eldahshan Wael , Abdelbary Mahmoud , Pillai Bindu , Althomali Waleed , Johnson Maribeth H. , Arbab Ali S. , Ergul Adviye , Fagan Susan C. 
Published: November 2020

AbstractPost-stroke cognitive impairment (PSCI) is a major source of disability, affecting up to two thirds of stroke survivors with no available therapeutic options. The condition remains understudied in preclinical models due to its delayed presentation. Although hypertension is a leading risk factor for dementia, how ischemic stroke contributes to this neurodegenerative condition is unknown. In this study, we used a model of hypertension to study the development of PSCI and its mechanisms. Spontaneously hypertensive rats (SHR) were compared to normotensive rats and were subjected to 1-h middle cerebral artery occlusion or sham surgery. Novel object recognition, passive avoidance test and Morris water maze were used to assess cognition. In addition, brain magnetic resonance images were obtained 12-weeks post-stroke and tissue was collected for immunohistochemistry and protein quantification. Stroked animals developed impairment in long-term memory at 4-weeks post-stroke despite recovery from motor deficits, with hypertensive animals showing some symptoms of anhedonia. Stroked SHRs displayed grey matter atrophy and had a two-fold increase in apoptosis in the ischemic borderzone and increased markers of inflammatory cell death and DNA damage at 12 weeks post-stroke. This indicates that preexisting hypertension exacerbates the development of secondary neurodegeneration after stroke beyond its acute effects on neurovascular injury.
How Joannites’ economy eradicated primeval forest and created anthroecosystems in medieval Central Europe
Authors: Lamentowicz Mariusz , Marcisz Katarzyna , Guzowski Piotr , Gałka Mariusz , Diaconu Andrei-Cosmin , Kołaczek Piotr 
Published: November 2020

AbstractDuring European states’ development, various past societies utilized natural resources, but their impact was not uniformly spatially and temporally distributed. Considerable changes resulted in landscape fragmentation, especially during the Middle Ages. Changes in state advances that affected the local economy significantly drove trajectories of ecosystems’ development. The legacy of major changes from pristine forest to farming is visible in natural archives as novel ecosystems. Here, we present a high-resolution densely dated multi-proxy study covering the last 1500 years from a peatland located in CE Europe. The economic activity of medieval societies was highly modified by new rulers—the Joannites (the Order of St. John of Jerusalem, Knights Hospitaller). We studied the record of these directorial changes noted in the peat profile. Our research revealed a rapid critical land-use transition in the late Middle Ages and its consequences on the peatland ecosystem. The shift from the virgin forest with regular local fires to agriculture correlates well with the raising of local economy and deforestations. Along with the emerging openness, the wetland switched from alkaline wet fen state to acidic, drier Sphagnum-dominated peatland. Our data show how closely the ecological state of wetlands relates to forest microclimate. We identified a significant impact of the Joannites who used the novel farming organization. Our results revealed the surprisingly fast rate of how feudal economy eliminated pristine nature from the studied area and created novel anthroecosystems.
Results of two consecutive treatment protocols in Polish children with acute lymphoblastic leukemia
Authors: Zawitkowska Joanna , Lejman Monika , Romiszewski Michał , Matysiak Michał , Ćwiklińska Magdalena , Balwierz Walentyna , Owoc-Lempach Joanna , Kazanowska Bernarda , Derwich Katarzyna , Wachowiak Jacek , Niedźwiecki Maciej , Adamkiewicz-Drożyńska Elżbieta , Trelińska Joanna , Młynarski Wojciech , Kołtan Andrzej , Wysocki Mariusz , Tomaszewska Renata , Szczepański Tomasz , Płonowski Marcin , Krawczuk-Rybak Maryna , Urbańska-Rakus Justyna , Machnik Katarzyna , Ociepa Tomasz , Urasiński Tomasz , Mizia-Malarz Agnieszka , Sobol-Milejska Grażyna , Karolczyk Grażyna , Kowalczyk Jerzy 
Published: November 2020

AbstractThe aim of the study was to retrospectively compare the effectiveness of the ALL IC-BFM 2002 and ALL IC-BFM 2009 protocols and the distribution of risk groups by the two protocols after minimal residual disease (MRD) measurement as well as its impact on survival. We reviewed the medical records of 3248 patients aged 1–18 years with newly diagnosed ALL who were treated in 14 hemato-oncological centers between 2002 and 2018 in Poland. The overall survival (OS) of 1872 children with ALL treated with the ALL IC 2002 protocol was 84% after 3 years, whereas the OS of 1376 children with ALL treated with the ALL IC 2009 protocol was 87% (P < 0.001). The corresponding event-free survival rates were 82% and 84% (P = 0.006). Our study shows that the ALL IC-BFM 2009 protocol improved the results of children with ALL compared to the ALL IC-BFM 2002 protocol in Poland. This analysis confirms that MRD marrow assessment on day 15 of treatment by FCM-MRD is an important predictive factor.
Enzymatic decolorization of melanin by lignin peroxidase from Phanerochaete chrysosporium
Authors: Sadaqat Beenish , Khatoon Nazia , Malik Aneela Younas , Jamal Asif , Farooq Uzma , Ali Muhammad Ishtiaq , He Huan , Liu Fang-Jing , Guo Hongguang , Urynowicz Michael , Wang Qiurong , Huang Zaixing 
Published: November 2020

AbstractSkin darkening results as a consequence of the accumulation of skin pigment melanin. To combat this, the amplitude of skin lightening agents are commercially available, most of which inhibit melanin synthesis. Decolorization of melanin is an alternative method of skin lightening. In this study, we show that lignin peroxidase (LiP), an extracellular enzyme purified from Phanerochaete chrysosporium NK-1 isolated from a forest soil can effectively degrade and decolorize melanin in vitro. Decolorization conditions including pH, temperature, incubation time, enzyme concentration, and mediator addition were investigated to optimize the reaction conditions. The results indicate that pH 3, 40 °C, 15 IU/ml, and 10 h incubation were the optimal conditions for the decolorization of the melanin. The use of the mediator, veratryl alcohol was also found effective to enhance the efficacy of the melanin decolonization, with up to 92% decolorization. The scanning electron microscopy results showed void spaces on the treated melanin granules as compared to the untreated sample, indicating the degradation of melanin. Changes in the fingerprint region of the melanin were observed. Between wavenumbers 1500–500 cm−1, for example, the presence of new peaks in the treated melanin at 1513, 1464, and 1139 cm−1 CH2, CH3 bend and C–O–C stretch represented structural changes. A new peak at 2144 cm−1 (alkynyl C≡C stretch) was also detected in the decolorized melanin. The cytotoxicity study has shown that the treated melanin and LiP have low cytotoxic effects; however, the mediator of veratryl alcohol could result in high mortality which suggests that its use should be meticulously tested in formulating health and skincare products. The findings of the study suggest that LiP produced by Phanerochaete chrysosporium has the potential to be used in the medical and cosmetic industries, particularly for the development of biobased cosmetic whitening agents.
Alternation of inverse problem approach and deep learning for lens-free microscopy image reconstruction
Authors: Hervé L. , Kraemer D. C. A. , Cioni O. , Mandula O. , Menneteau M. , Morales S. , Allier C. 
Published: November 2020

AbstractA lens-free microscope is a simple imaging device performing in-line holographic measurements. In the absence of focusing optics, a reconstruction algorithm is used to retrieve the sample image by solving the inverse problem. This is usually performed by optimization algorithms relying on gradient computation. However the presence of local minima leads to unsatisfactory convergence when phase wrapping errors occur. This is particularly the case in large optical thickness samples, for example cells in suspension and cells undergoing mitosis. To date, the occurrence of phase wrapping errors in the holographic reconstruction limits the application of lens-free microscopy in live cell imaging. To overcome this issue, we propose a novel approach in which the reconstruction alternates between two approaches, an inverse problem optimization and deep learning. The computation starts with a first reconstruction guess of the cell sample image. The result is then fed into a neural network, which is trained to correct phase wrapping errors. The neural network prediction is next used as the initialization of a second and last reconstruction step, which corrects to a certain extent the neural network prediction errors. We demonstrate the applicability of this approach in solving the phase wrapping problem occurring with cells in suspension at large densities. This is a challenging sample that typically cannot be reconstructed without phase wrapping errors, when using inverse problem optimization alone.
RNaseH-mediated simultaneous piggyback knockdown of multiple genes in adult zebrafish
Authors: Raman Revathi , Ryon Mia , Jagadeeswaran Pudur 
Published: November 2020

AbstractWe recently developed a piggyback knockdown method that was used to knockdown genes in adult zebrafish. In this method, a vivo morpholino (VMO) piggybacks an antisense deoxyoligonucleotide (dO) into the somatic cells and reduces the cognate mRNA levels. In this paper, we tested whether we can piggyback more than one dO with one VMO. We designed various hybrids that had more than one dO that could be piggybacked with one VMO. We chose f7, f8, and αIIb genes and tested their knockdown by the appropriate assays. The knockdown with piggybacking either two or three dOs by one VMO yielded > 85% knockdown efficiency. We also performed knockdown of argonautes and rnaseh separately along with f7. We found the knockdown of f7 occurs when knockdown of argonautes happens and not when rnaseh knockdown was performed, suggesting that RNaseH is involved in mRNA degradation. In conclusion, we developed a method where we could knockdown three genes at one time, and by increasing the concentration of VMO by twofold, we could knockdown six genes simultaneously. These multiple gene knockdowns will not only increase the efficiency of the method in whole genome-wide knockdowns but will also be useful to study multifactorial disorders.
Corneal confocal microscopy detects small fibre neurodegeneration in Parkinson's disease using automated analysis
Authors: Lim Sze Hway , Ferdousi Maryam , Kalteniece Alise , Kass-Iliyya Lewis , Petropoulos Ioannis N. , Malik Rayaz A. , Kobylecki Christopher , Silverdale Monty 
Published: November 2020

AbstractWe studied the utility of corneal confocal microscopy (CCM) in detecting a reduction in corneal nerve parameters in a large cohort of patients with Parkinson’s disease (PD) compared to controls using a fully automated potentially scalable method of analysis. We also assessed if CCM parameters are related to the severity and sub-type of PD. 98 participants with PD and 26 healthy controls underwent CCM with automated corneal nerve quantification, MDS-UPDRS III, Hoehn and Yahr scale, Montreal Cognitive Assessment, Parkinson’s Disease Questionnaire-39 and PD subtype assessment. Corneal nerve fibre density (mean difference: − 5.00 no/mm2, 95% confidence interval (CI) [− 7.89, − 2.12], p = 0.001), corneal nerve branch density (mean difference: − 10.71 no/mm2, 95% CI [− 16.93, − 4.48], p = 0.003), corneal total branch density (mean difference: − 14.75 no/mm2, 95% CI [− 23.58, − 5.92], p = 0.002), and corneal nerve fibre length (mean difference: − 2.57 mm/mm2, 95% CI [− 4.02, − 1.12], p = 0.001) were significantly lower in PD participants compared to controls. There was no correlation between corneal nerve parameters and duration, severity or subtype of PD, cognitive function or quality of life. CCM with automated corneal nerve analysis identifies nerve fibre damage and may act as a biomarker for neurodegeneration in PD.
Micro-computed tomography (micro-CT) for the assessment of myocardial disarray, fibrosis and ventricular mass in a feline model of hypertrophic cardiomyopathy
Authors: Novo Matos Jose , Garcia-Canadilla Patricia , Simcock Ian C. , Hutchinson J. Ciaran , Dobromylskyj Melanie , Guy Anna , Arthurs Owen J. , Cook Andrew C. , Luis Fuentes Virginia 
Published: November 2020

AbstractMicro-computed tomography (micro-CT) is a high-resolution imaging modality that provides accurate tissue characterization. Hypertrophic cardiomyopathy (HCM) occurs as a spontaneous disease in cats, and is characterized by myocardial hypertrophy, disarray and fibrosis, as in humans. While hypertrophy/mass (LVM) can be objectively measured, fibrosis and myocyte disarray are difficult to assess. We evaluated the accuracy of micro-CT for detection and quantification of myocardial disarray and fibrosis by direct comparison with histopathology. 29 cat hearts (12 normal and 17 HCM hearts) underwent micro-CT and pathologic examination. Myocyte orientation was assessed using structure tensor analysis by determination of helical angle (HA), fractional anisotropy (FA) and myocardial disarray index (MDI). Fibrosis was segmented and quantified based on comparison of gray-scale values in normal and fibrotic myocardium. LVM was obtained by determining myocardial volume. Myocardial segments with low FA, low MDI and disruption of normal HA transmural profile on micro-CT were associated with myocardial disarray on histopathology. FA was consistently lower in HCM than normal hearts. Assessment of fibrosis on micro-CT closely matched the histopathologic evaluation. LVM determined by micro-CT was higher in HCM than normal hearts. Micro-CT can be used to detect and quantify myocardial disarray and fibrosis and determine myocardial mass in HCM.
Glucokinase intrinsically regulates glucose sensing and glucagon secretion in pancreatic alpha cells
Authors: Moede Tilo , Leibiger Barbara , Vaca Sanchez Pilar , Daré Elisabetta , Köhler Martin , Muhandiramlage Thusitha P. , Leibiger Ingo B. , Berggren Per-Olof 
Published: November 2020

AbstractThe secretion of glucagon by pancreatic alpha cells is regulated by a number of external and intrinsic factors. While the electrophysiological processes linking a lowering of glucose concentrations to an increased glucagon release are well characterized, the evidence for the identity and function of the glucose sensor is still incomplete. In the present study we aimed to address two unsolved problems: (1) do individual alpha cells have the intrinsic capability to regulate glucagon secretion by glucose, and (2) is glucokinase the alpha cell glucose sensor in this scenario. Single cell RT-PCR was used to confirm that glucokinase is the main glucose-phosphorylating enzyme expressed in rat pancreatic alpha cells. Modulation of glucokinase activity by pharmacological activators and inhibitors led to a lowering or an increase of the glucose threshold of glucagon release from single alpha cells, measured by TIRF microscopy, respectively. Knockdown of glucokinase expression resulted in a loss of glucose control of glucagon secretion. Taken together this study provides evidence for a crucial role of glucokinase in intrinsic glucose regulation of glucagon release in rat alpha cells.
A serological assay to detect SARS-CoV-2 antibodies in at-home collected finger-prick dried blood spots
Authors: Karp Donna Grace , Danh Kenneth , Espinoza Noemi Fonseca , Seftel David , Robinson Peter V. , Tsai Cheng-ting 
Published: November 2020

AbstractAccurate surveillance of coronavirus disease 2019 (COVID-19) incidence requires large-scale testing of the population. Current testing methods require in-person collection of biospecimens by a healthcare worker, limiting access of individuals who do not have access to testing facilities while placing both patients and healthcare workers at risk of exposure to infection. We report the development and validation of a at-home finger-prick dried blood spot collection kit and an analysis method. We demonstrated 100% sensitivity and specificity using at-home collected specimens across the US. Such methods may facilitate the conduct of unbiased serosurveys within hard to reach populations and help reduce the sample collection burden of serological testing on both health care systems and individuals alike.
Frequency and prognostic value of mutations associated with the homologous recombination DNA repair pathway in a large pan cancer cohort
Authors: Principe Daniel R. , Narbutis Matthew , Koch Regina , Rana Ajay 
Published: November 2020

AbstractPARP inhibitors have shown remarkable efficacy in the clinical management of several BRCA-mutated tumors. This approach is based on the long-standing hypothesis that PARP inhibition will impair the repair of single stranded breaks, causing synthetic lethality in tumors with loss of high-fidelity double-strand break homologous recombination. While this is now well accepted and has been the basis of several successful clinical trials, emerging evidence strongly suggests that mutation to several additional genes involved in homologous recombination may also have predictive value for PARP inhibitors. While this notion is supported by early clinical evidence, the mutation frequencies of these and other functionally related genes are largely unknown, particularly in cancers not classically associated with homologous recombination deficiency. We therefore evaluated the mutation status of 22 genes associated with the homologous recombination DNA repair pathway or PARP inhibitor sensitivity, first in a pan-cancer cohort of 55,586 patients, followed by a more focused analysis in The Cancer Genome Atlas cohort of 12,153 patients. In both groups we observed high rates of mutations in a variety of HR-associated genes largely unexplored in the setting of PARP inhibition, many of which were associated also with poor clinical outcomes. We then extended our study to determine which mutations have a known oncogenic role, as well as similar to known oncogenic mutations that may have a similar phenotype. Finally, we explored the individual cancer histologies in which these genomic alterations are most frequent. We concluded that the rates of deleterious mutations affecting genes associated with the homologous recombination pathway may be underrepresented in a wide range of human cancers, and several of these genes warrant further and more focused investigation, particularly in the setting of PARP inhibition and HR deficiency.
Microscopic analyses of weathered granite in ion-adsorption rare earth deposit of Jianxi Province, China
Authors: Mukai Hiroki , Kon Yoshiaki , Sanematsu Kenzo , Takahashi Yoshio , Ito Motoo 
Published: November 2020

AbstractWeathered granite of ion-adsorption rare earth elements (REEs) ore collected at Jiangxi Province, China was investigated to identify the minerals abundant in REEs. The analyses of scanning electron microscopy (SEM)-energy dispersive spectrometry (EDS) and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) for individual mineral particles of the weathered granite showed that kaolinitic particles formed by K-feldspar weathering contained large amounts of REEs. Scanning transmission electron microscopy (STEM)-EDS analyses revealed that the kaolinitic particles were mainly composed of kaolinite, illite and hematite. The elemental maps by Nano-SIMS for the kaolinitic particle clarified that La and Y are particularly concentrated in illite. The presence of illite presumably contributes to the formation of the REE accumulation zone in weathered granite. Furthermore, in the in-situ desorption experiment, nearly half the REEs (45.5%) remained in the kaolinitic particle after the treatment with 0.5 M ammonium sulfate solution. The desorption ratio of heavy REEs (HREEs: Gd–Lu) (60.4%) was lower than that of light REEs (LREEs: La–Eu) apart from Ce (69.0%). These results suggest that REEs form inner-sphere complexes on the kaolinitic particle. It can be assumed that the inner-sphere complexation suppresses the extraction ratio of REEs from the ores by ion-exchange treatment.