bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of three different statistical approaches (non-linear least-squares regression, survival analysis and Bayesian inference) in their usefulness for estimating hydrothermal time models of seed germination
Authors: Moltchanova Elena , Sharifiamina Shirin , Moot Derrick J. , Shayanfar Ali , Bloomberg Mark 
Published: May 2020

AbstractHydrothermal time (HTT) models describe the time course of seed germination for a population of seeds under specific temperature and water potential conditions. The parameters of the HTT model are usually estimated using either a linear regression, non-linear least squares estimation or a generalized linear regression model. There are problems with these approaches, including loss of information, and censoring and lack of independence in the germination data. Model estimation may require optimization, and this can have a heavy computational burden. Here, we compare non-linear regression with survival and Bayesian methods, to estimate HTT models for germination of two clover species. All three methods estimated similar HTT model parameters with similar root mean squared errors. However, the Bayesian approach allowed (1) efficient estimation of model parameters without the need for computation-intensive methods and (2) easy comparison of HTT parameters for the two clover species. HTT models that accounted for a species effect were superior to those that did not. Inspection of credibility intervals and estimated posterior distributions for the Bayesian HTT model shows that it is credible that most HTT model parameters were different for the two clover species, and these differences were consistent with known biological differences between species in their germination behaviour.
Frequently asked questions regarding SARS-CoV-2 in cancer patients—recommendations for clinicians caring for patients with malignant diseases
Authors:   EHA Infectious Disease Scientific Working Group, von Lilienfeld-Toal Marie , Vehreschild Jörg Janne , Cornely Oliver , Pagano Livio , Compagno Francesca , Hirsch Hans H. 
Published: May 2020

AbstractSince early 2020, the SARS-CoV-2 pandemic has a massive impact on health care systems worldwide. Patients with malignant diseases are assumed to be at increased risk for a worse outcome of SARS-CoV-2 infection, and therefore, guidance regarding prevention and management of the infection as well as safe administration of cancer-therapy is required. Here, we provide recommendations for the management of patients with malignant disease in the times of COVID-19. These recommendations were prepared by an international panel of experts and then consented by the EHA Scientific Working Group on Infection in Hematology. The primary aim is to enable clinicians to provide optimal cancer care as safely as possible, since the most important protection for patients with malignant disease is the best-possible control of the underlying disease.
Postprandial blood glucose response: does the glycaemic index (GI) value matter even in the low GI range?
Authors: Kaur Bhupinder , Koh Melvin , Ponnalagu Shalini , Henry Christiani Jeyakumar 
Published: May 2020

AbstractA growing body of research over the last decades has shown that diets based on the low glycaemic index (GI) foods reduce the risk of developing diabetes and improve blood glucose control in people with diabetes. The range of inflexion on the glycaemic response of low GI (LGI) foods is an interesting observation that has not been studied by many. LGI 1 (GI 54 ± 3.3) biscuit was formulated using a basic formulation while the LGI 2 (23.8 ± 3.3) biscuits was a modification of LGI 1 recipe, formulated with the inclusion of functional ingredients. Biscuits were formulated to be iso-caloric (kcal/100 g: 521 ± 12). Each participant consumed identical standard meals for lunch and dinner. Biscuits were consumed as breakfast and mid-afternoon snack. Using a randomized, controlled, crossover study, 13 males [(means ± SD) age: 25.3 ± 1.0 years, BMI 21.6 ± 0.5 kg/m2, fasting blood glucose 4.7 ± 0.1 mmol/L] wore continuous glucose monitoring systems (CGMS™) for 3 days for each test session. The postprandial glycaemic response and insulin response were compared within participants. Total iAUC for breakfast and standard dinner were significantly lower for LGI 2 treatment (p < 0.05) than LGI 1 treatment. Second-meal glucose tolerance was observed at the dinner meal. The overall iAUC insulin response over 180 min was significantly lower for LGI 2 biscuits (p = 0.01). The postprandial glycaemic response of two types of biscuits that fall within the low GI classification (GI 24 and 54) differed with LGI 2 biscuits (GI 24) showing a more suppressed postprandial glycaemic response. Our study shows that even within the low GI range, the GI value matters in influencing postprandial glucose.
PROMPT intervention for children with severe speech motor delay: a randomized control trial
Authors: Namasivayam Aravind K. , Huynh Anna , Granata Francesca , Law Vina , van Lieshout Pascal 
Published: May 2020

AbstractBackgroundCurrently, there is limited information on the intervention efficacy for children with speech motor delay (SMD). This randomized control trial (RCT) study examined the effectiveness of Prompts for Restructuring Oral Muscular Phonetic Targets (PROMPT) intervention to improve the outcomes in children with SMD. We hypothesized that children with SMD receiving PROMPT intervention would improve more in the measured outcomes than those waitlisted and receiving home training.MethodsUsing a two-arm, parallel group, RCT, 49 children with SMD were allocated to either an intervention group (N = 24) that received 45 min of PROMPT intervention two times a week for 10 weeks or were waitlisted for the same duration and received only home training instructions (N = 25). Outcome measures for speech motor control, articulation, speech intelligibility (word and sentence levels), and functional communication were assessed at baseline and at a 10-week follow-up.ResultsPROMPT intervention was associated with notable improvements in speech motor control, speech articulation, and word-level speech intelligibility. Intervention allocation yielded weak improvements in sentence-level speech intelligibility and functional communication.ConclusionsPROMPT intervention is a clinically effective intervention approach for children with SMD.ImpactCurrently, there is limited information on the intervention efficacy for children with SMD.We report on the findings of a phase III intervention efficacy study on children with SMD using an RCT design.PROMPT intervention is a clinically effective intervention approach for children with SMD.Results of the study will be fundamental to the delivery of effective services for this population.These findings may facilitate the development of an evidence-based care pathway for children with severe speech sound disorders.
A novel neurodegenerative spectrum disorder in patients with MLKL deficiency
Authors: Faergeman Soren L. , Evans Hayley , Attfield Kathrine E. , Desel Christiane , Kuttikkatte Subita Balaram , Sommerlund Mette , Jensen Lise Torp , Frokiaer Jorgen , Friese Manuel A. , Matthews Paul M. , Luchtenborg Christian , Brügger Britta , Oturai Annette Bang , Dendrou Calliope A. , Fugger Lars 
Published: May 2020

AbstractMixed lineage kinase domain-like (MLKL) is the main executor of necroptosis, an inflammatory form of programmed cell death. Necroptosis is implicated in combating infections, but also in contributing to numerous other clinical conditions, including cardiovascular diseases and neurodegenerative disorders. Inhibition of necroptosis is therefore of therapeutic interest. Here we report two siblings both of whom over the course of 35 years developed a similar progressive, neurodegenerative spectrum disorder characterized by paresis, ataxia and dysarthria. Magnetic resonance imaging of their central nervous system (CNS) revealed severe global cerebral volume loss and atrophy of the cerebellum and brainstem. These brothers are homozygous for a rare haplotype identified by whole genome sequencing carrying a frameshift variant in MLKL, as well as an in-frame deletion of one amino acid in the adjacent fatty acid 2-hydroxylase (FA2H) gene. Functional studies of patient-derived primary cells demonstrated that the variant in MLKL leads to a deficiency of MLKL protein resulting in impairment of necroptosis. Conversely, shotgun lipidomic analysis of the variant in FA2H shows no impact on either the abundance or the enzymatic activity of the encoded hydroxylase. To our knowledge, this is the first report of complete necroptosis deficiency in humans. The findings may suggest that impaired necroptosis is a novel mechanism of neurodegeneration, promoting a disorder that shares some clinical features with primary progressive multiple sclerosis (PPMS) and other neurodegenerative diseases. Importantly, the necroptotic deficiency does not cause symptoms outside the nervous system, nor does it confer susceptibility to infections. Given the current interest in pharmacological inhibition of necroptosis by targeting MLKL and its associated pathways, this strategy should be developed with caution, with careful consideration of the possible development of adverse neurological effects.
Regulation of TFEB activity and its potential as a therapeutic target against kidney diseases
Authors: Zhang Weihuang , Li Xiaoyu , Wang Shujun , Chen Yanse , Liu Huafeng 
Published: May 2020

AbstractThe transcription factor EB (TFEB) regulates the expression of target genes bearing the Coordinated Lysosomal Expression and Regulation (CLEAR) motif, thereby modulating autophagy and lysosomal biogenesis. Furthermore, TFEB can bind to the promoter of autophagy-associated genes and induce the formation of autophagosomes, autophagosome–lysosome fusion, and lysosomal cargo degradation. An increasing number of studies have shown that TFEB stimulates the intracellular clearance of pathogenic factors by enhancing autophagy and lysosomal function in multiple kidney diseases, such as cystinosis, acute kidney injury, and diabetic nephropathy. Taken together, this highlights the importance of developing novel therapeutic strategies against kidney diseases based on TFEB regulation. In this review, we present an overview of the current data on TFEB and its implication in kidney disease.
Novel fluorinated polycationic delivery of anti-VEGF siRNA for tumor therapy
Authors: Yuan Zihan , Guo Xiaoshuang , Wei Minyan , Xu Yang , Fang Zhiwei , Feng Yun , Yuan Wei-En 
Published: May 2020

AbstractSmall-interfering RNA (siRNA) can specifically silence disease gene expression, bringing hope for the effective treatment of gene-related diseases. However, its use in vivo is limited due to the lack of efficient carriers. Therefore, it is necessary to construct carriers with high efficiency, low toxicity and serum stability. As a promising polycation carrier, polyethylenimine (PEI) can be further modified with a fluorine-containing alkyl chain that brings hydrophobic and oleophobic characteristics to its surface. In this study, low molecular weight PEI 1.8 kDa was selected and fluorinated through an anhydride reaction, and the product was named PEIF. In vitro experiments have shown that PEIF/siRNA polyplexes have suitable and stable particle size and potential, compress nucleic acids at a very low w/w ratio, and have the ability to effectively silence specific genes with low cytotoxicity. Compared with the polyplexes prepared using PEI 25 kDa, the PEIF/siRNA polyplexes were more stable in serum, showed a better antiangiogenic ability in in vivo experiments, and had a better tumor inhibition effect. The above results indicate that fluoropolymers based on the fluorine effect have great potential as gene delivery carriers for tumor therapy.
Breaking translational symmetry via polymer chain overcrowding in molecular bottlebrush crystallization
Authors: Qi Hao , Liu Xiting , Henn Daniel M. , Mei Shan , Staub Mark C. , Zhao Bin , Li Christopher Y. 
Published: May 2020

AbstractOne of the fundamental laws in crystallization is translational symmetry, which accounts for the profound shapes observed in natural mineral crystals and snowflakes. Herein, we report on the spontaneous formation of spherical hollow crystals with broken translational symmetry in crystalline molecular bottlebrush (mBB) polymers. The unique structure is named as mBB crystalsome (mBBC), highlighting its similarity to the classical molecular vesicles. Fluorescence resonance energy transfer (FRET) experiments show that the mBBC formation is driven by local chain overcrowding-induced asymmetric lamella bending, which is further confirmed by correlating crystalsome size with crystallization temperature and mBBʼs side chain grafting density. Our study unravels a new principle of spontaneous translational symmetry breaking, providing a general route towards designing versatile nanostructures.
Slip bursts during coalescence of slow slip events in Cascadia
Authors: Bletery Quentin , Nocquet Jean-Mathieu 
Published: May 2020

AbstractBoth laboratory experiments and dynamic simulations suggest that earthquakes can be preceded by a precursory phase of slow slip. Observing processes leading to an acceleration or spreading of slow slip along faults is therefore key to understand the dynamics potentially leading to seismic ruptures. Here, we use continuous GPS measurements of the ground displacement to image the daily slip along the fault beneath Vancouver Island during a slow slip event in 2013. We image the coalescence of three originally distinct slow slip fronts merging together. We show that during coalescence phases lasting for 2 to 5 days, the rate of energy (moment) release significantly increases. This observation supports the view proposed by theoretical and experimental studies that the coalescence of slow slip fronts is a possible mechanism for initiating earthquakes.
Lipid-protein interactions modulate the conformational equilibrium of a potassium channel
Authors: Gu Ruo-Xu , de Groot Bert L. 
Published: May 2020

AbstractCell membranes actively participate in the regulation of protein structure and function. In this work, we conduct molecular dynamics simulations to investigate how different membrane environments affect protein structure and function in the case of MthK, a potassium channel. We observe different ion permeation rates of MthK in membranes with different properties, and ascribe them to a shift of the conformational equilibrium between two states of the channel that differ according to whether a transmembrane helix has a kink. Further investigations indicate that two key residues in the kink region mediate a crosstalk between two gates at the selectivity filter and the central cavity, respectively. Opening of one gate eventually leads to closure of the other. Our simulations provide an atomistic model of how lipid-protein interactions affect the conformational equilibrium of a membrane protein. The gating mechanism revealed for MthK may also apply to other potassium channels.
Promoting H2O2 production via 2-electron oxygen reduction by coordinating partially oxidized Pd with defect carbon
Authors: Chang Qiaowan , Zhang Pu , Mostaghimi Amir Hassan Bagherzadeh , Zhao Xueru , Denny Steven R. , Lee Ji Hoon , Gao Hongpeng , Zhang Ying , Xin Huolin L. , Siahrostami Samira , Chen Jingguang G. , Chen Zheng 
Published: May 2020

AbstractElectrochemical synthesis of H2O2through a selective two-electron (2e−) oxygen reduction reaction (ORR) is an attractive alternative to the industrial anthraquinone oxidation method, as it allows decentralized H2O2production. Herein, we report that the synergistic interaction between partially oxidized palladium (Pdδ+) and oxygen-functionalized carbon can promote 2e−ORR in acidic electrolytes. An electrocatalyst synthesized by solution deposition of amorphous Pdδ+clusters (Pd3δ+and Pd4δ+) onto mildly oxidized carbon nanotubes (Pdδ+-OCNT) shows nearly 100% selectivity toward H2O2and a positive shift of ORR onset potential by ~320 mV compared with the OCNT substrate. A high mass activity (1.946 A mg−1at 0.45 V) of Pdδ+-OCNT is achieved. Extended X-ray absorption fine structure characterization and density functional theory calculations suggest that the interaction between Pd clusters and the nearby oxygen-containing functional groups is key for the high selectivity and activity for 2e−ORR.
Stability and nuclear localization of yeast telomerase depend on protein components of RNase P/MRP
Authors: Garcia P. Daniela , Leach Robert W. , Wadsworth Gable M. , Choudhary Krishna , Li Hua , Aviran Sharon , Kim Harold D. , Zakian Virginia A. 
Published: May 2020

AbstractRNase P and MRP are highly conserved, multi-protein/RNA complexes with essential roles in processing ribosomal and tRNAs. Three proteins found in both complexes, Pop1, Pop6, and Pop7 are also telomerase-associated. Here, we determine how temperature sensitive POP1 and POP6 alleles affect yeast telomerase. At permissive temperatures, mutant Pop1/6 have little or no effect on cell growth, global protein levels, the abundance of Est1 and Est2 (telomerase proteins), and the processing of TLC1 (telomerase RNA). However, in pop mutants, TLC1 is more abundant, telomeres are short, and TLC1 accumulates in the cytoplasm. Although Est1/2 binding to TLC1 occurs at normal levels, Est1 (and hence Est3) binding is highly unstable. We propose that Pop-mediated stabilization of Est1 binding to TLC1 is a pre-requisite for formation and nuclear localization of the telomerase holoenzyme. Furthermore, Pop proteins affect TLC1 and the RNA subunits of RNase P/MRP in very different ways.
SYNERGISTIC ON AUXIN AND CYTOKININ 1 positively regulates growth and attenuates soil pathogen resistance
Authors: Hurný Andrej , Cuesta Candela , Cavallari Nicola , Ötvös Krisztina , Duclercq Jerome , Dokládal Ladislav , Montesinos Juan Carlos , Gallemí Marçal , Semerádová Hana , Rauter Thomas , Stenzel Irene , Persiau Geert , Benade Freia , Bhalearo Rishikesh , Sýkorová Eva , Gorzsás András , Sechet Julien , Mouille Gregory , Heilmann Ingo , De Jaeger Geert , Ludwig-Müller Jutta , Benková Eva 
Published: May 2020

AbstractPlants as non-mobile organisms constantly integrate varying environmental signals to flexibly adapt their growth and development. Local fluctuations in water and nutrient availability, sudden changes in temperature or other abiotic and biotic stresses can trigger changes in the growth of plant organs. Multiple mutually interconnected hormonal signaling cascades act as essential endogenous translators of these exogenous signals in the adaptive responses of plants. Although the molecular backbones of hormone transduction pathways have been identified, the mechanisms underlying their interactions are largely unknown. Here, using genome wide transcriptome profiling we identify an auxin and cytokinin cross-talk component; SYNERGISTIC ON AUXIN AND CYTOKININ 1 (SYAC1), whose expression in roots is strictly dependent on both of these hormonal pathways. We show that SYAC1 is a regulator of secretory pathway, whose enhanced activity interferes with deposition of cell wall components and can fine-tune organ growth and sensitivity to soil pathogens.
Critical slowing down as a biomarker for seizure susceptibility
Authors: Maturana Matias I. , Meisel Christian , Dell Katrina , Karoly Philippa J. , D’Souza Wendyl , Grayden David B. , Burkitt Anthony N. , Jiruska Premysl , Kudlacek Jan , Hlinka Jaroslav , Cook Mark J. , Kuhlmann Levin , Freestone Dean R. 
Published: May 2020

AbstractThe human brain has the capacity to rapidly change state, and in epilepsy these state changes can be catastrophic, resulting in loss of consciousness, injury and even death. Theoretical interpretations considering the brain as a dynamical system suggest that prior to a seizure, recorded brain signals may exhibit critical slowing down, a warning signal preceding many critical transitions in dynamical systems. Using long-term intracranial electroencephalography (iEEG) recordings from fourteen patients with focal epilepsy, we monitored key signatures of critical slowing down prior to seizures. The metrics used to detect critical slowing down fluctuated over temporally long scales (hours to days), longer than would be detectable in standard clinical evaluation settings. Seizure risk was associated with a combination of these signals together with epileptiform discharges. These results provide strong validation of theoretical models and demonstrate that critical slowing down is a reliable indicator that could be used in seizure forecasting algorithms.
Lipid metabolism adaptations are reduced in human compared to murine Schwann cells following injury
Authors: Meyer zu Reckendorf Sofia , Brand Christine , Pedro Maria T. , Hegler Jutta , Schilling Corinna S. , Lerner Raissa , Bindila Laura , Antoniadis Gregor , Knöll Bernd 
Published: May 2020

AbstractMammals differ in their regeneration potential after traumatic injury, which might be caused by species-specific regeneration programs. Here, we compared murine and human Schwann cell (SC) response to injury and developed an ex vivo injury model employing surgery-derived human sural nerves. Transcriptomic and lipid metabolism analysis of murine SCs following injury of sural nerves revealed down-regulation of lipogenic genes and regulator of lipid metabolism, including Pparg (peroxisome proliferator-activated receptor gamma) and S1P (sphingosine-1-phosphate). Human SCs failed to induce similar adaptations following ex vivo nerve injury. Pharmacological PPARg and S1P stimulation in mice resulted in up-regulation of lipid gene expression, suggesting a role in SCs switching towards a myelinating state. Altogether, our results suggest that murine SC switching towards a repair state is accompanied by transcriptome and lipidome adaptations, which are reduced in humans.
Mega macromolecules as single molecule lubricants for hard and soft surfaces
Authors: Anilkumar Parambath , Lawson Taylor B. , Abbina Srinivas , Mäkelä Janne T. A. , Sabatelle Robert C. , Takeuchi Lily E. , Snyder Brian D. , Grinstaff Mark W. , Kizhakkedathu Jayachandran N. 
Published: May 2020

AbstractA longstanding goal in science and engineering is to mimic the size, structure, and functionality present in biology with synthetic analogs. Today, synthetic globular polymers of several million molecular weight are unknown, and, yet, these structures are expected to exhibit unanticipated properties due to their size, compactness, and low inter-chain interactions. Here we report the gram-scale synthesis of dendritic polymers, mega hyperbranched polyglycerols (mega HPGs), in million daltons. The mega HPGs are highly water soluble, soft, nanometer-scale single polymer particles that exhibit low intrinsic viscosities. Further, the mega HPGs are lubricants acting as interposed single molecule ball bearings to reduce the coefficient of friction between both hard and soft natural surfaces in a size dependent manner. We attribute this result to their globular and single particle nature together with its exceptional hydration. Collectively, these results set the stage for new opportunities in the design, synthesis, and evaluation of mega polymers.