bluuebunny/crossref_metadata_2025_split huggingface dataset:
PALM: Patient-centered Treatment Ranking via Large-scale Multivariate Network Meta-analysis
Authors: Duan Rui , Tong Jiayi , Lin Lifeng , Levine Lisa D , Sammel Mary D , Stoddard Joel , Li Tianjing , Schmid Christopher H , Chu Haitao , Chen Yong 
Published: November 2020

AbstractThe growing number of available treatment options have led to urgent needs for reliable answers when choosing the best course of treatment for a patient. As it is often infeasible to compare a large number of treatments in a single randomized controlled trial, multivariate network meta-analyses (NMAs) are used to synthesize evidence from existing trials of a subset of the available treatments, where outcomes related to both efficacy and safety are considered simultaneously. However, these large-scale multiple-outcome NMAs have created challenges to existing methods due to the increasingly complexity of the unknown correlation structures between different outcomes and treatment comparisons. In this paper, we proposed a new framework for PAtient-centered treatment ranking via Large-scale Multivariate network meta-analysis, termed as PALM, which includes a parsimonious modeling approach, a fast algorithm for parameter estimation and inference, a novel visualization tool for comparing treatments with multivariate outcomes termed as the star plot, as well as personalized treatment ranking procedures taking into account the individual’s considerations on multiple outcomes. In application to an NMA that compares 14 treatment options for labor induction over five modalities, we provided a comprehensive illustration of the proposed framework and demonstrated its computational efficiency and practicality. Our analysis leads to new insights on comparing these 14 treatment options based on joint inference of multiple outcomes that cannot be obtained from univariate NMAs, and novel visualizations of evidence to support patient-centered clinical decision making.
Preliminary Minimum Reporting Requirements for Reporting In-Vivo Neural Interface Research: I. Implantable Neural Interfaces
Authors: Eiber Calvin D. , Delbeke Jean , Cardoso Jorge , de Neeling Martijn , John Sam E. , Lee Chang Won , Skefos Jerry , Sun Argus , Prodanov Dimiter , McKinney Zach 
Published: November 2020

AbstractThe pace of research and development in neuroscience, neurotechnology, and neurorehabilitation is rapidly accelerating, with the number of publications doubling every 4.2 years. Maintaining this progress requires technological standards and scientific reporting guidelines to provide frameworks for communication and interoperability. The present lack of such standards for neurotechnologies limits the transparency, reproducibility, and meta-analysis of this growing body of research, posing an ongoing barrier to research, clinical, and commercial objectives.Continued neurotechnological innovation requires the development of some minimal standards to promote integration between this broad spectrum of technologies and therapies. To preserve design freedom and accelerate the translation of research into safe and effective technologies with maximal user benefit, such standards must be collaboratively co-developed by a full spectrum of neuroscience and neurotechnology stakeholders. This paper summarizes the preliminary recommendations of IEEE Working Group P2794, developing a Reporting Standard forin-vivoNeural Interface Research (RSNIR).Impact StatementThis work provides a preliminary set of reporting guidelines for implantable neural interface research, developed by IEEE WG P2794 in open collaboration between a range of stakeholders to accelerate the research, development, and integration of innovative neurotechnologies.
Enhanced olfactory memory performance in trap-design Y-mazes allows the study of novel memory phenotypes inDrosophila
Authors: Mohandasan Radhika , Iqbal Fathima Mukthar , Thakare Manikrao , Sridharan Madhav , Das Gaurav 
Published: November 2020

AbstractThe neural basis of behaviour is identified by systematically disrupting the activity of specific neurons and screening for loss in phenotype. Robust, high-scoring behavioural assays are thus necessary for identifying the neural circuits of novel behaviours. Here, we report the design and use of a Y-maze based classical olfactory learning and memory assay inDrosophila. Appetitive memory scores in our Y-mazes are considerably better and longer-lasting than that from a commonly used T-maze design. We found that the mechanism that traps flies in their choice of an odour is mainly responsible for the improving scores in the Y-mazes. Using Y-mazes, we could assay significant 24 h gustatory aversive memories in flies. These aversive memories are susceptible to protein synthesis inhibitor cycloheximide (CXM) and therefore embodies long-term memory (LTM). When anaesthesia resistant memory (ARM) deficientradishmutant flies are trained with dry sucrose, 24 h memory is severely disrupted. However, when we trained with 2 M sucrose-agar and tested in Y-mazes,radishmutants exhibited a residual 24 appetitive memory. This memory is not ARM, and we show that it is not CXM sensitive LTM either. It could be a third form of appetitive consolidated memory in flies. The Y-maze assembly described here is particularly sensitive and will thus enable the study of new memory phenotypes inDrosophila.
Proteomics on longitudinal serum samples differentiates localized and disseminated Lyme disease
Authors: Fatou Benoit , Smolen Kinga K. , Belperron Alexia A. , Wurie Zainab , Kleinstein Steven H. , Montgomery Ruth R. , Levy Ofer , Bockenstedt Linda K. , Steen Hanno 
Published: November 2020

AbstractLyme disease (LD) is the most prevalent vector-borne disease in North America, with ~300,000 new cases annually in the USA alone. LD is most often recognized by the appearance of the skin lesion erythema migrans (EM) at the tick bite site but also can present with signs of disseminated infection manifesting as multiple EM lesions and/or involvement of the heart, nervous system or joints. In this study, we examined the serum proteome of study participants presenting with either a single EM (localized LD) or early disseminated infection (disseminated LD). Samples collected at the time of diagnosis and at convalescent time points were assessed using our in-house developed MStern blotting-based serum proteomics platform. After technical validation of our platform, the temporal analysis from diagnosis to clinical resolution of the infection demonstrates LD stage-associated pathways activation such as a temporary upregulation of acute phase response specific to the participants with disseminated LD. In addition, we identified the members of the serum amyloid A protein family as potentially promising candidate biomarkers to identify those with disseminated LD. The results of this pilot study demonstrate the feasibility of using our time- and cost-effective sample sparing MStern blotting-based serum proteomics platform to efficiently interrogate proteome changes over time in those suffering infections such as LD. These observations establish a new approach to human serum proteomics, provide fresh insight into the host immune responses associated with disease severity (localized versus disseminated infection) and suggest novel biomarker candidate panels for LD stages.ImportanceWe investigated the proteome changes ofBorrelia burgdorferi-infected participants with either a single erythema migrans or early disseminated Lyme disease infection. Using our in-house time-and cost-effective proteomics platform, the temporal analysis from diagnosis to clinical resolution of the infection shows a temporary upregulation of the acute phase response specific to the participants with disseminated infection. Finally, specific protein panels were identified as possible biomarker candidates to categorize those having an initial diagnosis of disseminated manifestation using a reference cohort of acute localized infection and a clinically resolved convalescent phase disease samples from the same Lyme disease participants.
Diet and heat - one neuronal subset two responses
Authors: Prince Elodie , Kretzschmar Jenny , Trautenberg Laura C. , Brankatschk Marko 
Published: November 2020

ABSTRACTThe Insulin signal cascade is one of the best studied metabolic circuits, and shows a remarkable high molecular and functional conservation across the animal kingdom. Insulin-producing cells respond directly to nutritional cues in circulation and receive modulatory input from connected neuronal networks. Neuronal control is rapid and integrates a wide range of variables including dietary change or environmental temperature. However, despite various detailed studies that demonstrated the potential of neuronal regulation the physiological relevance of this circuit remains elusive.InDrosophila, Insulin-like peptide 7 (dIlp7)-producing neurons are wired with Insulin-producing cells. We found a dual role for this neuronal subset: a.) activated dilp7-producing neurons are required to facilitate development at high temperatures, and if confronted with calorie-rich food that represses neuronal activity b.) their product, dIlp7, regulates Insulin signalling levels. Our work shows that Insulin-producing cells not simply integrate signals from circulating nutritional cues and neuronal inputs, but switch to neuronal control in response to dietary composition.
Dehydration risk, not ambient incubation, limits nest attendance at high temperatures
Authors: Bourne Amanda R. , Ridley Amanda R. , McKechnie Andrew E. , Spottiswoode Claire N. , Cunningham Susan J. 
Published: November 2020

AbstractHigh air temperatures have measurable negative impacts on reproduction in wild animal populations, including during incubation in birds. Understanding the mechanisms driving these impacts requires comprehensive knowledge of animal physiology and behaviour under natural conditions. We used a novel combination of a non-invasive doubly-labelled water technique and behaviour observations in the field to examine effects of temperature, rainfall, and group size on physiology and behaviour during incubation in southern pied babblersTurdoides bicolor, a cooperatively-breeding passerine endemic to a semi-arid region in southern Africa. The proportion of time that clutches of eggs were incubated declined as air temperatures increased, traditionally interpreted as a benefit of ambient incubation. However, we show that a) clutches were less likely to hatch when exposed to high air temperatures; b) pied babbler groups incubated their nests almost constantly (97% of daylight hours) except on hot days; c) operative temperatures in unattended nests were substantially higher than air temperatures and frequently exceeded 40.5°C, above which bird embryos are at risk of death; d) pied babblers incubating for long periods of time failed to maintain water balance on hot days but not cool days; and e) pied babblers from incubating groups did not maintain body mass on hot days. These results suggest that, rather than taking advantage of opportunities for ambient incubation, pied babblers leave the nests during hot periods to avoid dehydration as a consequence of incubating at high operative temperatures. As mean air temperatures increase and extreme heat events become more frequent under climate change, birds will likely incur greater water costs during incubation, leading to compromised nest attendance and increased likelihood of eggs overheating, with implications for nest success and, ultimately, population persistence.
Mechanical Efficiency Investigation of an ankle-assisted robot for human walking with a backpack-load
Authors: Wang Zhihou , Huang Guowei , Liu Biao , Zhou Zikang , Liang Binghong , Liu Youwei , Xie Longhan 
Published: November 2020

AbstractLower limb assistive robots have a wide range of applications in medical rehabilitation, hiking, and the military. The purpose of this work is to investigate the efficiency of wearable assistive devices under different weight-bearing walking conditions. We designed an experimental platform, with a lightweight ankle-assisted robot weighing 5.2 kg and carried mainly on the back. Eight subjects were tested in three experimental conditions: free walk with load (FWL), power-off with load (POFL), and power-on with load (PONF) for different levels of force at a walking speed of 3.6 km/h. We recorded the metabolic expenditure and kinematics of the subjects under three levels of weight-bearing (equal to 10%, 20%, and 30% of body mass). The critical forces from the fit of the assistive force and metabolic depletion curves were 130 N, 160 N and 215 N at three different load levels. The intrinsic weight of our device increases mechanical work at the ankle as the load weight rises, with 2.08 J, 2.43 J, 2.73 J for one leg during a gait cycle. The ratio of the mechanical work input by the robot to the mechanical work output by the weight of the device decreases (0.904, 0.717, and 0.513 with different load carriages), verifying that the walking assistance efficiency of such devices decreases as the weight rises. In terms of mechanical work in the ankle joint, our results confirm that the efficiency of the ankle-assisted walking robot decreases as weight bearing increases, which provides important guidance for the lightweight design of portable weight-bearing walking robots.
Reef development and Sea level changes driveAcanthasterPopulation Expansion in the Indo-Pacific region
Authors: Pretorius P.C. , Hoareau T.B. 
Published: November 2020

AbstractMolecular clock calibration is central in population genetics as it provides an accurate inference of demographic history, whereby helping with the identification of driving factors of population changes in an ecosystem. This is particularly important for coral reef species that are seriously threatened globally and in need of conservation. Biogeographic events and fossils are the main source of calibration, but these are known to overestimate timing and parameters at population level, which leads to a disconnection between environmental changes and inferred reconstructions. Here, we propose the Last Glacial Maximum (LGM) calibration that is based on the assumptions that reef species went through a bottleneck during the LGM, which was followed by an early yet marginal increase in population size. We validated the LGM calibration using simulations and genetic inferences based on Extended Bayesian Skyline Plots. Applying it to mitochondrial sequence data of crown-of-thorns starfishAcanthaster spp., we obtained mutation rates that were higher than phylogenetically based calibrations and varied among populations. The timing of the greatest increase in population size differed slightly among populations, but all started between 10 and 20 kya. Using a curve-fitting method, we showed thatAcanthasterpopulations were more influenced by sea-level changes in the Indian Ocean and by reef development in the Pacific Ocean. Our results illustrate that the LGM calibration is robust and can probably provide accurate demographic inferences in many reef species. Application of this calibration has the potential to help identify population drivers that are central for the conservation and management of these threatened ecosystems.
Preclinical validation of a second generation leishmanization vaccine against vector transmitted fatal visceral leishmaniasis
Authors: Karmakar Subir , Ismail Nevien , Oliveira Fabiano , Oristian James , Zhang Wen Wei , Kaviraj Swarnendu , Singh Kamaleshwar P. , Mondal Abhishek , Das Sushmita , Pandey Krishna , Bhattacharya Parna , Volpedo Greta , Gannavaram Sreenivas , Satoskar Monika , Satoskar Sanika , Sastry Rajiv M. , Meneses Claudio , Hamano Shinjiro , Das Pradeep , Matlashewski Greg , Singh Sanjay , Kamhawi Shaden , Dey Ranadhir , Valenzuela Jesus G. , Satoskar Abhay , Nakhasi Hira L. 
Published: November 2020

AbstractVisceral Leishmaniasis (VL) is fatal if untreated. There is no licensed vaccine available against human leishmaniasis. We recently demonstrated protection in mice againstL. majorinfection using a CRISPR genome edited attenuatedLeishmania majorstrain (LmCen−/−). Here, as a pre-clinical step, we evaluated the protective efficacy ofLmCen−/−against VL induced by sand fly transmittedLeishmania donovaniin hamsters. Intradermal immunization of hamsters withLmCen−/−did not develop any lesion; while still priming a pro-inflammatory immune response. When challenged withL. donovanieither by intradermal needle injection or by infected sand flies,LmCen−/−-immunized hamsters were protected, not showing spleen or liver pathology averting VL fatality compared to control animals. Spleen cells fromLmCen−/−immunized and infected sand fly challenged hamsters produced significantly higher Th1-associated cytokines and chemokines including IFN-γ and TNF-α, and significantly reduced expression of the anti-inflammatory cytokines IL-10 and IL-21, compared to non-immunized challenged animals. We further developed a GLP-gradeLmCen−/−which showed equal protection as laboratory-gradeLmCen−/−parasites in hamsters. Importantly, GLP-gradeLmCen−/−parasites also induced a proinflammatory immune response in the PBMCs isolated from healthy people living in non-endemic and endemic for VL as well as cured VL people living in endemic region. Together, this study demonstrates that theLmCen−/−parasites are safe and efficacious against VL and it is a strong candidate vaccine to be tested in a human clinical trial.
Doxycycline interferes with tau amyloid aggregation abolishing its associated neuronal toxicity
Authors: Medina Luciana , González-Lizárraga Florencia , Dominguez-Meijide Antonio , Ploper Diego , Parrales Valeria , Sequeira Sabrina , Cima-Omori Maria Sol , Zweckstetter Markus , Del Bel Elaine , Michel Patrick P. , Outeiro Tiago Fleming , Raisman-Vozari Rita , Chehín Rosana , Socias Sergio B. 
Published: November 2020

AbstractTauopathies are neurodegenerative disorders with increasing incidence and still without cure. The extensive time required for development and approval of novel therapeutics highlights the need for testing and repurposing known safe molecules. Since doxycycline impacts α-synuclein aggregation and toxicity, herein we tested its effect on tau. We found that doxycycline reduces amyloid aggregation of the different isoforms of tau protein in a dose-dependent manner, remodeling the resultant species. Furthermore, doxycycline interacts with tau microtubule-binding domain preventing its aggregation. In a cell free system doxycycline also prevents tau seeding and in cell culture reduces toxicity of tau aggregates. Overall, our results expand the spectrum of action of doxycycline against aggregation-prone proteins, opening novel perspectives for its repurposing as a disease-modifying drug for tauopathies.
Optimal density of bacterial cells
Authors: Pang Tin Yau , Lercher Martin J. 
Published: November 2020

AbstractA substantial fraction of the bacterial cytosol is occupied by catalysts and their substrates. While a higher volume density of catalysts and substrates might boost biochemical fluxes, the resulting molecular crowding can slow down diffusion, perturb the reactions’ Gibbs free energies, and reduce the catalytic efficiency of proteins. Due to these tradeoffs, dry mass density likely possesses an optimum that facilitates maximal cellular growth and that is interdependent on the cytosolic molecule size distribution. Here, we analyze the balanced growth of a model cell, accounting systematically for crowding effects on reaction kinetics. Its optimal cytosolic volume occupancy depends on the nutrient-dependent resource allocation into large ribosomal vs. small metabolic macromolecules, reflecting a tradeoff between the saturation of metabolic enzymes, favoring larger occupancies with higher encounter rates, and the inhibition of the ribosomes, favoring lower occupancies with unhindered diffusion of tRNAs. Our predictions across growth rates are quantitatively consistent with the experimentally observed reduction in volume occupancy on rich media compared to minimal media inE. coli.Strong deviations from optimal cytosolic occupancy only lead to minute reductions in growth rate, which are nevertheless evolutionarily relevant due to large bacterial population sizes. In sum, cytosolic density variation in bacterial cells appears to be consistent with an optimality principle of cellular efficiency.
Diel Investments in Phytoplankton Metabolite Production Influenced by Associated Heterotrophic Bacteria
Authors: Uchimiya Mario , Schroer William , Olofsson Malin , Edison Arthur S. , Moran Mary Ann 
Published: November 2020

AbstractOrganic carbon transfer between photoautotrophic and heterotrophic microbes in the surface ocean mediated through metabolites dissolved in seawater is a central but poorly understood process in the global carbon cycle. In a synthetic microbial community in which diatom extracellular release of organic molecules sustained growth of a co-cultured bacterium, metabolite transfer was assessed over two diel cycles based on per cell quantification of phytoplankton endometabolites and bacterial transcripts. Of 31 phytoplankton endometabolites identified and classified into temporal abundance patterns, eight could be matched to patterns of bacterial transcripts mediating their uptake and catabolism. A model simulating the coupled endometabolite-transcription relationships hypothesized that one category of outcomes required an increase in phytoplankton metabolite synthesis in response to the presence of the bacterium. An experimental test of this hypothesis confirmed higher endometabolome accumulation in the presence of bacteria for all five compounds assigned to this category – leucine, glycerol-3-phosphate, glucose, and the organic sulfur compounds dihydroxypropanesulfonate and dimethylsulfoniopropionate. Partitioning of photosynthate into rapidly-cycling dissolved organic molecules at the expense of phytoplankton biomass production has implications for carbon sequestration in the deep ocean. That heterotrophic bacteria can impact this partitioning suggests a previously unrecognized influence on the ocean’s carbon reservoirs.Significance StatementMicrobes living in the surface ocean are critical players in the global carbon cycle, carrying out a particularly key role in the flux of carbon between the ocean and atmosphere. The release of metabolites by marine phytoplankton and their uptake by heterotrophic bacteria is one of the major routes of microbial carbon turnover. Yet the identity of these metabolites, their concentration in seawater, and the factors that affect their synthesis and release are poorly known. Here we provide experimental evidence that marine heterotrophic bacteria can affect phytoplankton production and extracellular release of metabolites. This microbial interaction has relevance for the partitioning of photosynthate between dissolved and particulate carbon reservoirs in the ocean, an important factor in oceanic carbon sequestration.