bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transformation of the Tanzania Medical Store Department through Global Fund support: lessons learned from the field
Authors: Githendu Patrick , Morrison Linden , Silaa Rosemary , Pothapregada Sai , Asiimwe Sarah , Idris Rafiu , Peterson Tatjana , Davidson Emma , Lesego Abaleng , Mwale Neema , Mwakalobo Sako , Bwanakunu Laurean , Achoki Tom 
Published: April 2020

AbstractBackgroundThe Tanzania government sought support from The Global Fund to Fight AIDs, Tuberculosis and Malaria (Global Fund) to reform its Medical Stores Department (MSD), with the aim of improving performance. Our study aimed to assess the impact of the reforms and document the lessons learned.MethodsWe applied quantitative and qualitative research methods to assess the impact of the reforms. The quantitative part entailed a review of operational and financial data covering the period before and after the implementation of the reforms. We applied interrupted time series analysis to determine the change in average availability of essential health commodities at health zones. Qualitative data was collected through 41 key informant interviews. Participants were identified through stakeholder mapping, purposive and snowballing sampling techniques, and responses were analyzed through thematic content analysis.ResultsAvailability of essential health commodities increased significantly by 12.6% (95%CI, 9.6-15.6), after the reforms and continued to increase on a monthly basis by 0.2% (95%CI, 0.0-0.3) relative to the preintervention trend. Sales increased by 56.6% while the cost of goods sold increased by 88.6% between 2014/15 and 2017/18. Surplus income increased by 56.4% between 2014/15 and 2017/18, with reductions in rent and fuel expenditure. There was consensus among participants that the reforms, were instrumental in improving performance of MSD.ConclusionMany positive results were realized through the reforms at MSD. However, despite the progress, there were risks such as the increasing government receivable that could jeopardize the gains. Multi-stakeholder efforts are necessary, to sustain the progress and expand public health.
Supramolecular Organization Predicts Protein Nanoparticle Delivery to Neutrophils for Acute Lung Inflammation Diagnosis and Treatment
Authors: Myerson Jacob W. , Patel Priyal N. , Habibi Nahal , Walsh Landis R. , Lee Yi-Wei , Luther David C. , Ferguson Laura T. , Zaleski Michael H. , Zamora Marco E. , Marcos-Contreras Oscar A. , Glassman Patrick M. , Johnston Ian , Hood Elizabeth D. , Shuvaeva Tea , Gregory Jason V. , Kiseleva Raisa Y. , Nong Jia , Rubey Kathryn M. , Greineder Colin F. , Mitragotri Samir , Worthen George S. , Rotello Vincent M. , Lahann Joerg , Muzykantov Vladimir R. , Brenner Jacob S. 
Published: April 2020

AbstractAcute lung inflammation has severe morbidity, as seen in COVID-19 patients. Lung inflammation is accompanied or led by massive accumulation of neutrophils in pulmonary capillaries (“margination”). We sought to identify nanostructural properties that predispose nanoparticles to accumulate in pulmonary marginated neutrophils, and therefore to target severely inflamed lungs. We designed a library of nanoparticles and conducted anin vivoscreen of biodistributions in naive mice and mice treated with lipopolysaccharides. We found that supramolecular organization of protein in nanoparticles predicts uptake in inflamed lungs. Specifically, nanoparticles with agglutinated protein (NAPs) efficiently home to pulmonary neutrophils, while protein nanoparticles with symmetric structure (e.g.viral capsids) are ignored by pulmonary neutrophils. We validated this finding by engineering protein-conjugated liposomes that recapitulate NAP targeting to neutrophils in inflamed lungs. We show that NAPs can diagnose acute lung injury in SPECT imaging and that NAP-like liposomes can mitigate neutrophil extravasation and pulmonary edema arising in lung inflammation. Finally, we demonstrate that ischemicex vivohuman lungs selectively take up NAPs, illustrating translational potential. This work demonstrates that structure-dependent interactions with neutrophils can dramatically alter the biodistribution of nanoparticles, and NAPs have significant potential in detecting and treating respiratory conditions arising from injury or infections.
Estimation of Tunisia COVID-19 infected cases based on mortality rate
Authors: Abdeljaoued-Tej Ines , Dhenain Marc 
Published: April 2020

ABSTRACTEstimating the number of people affected by COVID-19 is crucial in deciding which public health policies to follow. The authorities in different countries carry out mortality counts. We propose that the mortality reported in each country can be used to create an index of the number of actual cases at a given time. The specificity of whether or not deaths are rapid or not by COVID-19 also affects the number of actual cases. The number of days between the declaration of illness and death varies between 12 and 18 days. For a delay of 18 days, and using an estimated mortality rate of 2%, the number of cases in April 2020 in Tunisia would be5 580people. The pessimistic scenario predicts22 320infected people, and the most optimistic predicts 744 (which is the number of reported cases on April12, 2020). Modeling the occurrence of COVID-19 cases is critical to assess the impact of policies to prevent the spread of the virus.
The socio-economic determinants of the coronavirus disease (COVID-19) pandemic
Authors: Stojkoski Viktor , Utkovski Zoran , Jolakoski Petar , Tevdovski Dragan , Kocarev Ljupco 
Published: April 2020

AbstractThe magnitude of the coronavirus disease (COVID-19) pandemic has an enormous impact on the social life and the economic activities in almost every country in the world. Besides the biological and epidemiological factors, a multitude of social and economic criteria also govern the extent of the coronavirus disease spread in the population. Consequently, there is an active debate regarding the critical socio-economic determinants that contribute to the resulting pandemic. In this paper, we contribute towards the resolution of the debate by leveraging Bayesian model averaging techniques and country level data to investigate the potential of 35 determinants, describing a diverse set of socio-economic characteristics, in explaining the coronavirus pandemic outcome.
Relative adrenal insufficiency is a risk factor and an endotype of sepsis - A proof of concept study to support a precision medicine approach for glucocorticoid sepsis therapy
Authors: Wu Chia-Hua , Guo Ling , Wang Qian , Ye Xiang , Mineo Chieko , Shaul Philip W. , Li Xiang-An 
Published: April 2020

AbstractRational25-60% of septic patients experience relative adrenal insufficiency (RAI) and glucocorticoid (GC) is frequently used in septic patients. However, the efficacy of GC therapy and whether the GC therapy should be based on the status of RAI are highly controversial. Critical barriers include technical limitations in properly identifying RAI in septic patients and a lack of RAI animal model.ObjectivesWe established a new RAI animal model to test our hypothesis that precision medicine approach should be used for GC sepsis therapy - only applying GC to a subgroup of septic mice with RAI.MethodsWe generated SF1CreSR-BIfl/flconditional knockout mice. The mice exhibited specific depletion of SR-BI expression in adrenal gland, resulting in a lack of production of inducible GC in response to ACTH stimulation or sepsis, but the mice had normal basal GC levels. Mice were treated with cecal ligation and puncture to develop sepsis. Mice were also supplemented with or without GC to study the effect of GC in sepsis therapy. Plasma and organs were collected for biochemical assays. BODIPY™FL-conjugatedEscherichia coliwas used for phagocytosis assay. Macrophages were used to study effects of GC on inflammatory responses.Measurements and Main ResultsUsing SF1CreSR-BIfl/flmice as a RAI model, we found that mice with RAI were susceptible to CLP-induced sepsis compared to controls (6.7% survival in SF1CreSR-BIfl/flmice versus 86.4% in SR-BIfl/flmice; p=0.0001). Supplementation of hydrocortisone significantly improved survival in CLP-treated SF1CreSR-BIfl/flmice. Surprisingly, wild type mice receiving GC treatment exhibited significantly less survival compared to wild type mice without GC treatment. We further found that, in contrast to wild type mice which displayed a well-controlled systemic inflammatory response, the mice with RAI featured a persisted systemic response as shown by high levels of plasma inflammatory cytokines/chemokines 20 hours post CLP, and supplementation of GC kept the inflammatory response under control. In vitro analysis revealed that stress level of GC is required to suppress inflammatory response through modulating MAPK signaling in macrophages.ConclusionsWe demonstrate that RAI is a risk factor and an endotype for sepsis, and GC treatment benefits mice with RAI but harms mice without RAI. We further demonstrate that inducible GC functions to keep the systemic inflammatory response under control through modulating MAPK signaling, but mice with RAI lose such protection and supplementation of GC regains the protection. Our study provides a proof of concept to support the use of a precision medicine approach for sepsis therapy – selectively applying GC therapy for a subgroup of patients with RAI.
Two dynamically distinct circuits driving inhibition in sensory thalamus
Authors: Martinez-Garcia Rosa I. , Voelcker Bettina , Zaltsman Julia B. , Patrick Saundra L. , Stevens Tanya R. , Connors Barry W. , Cruikshank Scott J. 
Published: April 2020

AbstractMost sensory information destined for the neocortex is relayed through the thalamus, where considerable transformation occurs1,2. One powerful means of transformation involves interactions between excitatory thalamocortical neurons that carry data to cortex and inhibitory neurons of the thalamic reticular nucleus (TRN) that regulate flow of those data3-6. Despite enduring recognition of its importance7-9, understanding of TRN cell types, their organization, and their functional properties has lagged that of the thalamocortical systems they control.Here we address this, investigating somatosensory and visual circuits of the TRN. In the somatosensory TRN we observed two groups of genetically defined neurons that are topographically segregated, physiologically distinct, and connect reciprocally with independent thalamocortical nuclei via dynamically divergent synapses. Calbindin-expressing cells, located in the central core, connect with the ventral posterior nucleus (VP), the primary somatosensory thalamocortical relay. In contrast, somatostatin-expressing cells, residing along the surrounding edges of TRN, synapse with the posterior medial thalamic nucleus (POM), a higher-order structure that carries both top-down and bottom-up information10-12. The two TRN cell groups process their inputs in pathway-specific ways. Synapses from VP to central TRN cells transmit rapid excitatory currents that depress deeply during repetitive activity, driving phasic spike output. Synapses from POM to edge TRN cells evoke slower, less depressing excitatory currents that drive more persistent spiking. Differences in intrinsic physiology of TRN cell types, including state-dependent bursting, contribute to these output dynamics. Thus, processing specializations of two somatosensory TRN subcircuits appear to be tuned to the signals they carry—a primary central subcircuit to discrete sensory events, and a higher-order edge subcircuit to temporally distributed signals integrated from multiple sources. The structure and function of visual TRN subcircuits closely resemble those of the somatosensory TRN. These results provide fundamental insights about how subnetworks of TRN neurons may differentially process distinct classes of thalamic information.
Self-organized patterning of cell morphology via mechanosensitive feedback
Authors: Dye Natalie A. , Popovic Marko , Iyer K. Venkatesan , Eaton Suzanne , Julicher Frank 
Published: April 2020

ABSTRACTTissue organization is often characterized by specific patterns of cell morphology. How such patterns emerge in developing tissues is a fundamental open question. Here, we investigate the emergence of tissue-scale patterns of cell shape and mechanical tissue stress in theDrosophilawing imaginal disc during larval development. Using quantitative analysis of the cellular dynamics, we reveal a pattern of radially oriented cell rearrangements that is coupled to the buildup of tangential cell elongation. Developing a laser ablation method, we map tissue stresses and extract key parameters of tissue mechanics. We present a continuum theory showing that this pattern of cell morphology and tissue stress can arise via self-organization of a mechanical feedback that couples cell polarity to active cell rearrangements. The predictions of this model are supported by knockdown of MyoVI, a component of mechanosensitive feedback. Our work reveals a mechanism for the emergence of cellular patterns in morphogenesis.
ReactomeGSA - Efficient Multi-Omics Comparative Pathway Analysis
Authors: Griss Johannes , Viteri Guilherme , Sidiropoulos Konstantinos , Nguyen Vy , Fabregat Antonio , Hermjakob Henning 
Published: April 2020

AbstractPathway analyses are key methods to analyse ‘omics experiments. Nevertheless, integrating data from different ‘omics technologies and different species still requires considerable bioinformatics knowledge.Here we present the novel ReactomeGSA resource for comparative pathway analyses of multi-omics datasets. ReactomeGSA can be used through Reactome’s existing web interface and the novel ReactomeGSA R Bioconductor package with explicit support for scRNA-seq data. Data from different species is automatically mapped to a common pathway space. Public data from ExpressionAtlas and Single Cell ExpressionAtlas can be directly integrated in the analysis. ReactomeGSA thereby greatly reduces the technical barrier for multi-omics, cross-species, comparative pathway analyses.We used ReactomeGSA to characterise the role of B cells in anti-tumour immunity. We compared B cell rich and poor human cancer samples from five TCGA transcriptomics and two CPTAC proteomics studies. There, B cell-rich lung adenocarcinoma samples lack the otherwise present activation through NFkappaB. This may be linked to the presence of a specific subset of tumour associated IgG+ plasma cells that lack NFkappaB activation in scRNA-seq data from human melanoma. This showcases how ReactomeGSA can derive novel biomedical insights by integrating large multi-omics datasets.
The determinants of aggression in male Siamese fighting fish,Betta splendens
Authors: McGoran R. E. , Papworth S. K. , Portugal S. J. 
Published: April 2020

ABSTRACTSiamese fighting fish,Betta splendens, have been extensively studied due to their aggression and stereotypical displays. Many studies have focused on their characteristic opercular flaring, while the less aggressive and less energetically costly lateral display have been comparatively understudied. Many factors have been shown to influence aggression inBettas, notably body length and the personality trait of boldness, however, the role that colour plays in determining an individual’s aggressiveness is much less clear. The role of colour has only been briefly studied, and based on human interpretations of colour, i.e. limited to what the receivers’ eyes and sensory systems actually can process and discriminate, with results suggesting blue males are more aggressive than red males. Using male-male interactions, measuring opercular flaring and lateral display we found that colour and personality do play a role in determining the degree of aggressiveness inBetta splendens. Blue-finned males were more aggressive, performing longer lateral displays more frequently. Blue fins are a phenotype observed in wild type males and is likely selected for to allow visual cues to travel through the murky water they inhabit. Body mass was positively correlated with lateral display frequency, and opercular flare frequency and duration. Finally, neophobic individuals – individuals that were less willing to approach a novel object – were more aggressive, performing significantly more lateral displays. This indicates that personality may impact fighting strategy, with males either choosing to end conflicts quickly with more aggressive displays or to outlast their opponent with less energetically costly displays.
Transcranial Focused Ultrasound Generates Skull-Conducted Shear Waves: Computational Model and Implications for Neuromodulation
Authors: Salahshoor Hossein , Shapiro Mikhail G. , Ortiz Michael 
Published: April 2020

ABSTRACTFocused ultrasound (FUS) is an established technique for non-invasive surgery and has recently attracted considerable attention as a potential method for non-invasive neuromodulation. While the pressure waves generated by FUS in this context have been extensively studied, the accompanying shear waves are often neglected due to the relatively high shear compliance of soft tissues. However, in bony structures such as the skull, acoustic pressure can also induce significant shear waves that could propagate outside the ultrasound focus. Here, we investigate wave propagation in the human cranium by means of a finite-element model that accounts for the anatomy, elasticity and viscoelasticity of the skull and brain. We show that, when a region on the frontal lobe is subjected to FUS, the skull acts as a wave guide for shear waves, resulting in their propagation to off-target structures such as the cochlea. This effect helps explain the off-target auditory responses observed during neuromodulation experiments and informs the development of mitigation and sham control strategies.
Holistic Characterization of Single Hepatocyte Transcriptome Responses to High Fat Diet
Authors: Park Sung Rye , Cho Chun-Seok , Xi Jingyue , Kang Hyun Min , Lee Jun Hee 
Published: April 2020

AbstractDuring nutritional overload and obesity, hepatocyte function is grossly altered, and a subset of hepatocytes begins to accumulate fat droplets, leading to non-alcoholic fatty liver disease (NAFLD). Recent single cell studies revealed how non-parenchymal cells, such as macrophages, hepatic stellate cells, and endothelial cells, heterogeneously respond to NAFLD. However, it remains to be characterized how hepatocytes, the major constituents of the liver, respond to nutritional overload in NAFLD. Here, using droplet-based single cell RNA-sequencing (Drop-seq), we characterized how the transcriptomic landscape of individual hepatocytes is altered in response to high-fat diet (HFD) and NAFLD. We showed that the entire hepatocytes population undergoes substantial transcriptome changes upon HFD, although the patterns of alteration were highly heterogeneous with zonation-dependent and –independent effects. Periportal (zone 1) hepatocytes downregulated many zone 1-specific marker genes, while a small number of genes mediating gluconeogenesis were upregulated. Pericentral (zone 3) hepatocytes also downregulated many zone 3-specific genes; however, they upregulated several genes that promote HFD-induced fat droplet formation, consistent with findings that zone 3 hepatocytes accumulate more lipid droplets. Zone 3 hepatocytes also upregulated ketogenic pathways as an adaptive mechanism to HFD. Interestingly, many of the top HFD-induced genes, which encode proteins regulating lipid metabolism, were strongly co-expressed with each other in a subset of hepatocytes, producing a variegated pattern of spatial co-localization that is independent of metabolic zonation. In conclusion, our dataset provides a useful resource for understanding hepatocellular alteration during NAFLD at single cell level.
Comprehension of computer code relies primarily on domain-general executive brain regions
Authors: Ivanova Anna A. , Srikant Shashank , Sueoka Yotaro , Kean Hope H. , Dhamala Riva , O’Reilly Una-May , Bers Marina U. , Fedorenko Evelina 
Published: April 2020

AbstractComputer programming is a novel cognitive tool that has transformed modern society. What cognitive and neural mechanisms support this skill? Here, we used fMRI to investigate two candidate brain systems: the multiple demand (MD) system, typically recruited during math, logic, problem solving, and executive tasks, and the language system, typically recruited during linguistic processing. We examined MD and language system responses to code written in Python, a text-based programming language (Experiment 1) and in ScratchJr, a graphical programming language (Experiment 2); for both, we contrasted responses to code problems with responses to content-matched sentence problems. We found that the MD system exhibited strong bilateral responses to code in both experiments, whereas the language system responded strongly to sentence problems, but weakly or not at all to code problems. Thus, the MD system supports the use of novel cognitive tools even when the input is structurally similar to natural language.
Horseshoe crab genomes reveal the evolutionary fates of genes and microRNAs after three rounds (3R) of whole genome duplication
Authors: Nong Wenyan , Qu Zhe , Li Yiqian , Barton-Owen Tom , Wong Annette Y.P. , Yip Ho Yin , Lee Hoi Ting , Narayana Satya , Baril Tobias , Swale Thomas , Cao Jianquan , Chan Ting Fung , Kwan Hoi Shan , Ming Ngai Sai , Panagiotou Gianni , Qian Pei-Yuan , Qiu Jian-Wen , Yip Kevin Y. , Ismail Noraznawati , Pati Siddhartha , John Akbar , Tobe Stephen S. , Bendena William G. , Cheung Siu Gin , Hayward Alexander , Hui Jerome H. L. 
Published: April 2020

AbstractWhole genome duplication (WGD) has occurred in relatively few sexually reproducing invertebrates. Consequently, the WGD that occurred in the common ancestor of horseshoe crabs ~135 million years ago provides a rare opportunity to decipher the evolutionary consequences of a duplicated invertebrate genome. Here, we present a high-quality genome assembly for the mangrove horseshoe crabCarcinoscorpius rotundicauda(1.7Gb, N50 = 90.2Mb, with 89.8% sequences anchored to 16 pseudomolecules, 2n = 32), and a resequenced genome of the tri-spine horseshoe crabTachypleus tridentatus(1.7Gb, N50 = 109.7Mb). Analyses of gene families, microRNAs, and synteny show that horseshoe crabs have undergone three rounds (3R) of WGD, and that these WGD events are shared with spiders. Comparison of the genomes ofC. rotundicaudaandT. tridentatuspopulations from several geographic locations further elucidates the diverse fates of both coding and noncoding genes. Together, the present study represents a cornerstone for a better understanding of the consequences of invertebrate WGD events on evolutionary fates of genes and microRNAs at individual and population levels, and highlights the genetic diversity with practical values for breeding programs and conservation of horseshoe crabs.