Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic tools to study complexity of striatal function

As the main input structure of the basal ganglia (BG), the striatum collects and integrates information from several brain areas and funnels them forward to other BG nuclei. The striatal projection neurons are medium‐sized spiny neurons classified in two main subpopulations, based on their neurochemical characterization and projection targets. These subpopulations are segregated into two distinct circuits, the direct and the indirect pathway, which originate in the striatum and interconnect the BG, ultimately reaching their output nuclei. In this review, we discuss current opinions on the striatal circuit and present different strategies to decipher this circuit complexity by utilizing cell ablation, opto‐ and chemogenetics, tetanus toxin‐induced neuronal silencing, and calcium imaging techniques. We also describe genetically encoded biosensors to monitor signaling dynamics in the striatal circuit with high spatial and temporal resolution by targeting both glutamate and dopamine transmission together with downstream signaling effectors. Recent findings revealing transcriptional, functional diversity, and regionally distinct signaling properties of spiny projection neurons argue that refined interrogation will be pertinent for a deeper understanding of this circuit. Moreover, future mapping the G‐protein–coupled receptor repertoire in SPNs will potentially enable pathway‐specific modulation of SPN activity and provide a novel framework for targeting BG diseases. Overall, these tools will be critical for designing next‐generation treatments for BG diseases.
Ranking-Preserving Cross-Source Learning for Image Retargeting Quality Assessment

Image retargeting techniques adjust images into different sizes and have attracted much attention recently. Objective quality assessment (OQA) of image retargeting results is often desired to automatically select the best results. Existing OQA methods train a model using some benchmarks (e.g., RetargetMe), in which subjective scores evaluated by users are provided. Observing that it is challenging even for human subjects to give consistent scores for retargeting results of different source images (diff-source-results), in this paper we propose a learning-based OQA method that trains a General Regression Neural Network (GRNN) model based on relative scores—which preserve the ranking—of retargeting results of the same source image (same-source-results). In particular, we develop a novel training scheme with provable convergence that learns a common base scalar for same-source-results. With this source specific offset, our computed scores not only preserve the ranking of subjective scores for same-source-results, but also provide a reference to compare the diff-source-results. We train and evaluate our GRNN model using human preference data collected in RetargetMe. We further introduce a subjective benchmark to evaluate the generalizability of different OQA methods. Experimental results demonstrate that our method outperforms ten representative OQA methods in ranking prediction and has better generalizability to different datasets.
Alkaloids of genus Erythrina: An updated review

Abstract Genus Erythrina (Fabaceae) comprises several species, which are widely distributed in tropical and subtropical regions of the world. The plants of this genus exhibited significant role in traditional medicine targeting different diseases. Alkaloids and flavonoids were reported as the chief bioactive constituents of this genus with a wide range of biological activities. About 143 alkaloids were isolated from Erythrina sp. Anticonvulsant, anxiolytic, curare-like activity, insecticidal and cytotoxic activities were reported for Erythrina sp. alkaloids. The present work is an overview of the isolated alkaloids from Erythrina sp. with their reported biological activities. Abbreviations: CHCl3: Chloroform; CNS: Central nervous system; DCM: Methylene chloride; DPPH: 2,2-Diphenyl-1-picrylhydrazyl; E. : Erythrina; ERα/β: Estrogen receptors α/β; EtOAc: Ethyl acetate; EtOH: Ethanol; Hep-G2: Human liver carcinoma cell lines; HIV: Human immunodeficiency virus; HL-60: Human promyelocytic leukemia cells; K-562: Human immortalized myelogenous leukemia cell line; LPS: Lipopolysaccharide; MeOH: Methanol; MOLT-4: Acute lymphoblastic leukemia cell line; nAChRs: nicotinic acetylcholine receptors; NO: Nitric oxide; NREM: non-rapid eye movement; Pet. ether: Petroleum ether; RBA: Receptor binder affinity; TRAIL: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand
Influenza vaccine programs for children in low- and middle-income countries: current status and way forward

ABSTRACT Introduction: Influenza vaccines are safe and effective, yet they are infrequently used in low- and middle-income countries (LMICs). Areas covered: We examine influenza vaccine programs for children from within a framework of new vaccine adoption in LMICs. We review the available evidence on disease burden and vaccine introduction, the current global and financing policies, and the current status of vaccine availability, and country readiness for implementation. Expert commentary: Access to appropriate formulations of influenza vaccines and existing immunization infrastructures must be strengthened if influenza vaccine programs are to be expanded in LMICs. While WHO recommends that implementation of influenza vaccine programs should be a country decision based on national goals, capacities, and data review, vaccine decision makers from many LMICs will likely need more evidence to inform the value proposition of program investment for pediatric vaccination, particularly related to alternative immunization strategies that align with current vaccine delivery platforms, anticipated program impact on severe illness endpoints, and program costs and economic benefits. Targeted research and development to address the specific needs of LMICs may be needed to demonstrate the value proposition of influenza vaccines and to expand influenza vaccine programs in these settings.
Principles of Business Forecasting

Ord/Fildes PRINCIPLES OF BUSINESS FORECASTING, 1E gives users the tools and insight to make the most effective forecasts drawing on the latest research ideas. Ord and Fildes have designed PRINCIPLES OF BUSINESS FORECASTING for users who have taken a first course in applied statistics or who have an equivalent background. Whether used by students or current practitioners, this book provides an introduction to both standard and advanced forecasting methods and their underlying models, and also includes general principles to guide and simplify forecasting practice. A key strength of the book is its emphasis on real data sets, taken from government and business sources and used in each chapter's examples. Forecasting techniques are demonstrated using a variety of software platforms and the companion website provides easy-to-use Excel macros to support the basic methods. After the introductory chapters, the focus shifts to using extrapolative methods (exponential smoothing and ARIMA) and then to statistical model-building using multiple regression. In later chapters, the authors cover more novel techniques such as data mining and judgmental methods, and also examine organizational issues of implementation and the development of a forecasting support system within an organization.
Enabling full‐length evolutionary profiles based deep convolutional neural network for predicting DNA‐binding proteins from sequence

Sequence based DNA‐binding protein (DBP) prediction is a widely studied biological problem. Sliding windows on position specific substitution matrices (PSSMs) rows predict DNA‐binding residues well on known DBPs but the same models cannot be applied to unequally sized protein sequences. PSSM summaries representing column averages and their amino‐acid wise versions have been effectively used for the task, but it remains unclear if these features carry all the PSSM's predictive power, traditionally harnessed for binding site predictions. Here we evaluate if PSSMs scaled up to a fixed size by zero‐vector padding (pPSSM) could perform better than the summary based features on similar models. Using multilayer perceptron (MLP) and deep convolutional neural network (CNN), we found that (a) Summary features work well for single‐genome (human‐only) data but are outperformed by pPSSM for diverse PDB‐derived data sets, suggesting greater summary‐level redundancy in the former, (b) even when summary features work comparably well with pPSSM, a consensus on the two outperforms both of them (c) CNN models comprehensively outperform their corresponding MLP models and (d) actual predicted scores from different models depend on the choice of input feature sets used whereas overall performance levels are model‐dependent in which CNN leads the accuracy.
Genome wide analysis of 3′ UTR sequence elements and proteins regulating mRNA stability during maternal-to-zygotic transition in zebrafish

Posttranscriptional regulation plays a crucial role in shaping gene expression. During the maternal-to-zygotic transition (MZT), thousands of maternal transcripts are regulated. However, how different cis-elements and trans-factors are integrated to determine mRNA stability remains poorly understood. Here, we show that most transcripts are under combinatorial regulation by multiple decay pathways during zebrafish MZT. By using a massively parallel reporter assay, we identified cis-regulatory sequences in the 3′ UTR, including U-rich motifs that are associated with increased mRNA stability. In contrast, miR-430 target sequences, UAUUUAUU AU-rich elements (ARE), CCUC, and CUGC elements emerged as destabilizing motifs, with miR-430 and AREs causing mRNA deadenylation upon genome activation. We identified trans-factors by profiling RNA–protein interactions and found that poly(U)-binding proteins are preferentially associated with 3′ UTR sequences and stabilizing motifs. We show that this activity is antagonized by C-rich motifs and correlated with protein binding. Finally, we integrated these regulatory motifs into a machine learning model that predicts reporter mRNA stability in vivo.
Reviewing Competence in Practice: Reform of Continuing Professional Development for Irish Pharmacists

There has been significant reform of the Continuing Professional Development (CPD) requirements for Irish pharmacists over the past five years. In 2015, a new system was established that includes quality assurance of practitioner engagement in CPD and quality assurance of practitioner competence. Pharmacists must now plan and document their learning activities in an electronic portfolio (ePortfolio) and they must participate in an ePortfolio Review process once every five-year period. A random sample is chosen each year to participate in a review of their practice for pharmacists in patient-facing roles. This paper provides an overview of the development and implementation of these quality assurance processes and it considers the outcomes that were observed in the first four years of implementation. By April 2019, almost 3000 pharmacists had participated in the ePortfolio Review process over the preceding three years, of which 96.2% demonstrated appropriate engagement in CPD. In the preceding two years, almost 200 pharmacists had participated in Practice Review, of which 97.5% have demonstrated the required level of competence across four competencies. All of the pharmacists who did not demonstrate the required level of competence in one or more competency area during Practice Review had previously demonstrated appropriate engagement in CPD through the ePortfolio Review process. This raises interesting questions regarding the use of engagement in continuing education (CE) or CPD as a surrogate measure for competence by professions.
Intussusceptive Lymphangiogenesis in Lymphatic Malformations/Lymphangiomas

Intussusception in lymphatic vessels has received less attention than in blood vessels. In tumors and pseudotumors of blood vessels with intravascular papillary structures, including sinusoidal hemangioma and intravascular papillary endothelial hyperplasia, we observed exuberant intussusceptive angiogenesis, as well as the similarity between papillae (term used by pathologists) and pillars/folds (hallmarks of intussusceptive angiogenesis). A similar response could be expected in lymphangiomas (lymphatic malformations and reactive processes rather than tumors) with papillae. The aim of this work is to assess whether papillae/pillars/folds and associated structures (vessel loops and septa) are present in lymphangiomas, and to establish the characteristics and formation of these structures. For this purpose, we selected lymphangiomas with intraluminal papillae (n = 18), including cystic, cavernous, circumscriptum, and progressive types, of which two cases of each type with a greater number of papillae were used for serial histologic sections and immunohistochemistry. The studies showed a) dilated lymphatic spaces giving rise to lymphatic–lymphatic vascular loops, which dissected and encircled perilymphatic structures (interstitial tissue structures/ITSs and pillars/posts), b) ITSs and pillars, surrounded by anti‐podoplanin‐positive endothelial cells, protruding into the lymphatic spaces (papillary aspect), and c) splitting, remodeling, linear arrangement, and fusion of papillae/pillars/folds, forming papillary networks and septa. In conclusion, as occurs in blood vessel diseases, the development of lymphatic vessel loops, papillae/pillars/folds, and septa (segmentation) supports intussusceptive lymphangiogenesis and suggests a piecemeal form of intussusception. This intussusceptive lymphangiogenesis in lymphatic diseases can provide a basis for further studies of lymphatic intussusception in other conditions, with clinical and therapeutic implications. Anat Rec, 302:2003–2013, 2019. © 2019 American Association for Anatomy
Recent Advances in Droplet-based Microfluidic Technologies for Biochemistry and Molecular Biology

Recently, droplet-based microfluidic systems have been widely used in various biochemical and molecular biological assays. Since this platform technique allows manipulation of large amounts of data and also provides absolute accuracy in comparison to conventional bioanalytical approaches, over the last decade a range of basic biochemical and molecular biological operations have been transferred to drop-based microfluidic formats. In this review, we introduce recent advances and examples of droplet-based microfluidic techniques that have been applied in biochemistry and molecular biology research including genomics, proteomics and cellomics. Their advantages and weaknesses in various applications are also comprehensively discussed here. The purpose of this review is to provide a new point of view and current status in droplet-based microfluidics to biochemists and molecular biologists. We hope that this review will accelerate communications between researchers who are working in droplet-based microfluidics, biochemistry and molecular biology.
Impaired Glycoprotein VI-Mediated Signaling and Platelet Functional Responses in CD45 Knockout Mice

Abstract Background and Objective CD45 is a receptor protein tyrosine phosphatase present on the surface of all hematopoietic cells except for erythrocytes and platelets. Proteomics studies, however, have demonstrated the presence of a CD45 c-terminal catalytic peptide in platelets. Therefore, we investigated the functional role of this truncated isoform of CD45 in platelets, which contains the c-terminal catalytic domain but lacks the extracellular region. Methods and Results We used an antibody specific to the c-terminus of CD45 to confirm the presence of a truncated CD45 isoform in platelets. We also examined ex vivo and in vivo platelet function using CD45 knockout (KO) mice. Aggregation and secretion mediated by the glycoprotein VI (GPVI) receptor was impaired in CD45 KO platelets. Consequently, CD45 KO mice had impaired hemostasis indicated by increased tail bleeding times. Also, using a model of pulmonary embolism we showed that CD45 KO mice had defective in vivo thrombus formation. Next, we investigated whether or not the truncated isoform of CD45 had a role in GPVI signaling. The full-length isoform of CD45 is known to regulate Src family kinase (SFK) activation in lymphocytes. We find a similar role for the truncated isoform of CD45 in platelets. SFK activation was impaired downstream of the GPVI receptor in the CD45 KO murine platelets. Consequently, Syk, PLCγ2, and pleckstrin phosphorylations were also impaired in CD45 KO murine platelets. Conclusion We conclude that the truncated CD45 isoform regulates GPVI-mediated signaling and platelet functional responses by regulating SFK activation.
Dengue in New Caledonia: Knowledge and Gaps

Arboviruses are viruses transmitted to humans by the bite of infected mosquito vectors. Over the last decade, arbovirus circulation has increasingly been detected in New Caledonia (NC), a French island territory located in the subtropical Pacific region. Reliable epidemiological, entomological, virological and climate data have been collected in NC over the last decade. Here, we describe these data and how they inform arboviruses’ epidemiological profile. We pinpoint areas which remain to be investigated to fully understand the peculiar epidemiological profile of arbovirus circulation in NC. Further, we discuss the advantages of conducting studies on arboviruses dynamics in NC. Overall, we show that conclusions drawn from observations conducted in NC may inform epidemiological risk assessments elsewhere and may be vital to guide surveillance and response, both in New Caledonia and beyond.
Efficacy of prefabricated carbon-composite ankle foot orthoses for children with unilateral spastic cerebral palsy exhibiting a drop foot pattern.

PURPOSE This study aims to evaluate the effectiveness of a prefabricated carbon-composite ankle foot orthoses (c-AFOs) on gait parameters in children with unilateral spastic cerebral palsy (USCP) exhibiting a drop foot pattern. METHODS Sixteen ambulatory children with USCP and a drop foot pattern were included (mean age: 9 years; gross motor function classification system: I = 14, II = 2) and three-dimensional gait analysis was applied under randomly assigned conditions (barefoot; shoe; c-AFO). Kinematics, kinetics, time-distance parameters and gait indices were investigated. RESULTS Effects on the drop foot pattern were investigated while the children walked in shoes only. The shoes already increased the maximum ankle dorsiflexion in swing (p= 0.004) and initiated more knee flexion during single support (p⩽ 0.013). Compared to shoe walking, the c-AFO led to additional benefits regarding further ankle dorsiflexion during swing (p⩽ 0.001) and initial contact (p< 0.001), ankle movement during loading response (p= 0.002), improved the sole angle during initial contact (p< 0.001) and during mid stance (p= 0.015). Plantarflexion and ankle power generation during push-off decreased when wearing the c-AFO (p⩽ 0.008). CONCLUSION Investigated c-AFOs are beneficial for improving drop foot patterns in children with USCP. Significant effects on pathological barefoot pattern were already achieved with the child's regular shoes. This could be considered in clinical decision processes. In comparison to shoe walking, c-AFO additionally improved foot clearance and normalized initial heel contact. The third rocker deteriorates with the c-AFO. Since kinematics improved with the orthoses during swing and early stance phase, c-AFOs might reduce tripping and falling caused by a drop foot during long distance walking.
Patient-Derived Xenograft Models of Breast Cancer and Their Application

Recently, patient-derived xenograft (PDX) models of many types of tumors including breast cancer have emerged as a powerful tool for predicting drug efficacy and for understanding tumor characteristics. PDXs are established by the direct transfer of human tumors into highly immunodeficient mice and then maintained by passaging from mouse to mouse. The ability of PDX models to maintain the original features of patient tumors and to reflect drug sensitivity has greatly improved both basic and clinical study outcomes. However, current PDX models cannot completely predict drug efficacy because they do not recapitulate the tumor microenvironment of origin, a failure which puts emphasis on the necessity for the development of the next generation PDX models. In this article, we summarize the advantages and limitations of current PDX models and discuss the future directions of this field.
Secreted protein acidic and rich in cysteine (SPARC) improves glucose tolerance via AMP‐activated protein kinase activation

During exercise, skeletal muscles release cytokines, peptides, and metabolites that exert autocrine, paracrine, or endocrine effects on glucose homeostasis. In this study, we investigated the effects of secreted protein acidic and rich in cysteine (SPARC), an exercise‐responsive myokine, on glucose metabolism in human and mouse skeletal muscle. SPARC‐knockout mice showed impaired systemic metabolism and reduced phosphorylation of AMPK and protein kinase B in skeletal muscle. Treatment of SPARC‐knockout mice with recombinant SPARC improved glucose tolerance and concomitantly activated AMPK in skeletal muscle. These effects were dependent on AMPK‐γ3 because SPARC treatment enhanced skeletal muscle glucose uptake in wild‐type mice but not in AMPK‐γ3–knockout mice. SPARC strongly interacted with the voltage‐dependent calcium channel, and inhibition of calcium‐dependent signaling prevented SPARC‐induced AMPK phosphorylation in human and mouse myotubes. Finally, chronic SPARC treatment improved systemic glucose tolerance and AMPK signaling in skeletal muscle of high‐fat diet–induced obese mice, highlighting the efficacy of SPARC treatment in the management of metabolic diseases. Thus, our findings suggest that SPARC treatment mimics the effects of exercise on glucose tolerance by enhancing AMPK‐dependent glucose uptake in skeletal muscle. —Aoi, W. , Hirano, N. , Lassiter, D. G. , Björnholm, M. , Chibalin, A. V. , Sakuma, K. , Tanimura, Y. , Mizushima, K. , Takagi, T. , Naito, Y. , Zierath, J. R. , Krook, A. Secreted protein acidic and rich in cysteine (SPARC) improves glucose tolerance via AMP‐activated protein kinase activation. FASEB J. 33, 10551–10562 (2019). www.fasebj. org