bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effectiveness of paediatric influenza vaccination in the Netherlands
Authors: de Boer Pieter T. , Dolk Franklin C.K. , Nagy Lisa , Wilschut Jan C. , Pitman Richard , Postma Maarten J. 
Published: March 2020

AbstractBackgroundThis study evaluates the cost-effectiveness of extending the Dutch influenza vaccination programme for elderly and clinical risk groups to include paediatric influenza vaccination, taking indirect protection into account.MethodsAn age-structured dynamic transmission model was used that was calibrated to influenza-associated GP visits over four seasons (2010/11 to 2013/14). The clinical and economic impact of different paediatric vaccination strategies were compared over 20 years, varying the targeted age range, the vaccine type for children and the vaccine type for elderly and clinical risk groups. Outcome measures include averted symptomatic infections and deaths, societal costs and quality-adjusted life years (QALYs), incremental cost-effectiveness ratios, and net health benefits (NHBs), using a willingness-to-pay threshold of €20,000 per QALY gained.ResultsAt an assumed coverage of 50%, adding vaccination of 2- to 17-year-olds with quadrivalent-live-attenuated influenza vaccine (Q-LAIV) to the current influenza vaccination programme was estimated to avert on average 406,270 symptomatic cases and 83 deaths per season compared to vaccination of elderly and risk groups with trivalent inactivated vaccine (TIV), and was cost-saving (cumulative 20-year savings of 36,396 QALYs and €1,680 million; NHB: 120,411 QALYs). This strategy dominated paediatric vaccination strategies targeting 2- to 6-year-olds or 2- to 12-year-olds, or paediatric vaccination strategies with TIV. The highest NHB was obtained when 2- to 17-year-olds were vaccinated with Q-LAIV and existing target groups switched from TIV to quadrivalent inactivated vaccine (NHB: 132,907 QALYs).ConclusionModelling indicates that paediatric influenza vaccination reduces the disease burden of influenza substantially and is cost-saving.
Immunodepletion with Hypoxemia: A Potential High Risk Subtype of Coronavirus Disease 2019
Authors: Yu Lilei , Tong Yongqing , Shen Gaigai , Fu Aisi , Lai Yanqiu , Zhou Xiaoya , Yuan Yuan , Wang Yuhong , Pan Yuchen , Yu Zhiyao , Li Yan , Liu Tiangang , Jiang Hong 
Published: March 2020

AbstractBackgroundThe outbreak of COVID-2019 is becoming a global public health emergency. Although its basic clinical features have been reported, the dynamic characteristics of immune system in COVID-2019 patients, especially those critical patients with refractory hypoxemia, are not yet well understood. We aim to describe the dynamic characteristics of immune system in 3 critical patients with refractory hypoxemia, and discuss the relationship between hypoxemia severity and immune cell levels, and the changes of gut microbes of COVID-2019 patient.MethodsThis is a retrospective study from 3 patients with 2019-nCoV infection admitted to Renmin Hospital of Wuhan University, a COVID-2019 designated hospital in Wuhan, from January 31 to February 6, 2020. All patients were diagnosed and classified based on the Diagnosis and Treatment of New Coronavirus Pneumonia (6th edition) published by the National Health Commission of China4. We recorded the epidemiological history, demographic features, clinical characteristics, symptoms and signs, treatment and clinical outcome in detail. Blood samples were collected and we determined the expression levels of immune cells (CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD16+56+ NK cells) in different time points. Nanopore Targeted Sequencing was used to determine the alterations of gut microbiota homeostasis.ResultsApart from the clinical features described previously4, we found that four patients had decreased immune cells and refractory hypoxemia during the hospitalization, and the severity of hypoxemia was strongly correlated to the expression levels of immune cells. Additionally, we found that the proportion of probiotics was significantly reduced, such as Bifidobacterium, Lactobacillus, and Eubacterium, and the proportion of conditioned pathogenic bacteria was significantly increased, such as Corynebacterium of Actinobacteria and Ruthenibacterium of Firmicutes. Notably, all patients died.ConclusionsWe discussed the dynamic characteristics of host immune system and the imbalance of gut microbiota in 3 critical patients with COVID-2019. Hypoxemia severity was closely related with host immune cell levels, and the vicious circle between immune disorder and gut microbiota imbalance may be a high risk of fatal pneumonia. To the best of our knowledge, this is the first study which revealing that immunodepletion with refractory hypoxemia is a potential high risk subtype of COVID-2019 and the vicious circle between immune disorder and gut dysbiosis may be a high risk of fatal pneumonia.
Associations betweenCYP3A4, CYP3A5andSCN1APolymorphisms and Carbamazepine Metabolism in Epilepsy: A Meta-analysis
Authors: Zhao Gui-Xin , Zhang Zheng , Cai Wen-Ke , Shen Ming-Li , Wang Ping , He Gong-Hao 
Published: March 2020

AbstractBackground and objectiveCYP3A4(rs2242480),CYP3A5(rs776746) andSCN1A(rs3812718 and rs2298771) gene polymorphisms were previously indicated to be associated with carbamazepine (CBZ) metabolism and resistance in epilepsy. However, previous studies regarding the effects of these polymorphisms still remain controversial. Therefore, we performed a meta-analysis to evaluate whether the four polymorphisms are associated with CBZ metabolism and resistance.MethodsThe PubMed, EMBASE, Cochrane library, Chinese National Knowledge Infrastructure, Chinese Science and Technique Journals Database, China Biology Medicine disc and Wan fang Database were searched up to January 2020 for appropriate studies regarding the association of rs2242480, rs776746, rs3812718 and rs2234922 polymorphisms with metabolism and resistance to CBZ. The meta-analysis was conducted by Review Manager 5.3 software.ResultsEighteen studies involving 2574 related epilepsy patients were included. Significant associations betweenCYP3A4rs2242480,CYP3A5rs776746 andSCN1Ars3812718 polymorphisms and plasma concentrations of CBZ were observed. Additionally,SCN1Ars3812718 polymorphism was significantly associated with CBZ resistance. However, no association was observed betweenSCN1Ars2298771 polymorphism and metabolism and resistance to CBZ.ConclusionTheCYP3A4rs2242480,CYP3A5rs776746 andSCN1Ars3812718 polymorphisms may play important roles in metabolism and resistance to CBZ, whileSCN1Ars2298771 polymorphism is not associated with CBZ in epilepsy. These findings would improve the individualized therapy of epileptic patients in clinics.
Acoustofluidic Assembly of 3D Neurospheroids to Model Alzheimer’s Disease
Authors: Cai Hongwei , Ao Zheng , Hu Liya , Moon Younghye , Wu Zhuhao , Lu Hui-Chen , Kim Jungsu , Guo Feng 
Published: March 2020

AbstractNeuroinflammation plays a central role in the progression of many neurodegenerative diseases such as Alzheimer’s disease, and challenges remain in modeling the complex pathological or physiological processes. Here, we report an acoustofluidic 3D cell culture device that can rapidly construct 3D neurospheroids and inflammatory microenvironments for modeling microglia-mediated neuroinflammation in Alzheimer’s disease. By incorporating a unique contactless and label-free acoustic assembly, this cell culture platform can assemble dissociated embryonic mouse brain cells into hundreds of uniform 3D neurospheroids with controlled cell numbers, composition (e.g. neurons, astrocytes, and microglia), and environmental components (e.g. amyloid-β aggregates) in hydrogel within minutes. Moreover, this platform can maintain and monitor the interaction among neurons, astrocytes, microglia, and amyloid-β aggregates in real-time for several days to weeks, after the integration of a high-throughput, time-lapse cell imaging approach. We demonstrated that our engineered 3D neurospheroids can represent the amyloid-β neurotoxicity, which is one of the main pathological features of Alzheimer’s disease. Using this method, we also investigated the microglia migratory behaviors and activation in the engineered 3D inflammatory microenvironment at a high throughput manner, which is not easy to achieve in 2D neuronal cultures or animal models. Along with the simple fabrication and setup, the acoustofluidic technology is compatible with conventional Petri dishes and well-plates, supports the fine-tuning of the cellular and environmental components of 3D neurospheroids, and enables the high-throughput cellular interaction investigation. We believe our technology may be widely used as in vitro brain models for modeling neurodegenerative diseases, discovering new drugs, and testing neurotoxicity.
Low expression of ANT1 confers oncogenic properties to rhabdomyosarcoma tumor cells via modulating metabolism and death pathways
Authors: Vial J , Huchedé P , Fagault S , Basset F , Rossi M , Geoffray J , Bisaccia J , Creveaux M , Neves D , Fauvelle F , Castets P , Carré M , Weber K , Castets M 
Published: March 2020

ABSTRACTRhabdomyosarcoma (RMS) is the most frequent form of pediatric soft-tissue sarcoma. It is divided into 2 main subtypes: ERMS (embryonal) and ARMS (alveolar). Current treatments are based on chemotherapy, surgery and radiotherapy. 5-year survival rate remains of 70% since 2000, despite several clinical trials.RMS cells are thought to derive from muscle lineage precursors. During development, myogenesis is characterized by primary expansion of myoblasts, elimination of those in excess by cell death and the differentiation of the remaining ones into myotubes and myofibers. The idea that these processes could be hijacked by tumor cells to sustain their oncogenic transformation has emerged, while RMS is being considered as the Mister Hyde’s side of myogenesis. Thus, focusing on myogenic developmental programs could help understanding RMS molecular aetiology.Following this idea, we decided to concentrate on ANT1, which is involved in myogenesis and is the underlying cause of genetic disorders associated with muscle degeneration. ANT1 is a mitochondrial protein, which has a functional duality, as it is involved both in metabolism via regulation of ATP/ADP release from mitochondria, but also in apoptosis as part as the mitochondria Permeability Transition Pore (mPTP). By bioinformatic analysis of transcriptomic datasets, we observed that ANT1 is expressed at low levels in RMS. Using CRISPR-Cas9 technology, we showed that decreased ANT1 expression confers selective advantages to RMS cells in terms of proliferation and resistance to stress-induced death. These effects result notably from a metabolic switch. Restoration of ANT1 expression using a Tet-On system is sufficient to prime tumor cells to death and to increase their sensitivity to chemotherapies. Thus, modulation of ANT1 activity could appear as an appealing therapeutic approach in RMS management.
Simulating future rewards: exploring the impacts of implicit context association and arithmetic booster in delay discounting
Authors: Hwang Minho , Kim Sung-Phil , Chung Dongil 
Published: March 2020

AbstractPeople have higher preference for immediate over delayed rewards, and it is suggested that such an impulsive tendency is governed by one’s ability to simulate future rewards. Consistent with this view, recent studies have shown that enforcing individuals to focus on episodic future thoughts reduces their impulsivity. Inspired by these successful reports, we hypothesized that administration of a simple cognitive task which is linked with future thinking might also function as an effective tool for modulating individuals’ preference for immediate (or delayed) rewards. Specifically, we used one associative memory task and one working memory task that each of which was administered to intervene acquired amount of information and individuals’ ability to construct a coherent future event, respectively. Among the set of cognitive tasks, we found that only the arithmetic working memory task had a significant effect of reducing individuals’ impulsivity. However, in our follow-up experiment, this result was not replicated. Across these two independent experiments, we observed a significant main effect of repetition in individuals’ impulsivity measure, such that participants showed more patient choices at the second compared to the first assessment task. In conclusion, there was no clear evidence supporting that our suggested intervention tasks effectively reduce individuals’ impulsivity, while the current results call attention to the importance of taking into account task repetition effects in studying the impacts of cognitive training and intervention.
Why the middle ear piston prosthesis is not effective enough and how to change it?
Authors: Gambin Wiktor L. 
Published: March 2020

AbstractPiston prostheses of the middle ear do not ensure sufficient audibility of high and low sounds. To find out the reason, the amplitudes of the vibrations for the stapes footplate and the piston end were compared. It was seen that for a given force that oscillates with a low frequency, the amplitude of the piston end was higher than the amplitude of the stapes footplate. This means that the stiffness of the tissue sealing up the piston in the footplate hole is lower than the stiffness of the stapes plate suspension. It was shown that as a result, for the case of the higher frequencies, the amplitude of the piston vibrations drops several times. Next, it was compared a sound propagation in the healthy ear with that in the ear after the stapedotomy. To do it, a previously prepared model of sound propagation in the ear was used. The model is simplified, but it gives all parameters of the sound wave in the cochlear fluid. According to it, a motion of the stapes footplate forms a plane wave, while the piston motion initially gives a wave similar to the spherical one. A part of the spherical wave with the front directed towards the apex forms the primary wave running in the cochlea. However, the rest of this wave has the front directed towards the stapes footplate. This wave part, after a reflection from the stapes footplate, creates a secondary wave that follows the primary wave. A splitting of the wavefront around the edge of the piston end is a source of disruptions in the sound perception. The shift of the secondary wave reduces the power of the primary wave; it disturbs the waving of the basilar membrane and may cause extra noise. To justify it, a graph of the level of the cochlear amplification for the ear with the piston prosthesis was shown. The result compared with a simulation for the healthy ear gave the values 5 dB lower. To remove these drawbacks, it was proposed to place the piston end, not inside the cochlea, but in a guide in the form of a tube ended with a funnel fixed in the hole made in the stapes footplate. The piston was suspended in a guide tube on an O-ring formed of silicone gel. It was shown that when the piston is in the guide, the level of cochlear amplification was the same as that in the healthy ear. Some design details of the new piston guide are given. It enables us to make the new piston prosthesis easily and put it into practice.
Effect of interglomerular inhibitory networks on olfactory bulb odor representations
Authors: Zavitz Daniel , Youngstrom Isaac A. , Borisyuk Alla , Wachowiak Matt 
Published: March 2020

AbstractLateral inhibition is a fundamental feature of circuits that process sensory information. In the mammalian olfactory system, inhibitory interneurons called short axon cells comprise the first network mediating lateral inhibition between glomeruli, the functional units of early olfactory coding and processing. The connectivity of this network and its impact on odor representations is not well understood. To explore this question, we constructed a computational model of the interglomerular inhibitory network using detailed characterizations of short axon cell morphologies taken from mouse olfactory bulb. We then examined how this network transformed glomerular patterns of odorant-evoked sensory input (taken from previously-published datasets) as a function of the selectivity of interglomerular inhibition. We examined three connectivity schemes: selective (each glomerulus connects to few others with heterogeneous strength), nonselective (glomeruli connect to most others with heterogenous strength) or global (glomeruli connect to all others with equal strength). We found that both selective and nonselective interglomerular networks could mediate heterogeneous patterns of inhibition across glomeruli when driven by realistic sensory input patterns, but that global inhibitory networks were unable to produce input-output transformations that matched experimental data and were poor mediators of intensity-dependent gain control. We further found that networks whose interglomerular connectivity was tuned by sensory input profile decorrelated odor representations more effectively. These results suggest that, despite their multiglomerular innervation patterns, short axon cells are capable of mediating odorant-specific patterns of inhibition between glomeruli that could, theoretically, be tuned by experience or evolution to optimize discrimination of particular odorants.Significance StatementLateral inhibition is a key feature of circuitry in many sensory systems including vision, audition, and olfaction. We investigate how lateral inhibitory networks mediated by short axon cells in the mouse olfactory bulb might shape odor representations as a function of their interglomerular connectivity. Using a computational model of interglomerular connectivity derived from experimental data, we find that short axon cell networks, despite their broad innervation patterns, can mediate heterogeneous patterns of inhibition across glomeruli, and that the canonical model of global inhibition does not generate experimentally observed responses to stimuli. In addition, inhibitory connections tuned by input statistics yield enhanced decorrelation of similar input patterns. These results elucidate how the organization of inhibition between neural elements may affect computations.
CrudeNecator americanusworm extract diminishes pancreatic islets destruction in diabetic non-obese mice (NOD)
Authors: Velikkakam Teresiama , de Araujo Bruna Garzedim , Alves Érica Alessandra Rocha , Fujiwara Ricardo Toshio , Bueno Lilian Lacerda , Fiuza Jacqueline Araújo , Gaze Soraya 
Published: March 2020

ABSTRACTHygiene hypothesis dictates that the lack of microbial interaction during the first childhood increases the chance of developing autoimmune diseases due to not proper immune system maturation. Helminthes are known by their Th2 and modulatory immune response induction. Here, it was evaluated the influence ofNecator americanusantigens during type 1 experimental mouse model (non-obese diabetic – NOD). Intraperitoneal injections for 18 weeks did not impair an inflammatory response, but induced a mixed Th1/Th2 response with presence of IL4 and IL10 from different sources. However, the induced immune response was not sufficient to decrease glucose levels but showed a change in the inflammatory infiltrate in the pancreas. It is necessary more refined studies to clarify the mechanisms of howNecator americanuscould impair diabetes progression in mice.
Do human recordings reveal drastic modulations in the discharge of striatal projection neurons in Parkinson’s disease?
Authors: Valsky Dan , Israel Zvi , Boraud Thomas , Bergman Hagai , Deffains Marc 
Published: March 2020

AbstractDopamine depletion of the striatum plays a key role in the pathophysiology of Parkinson’s disease (PD), but our understanding of the changes in the discharge rate and pattern of the striatal projection neurons (SPNs) remains limited. Here, we recorded multi-unit signals from the striatum of PD (N = 934) and dystonic (N = 718) patients undergoing deep brain stimulation surgeries. Using an innovative automated data-driven approach to classify striatal units, we showed that the SPN discharge rate is inversely proportional to the isolation quality and stationarity of the SPNs. In contrast to earlier studies in both PD patients and the non-human primate model of PD, we found no drastic changes in the spiking activity (discharge rate and pattern) of the well-isolated and stationary SPNs of PD patients compared to either dystonic patients or the normal levels of striatal activity reported in healthy animals. Moreover, cluster analysis using SPN discharge properties did not characterize two well-separated SPN subpopulations. There was therefore no specific SPN subpopulation (D1 or D2 SPNs) strongly affected by the pathological state. Instead, our results suggest that moderate changes in SPN discharge are most likely amplified by basal ganglia downstream structures, thus leading to the clinical (motor and non-motor) symptoms of PD.Significance statementIn Parkinson’s disease (PD), the loss of the midbrain dopaminergic neurons leads to massive striatal dopamine depletion that provokes abnormal activity throughout the basal ganglia. However, the impact of dopamine depletion on neuronal activity in the striatum is still highly debated. We recorded and examined the neuronal activity in striatum of PD and dystonic patients undergoing deep brain stimulation surgeries. We found that striatal activity was not drastically higher in PD patients compared to either dystonic patients or the normal levels of striatal activity reported in animal studies. In PD, moderate changes in striatal basal activity are therefore most likely amplified by basal ganglia downstream structures.
Post-perturbational transcriptional signatures of cancer cell line vulnerabilities
Authors: Jones Andrew , Tsherniak Aviad , McFarland James M. 
Published: March 2020

AbstractWhile chemical and genetic viability screens in cancer cell lines have identified many promising cancer vulnerabilities, simple univariate readouts of cell proliferation fail to capture the complex cellular responses to perturbations. Complementarily, gene expression profiling offers an information-rich measure of cell state that can provide a more detailed account of cellular responses to perturbations. Relatively little is known, however, about the relationship between transcriptional responses to per-turbations and the long-term cell viability effects of those perturbations. To address this question, we integrated thousands of post-perturbational transcriptional profiles from the Connectivity Map with large-scale screens of cancer cell lines’ viability response to genetic and chemical perturbations. This analysis revealed a generalized transcriptional signature associated with reduced viability across perturbations, which was consistent across post-perturbation time-points, perturbation types, and viability datasets. At a more granular level, we lay out the landscape of treatment-specific expression-viability relationships across a broad panel of drugs and genetic reagents, and we demonstrate that these post-perturbational expression signatures can be used to infer long-term viability. Together, these results help unmask the transcriptional changes that are associated with perturbation-induced viability loss in cancer cell lines.