bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 experience: first Italian survey on healthcare staff members from a Mother-Child Research Hospital using combined molecular and rapid immunoassays test
Authors: Comar Manola , Brumat Marco , Concas Maria Pina , Argentini Giorgia , Bianco Annamonica , Bicego Livia , Bottega Roberta , Carli Petra , Cassone Andrea , Catamo Eulalia , Cocca Massimiliano , Del Pin Massimo , Di Stazio Mariateresa , Feresin Agnese , Bianca Martina La , Morassut Sara , Morgan Anna , Pelliccione Giulia , Petix Vincenzo , Ragusa Giulia , Robino Antonietta , Russian Stefano , Spedicati Beatrice , Suergiu Sarah , Urriza Marianela , Vascotto Fulvia , Toscani Paola , Girotto Giorgia , Gasparini Paolo 
Published: April 2020

AbstractThe fast spread of the novel coronavirus (SARS-CoV-2) has become a global threat hitting the worldwide fragile health care system. In Italy, there is a continued COVID-19 growth of cases and deaths that requires control measures for the correct management of the epidemiological emergency. To contribute to increasing the overall knowledge of COVID-19, systematic tests in the general population are required.Here, we describe the first Italian survey performed in 727 employees belonging to a Mother-Child Research hospital tested for both viral (nasopharyngeal and oropharyngeal swabs) and antibody presence. Individuals were divided into three risk categories (high, medium and low) according to their job activity. Only one subject was positive at the swab test while 17.2% of the cohort was positive for the presence of antibodies. Results highlighted that the presence of Positive antibodies is significantly associated with high and medium risk exposure occupation (p-value=0.026) as well as cold and conjunctivitis symptoms (p-value=0.016 and 0.042 respectively). Moreover, among healthcare professionals, the category of medical doctors showed a significant association with the presence of antibodies against SARS-CoV-2 (p-value=0.0127). Finally, we detected a rapid decrease in antibody intensity between two assessments performed within a very short period (p-value=0.009). Overall, the present study increases our knowledge of the epidemiological data of COVID-19 infection in Italy, suggesting a high prevalence of immune individuals (i.e. at least among at-risk categories) and the efficacy of the combined diagnostic protocol to monitor the possible outbreak.
COVID-19 Outbreak in Post-Soviet States: Modeling the Best and Worst Possible Scenarios
Authors: Issanov Alpamys , Amanbek Yerlan , Abbay Anara , Adambekov Shalkar , Aljofan Mohamad , Kashkynbayev Ardak , Gaipov Abduzhappar 
Published: April 2020

ABSTRACTBackgroundCOVID-19 pandemic has presented extreme challenges to developing countries across the world. Post-Soviet states are facing unique challenges due to their developing healthcare systems and unstable economy. The aim of this paper was to provide estimates for current development COVID-19 pandemic in the Post-Soviet states and forecast potential best and worst scenarios for spread of this deadly infection.MethodsThe data on confirmed cases and deaths were extracted from official governmental sources for a period from beginning of outbreak dates for each country until April 18, 2020. A modified SEIR (Susceptible-Exposed-Infected-Recovered) modelling was used to plot the parameters of epidemic in 10 post-Soviet states and forecast the number of cases over a period of 10, 30 and 60 days. We also estimated the numbers of cases based on the optimal measures (best scenario) and suboptimal measures (worst scenarios) of potential spread of COVID-19 in these countries.ResultsIt was estimated that Armenia and Azerbaijan have reached their peaks, Kazakhstan, Kyrgyzstan, Moldova and Uzbekistan are expected to reach their peaks in the coming week (April 29 – May 7, 2020), with comparatively low cases of COVID-19 and loss of lives in the best-case scenario. In contrast, Belarus, Russia, and Ukraine would likely see the outbreaks with the largest number of COVID-19 cases amongst the studied Post-Soviet States in the worst scenario during the next 30 and 60 days. Geographical remoteness and small number of international travelers from the countries heavily affected by the pandemic could also have contributed to delay in the spread of COVID-19.ConclusionGovernmental response was shown to be as an important determining factor responsible for the development of COVID-19 epidemic in Post-Soviet states. The current protection rates should be maintained to reduce active cases during upcoming 30 and 60 days. The estimated possible scenarios based on the proposed model can potentially be used by healthcare professionals from each studied Post-Soviet States as well as others to improve plans to contain the current and future epidemic.
Influence of blood pressure on pneumonia risk: Epidemiological association and Mendelian randomisation in the UK Biobank
Authors: Zekavat Seyedeh M. , Honigberg Michael , Pirruccello James , Kohli Puja , Karlson Elizabeth W. , Newton-Cheh Christopher , Zhao Hongyu , Natarajan Pradeep 
Published: April 2020

AbstractObjectivesTo determine whether elevated blood pressure influences risk for respiratory infection.DesignProspective, population-based epidemiological and Mendelian randomisation studies.SettingUK Biobank.Participants377,143 self-identified British descent (54% women; median age 58 years) participants in the UK Biobank.Main outcome measuresFirst incident pneumonia over an average of 8 follow-up years.Results107,310 (30%) participants had hypertension at UK Biobank enrolment, and 9,969 (3%) developed a pneumonia during follow-up. Prevalent hypertension at baseline was significantly associated with increased risk for incident respiratory disease including pneumonia (hazard ratio 1.36 (95% confidence interval 1.29 to 1.43), P<0.001), acute respiratory distress syndrome or respiratory failure (1.43 (1.29 to 1.59), P<0.001), and chronic lower respiratory disease (1.30 (1.25 to 1.36), P<0.001), independent of age, age2, sex, smoking status, BMI, prevalent diabetes mellitus, prevalent coronary artery disease, and principal components of ancestry. Mendelian randomisation analyses indicated that genetic predisposition to a 5 mmHg increase in blood pressure was associated with increased risk of incident pneumonia for SBP (1.08, (1.04 to 1.13), P<0.001) and DBP (1.11 (1.03 to 1.20), P=0.005). Additionally, consistent with epidemiologic associations, increase in blood pressure genetic risk was significantly associated with reduced forced expiratory volume in the first second, forced vital capacity, and the ratio of the two (P<0.001 for all).ConclusionsThese results strongly suggest that elevated blood pressure independently increases risk for pneumonia and reduces pulmonary function. Maintaining adequate blood pressure control, in addition to other measures, may reduce risk for pneumonia. Whether the present findings are generalizable to novel coronavirus disease 2019 (COVID-19) require further study.Summary BoxSection 1: What is already known on this topicHypertension has been associated with pneumonia in small observational studies.Based on early epidemiologic analyses, hypertension is described as a risk factor for SARS-CoV-2 infection and associated novel coronavirus disease 2019 (COVID-19).The influence of hypertension on pneumonia risk is difficult to assess in traditional observational studies.Section 2: What this study addsOur pre-COVID-19 analyses are consistent with a causal relationship between increased blood pressure and increased risk for incident respiratory infections, as well as between increased blood pressure and reduced pulmonary function.These results support hypertension as a pneumonia risk factor; efforts to optimize blood pressure may reduce risk for pneumonia.
A semi-analytic elastic rod model of pediatric spinal deformity
Authors: Neelakantan Sunder , Purohit Prashant K. , Pasha Saba 
Published: April 2020

AbstractThe mechanism of the scoliotic curve development in healthy adolescents remains unknown in the field of orthopedic surgery. Variations in the sagittal curvature of the spine are believed to be a leading cause of scoliosis in this patient population. Here, we formulate the mechanics of S-shaped slender elastic rods as a model for pediatric spine under physiological loading. Secondarily, applying inverse mechanics to clinical data of the scoliotic spines, with characteristic 3D deformity, we determine the undeformed geometry of the spine before the induction of scoliosis. Our result successfully reproduces the clinical data of the deformed spine under varying loads confirming that the pre-scoliotic sagittal curvature of the spine impacts the 3D loading that leads to scoliosis.
Monitoring ligand-induced changes in receptor conformation with NanoBiT conjugated nanobodies
Authors: Soave Mark , Heukers Raimond , Kellam Barrie , Woolard Jeanette , Smit Martine J. , Briddon Stephen J. , Hill Stephen J. 
Published: April 2020

SummaryCamelid single-domain antibody fragments (nanobodies) offer the specificity of an antibody in a single 15kDa immunoglobulin domain. Their small size allows for easy genetic manipulation of the nanobody sequence to incorporate protein tags, facilitating their use as biochemical probes. The nanobody VUN400, which recognises the second extracellular loop of the human CXCR4 chemokine receptor, was used as a probe to monitor specific CXCR4 conformations. VUN400 was fused via its C-terminus to the 11-amino acid HiBiT tag (VUN400-HiBiT) which complements to LgBiT protein, forming a full length functional NanoLuc luciferase. Here, complemented luminescence was used to detect VUN400-HiBiT binding to CXCR4 receptors expressed in living HEK293 cells. VUN400-HiBiT binding to CXCR4 could be prevented by orthosteric and allosteric ligands, allowing VUN400-HiBiT to be used as a probe to detect specific conformations of CXCR4. These data demonstrate that the high specificity offered by extracellular-targeted nanobodies can be utilised to probe receptor pharmacology.
Population genetics of sugar kelp in the Northwest Atlantic region using genome-wide markers
Authors: Mao Xiaowei , Augyte Simona , Huang Mao , Hare Matthew P. , Bailey David , Umanzor Schery , Marty-Rivera Michael , Robbins Kelly R , Yarish Charles , Lindell Scott , Jannink Jean-Luc 
Published: April 2020

ABSTRACTAn assessment of genetic diversity of marine populations is critical not only for the understanding and preservation of natural biodiversity but also for its economic potential. As commercial demand rises for marine resources, it is critical to generate baseline information for monitoring wild populations. Furthermore, anthropogenic stressors on the coastal environment, such as warming sea surface temperatures and overharvesting of wild populations, are leading to the destruction of keystone marine species such as kelps. In this study, we conducted a fine-scale genetic analysis using genome-wide high-density markers on Northwest Atlantic sugar kelp species,Saccharina latissimaand putative species,Saccharina angustissima. The population structure for a total of 149 samples from the Gulf of Maine (GOM) and Southern New England (SNE) was investigated using AMOVA, Fst, admixture, and PCoA. Genome-wide association analyses were conducted for six morphological traits, and the extended Lewontin and Krakauer (FLK) test was used to detect selection signatures. Our results indicate that the GOM region is moderately more heterogeneous than SNE. While admixture was observed between regions, these results confirm that Cape Cod acts as a biogeographic barrier for sugar kelp gene flow. We detected one significant SNP (P-value=2.03×10−7) associated with stipe length, and 243 SNPs with higher-than-neutral differentiation. The findings of this study provide fundamental knowledge on sugar kelp population genetics for future monitoring, managing and potentially restoring wild populations, as well as assisting in selective breeding to improve desirable traits for cultivation and bioenergy production.
Bayesian neural networks for the optimisation of biological clocks in humans
Authors: Alfonso G , Gonzalez Juan R 
Published: April 2020

AbstractDNA methylation is related to aging. Some researchers, such as Horvath or Levine have managed to create epigenetic and biological clocks that predict chronological age using methylation data. These authors used Elastic Net methodology to build age predictors that had a high prediction accuracy. In this article, we propose to improve their performance by incorporating an additional step using neural networks trained with Bayesian learning. We shown that this approach outperforms the results obtained when using Horvath’s method, neural networks directly, or when using other training algorithms, such as Levenberg-Marquardt’s algorithm. The R-squared value obtained when using our proposed approach in empirical (out-of sample) data was 0.934, compared to 0.914 when using a different training algorithm (Levenberg Marquard), or 0.910 when applying the neural network directly (e.g. without first reducing the dimensionality of the data). The results were also tested in independent datasets that were not used during the training phase. Our method obtained better R-squared values and RMSE than Horvath’s and Levine’s method in 8 independent datasets. We demonstrate that building an age predictor using a Bayesian based algorithm provides accurate age predictions. This method is implemented in an R function, which is available through a package created for predicting purposes and is applicable to methylation data. This will help to elucidate the role of DNA methylation age in complex diseases or traits related to aging.
Redesigned Reporter Gene for Improved Proton Exchange-based Molecular MRI Contrast
Authors: Perlman Or , Ito Hirotaka , Gilad Assaf A. , McMahon Michael T. , Chiocca E. Antonio , Nakashima Hiroshi , Farrar Christian T. 
Published: April 2020

AbstractReporter gene imaging allows for non-invasive monitoring of molecular processes in living cells, providing insights on the mechanisms underlying pathology and therapy. A lysine-rich protein (LRP) chemical exchange saturation transfer (CEST) MRI reporter gene has previously been developed and used to image tumor cells, cardiac viral gene transfer, and oncolytic virotherapy. However, the highly repetitive nature of the LRP reporter gene sequence leads to DNA recombination events and the expression of a range of truncated LRP protein fragments, thereby greatly limiting the CEST sensitivity. Here we report the use of a redesigned LRP reporter (rdLRP), aimed to provide excellent stability and CEST sensitivity. The rdLRP contains no DNA repeats or GC rich regions and 30% less positively charged amino-acids. RT-PCR of cell lysates transfected with rdLRP demonstrated a stable reporter gene with a single distinct band corresponding to full-length DNA. A distinct increase in CEST-MRI contrast was obtained in cell lysates of rdLRP transfected cells and inin vivoLRP expressing mouse brain tumors (p=0.0275, n=10).
Serpins: Purification and characterization of potent protease inhibitors fromClostridium thermocellum
Authors: Mushtaq Maria , Asad Muhammad Javaid , Hyder Muhammad Zeeshan , Naqvi Syed Muhammad Saqlan , Malik Saad Imran , Mehmood Raja Tahir 
Published: April 2020

AbstractClostridium thermocellumproduces an extracellular cellulosome (a multiprotein complex produced by firmicutes bacteria), which, owing to its extracellular location, is open to protease attack. Serine protease inhibitors (serpins) protect bacteria against protease attack. However, their structure and function are poorly characterized. This study identified and amplified the serpin 1270 gene from the C. thermocellum genome. Purified serpins were cloned into the pTXB1 vector using the one-step sequence and ligation-independent cloning reaction and transformed into Escherichia coli BL21 DE3 cells. Enzyme overexpression and purification and enzyme inhibitory assays were performed. The results showed that serpin 1270 has 89% inhibition against Bacillus subtilisin and 64% inhibition against trypsin, chymotrypsin, and papain.
Excitatory and inhibitory L2/3 neurons in mouse primary visual cortex are balanced in their input connectivity
Authors: Brown Alexander P.Y. , Cossell Lee , Margrie Troy W. 
Published: April 2020

AbstractQuantitatively characterising brain-wide connectivity of neural circuits is of vital importance in understanding the function of the mammalian cortex. Here we have designed an analytical approach to examine data from hierarchical segmentation ontologies, and applied it in the comparison of long-range presynaptic connectivity onto excitatory and inhibitory neurons in layer 2/3 (L2/3) of mouse primary visual cortex (V1). We find that long-range connections onto these two general cell classes in L2/3 originate from highly similar brain regions, and in similar proportions, when compared to input to layer 6. These anatomical data suggest that distal information received by excitatory and inhibitory networks is highly homogenous in L2/3.
The Impact of Hand Movement Velocity on Cognitive Conflict Processing in a 3D Object Selection Task in Virtual Reality
Authors: Singh Avinash K , Gramann Klaus , Chen Hsiang-Ting , Lin Chin-Teng 
Published: April 2020

AbstractDetecting and correcting incorrect body movements is an essential part of everyday interaction with one’s environment. The human brain provides a monitoring system that constantly controls and adjusts our actions according to our surroundings. However, when our brain’s predictions about a planned action do not match the sensory inputs resulting from that action, cognitive conflict occurs. Much is known about cognitive conflict in 1D/2D environments; however, less is known about the role of movement characteristics associated with cognitive conflict in 3D environment. Hence, we devised an object selection task in a virtual reality (VR) environment to test how the velocity of hand movements impacts human brain responses. From a series of analyses of EEG recordings synchronized with motion capture, we found that the velocity of the participants’ hand movements modulated the brain’s response to proprioceptive feedback during the task and induced a prediction error negativity (PEN). Additionally, the PEN originates in the anterior cingulate cortex and is itself modulated by the ballistic phase of the hand’s movement. These findings suggest that velocity is an essential component of integrating hand movements with visual and proprioceptive information during interactions with real and virtual objects.
Highly accurate random DNA sequencing using inherent interlayer potential traps of bilayer MoS2nanopores
Authors: Sen Payel , Hoi Hiofan , Nandi Dipanjan , Gupta Manisha 
Published: April 2020

AbstractSolid-state MoS2nanopores are emerging as potential real-time DNA sequencers due to their ultra-thinness and pore stability. One of the major challenges in determining random nucleotide sequence (unlike polynucleotide strands) is the non-homogeneity of the charge interaction and velocity during DNA translocation. This results in varying blockade current for the same nucleotide, reducing the sequencing confidence. In this work, we studied the inherent impedance-tunability (due to vertical interlayer potential gradient and ion accumulation) of multilayered MoS2nanopores along with its effect on improving analyte capture and charge interaction, for more sensitive and confident sensing. Experimentally we demonstrate that 2-3 nm diameter bilayer MoS2pores are best suited for high accuracy (~90%) sequencing of mixed nucleotides with signal-to-noise-ratio greater than 11 in picomolar concentration solutions. High temporal resolution demonstrated by bilayer MoS2nanopores can help detect neutral proteins in future. The high accuracy detection in low concentration analyte can hence be applied for control and prevention of hereditary diseases and understanding health effects of rare microbial strains.
TGF-beta/Activin ligand Myoglianin couples muscle growth to the initiation of metamorphosis
Authors: He Lorrie L. , Shin Sara Hyun Joo , Wang Zhou , Yuan Isabelle , Weschler Ruthie , Chiou Allie , Koyama Takashi , Nijhout H. Frederik , Suzuki Yuichiro 
Published: April 2020

ABSTRACTAlthough the mechanisms that control growth are now well understood, the mechanism by which animals assess their body size remains one of the great puzzles in biology. The final larval instar of holometabolous insects, after which growth stops and metamorphosis begins, is specified by a threshold size. We investigated the mechanism of threshold size assessment in the tobacco hornworm,Manduca sexta. The threshold size was found to change depending on the amount of exposure to poor nutrient conditions whereas hypoxia treatment consistently led to a lower threshold size. Under these various conditions, the mass of the muscles plus integuments was correlated with the threshold size. Furthermore, the expression ofmyoglianin(myo) increased at the threshold size in bothM. sextaandTribolium castaneum. Knockdown ofmyoinT. castaneumled to larvae that underwent supernumerary larval molts and stayed in the larval stage permanently even after passing the threshold size. We propose that increasing levels of Myo produced by the growing tissues allow larvae to assess their body size and trigger metamorphosis at the threshold size.
A midbrain dynorphin circuit promotes threat generalization
Authors: Fellinger Lizz , Jo Yong S. , Hunker Avery C. , Soden Marta E. , Zweifel Larry S. 
Published: April 2020

SummaryDiscrimination between predictive and non-predictive threat stimuli decrease as threat intensity increases. The central mechanisms that mediate the transition from discriminatory to generalized threat responding remain poorly resolved. Here, we identify the stress- and dysphoria-associated kappa opioid receptor (KOR) and its ligand dynorphin (Dyn), acting in the ventral tegmental area (VTA), as a key substrate for regulating threat generalization. We identified several dynorphinergic inputs to the VTA and demonstrate that projections from the bed nucleus of the stria terminalis (BNST) and dorsal raphe nucleus (DRN) both contribute to anxiety-like behavior but differentially affect threat generalization. These data demonstrate that conditioned threat discrimination has an inverted ‘U’ relationship with threat intensity and establish a role for KOR/Dyn signaling in the midbrain for promoting threat generalization.
A meta-learning approach for genomic survival analysis
Authors: Qiu Yeping Lina , Zheng Hong , Devos Arnout , Gevaert Olivier 
Published: April 2020

AbstractRNA sequencing has emerged as a promising approach in cancer prognosis as sequencing data becomes more easily and affordably accessible. However, it remains challenging to build good predictive models especially when the sample size is limited and the number of features is high, which is a common situation in biomedical settings. To address these limitations, we propose a meta-learning framework based on neural networks for survival analysis and evaluate it in a genomic cancer research setting. We demonstrate that, compared to regular transfer-learning, meta-learning is a significantly more effective paradigm to leverage high-dimensional data that is relevant but not directly related to the problem of interest. Specifically, meta-learning explicitly constructs a model, from abundant data of relevant tasks, to learn a new task with few samples effectively. For the application of predicting cancer survival outcome, we also show that the meta-learning framework with a few samples is able to achieve competitive performance with learning from scratch with a significantly larger number of samples. Finally, we demonstrate that the meta-learning model implicitly prioritizes genes based on their contribution to survival prediction and allows us to identify important pathways in cancer.