bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhaled Prostacyclin Improves Oxygenation in Patients with COVID-19-induced Acute Respiratory Distress Syndrome
Authors: Haeberle Helene A. , Calov Stefanie , Martus Peter , Higuita Lina Maria Serna , Koeppen Michael , Goll Almuth , Zarbock Alexander , Meersch Melanie , Weiss Raphael , Mehrländer Martin , Marx Gernot , Putensen Christian , Nieswandt Bernhard , Mirakaj Valbona , Rosenberger Peter 
Published: November 2021

SummaryBackgroundAcute Respiratory Distress Syndrome (ARDS) results in significant hypoxia, and ARDS is the central pathology of COVID-19. Inhaled prostacyclin has been proposed as a therapy for ARDS, but data regarding its role in this syndrome are unavailable. Therefore, we investigated whether inhaled prostacyclin would affect the oxygenation and survival of patients suffering from ARDS.MethodsWe performed a prospective randomized controlled single-blind multicenter trial across Germany. The trial was conducted from March 2019 with final follow-up on 12th of August 2021. Patients with moderate to severe ARDS were included and randomized to receive either inhaled prostacyclin (3 times/day for 5 days) or sodium chloride. The primary outcome was the oxygenation index in the intervention and control groups on Day 5 of therapy. Secondary outcomes were mortality, secondary organ failure, disease severity and adverse events.FindingsOf 707 patients approached 150 patients were randomized to receive inhaled prostacyclin (n=73) or sodium chloride (n=77). Data from 144 patients were analyzed. The baseline oxygenation index did not differ between groups. The primary analysis of the study was negative, and prostacyclin improved oxygenation by 20 mmHg more than NaCl (p=0·17). Oxygenation was significantly improved in patients with ARDS who were COVID-19-positive (34 mmHg, p=0·04). Mortality did not differ between groups. Secondary organ failure and adverse events were similar in the intervention and control groups.InterpretationAlthough the primary result of our study was negative, our data suggest that inhaled prostacyclin might be a more beneficial treatment than standard care for patients with ARDS.
Dengue Fever Distribution, Climate and Visitors: A Study from Badung District of Bali, Indonesia
Authors: Maulana Mochamad Rizal , Yudhastuti Ririh , Lusno Muhammad Farid Dimjati , Mirasa Yudied Agung , Haksama Setya , Husnina Zida 
Published: November 2021

ABSTRACTAs a national and international tourism destination, Badung district has recorded the highest dengue fever (DF) in Bali Province with multiple suspected influencing factors. This research presents the distribution of dengue fever (DF) incidence in Badung district and analyses its association with climate and visitors. The monthly data of DF surveillance, climate and reported number of visitors during January 2013 – December 2017 was analysed using Poisson Regression. 10689 new DF cases were notified from January 2013 to December 2017 while 2016 was recorded as the heaviest DF incidence. Monthly DF cases have positive association with average temperature, precipitation, humidity and local visitors. While negative association was shown between DF cases with foreign visitors. This study underlines the urgency to integrate climate and tourism for dengue fever control. Further study is recommended to take both factors together with population mobility at finer spatial and time unit of analysis.
Seasonal variation in blood pressure recorded in routine primary care
Authors: Shahsanai Armindokht , Kalia Sumeet , Aliarzadeh Babak , Moineddin Rahim , Bhatt Aashka , Greiver Michelle 
Published: November 2021

AbstractObjectiveSeasonal variations in blood pressure (BP) exist. There is limited information about important clinical factors associated with increased BP and the strength and amplitude of seasonal variation in primary care.MethodsThis was a repeated cross-sectional observational study of routinely measured BPs in primary care using data from electronic medical records in the greater Toronto region, from January 2009 to June 2019. We used time-series models and mean monthly systolic BPs (SBPs) and diastolic BPs (DBPs) to estimate the strength and amplitude of seasonal oscillations, as well as their associations with patient characteristics.Results314,518 patients were included. Mean SBPs and DBPs were higher in winter than summer. There was strong or perfect seasonality for all characteristics studied, except for BMI less than 18.5 (underweight). Overall, the mean maximal amplitude of the oscillation was 1.51mmHg for SPB (95% CI 1.30mmHg to 1.72mmHg) and 0.59mmHg for DBP (95% CI 0.44mmHg to 0.74mmHg). Patients aged 81 years or older had larger SBP oscillations than younger patients aged 18 to 30 years; the difference was 1.20mmHg (95% CI 1.15mmHg to 1.66mmHg). Hypertension was also associated with greater oscillations, difference 0.53mmHg (95% CI 0.18mmHg to 0.88mmHg). There were no significant differences in SBP oscillations by other patient characteristics, and none for DBP.ConclusionStrong seasonality was detected for almost all patient subgroups studied and was greatest for older patients and for those with hypertension. The variation in BP between summer and winter should be considered by clinicians when making BP treatment decisions.
The hospital burden of intergenerational contact with the welfare system:A whole-of-population liked data study
Authors: Procter Alexandra M , Chittleborough Catherine R , Pilkington Rhiannon M , Pearson Odette , Montgomerie Alicia , Lynch John W 
Published: November 2021

ABSTRACTBackgroundIntergenerational welfare contact (IWC) is a policy issue because of the personal and social costs of intergenerational disadvantage. We estimated the hospital burden of IWC for children aged 11-20 years.MethodsThis linked data study of children born in South Australia, 1991-1995 (n=94,358), and their parent/s (n=143,814) used de-identified data from the Better Evidence Better Outcomes Linked Data platform. Using Australian Government Centrelink data, welfare contact (WC) was defined as parent/s receiving a means-tested welfare payment (low-income, unemployment, disability or caring) when children were aged 11-15, or children receiving payment at ages 16-20. IWC was WC occurring in both parent and child generations. Children were classified as: No WC, parent only WC, child only WC, or IWC. Hospitalisation rates and cumulative incidence were estimated by age and WC group.FindingsIWC affected 34.9% of children, who had the highest hospitalisation rate (133.5 per 1,000 person-years) compared to no WC (46.1 per 1,000 person-years), parent only WC (75.0 per 1,000 person-years), and child only WC (87.6 per 1,000 person-years). Of all IWC children, 43.0% experienced at least one hospitalisation between 11-20, frequently related to injury, mental health, and pregnancy.InterpretationChildren experiencing IWC represent a third of the population aged 11-20. Compared to children with parent-only WC, IWC children had 78% higher hospitalisation rates from age 11 to 20, accounting for over half of all hospitalisations in this age group. Frequent IWC hospitalisation causes were injuries, mental health, and pregnancy.FundingMedical Research Future Fund, National Health and Medical Research Council, Westpac Scholars Trust.
Cortex-independent open-loop control of a voluntary orofacial motor action
Authors: Elbaz Michaël , Demers Maxime , Kleinfeld David , Ethier Christian , Deschênes Martin 
Published: November 2021

AbstractWhether using our eyes or our hands, we interact with our environment through mobile sensors. The efficient use of these sensory organs implies the ability to track their position; otherwise, perceptual stability and prehension would be profoundly impeded1,2. The nervous system may be informed about the position of a sensory organ via two complementary feedback mechanisms: peripheral reafference (external, sensory feedback) and efference copy (internal feedback)3-6. Yet, the potential contributions of these mechanisms remain largely unexplored. By training rats to place their vibrissae within a predetermined angular range without contact, a task that depends on knowledge of vibrissa position relative to their face, we found that peripheral reafference is not required. The presence of motor cortex is not required either, even in the absence of peripheral reafference. On the other hand, the red nucleus, which receives descending inputs from motor cortex and the cerebellum and projects to facial motoneurons7-10, is critical for the execution of the vibrissa task. All told, our results demonstrate the existence of an open-loop control by an internal model that is sufficient to drive voluntary motion. The internal model is independent of motor cortex and likely contains the cerebellum and associated nuclei.
An atypical NLR protein modulates the NRC immune receptor network
Authors: Adachi Hiroaki , Sakai Toshiyuki , Harant Adeline , Duggan Cian , Bozkurt Tolga O , Wu Chih-hang , Kamoun Sophien 
Published: November 2021

ABSTRACTThe NRC immune receptor network has evolved in asterid plants from a pair of linked genes into a genetically dispersed and phylogenetically structured network of sensor and helper NLR (nucleotide-binding domain and leucine-rich repeat-containing) proteins. In some species, such as the model plant Nicotiana benthamiana and other Solanaceae, the NRC network forms up to half of the NLRome, and NRCs are scattered throughout the genome in gene clusters of varying complexities. Here, we describe NRCX, an atypical, but essential member of the NRC family that lacks canonical features of these NLR helper proteins, such as a functional N-terminal MADA motif and the capacity to trigger autoimmunity. In contrast to other NRCs, systemic gene silencing of NRCX markedly impairs plant growth resulting in a dwarf phenotype. Remarkably, dwarfism of NRCX silenced plants is partially dependent on NRCX paralogs NRC2 and NRC3, but not NRC4. Despite its negative impact on plant growth when silenced systemically, transient RNA interference of NRCX in mature N. benthamiana leaves doesn’t result in visible cell death phenotypes. However, alteration of NRCX expression modulates the hypersensitive response mediated by NRC2 and NRC3 in a manner consistent with a negative role for NRCX in the NRC network. We conclude that NRCX is an atypical member of the NRC network that has evolved to contribute to the homeostasis of this genetically unlinked NLR network.
The effect of sequencing and assembly on the inference of horizontal gene transfer on chromosomal and plasmid phylogenies
Authors: Huisman Jana S. , Vaughan Timothy G. , Egli Adrian , Tschudin-Sutter Sarah , Stadler Tanja , Bonhoeffer Sebastian 
Published: November 2021

AbstractThe spread of antibiotic resistance genes on plasmids is a threat to human and animal health. Phylogenies of bacteria and their plasmids contain clues regarding the frequency of plasmid transfer events, as well as the co-evolution of plasmids and their hosts. However, whole genome sequencing data from diverse ecological or clinical bacterial samples is rarely used to study plasmid phylogenies and resistance gene transfer. This is partially due to the difficulty to extract plasmids from short-read sequencing data. Here, we use both short- and long-read sequencing data of 24 clinical extended-spectrum β-lactamase producing Escherichia coli to estimate chromosomal and plasmid phylogenies. We compare the impact of different sequencing and assembly methodologies on these phylogenies and on the inference of horizontal gene transfer. We find chromosomal phylogenies can be estimated robustly with all methods, whereas plasmid phylogenies have more variable topology and branch lengths across the methods used. Specifically, hybrid methods that use long reads to resolve short-read assemblies (HybridSPAdes and Unicycler) perform better than those that started from long-reads during assembly graph generation (Canu). In contrast, the inference of plasmid and antibiotic resistance gene transfer using a parsimony-based criterion is mostly robust to the choice of sequencing and assembly method.
The assessment of similarity vectors of fingerprint and UMLS in adverse drug reaction prediction
Authors: Beshartifard Milad , Ghorbanali Zahra , Zare-Mirakabad Fatemeh 
Published: November 2021

AbstractIdentifying and controlling adverse drug reactions is a complex problem in the pharmacological field. Despite the studies done in different laboratory stages, some adverse drug reactions are recognized after being released, such as Rosiglitazone. Due to such experiences, pharmacists are now more interested in using computational methods to predict adverse drug reactions. In computational methods, finding and representing appropriate drug and adverse reaction features are one of the most critical challenges. Here, we assess fingerprint and target as drug features; and phenotype and unified medical language system as adverse reaction features to predict adverse drug reaction. Meanwhile, we show that drug and adverse reaction features represented by similarity vectors can improve adverse drug prediction. In this regard, we propose four frameworks. Two frameworks are based on random forest classification and neural networks as machine learning methods called F_RF and F_NN, respectively. The rest of them improve two state-of-art matrix factorization models, CS and TMF, by considering target as a drug feature and phenotype as an adverse reaction feature. However, machine learning frameworks with fewer drug and adverse reaction features are more accurate than matrix factorization frameworks. In addition, the F_RF framework performs significantly better than F_NN with ACC = %89.15, AUC = %96.14 and AUPRC = %92.9. Next, we contrast F_RF with some well-known models designed based on similarity vectors of drug and adverse reaction features. Unlike other methods, we do not remove rare reactions from the data set in our frameworks. The data and implementation of proposed frameworks are available at http://bioinformatics.aut.ac.ir/ADRP-ML-NMF/.
Neural decoding dissociates perceptual grouping between proximity and similarity in visual perception
Authors: Hua Lin , Gao Fei , Leong Chantat , Yuan Zhen 
Published: November 2021

AbstractPrevious research on perceptual grouping primarily focused on the dynamics of single grouping principle in light of the Gestalt psychology. Yet, there has been comparatively little emphasis on the dissociation across two or more grouping principles. To tackle this issue, the current study aims at investigating how, when, and where the processing of two grouping principles (proximity and similarity) are established in the human brain by using a dimotif lattice paradigm and adjusting the strength of one grouping principle. Specifically, we measured the modulated strength of the other grouping principle, thus forming six visual stimuli. The current psychophysical results showed that similarity grouping effect was enhanced with reduced proximity effect when the grouping cues of proximity and similarity were presented simultaneously. Meanwhile, electrophysiological (EEG) response patterns were able to decode the specific pattern out of the six visual stimuli involving both principles in each trail by using time-resolved multivariate pattern analysis (MVPA). The onsets of the dissociation between the two grouping principles coincided within three time windows: the earliest proximity-defined local visual element arrangement in the middle occipital cortex, the middle-stage processing for feature selection modulating low-level visual cortex in the inferior occipital cortex and fusiform cortex, and the higher-level cognitive integration to make decisions for specific grouping preference in the parietal areas. In addition, brain responses were highly correlated with behavioral grouping. The results therefore provide direct evidence for a link between human perceptual space of grouping decision-making and neural space of these brain response patterns.Significance statementHow does our brain aggregate meaningless local elements to meaningful global patterns? Here, we used visual stimuli that can be perceived as a whole orientation from one of the two grouping cues (proximity and similarity) when they were presented simultaneously. Behavioral responses showed a trade-off between proximity and similarity. Further, time-resolved MVPA and source estimation results showed three stages for the processing of two grouping cues, involving an early stage in the low-level visual cortex, then the middle stage in the lateral visual cortex, and finally the late stage in the parietal areas. This was among the first attempt employing multivariate analysis to decode the dissociative processing of both proximity and similarity principles within one single study.
Ly6Chi monocytes are metabolically reprogrammed in the blood during inflammatory stimulation allowing for macrophage lineage commitment
Authors: Purvis Gareth S.D. , McNeill Eileen , Wright Benjamin , Revale Santiago , Lockstone Helen , Channon Keith M. , Greaves David R. 
Published: November 2021

AbstractAcute inflammation is a rapid and dynamic process involving the recruitment and activation of multiple cell types in a co-ordinated and precise manner. Using cell tracking, linage tracing and single cell transcriptomics we investigated the origin and transcriptional reprogramming of monocytes and macrophages in acute inflammation.Monocyte trafficking and adoptive transfer experiments revealed that monocytes undergo rapid phenotypic change as they exit the blood and give rise to monocyte-derived macrophages that persist during the resolution of inflammation. Single cell transcriptomics revealed significant heterogeneity within the surface marker defined CD11b+Ly6G-Ly6Chi monocyte population within the blood and at the site of inflammation. Lineage trajectory analysis revealed that Ly6Chi monocytes in the blood are re-programmed into a defined differentiation pathway following inflammatory stimulus. We show that two major transcriptional reprogramming events occur during the initial 6 h of Ly6Chi monocyte mobilisation, one in the blood priming monocytes for migration and a second at the site of inflammation. Pathway analysis revealed an important role for oxidative phosphorylation (OxPhos) during both these reprogramming events in a subset of M2-like cells. Experimentally we also demonstrate that OxPhos is essential for murine and human monocyte chemotaxis. These new findings opening up the possibility that altering monocyte metabolic capacity towards OxPhos could facilitate enhanced macrophage M2-like polarisation to aid inflammation resolution and tissue repair.
Postnatal development of centrifugal inputs to the olfactory bulb
Authors: Kostka Johanna K. , Bitzenhofer Sebastian H. 
Published: November 2021

AbstractProcessing in primary sensory areas is influenced by centrifugal inputs from higher brain areas, providing information about behavioral state, attention, or context. Activity in the olfactory bulb, the first central processing stage of olfactory information, is dynamically modulated by direct projections from a variety of areas in adult mice. Despite the early onset of olfactory sensation compared to other senses, the development of centrifugal inputs to the olfactory bulb remains largely unknown. Using retrograde tracing across development, we show that centrifugal projections to the olfactory bulb are established during the postnatal period in an area-specific manner. While feedback projections from the piriform cortex are already present shortly after birth, they strongly increase in number during postnatal development with an anterior-posterior gradient. Contralateral projections from the anterior olfactory nucleus are present at birth but only appeared postnatally for the nucleus of the lateral olfactory tract. Numbers of olfactory bulb projecting neurons from the lateral entorhinal cortex, ventral hippocampus, and cortical amygdala show a sudden increase at the beginning of the second postnatal week and a delayed development compared to more anterior areas. These anatomical data suggest that limited top-down influence on odor processing in the olfactory bulb may be present at birth, but strongly increases during postnatal development and is only fully established later in life.
Protein Engineering with A Glycosylation Circuit Enables Improved Enzyme Characteristics
Authors: Bozkurt Eray Ulaş , Çağıl İrem Niran , Kehribar Ebru Şahin , Işılak Musa Efe , Şeker Urartu Özgür Şafak 
Published: November 2021

AbstractProtein glycosylation is one of the most crucial and common post-translational modifications. It plays a fate-determining role and can alter many properties of proteins, making it an interesting for many biotechnology applications. The discovery of bacterial glycosylation mechanisms, opened a new perspective and transfer of C.jejuni N-linked glycosylation into laboratory work-horse E. coli increased research pace in the field exponentially. It has been previously showed that utilizing N-Linked Glycosylation, certain recombinant proteins have been furnished with improved features, such as stability and solubility. In this study, we utilized N-linked Glycosylation to glycosylate alkaline phosphatase (ALP) enzyme in E. coli and investigate the effects of glycosylation on an enzyme. Considering the glycosylation mechanism is highly dependent on the acceptor protein, ALP constructs carrying glycosylation tag at different locations of the gene has been created and glycosylation rates have been calculated. The most glycosylated construct has been selected for comparison with the native enzyme. We investigated the performance of glycosylated ALP in terms of its thermostability, proteolytic stability, tolerance to suboptimal pH and under denaturing conditions. Studies showed that glycosylated ALP performed remarkably better at optimal and harsh conditions Therefore, N-linked Glycosylation mechanism can be employed for enzyme engineering purposes and is a useful tool for industrial applications that require enzymatic activity.