bluuebunny/crossref_metadata_2025_split huggingface dataset:
Semiquantitative Chest Computed Tomography Assessment Identifies Expiratory Central Airway Collapse in Symptomatic Military Personnel Deployed to Iraq and Afghanistan
Authors: Krefft Silpa D. , Oh Andrea , Zell-Baran Lauren M. , Wolff Jenna , Moore Camille M. , Macedonia Tony V. , Rose Cecile S. 
Published: June 2021

Purpose:
We noted incidental findings on chest computed tomography (CT) imaging of expiratory central airway collapse (ECAC) in dyspneic patients after military deployment to southwest Asia (mainly Iraq and Afghanistan). We developed a standardized chest CT protocol with dynamic expiration to enhance diagnostic reliability and investigated demographic, clinical, and deployment characteristics possibly associated with ECAC.

Materials and Methods:
We calculated ECAC in 62 consecutive post-9/11 deployers with dyspnea who underwent multi-detector chest CT acquisition. ECAC was defined as ≥70% reduction in the cross-sectional tracheal area at dynamic expiration. We compared demographics (age, smoking, body mass index), comorbid conditions (gastroesophageal reflux, obstructive sleep apnea [OSA]), and clinical findings (air trapping, forced expiratory volume in 1 second percent predicted) in deployers with and without ECAC. We examined associations between ECAC and forced expiratory volume in 1 second percent predicted, air trapping, OSA, deployment duration, and blast exposure.

Results:
Among 62 consecutive deployers with persistent dyspnea, 37% had ECAC. Three had severe (>85%) collapse. Those with ECAC were older (mean age 46 vs. 40 y, P=0.02), but no other demographic or clinical characteristics were statistically different among the groups. Although not statistically significant, ECAC odds were 1.5 times higher (95% confidence interval: 0.9, 2.5) for each additional year of southwest Asia deployment. Deployers with ECAC had 1.6 times greater odds (95% confidence interval: 0.5, 4.8) of OSA.

Conclusions:
Findings suggest that ECAC is common in symptomatic southwest Asia deployers. Chest high-resolution CT with dynamic expiration may provide an insight into the causes of dyspnea in this population, although risk factors for ECAC remain to be determined. A standardized semiquantitative approach to CT-based assessment of ECAC should improve reliable diagnosis in dyspneic patients.
Introduction to the theme issue: Measuring physiology in free-living animals
Authors: Hawkes L. A. , Fahlman A. , Sato K. 
Published: June 2021

By describingwhereanimals go, biologging technologies (i.e. animal attached logging of biological variables with small electronic devices) have been used to document the remarkable athletic feats of wild animals since the 1940s. The rapid development and miniaturization of physiologging (i.e. logging of physiological variables such as heart rate, blood oxygen content, lactate, breathing frequency and tidal volume on devices attached to animals) technologies in recent times (e.g. devices that weigh less than 2 g mass that can measure electrical biopotentials for days to weeks) has provided astonishing insights into the physiology of free-living animals to documenthowandwhywild animals undertake these extreme feats. Now, physiologging, which was traditionally hindered by technological limitations, device size, ethics and logistics, is poised to benefit enormously from the on-going developments in biomedical and sports wearables technologies. Such technologies are already improving animal welfare and yield in agriculture and aquaculture, but may also reveal future pathways for therapeutic interventions in human health by shedding light on the physiological mechanisms with which free-living animals undertake some of the most extreme and impressive performances on earth.This article is part of the theme issue ‘Measuring physiology in free-living animals (Part I)’.
Diving physiology of marine mammals and birds: the development of biologging techniques
Authors: Williams Cassondra L. , Ponganis Paul J. 
Published: June 2021

In the 1940s, Scholander and Irving revealed fundamental physiological responses to forced diving of marine mammals and birds, setting the stage for the study of diving physiology. Since then, diving physiology research has moved from the laboratory to the field. Modern biologging, with the development of microprocessor technology, recorder memory capacity and battery life, has advanced and expanded investigations of the diving physiology of marine mammals and birds. This review describes a brief history of the start of field diving physiology investigations, including the invention of the time depth recorder, and then tracks the use of biologging studies in four key diving physiology topics: heart rate, blood flow, body temperature and oxygen store management. Investigations of diving heart rates in cetaceans and O2store management in diving emperor penguins are highlighted to emphasize the value of diving physiology biologging research. The review concludes with current challenges, remaining diving physiology questions and what technologies are needed to advance the field.This article is part of the theme issue ‘Measuring physiology in free-living animals (Part I)’.
Convalescent Plasma in Critically ill Patients with Covid-19
Authors:   The REMAP-CAP Investigators, Estcourt Lise J. 
Published: June 2021

AbstractBACKGROUNDThe evidence for benefit of convalescent plasma for critically ill patients with Covid-19 is inconsistent. We hypothesized that convalescent plasma would improve outcomes for critically ill adult patients with Covid-19.METHODSIn an ongoing adaptive platform trial, critically ill patients with confirmed Covid-19, defined as receiving intensive care-level organ support, were randomized to open-label convalescent plasma or not (i.e., control group). The primary end point was organ support-free days (i.e., days alive and free of ICU-based organ support) up to day 21. The primary analysis was a Bayesian cumulative logistic model with predefined criteria for superiority or futility. An odds ratio greater than 1 represented improved survival, more organ support–free days, or both.RESULTSThe convalescent plasma intervention was stopped after pre-specified criteria for futility were met. At that time, 1084 participants had been randomized to convalescent plasma and 916 to no convalescent plasma (control). The median organ support-free days were 0 (interquartile range, -1 to 16) for the convalescent plasma group and 3 (interquartile range, -1 to 16) days for the control group. The median adjusted odds ratio (OR) was 0.97 (95% credible interval 0.83 to 1.15) and posterior probability of futility (OR < 1.2) was 99.4% for convalescent plasma compared to control. In-hospital mortality was 37.3% (401/1075) in convalescent plasma group, and 38.4% (347/904) in controls. The observed treatment effects were consistent across primary and secondary outcomes.CONCLUSIONSIn critically ill adults with confirmed Covid-19, treatment with convalescent plasma, did not improve clinical outcomes.Clinicaltrials.gov:NCT02735707
UK B.1.1.7 variant exhibits increased respiratory replication and shedding in nonhuman primates
Authors: Rosenke K. , Feldmann F. , Okumura A. , Hansen F. , Tang-Huau T. , Meade-White K. , Kaza B. , Smith B.J. , Hanley P. W. , Lovaglio J. , Jarvis M. A. , Shaia C. , Feldmann H. 
Published: June 2021

AbstractThe continuing emergence of SARS-CoV-2 variants calls for regular assessment to identify differences in viral replication, shedding and associated disease. In this study, African green monkeys were infected intranasally with either a contemporary D614G or the UK B.1.1.7 variant. Both variants caused mild respiratory disease with no significant differences in clinical presentation. Significantly higher levels of viral RNA and infectious virus were found in upper and lower respiratory tract samples and tissues from B.1.1.7 infected animals. Interestingly, D614G infected animals showed significantly higher levels of viral RNA and infectious virus in rectal swabs and gastrointestinal tract tissues. Our results indicate that B.1.1.7 infection in African green monkeys is associated with increased respiratory replication and shedding but no disease enhancement similar to human B.1.1.7 cases.One-Sentence SummaryUK B.1.1.7 infection of African green monkeys exhibits increased respiratory replication and shedding but no disease enhancement
Further Theoretical Considerations for Next-Generation Proteomics
Authors: Palmblad Magnus 
Published: June 2021

AbstractIn a recent Journal of Proteome Researchpaper, I described some general properties and constraints of a hypothetical next generation of proteomics technology based on single-molecule peptide sequencing. This work prompted many interesting questions, both from the reviewers of the initial manuscript and later from readers and colleagues. This follow-up paper addresses some of questions by clarifying the original results, considering alternative metrics, and a number of new simulations. Specifically, the discriminative power of individual amino acids is revisited, simulating additional proteolytic agents. These simulations show allowing missed cleavages generally increases the discriminative power of the amino acids in the proteolytic motif. Additional simulations show the effect of non-ideal conditions modelled on the number of proteins lacking proteotypic reads is very small, and that the average number of proteotypic reads per protein follow the same rule on the performance of the optimal choice of labeled amino acids as the number of distinguishable proteins in NeXtProt. The goal of this paper is to expand prior results and continue the scientific discussion on the possibilities of future proteomics technologies.
The underlying mechanisms of alignment in error backpropagation through arbitrary weights
Authors: Rahmansetayesh Alireza , Ghazizadeh Ali , Marvasti Farokh 
Published: June 2021

AbstractUnderstanding the mechanisms by which plasticity in millions of synapses in the brain is orchestrated to achieve behavioral and cognitive goals is a fundamental quest in neuroscience. In this regard, insights from learning methods in artificial neural networks (ANNs) and in particular supervised learning using backpropagation (BP) seem inspiring. However, the implementation of BP requires exact matching between forward and backward weights, which is unrealistic given the known connectivity pattern in the brain (known as “weight transport problem”). Notably, it has been shown that under certain conditions, errorBackPropagationThroughArbitraryWeights (BP-TAW) can lead to a partial alignment between forward and backward weights (weight alignment or WA). This learning algorithm, which is also known as feedback alignment (FA), can result in surprisingly good degrees of accuracy in simple classification tasks. However, the underlying mechanisms and mathematical basis of WA are not thoroughly understood. In this work, we show that the occurrence of WA is governed by statistical properties of the output and error signals of neurons, such as autocorrelation and cross-correlation, and can happen even in the absence of learning or reduction of the loss function. Moreover, we show that WA can be improved significantly by limiting the norm of input weights to neurons and that such a weight normalization (WN) method can improve the classification accuracy of BP-TAW. The findings presented can be used to further improve the performance of BP-TAW and open new ways for exploring possible learning mechanisms in biological neural networks without exact matching between forward and backward weights.
The activity and functions of soil microbial communities in the Finnish sub-Arctic vary across vegetation types
Authors: Viitamäki Sirja , Pessi Igor S. , Virkkala Anna-Maria , Niittynen Pekka , Kemppinen Julia , Eronen-Rasimus Eeva , Luoto Miska , Hultman Jenni 
Published: June 2021

AbstractIncreased microbial activity in high-latitude soils due to climate change might lead to higher greenhouse gas (GHG) emissions. However, mechanisms of microbial GHG production and consumption in tundra soils are not thoroughly understood. We analyzed 116 soil metatranscriptomes from 73 sites in the Finnish sub-Arctic to investigate how the diversity and functional potential of bacterial and archaeal communities vary across vegetation types and soil layers. Soils differed in physicochemical conditions, with meadow soils being characterized by higher pH and low soil organic matter (SOM) and carbon/nitrogen ratio whereas dwarf shrub-dominated ecosystems with high SOM and low pH. Actinobacteria, Acidobacteria, Alphaproteobacteria, and Planctomycetes predominated all communities but there were significant differences on genus level between vegetation types, as plant polymer degrading groups were more active in shrub-dominated soils compared to meadows. Given that climate change scenarios predict expansion in dwarf shrubs at high latitudes, our results indicate that the rate of carbon turnover in tundra soils may increase in the future. Additionally, transcripts of methanotrophs were detected in the mineral layer of all soils, potentially moderating methane fluxes from deeper layers. In all, this study provides new insights into possible shifts in tundra microbial diversity and activity with climate change.
Regulatory dissection of the severe COVID-19 risk locus introgressed by Neanderthals
Authors: Jagoda Evelyn , Marnetto Davide , Montinaro Francesco , Richard Daniel , Pagani Luca , Capellini Terence D. 
Published: June 2021

AbstractIndividuals infected with the SARS-CoV-2 virus present with a wide variety of phenotypes ranging from asymptomatic to severe and even lethal outcomes. Past research has revealed a genetic haplotype on chromosome 3 that entered the human population via introgression from Neanderthals as the strongest genetic risk factor for the severe COVID-19 phenotype. However, the specific variants along this introgressed haplotype that contribute to this risk and the biological mechanisms that are involved remain unclear. Here, we assess the variants present on the risk haplotype for their likelihood of driving the severe COVID-19 phenotype. We do this by first exploring their impact on the regulation of genes involved in COVID-19 infection using a variety of population genetics and functional genomics tools. We then perform an locus-specific massively parallel reporter assay to individually assess the regulatory potential of each allele on the haplotype in a multipotent immune-related cell line. We ultimately reduce the set of over 600 linked genetic variants to identify 4 introgressed alleles that are strong functional candidates for driving the association between this locus and severe COVID-19. These variants likely drive the locus’ impact on severity by putatively modulating the regulation of two critical chemokine receptor genes: CCR1 and CCR5. These alleles are ideal targets for future functional investigations into the interaction between host genomics and COVID-19 outcomes.
Brain network dynamics codify heterogeneity in seizure propagation
Authors: Rungratsameetaweemana Nuttida , Lainscsek Claudia , Cash Sydney S. , Garcia Javier O. , Sejnowski Terrence J. , Bansal Kanika 
Published: June 2021

AbstractDynamic functional brain connectivity facilitates adaptive cognition and behavior. Abnormal alterations within such connectivity could result in disrupted functions observed across various neurological conditions. As one of the most common neurological disorders, epilepsy is defined by the seemingly random occurrence of spontaneous seizures. A central but unresolved question concerns the mechanisms by which extraordinarily diverse dynamics of seizures emerge. Here, we apply a graph-theoretical approach to assess dynamic reconfigurations in the functional brain connectivity before, during, and after seizures that display heterogeneous propagation patterns despite sharing similar origins. We demonstrate unique reconfigurations in globally-defined network properties preceding seizure onset that predict propagation patterns of impending seizures, and in locally-defined network properties that differentiate post-onset dynamics. These results characterize quantitative network features underlying the heterogeneity of seizure dynamics and the accompanying clinical manifestations. Decoding these network properties could improve personalized preventative treatment strategies for epilepsy as well as other neurological disorders.
In silico study for decoding the correlated role of MCM7 gene in progression of breast cancer and Alzheimer’s disorder
Authors: Sriram Navneeth , Mukherjee Sunny , Sah Mahesh Kumar 
Published: June 2021

ABSTRACTBreast cancer and Alzheimer’s disease (AD) are two of the progressive and detrimental disorders affecting large population around the globe. While the chemotherapy of breast cancer is well established and enriched, the AD still lacks it due to unrecognized peripheral biomarkers for detection and targeted therapy. This study aimed to identify common molecular signature markers in breast cancer (grade 1, 2, and 3) and AD for the diagnosis and prognosis. We used two microarray datasets (GSE42568, GSE33000) respectively for both disorders that led to identification of two common differentially expressed genes (DEGs), namely MCM7 and CD209, as common players in both these two conditions. While the pattern of expression of CD209 gene running upregulated in both disorders, the MCM7 showed unusual contrary in its pattern of expression. The expression of MCM7 is downregulated in breast cancer but upregulated in AD. Gene set and protein overrepresentation analysis, protein-protein interaction (PPI), and protein subcellular localizations analyses of this underrated MCM7 gene was performed with further prediction and validation of its structure. The findings may pave the way in designing therapeutic approaches to ameliorate AD.
Increased apoptotic priming of glioblastoma enables therapeutic targeting by BH3-mimetics
Authors: Koessinger Anna L , Koessinger Dominik , Kinch Kevin , Martínez-Escardó Laura , Paul Nikki R , Elmasry Yassmin , Malviya Gaurav , Cloix Catherine , Campbell Kirsteen J , Bock Florian J , O’Prey Jim , Stevenson Katrina , Nixon Colin , Jackson Mark R , Ichim Gabriel , Stewart William , Blyth Karen , Ryan Kevin M , Chalmers Anthony J , Norman Jim C , Tait Stephen WG 
Published: June 2021

AbstractIDH wild-type glioblastoma (GBM) is the most prevalent malignant primary brain tumour in adults. GBM typically has a poor prognosis, mainly due to a lack of effective treatment options leading to tumour persistence or recurrence. Tackling this, we investigated the therapeutic potential of targeting anti-apoptotic BCL-2 proteins in GBM. Levels of anti- apoptotic BCL-xL and MCL-1 were consistently increased in GBM compared with non- malignant cells and tissue. Moreover, we found that relative to their differentiated counterparts, patient-derived GBM stem-like cells also displayed higher expression of anti- apoptotic BCL-2 family members. Surprisingly, high anti-apoptotic BCL-xL and MCL-1 expression correlated with heightened susceptibility of GBM to BCL-2 family protein- targeting BH3-mimetics. This is indicative of increased apoptotic priming. Indeed, GBM displayed an obligate requirement for MCL-1 expression in both tumour development and maintenance. Investigating this apoptotic sensitivity, we found that sequential inhibition of BCL-xL and MCL-1 led to robust anti-tumour responses in vivo, in the absence of overt toxicity. These data demonstrate that BCL-xL and MCL-1 pro-survival function is a fundamental prerequisite for GBM survival that can be therapeutically exploited by BH3- mimetics.
Reservoir water in Singapore contains ESBL-producing and carbapenem-resistant bacteria with conjugatable conserved gene cluster transfer between different species
Authors: Zhong Yang , Guo Siyao , Schlundt Joergen 
Published: June 2021

AbstractAs the role of the aquatic environment in the “One Health” approach has called increasing attention, the studies of Antimicrobial resistance (AMR) spreading in the water bodies have been reported worldwide. However, there are still limited studies on the AMR carrier in the reservoir water in Singapore. Since 2018, our group has collect water samples from six reservoirs in Singapore and isolated the beta-lactam resistant bacteria from them. We then characterized the isolates with Whole-genome sequencing (WGS) and successfully identified ESBL-producing bacteria from three sampling reservoirs, and confirmed their resistance with both phenotypic and sequencing methods. To better understand the AMR spreading locally, we compared our isolates with isolates from other WGS studies in Singapore covered humans, food, and the enviroment. From there, we noticed the same sequence type (ST) as ST10, ST23, and ST38 has been shared among the environment, food, and humans, as well as the same beta-lactamase genes, are widely distributed among multiple sources. Further genetic environment comparison of beta-lactamase has suggested their spreading as conserved gene clusters among different species and sources. And this hypothesis has been supported by the successful conjugation of blaCTX-M-15 from Klebsiella pneumonia to Escherichia coli (E .coli). We also applied the shotgun metagenomic sequencing to understand the community of bacteria in reservoir water and detect the AMR genes. The composition of bacteria has shown different diversity among different samples. Besides, different beta-lactamase genes have been identified compared to culture depended methods. Here, we suggest that sequencing analysis has great potential in understanding AMR spreading in the “One-Health” approach. A genetic-based AMR risk assessment is in urgent need in Singapore.
Early functional connectivity in the developing sensorimotor network that is independent of sensory experience
Authors: Cross Christine M. , Santos Laura Mediavilla , Whiteley Nick , Luyt Karen , Ashby Michael C. 
Published: June 2021

AbstractNeonatal sensory experience shapes development of neural pathways carrying sensory information to the cortex. These pathways link to wider functional networks that coordinate activity of separate cortical regions, but it remains unknown when these broader networks emerge or how their maturation is influenced by sensory experience. By imaging activity across the cortex in neonatal mice, we have found unexpectedly early emergence of coordinated activity within a sensorimotor network that includes whisker-related somatosensory cortex and motor cortex. This network is spontaneously active but is not engaged by sensory stimulation, even though whisker deflection reliably drives cortical activity within barrel cortex. Acute silencing of the sensory periphery ablated spontaneous activity that was restricted to barrel cortex but spared this early sensorimotor network coactivity, suggesting that it is driven from elsewhere. Furthermore, perturbing sensory experience by whisker trimming did not impact emergence or early maturation of spontaneous activity in the sensorimotor network. As such, functional sensorimotor cortical networks develop early, in parallel with development of ascending sensory pathways, and their initial maturation is independent of sensory experience.