bluuebunny/crossref_metadata_2025_split huggingface dataset:
‘The Thousand Polish Genomes Project’ - a national database of Polish variant allele frequencies
Authors: Kaja Elżbieta , Lejman Adrian , Sielski Dawid , Sypniewski Mateusz , Gambin Tomasz , Suchocki Tomasz , Dawidziuk Mateusz , Golik Paweł , Wojtaszewska Marzena , Stępień Maria , Szyda Joanna , Lisiak-Teodorczyk Karolina , Wolbach Filip , Kołodziejska Daria , Ferdyn Katarzyna , Woźna Alicja , Żytkiewicz Marcin , Bodora-Troińska Anna , Elikowski Waldemar , Król Zbigniew , Zaczyński Artur , Pawlak Agnieszka , Gil Robert , Wierzba Waldemar , Dobosz Paula , Zawadzka Katarzyna , Zawadzki Paweł , Sztromwasser Paweł 
Published: July 2021

AbstractAlthough Slavic populations account for over 3.5% of world inhabitants, no centralized, open source reference database of genetic variation of any Slavic population exists to date. Such data are crucial for either biomedical research and genetic counseling and are essential for archeological and historical studies. Polish population, homogenous and sedentary in its nature but influenced by many migrations of the past, is unique and could serve as a good genetic reference for middle European Slavic nations.The aim of the present study was to describe first results of analyses of a newly created national database of Polish genomic variant allele frequencies. Never before has any study on the whole genomes of Polish population been conducted on such a large number of individuals (1,079).A wide spectrum of genomic variation was identified and genotyped, such as small and structural variants, runs of homozygosity, mitochondrial haplogroups and Mendelian inconsistencies. The allele frequencies were calculated for 943 unrelated individuals and released publicly as The Thousand Polish Genomes database. A precise detection and characterisation of rare variants enriched in the Polish population allowed to confirm the allele frequencies for known pathogenic variants in diseases, such as Smith-Lemli-Opitz syndrome (SLOS) or Nijmegen breakage syndrome (NBS). Additionally, the analysis of OMIM AR genes led to the identification of 22 genes with significantly different cumulative allele frequencies in the Polish (POL) vs European NFE population. We hope that The Thousand Polish Genomes database will contribute to the worldwide genomic data resources for researchers and clinicians.
Holistic Characterization of Tumor Monocyte-to-Macrophage Differentiation Integrates Distinct Immune Phenotypes in Kidney Cancer
Authors: Mujal Adriana M. , Combes Alexis J. , Rao Arjun R. , Binnewies Mikhail , Samad Bushra , Tsui Jessica , Boissonnas Alexandre , Pollack Joshua L. , Argüello Rafael J. , Ruhland Megan K. , Barry Kevin C. , Chan Vincent , Krummel Matthew F. 
Published: July 2021

AbstractThe tumor immune microenvironment (TIME) is commonly infiltrated by diverse collections of myeloid cells. Yet, the complexity of myeloid cell identity and plasticity has challenged efforts to define bona fide populations and determine their connections to T cell function and their relation to patient outcome. Here we leverage single-cell RNA-sequencing (scRNA-seq) analysis of several mouse and human tumors and find that monocyte-macrophage diversity is characterized by a combination of conserved lineage states as well as transcriptional programs accessed along the differentiation trajectory. Using mouse models, we also find that tumor monocyte-to-macrophage progression is profoundly tied to regulatory T cell (Treg) abundance. Importantly, in human kidney cancer, heterogeneity in macrophage accumulation and myeloid composition corresponded to variance in, not only Treg density, but also the quality of infiltrating CD8+ T cells. In this way, holistic analysis of monocyte-to-macrophage differentiation creates a framework for critically different immune states in kidney tumors.
Atomistic Simulations and Deep Mutational Scanning of Protein Stability and Binding Interactions in the SARS-CoV-2 Spike Protein Complexes with Nanobodies: Molecular Determinants of Mutational Escape Mechanisms
Authors: Verkhivker Gennady M. , Agajanian Steve , Oztas Deniz Yasar , Gupta Grace 
Published: July 2021

AbstractStructural and biochemical studies have recently revealed a range of rationally engineered nanobodies with efficient neutralizing capacity against SARS-CoV-2 virus and resilience against mutational escape. In this work, we combined atomistic simulations and conformational dynamics analysis with the ensemble-based mutational profiling of binding interactions for a diverse panel of SARS-CoV-2 spike complexes with nanobodies. Using this computational toolkit we identified dynamic signatures and binding affinity fingerprints for the SARS-CoV-2 spike protein complexes with nanobodies Nb6 and Nb20, VHH E, a pair combination VHH E+U, a biparatopic nanobody VHH VE, and a combination of CC12.3 antibody and VHH V/W nanobodies. Through ensemble-based deep mutational profiling of stability and binding affinities, we identify critical hotspots and characterize molecular mechanisms of SARS-CoV-2 spike protein binding with single ultra-potent nanobodies, nanobody cocktails and biparatopic nanobodies. By quantifying dynamic and energetic determinants of the SARS-CoV-2 S binding with nanobodies, we also examine the effects of circulating variants and escaping mutations. We found that mutational escape mechanisms may be controlled through structurally and energetically adaptable binding hotspots located in the host receptor-accessible binding epitope that are dynamically coupled to the stability centers in the distant epitope targeted by VHH U/V/W nanobodies. The results of this study suggested a mechanism in which through cooperative dynamic changes, nanobody combinations and biparatopic nanobody can modulate the global protein response and induce the increased resilience to common escape mutants.
Symptomatic, Presymptomatic, and Asymptomatic Transmission of SARS-CoV-2
Authors: Krieg Steven J. , Schnur Jennifer J. , Miranda Marie L. , Pfrender Michael E. , Chawla Nitesh V. 
Published: July 2021

ABSTRACTImportanceAsymptomatic and presymptomatic carriers of SARS-CoV-2 are an ongoing and significant risk for community spread of the virus, especially with the majority of the world still unvaccinated and new variants emerging.ObjectiveTo quantify the presence and effects of symptom presentation (or lack thereof) on the community transmission of SARS-CoV-2.DesignA cohort of 12,960 young adults participated in health reporting, contact tracing, and COVID-19 testing for 103 days between August 10 and November 20, 2020.SettingA mid-sized university campus in Indiana, United States.ParticipantsUniversity students, most of whom are 18-23 years old (67%) and living in congregate on-campus housing (60%). Of the 12,960 students, 1,556 (12.0%) tested positive for COVID-19 during the 103 day period. Of the positive cases, 1,198 reported sufficient health check data (7 days prior and 7 days post diagnosis) to be classified as asymptomatic or symptomatic.Main OutcomeSecondary attack rate, based on presentation or absence of symptoms and type of symptoms calculated with respect to confirmed close contacts and a 14-day incubation period, varies on the type of symptom, timing of symptoms, and absence of symptoms. A quantifiable understanding of SAR on the longitudinal data of more than one thousand subjects in a university environment provides keen insights about developing strategies to respond to the continued prevalence of COVID-19 in the unvaccinated world and growth of variants.Results32.5% of all cases reported no symptoms within a 15-day window centered on their positive test (7 days prior, the day of the positive test, and 7 days after). The secondary attack rate (SAR) of asymptomatic COVID-19 index cases was 19.1%. The SAR of symptomatic index cases was 25.4%, and while the onset timing of symptoms did not affect transmission, the presence of certain symptoms like fever, shortness of breath, and dry cough increased the SAR as high as 30.0%.Conclusions and RelevanceAsymptomatic rates of transmission of SARS-CoV-2 are much higher than has been estimated in prior studies and continue to pose a significant and ongoing risk in the pandemic, especially with the prevalence of variants like the Delta variant. In addition, different symptoms are associated with varying rates of transmission, posing a significant challenge in how to diagnose or assess risk through mechanisms such as daily health checks for symptom reporting, a practice commonly in place for entry into schools, offices, restaurants, etc. Given the uncertain nature of symptoms and varied transmission rates, this study suggests a broader embrace of masking, social distancing and testing might be needed to counter the variants until higher global vaccination rates can be achieved.
Anxiety and Depression among Medical Doctors in Catalonia, Italy, and the UK during the COVID-19 Pandemic
Authors: Quintana-Domeque Climent , Lee Ines , Zhang Anwen , Proto Eugenio , Battisti Michele , Ho Antonia 
Published: July 2021

AbstractHealthcare workers have had the longest and most direct exposure to COVID-19 and consequently may suffer from poor mental health. We conducted one of the first repeated multi-country analysis of the mental wellbeing of medical doctors (n=5,275) at two timepoints during the COVID-19 pandemic (June 2020 and November/December 2020) to understand the prevalence of anxiety and depression, as well as associated risk factors. Rates of anxiety and depression were highest in Italy (24.6% and 20.1%, June 2020), second highest in Catalonia (24.6% and 17.4%, June 2020), and lowest in the UK (11.7% and 13.7%, June 2020). Across all countries, higher risk of anxiety and depression symptoms are found among women, individuals below 60 years old, those feeling vulnerable/exposed at work, and those in poor health. We did not find systematic differences in mental health measures between the two rounds of data collection, hence we cannot discard that the mental health repercussions of the pandemic are persistent.
Simplified point-of-care full SARS-CoV-2 genome sequencing using nanopore technology
Authors: Pembaur Anton , Sallard Erwan , Weil Patrick Philipp , Ortelt Jennifer , Ahmad-Nejad Parviz , Postberg Jan 
Published: July 2021

AbstractBackgroundThe scale of the ongoing SARS-CoV-2 pandemic warrants the urgent establishment of a global decentralized surveillance system to recognize local outbreaks and the emergence of novel variants-of-concern. Among available deep-sequencing technologies, nanopore-sequencing could be an important cornerstone, since it is mobile, scalable and costs-effective. Therefore, streamlined nanopore-sequencing protocols need to be developed and optimized for SARS-CoV-2 variants identification.ResultsWe adapted and simplified existing workflows using the ‘midnight’ 1,200 bp amplicon split primer sets for PCR, which produce tiled overlapping amplicons covering almost the entire SARS-CoV-2 genome. Subsequently, we applied Oxford Nanopore Rapid Barcoding and the portable MinION Mk1C sequencer combined with the interARTIC bioinformatics pipeline. We tested a simplified and less time-consuming workflow using SARS-CoV-2-positive specimens from clinical routine and identified pre-analytical parameters, which may help to decrease sequencing failures rates. Complete pipeline duration was approx. 7 hrs for one specimen and approx. 11 hrs for 12 multiplexed barcoded specimens.ConclusionsThe adapted protocol contains less processing steps and can be completely conducted within one working-day. Diagnostic CT values are principal criteria for specimen selection.
Lifelong learning of cognitive strategies for physical problem-solving: the effect of embodied experience
Authors: Allen Kelsey R. , Smith Kevin A. , Bird Laura-Ashleigh , Tenenbaum Joshua B. , Makin Tamar R. , Cowie Dorothy 
Published: July 2021

Abstract‘Embodied cognition’ suggests that our bodily experiences broadly shape our cognitive capabilities. We study how embodied experience affects the abstract physical problem-solving strategies people use in a virtual task where embodiment does not affect action capabilities. We compare how groups with different embodied experience – 25 children and 35 adults with congenital limb differences versus 45 children and 40 adults born with two hands – perform this task, and find that while there is no difference in overall competence, the groups use different cognitive strategies to find solutions. People born with limb differences think more before acting, but take fewer attempts to reach solutions. Conversely, development affects the particular actions children use, as well as their persistence with their current strategy. Our findings suggest that while development alters action choices and persistence, differences in embodied experience drive strategic changes in the acquisition of cognitive strategies for balancing acting with thinking.Statement of RelevanceTheories of embodied cognition suggest our cognitive and perceptual capabilities are shaped by how our bodies constrain our interactions with the world; however, these tasks often study short-term effects or setups where body differences impact task solutions. Here we compare the performance of children and adults with and without congenital limb differences (missing hands/upper limbs) on a virtual physical problem-solving task, where both groups had equal motor capabilities for interacting with the world. Across ages, participants with limb differences solved these tasks as proficiently as those without limb differences, but took fewer attempts to come to solutions, with more time spent thinking between attempts. This suggests that early life differences in embodied experience cause changes in individuals’ “cognitive strategies” for allocating time between thinking and acting.
Emergent collective locomotion in an active polymer model of entangled worm blobs
Authors: Nguyen Chantal , Ozkan-Aydin Yasemin , Tuazon Harry , Goldman Daniel I. , Bhamla M. Saad , Peleg Orit 
Published: July 2021

AbstractNumerous worm and arthropod species form physically-connected aggregations in which interactions among individuals give rise to emergent macroscale dynamics and functionalities that enhance collective survival. In particular, some aquatic worms such as the California blackworm (Lumbriculus variegatus) entangle their bodies into dense blobs to shield themselves against external stressors and preserve moisture in dry conditions. Motivated by recent experiments revealing emergent locomotion in blackworm blobs, we investigate the collective worm dynamics by modeling each worm as a self-propelled Brownian polymer. Though our model is two-dimensional, compared to real three-dimensional worm blobs, we demonstrate how a simulated blob can collectively traverse temperature gradients via the coupling between the active motion and the environment. By performing a systematic parameter sweep over the strength of attractive forces between worms, and the magnitude of their directed self-propulsion, we obtain a rich phase diagram which reveals that effective collective locomotion emerges as a result of finely balancing a tradeoff between these two parameters. Our model brings the physics of active filaments into a new meso- and macroscale context and invites further theoretical investigation into the collective behavior of long, slender, semi-flexible organisms.
Founder cell configuration drives competitive outcome within colony biofilms
Authors: Eigentler Lukas , Kalamara Margarita , Ball Graeme , MacPhee Cait E. , Stanley-Wall Nicola R. , Davidson Fordyce A. 
Published: July 2021

AbstractBacteria typically form dense communities called biofilms, where cells are embedded in a self-produced extracellular matrix. Competitive interactions between strains within the biofilm context are studied due to their potential applications in biological, medical, and industrial systems. Combining mathematical modelling with experimental assays, we reveal that the spatial structure and the competitive dynamics within biofilms are significantly affected by the location and density of founder cells. Using an isogenic pair of Bacillus subtilis strains, we show that the observed spatial structure and relative strain biomass in a mature biofilm can be mapped directly to the locations of founder cells. Moreover, we define a predictor of competitive outcome that accurately forecasts relative abundance of strains based solely on the founder cells’ access to free space. Consequently, we reveal that variability of competitive outcome in biofilms inoculated at low founder density is a natural consequence of the random positioning of founding cells in the inoculum. Extending our study to non-isogenic strain pairs of B. subtilis, we show that even for strains with different antagonistic strengths, a race for space remains the dominant mode of competition in biofilms inoculated at low founder densities. Our results highlight the importance of spatial dynamics on competitive interactions within biofilms and hence to related applications.
Melanopic stimulation does not affect psychophysical threshold sensitivity for luminance flicker
Authors: Vincent Joris , Haggerty Edda B. , Brainard David H. , Aguirre Geoffrey K. 
Published: July 2021

AbstractIn addition to the cone photoreceptors the retina contains intrinsically photosensitive retinal ganglion cells (ipRGCs). These cells express the photopigment melanopsin and are known to be involved in reflexive visual functions such as pupil response and photo-entrainment of the circadian rhythm. It is possible that the ipRGCs contribute to conscious visual perception, either by providing an independent signal to the geniculo-striate pathway, or by interacting with and thus modifying signals arising from “classical” retinal ganglion cells that combine and contrast cone input. Here, we tested for the existence of an interaction by asking if a 350% change in melanopsin stimulation alters psychophysical sensitivity for the detection of luminance flicker. In Experiment 1, we tested for a change in the threshold for detecting luminance flicker in three participants after they adapted to backgrounds with different degrees of tonic melanopsin stimulation. In Experiments 2 and 3, this test was repeated, but now for luminance flicker presented on a transient pedestal of melanopsin stimulation. Across the three experiments, no effect of melanopsin stimulation upon threshold flicker sensitivity was found. Our results suggest that even large changes in melanopsin stimulation do not affect near-threshold, cone-mediated visual perception.
Lung adenocarcinoma cell-derived exosomal miR-328 promote osteoclastogenesis by targeting Nrp2
Authors: Zhang Chengcheng , Qin Jingru , Yang Lu , Zhu Zhiyao , Yang Jia , Su Wan , Deng Haibin , Wang Zhongqi 
Published: July 2021

AbstractBone metastasis of lung cancer and detailed mechanisms are still elusive, and the roles of exosomes derived from lung adenocarcinoma cells in this process have attracted much attention. In this study, we found that A549 cell-derived exosomes (A549-Exos) promoted osteogenesis and bone resorption in vitro. Furthermore, A549-Exos target bone in vivo and promoted bone resorption in vivo. Mechanistically, A549-Exosomal miR-328 promoted bone resorption by targeting Nrp2 and A549-ExosmiR-328 Inhibitors inhibited bone resorption in vivo. Thus, A549-Exosomal miR-328 promote osteoclastogenesis by targeting Nrp2 and A549-ExosmiR-328 Inhibitors may serve as a potential nanomedicine for the treatment of bone metastasis.
Cerebellar Control of a Unitary Head Direction Sense
Authors: Fallahnezhad Mehdi , Le Méro Julia , Zenelaj Xhensjana , Vincent Jean , Rochefort Christelle , Rondi-Reig Laure 
Published: July 2021

SUMMARYHead direction (HD) cells, key neuronal elements in the mammalian’s navigation system, are hypothesized to act as a continuous attractor network, in which temporal coordination between cell members is maintained under different brain states or external sensory conditions, resembling a unitary neural representation of direction. Whether and how multiple identified HD signals in anatomically separate HD cell structures are part of a single and unique attractor network is currently unknown. By manipulating the cerebellum, we identified pairs of thalamic and retrosplenial HD cells that lose their temporal coordination in the absence of external sensory drive, while the neuronal coordination within each of these brain regions remained intact. Further, we show that distinct cerebellar mechanisms are involved in the stability of direction representation depending on external sensory conditions. These results put forward a new role for the cerebellum in mediating stable and coordinated HD neuronal activity toward a unitary thalamocortical representation of direction.
NGS comparison of Downy and Powdery mildew resistance genomic regions between ‘Regent’ and ‘Red Globe’
Authors: van Heerden CJ , Burger P , Burger JT , Prins R 
Published: July 2021

ABSTRACTPowdery and downy mildew have a large negative impact on grape production worldwide. Quantitative trait loci (QTL) mapping projects have identified several loci for the genetic factors responsible for resistance to these pathogens. Several of these studies have focused on the cultivar ‘Regent’, which carries the resistance loci to downy mildew on chromosome 18 (Rpv3), as well powdery mildew on chromosome 15 (Ren3, Ren9). Several other minor resistance loci have also been identified on other chromosomes.Here we report on the re-sequencing of the ‘Regent’ and ‘Red Globe’ (susceptible) genomes using next generation sequencing. While the genome of ‘Regent’ has more SNP variants than ‘Red Globe’, the distribution of these variants across the two genomes is not the same, nor is it uniform. The variation per gene shows that some genes have higher SNP density than others and that the number of SNPs for a given gene is not always the same for the two cultivars. In this study, we investigate the effectiveness of studying the variation of non-synonymous to synonymous SNP ratio’s between resistant and susceptible cultivars in the target QTL regions as a strategy to narrow down the number of likely candidate genes for Rpv3, Ren3 and Ren9.
House of quality: a method to identify landscape design requirements
Authors: El Sawalhi Nabil I. , Yazgi Aisha N. 
Published: July 2021

Purpose
The level of live, reduction of pollution and positive human health is affected by the quality of landscape. In addition, many benefits such as aesthetic, psychological and social can be achieved. The quality of landscape is integrated with the individual’s needs. The scope of landscape must be determined according to user needs and planning methods. The purpose of this study is to propose a house of quality (HOQ) model to identify the landscape design requirements. The Islamic University of Gaza (IUG) was used as a case study. The need to implement the proposed HOQ model has been identified. Also, the male and female students’ priorities have been identified, and the weight of campus landscape design elements was extracted.

Design/methodology/approach
The male and female IUG students’ needs were identified using a questionnaire survey. The data were analyzed for testing statistical validity and reliability using SPSS. HOQ model was built using EDRAW Max program.

Findings
The ten most important student needs are “cleanliness, praying, feeling safe, feeling comfortable psychic, drinking, spaciousness and breadth, shading, quiet, rest and sitting, and fresh air.” Based on these results and needs assessment, the HOQ was constructed. The most important design elements are “group of seats, shrubs, trees, lawns, pergola, and seats chairs or benches.”

Originality/value
This study adds to the designer’s knowledge about HOQ application in design, and contributes significantly to consider public participation as a way in collecting the voice of customers.