bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperplex PCR enables the next-generation of wastewater-based surveillance systems: long-term SARS-CoV-2 variant surveillance in Sweden as a case study
Authors: Soares Ruben R. G. , Varg Javier Edo , Szabó Attila , Psallida Margarita , Olszewski Paweł , Nikou Danai V. , Naseem Umear , Malmberg Maja , Székely Anna J. 
Published: June 2024

AbstractWastewater-based epidemiology aims at measuring pathogens in wastewater as a means of deriving unbiased epidemiological information at a population scale, ranging from buildings and aircrafts to entire cities or countries. After gaining significant mainstream attention during the SARS-CoV-2 pandemic, the field holds significant promise as a continuous monitoring and early warning system tracking emerging viral variants or new pathogens with pandemic potential.To expand the current toolbox of analytical techniques for wastewater analysis, we explored the use of Hyperplex PCR (hpPCR) to analyse SARS-CoV-2 mutations in wastewater samples collected weekly in up to 22 sites across Sweden between October 2022 and December 2023. Approximately 900 samples were tested using a dynamic probe panel with a multiplexity ranging from 10-to 18-plex, continuously adapted within 1-2 weeks to quantify relevant mutations of concern over time. The panel simultaneously covered deletions, single nucleotide substitutions, as well as variable regions resorting to probe degeneracy. By analysing all samples in parallel resorting to gold standard methods including qPCR and two different NGS technologies, the performance of hpPCR is herein shown to bridge the gap between these methods by providing (1) systematic single nucleotide sensitivity with a simple probe design, (2) high multiplexity without panel re-optimization requirements and (3) 4-5-week earlier mutation detection compared to NGS with excellent quantitative linearity and a good correlation for mutation frequency (r=0.88). Based on the demonstrated performance, the authors propose the combined use of NGS and hpPCR for routine discovery and high-frequency monitoring of key pathogens/variants as a potential alternative to the current analysis paradigm.
PVC Variability and Impact on Meeting Expert Consensus Cutoffs of ≥10,000 PVCs/day and ≥15% PVCs
Authors: Amara Richard S. , Appelbaum Jason , Abutaleb Ameer , Vunnam Rama , Shorofsky Stephen R. , Rottman Jeffrey N. , Kacorri Ardit , Dickfeld Timm M. 
Published: June 2024

ABSTRACTBackgroundFrequent PVCs have been associated with a reversible cardiomyopathy. Cutoffs of ≥10,000 PVCs/day and ≥15% PVCs have been suggested by the 2014 EHRA/HRS/APHRS and 2017 AHA/ACC/HRS Expert Consensus guidelines, respectively, for PVC suppression.Methods606 patients with 14 day ZIO® monitor datasets with ≥10,000 PVCs on at least one day were identified (2014 Guidelines Cohort). Of these patients, 325 had at least one day of ≥15% PVCs (2017 Guidelines Cohort). Analysis was performed on these cohorts to investigate the impact of PVC variability on meeting guideline thresholds.ResultsWithin the 2014 Guidelines Cohort, mean daily PVC burden was 12,188±8,300 [range 0-64,188]. Intra-patient daily PVCs were highly variable (median 3.6-fold change between max and min PVC days (Q1/3: 2.22/10.15) with instances of >10,000-fold change observed. 54.3% and 19.5% of patients had days with <5,000 and <1,000 PVCs, respectively. Even patients with days of 0 PVCs (0.5%) were observed. 72h monitoring detected 69% of patients with ≥10,000 PVCs/24h with an additional 2-4% of patients crossing the threshold each additional day. A bimodal distribution of number of days meeting PVC thresholds/corresponding PVC counts was observed, suggesting a previously unidentified pattern of distinct populations – “low frequency/low PVC” (≤3/14 above-threshold days/mean 12,342 PVCs those days) vs “high frequency/high PVC” (14/14 above-threshold days/mean 24,580 PVCs those days). The 2017 Guidelines Cohort demonstrated similar findings.ConclusionDaily PVC burdens vary greatly. More sensitive detection of guideline-suggested cut-offs requires prolonged monitoring. Novel potential PVC patterns may allow for better identification of candidates for PVC suppression.
A suite of enhancer AAVs and transgenic mouse lines for genetic access to cortical cell types
Authors: Ben-Simon Yoav , Hooper Marcus , Narayan Sujatha , Daigle Tanya , Dwivedi Deepanjali , Way Sharon W. , Oster Aaron , Stafford David A. , Mich John K. , Taormina Michael J. , Martinez Refugio A. , Opitz-Araya Ximena , Roth Jada R. , Allen Shona , Ayala Angela , Bakken Trygve E. , Barcelli Tyler , Barta Stuard , Bendrick Jacqueline , Bertagnolli Darren , Bowlus Jessica , Boyer Gabriella , Brouner Krissy , Casian Brittny , Casper Tamara , Chakka Anish B. , Chakrabarty Rushil , Chance Rebecca K. , Chavan Sakshi , Departee Maxwell , Donadio Nicholas , Dotson Nadezhda , Egdorf Tom , Gabitto Mariano , Garcia Jazmin , Gary Amanda , Gasperini Molly , Goldy Jeff , Gore Bryan B. , Graybuck Lucas , Greisman Noah , Haeseleer Francoise , Halterman Carliana , Helback Olivia , Hockemeyer Dirk , Huang Cindy , Huff Sydney , Hunker Avery , Johansen Nelson , Juneau Zoe , Kalmbach Brian , Khem Shannon , Kussick Emily , Kutsal Rana , Larsen Rachael , Lee Changkyu , Lee Angus Y. , Leibly Madison , Lenz Garreck H. , Liang Elizabeth , Lusk Nicholas , Malone Jocelin , Mollenkopf Tyler , Morin Elyse , Newman Dakota , Ng Lydia , Ngo Kiet , Omstead Victoria , Oyama Alana , Pham Trangthanh , Pom Christina A. , Potekhina Lydia , Ransford Shea , Rette Dean , Rimorin Christine , Rocha Dana , Ruiz Augustin , Sanchez Raymond E.A. , Sedeno-Cortes Adriana , Sevigny Joshua P. , Shapovalova Nadiya , Shulga Lyudmila , Sigler Ana R. , Siverts La’ Akea , Somasundaram Saroja , Stewart Kaiya , Szelenyi Eric , Tieu Michael , Trader Cameron , van Velthoven Cindy T.J. , Walker Miranda , Weed Natalie , Wirthlin Morgan , Wood Toren , Wynalda Brooke , Yao Zizhen , Zhou Thomas , Ariza Jeanelle , Dee Nick , Reding Melissa , Ronellenfitch Kara , Mufti Shoaib , Sunkin Susan M. , Smith Kimberly A. , Esposito Luke , Waters Jack , Thyagarajan Bargavi , Yao Shenqin , Lein Ed S. , Zeng Hongkui , Levi Boaz P. , Ngai John , Ting Jonathan , Tasic Bosiljka 
Published: June 2024

SummaryThe mammalian cortex is comprised of cells classified into types according to shared properties. Defining the contribution of each cell type to the processes guided by the cortex is essential for understanding its function in health and disease. We used transcriptomic and epigenomic cortical cell type taxonomies from mouse and human to define marker genes and putative enhancers and created a large toolkit of transgenic lines and enhancer AAVs for selective targeting of cortical cell populations. We report evaluation of fifteen new transgenic driver lines, two new reporter lines, and >800 different enhancer AAVs covering most subclasses of cortical cells. The tools reported here as well as the scaled process of tool creation and modification enable diverse experimental strategies towards understanding mammalian cortex and brain function.
C-LTMRs mediate wet dog shakes via the spinoparabrachial pathway
Authors: Zhang Dawei , Turecek Josef , Choi Seungwon , Delisle Michelle , Pamplona Caroline L. , Meltzer Shan , Ginty David D. 
Published: June 2024

AbstractMammals perform rapid oscillations of their body- “wet dog shakes” -to remove water and irritants from their back hairy skin. The somatosensory mechanisms underlying this stereotypical behavior are unknown. We report that Piezo2-dependent mechanosensation mediates wet dog shakes evoked by water or oil droplets applied to hairy skin of mice. Unmyelinated low-threshold mechanoreceptors (C-LTMRs) were strongly activated by oil droplets and their optogenetic activation elicited wet dog shakes. Ablation of C-LTMRs attenuated this behavior. Moreover, C-LTMRs synaptically couple to spinoparabrachial (SPB) neurons, and optogenetically inhibiting SPB neuron synapses and excitatory neurons in the parabrachial nucleus impaired both oil droplet- and C-LTMR-evoked wet dog shakes. Thus, a C-LTMR– spinoparabrachial pathway mediates wet dog shakes for rapid and effective removal of foreign particles from back hairy skin.
Congenital heart defects differ following left versus right avian cardiac neural crest ablation
Authors: Solovieva Tatiana , Bronner Marianne E. 
Published: June 2024

ABSTRACTThe cardiac neural crest is critical for the normal development of the heart, as its surgical ablation in the chick recapitulates common human congenital heart defects such as ‘Common Arterial Trunk’ and ‘Double Outlet Right Ventricle’ (DORV). While left-right asymmetry is known to be important for heart development, little is known about potential asymmetric differences between right and left cardiac neural folds with respect to heart development. Here, through surgical ablation of either left or right cardiac neural crest, we find that right ablation results in more varied and more severe heart defects. Embryos with Common Arterial Trunk and with missing arteries occurred in right-ablated embryos but were not observed in left-ablated embryos; moreover, embryos with DORV and with misalignment of the arteries were more prevalent following right versus left cardiac crest ablation. In addition, survival of right-ablated embryos was lower than left-ablated embryos. Together, these data raise the intriguing possibility that there may be differences in left versus right cardiac neural crest during heart development.
Dbf4-Dependent Kinase Finetunes INO80 Function at Chromosome Replication Origins
Authors: Bansal Priyanka , Lahiri Shibojyoti , Kumar Chandni , Galanti Lorenzo , Chacin Erika , Ortíz-Bazán María Ángeles , Müller Marisa , Vizjak Petra , Straub Tobias , Müller-Planitz Felix , Aguilera Andrés , Gómez-González Belen , Pfander Boris , Imhof Axel , Kurat Christoph F. 
Published: June 2024

SummaryThe highly conserved Dbf4-Dependent Kinase (DDK) plays a pivotal role in the nucleus during S phase, where it directly phosphorylates the replicative helicase, the minichromosome maintenance (MCM) complex. This leads to the initiation of chromosome replication. However, aside from the MCM complex, few other targets have been identified to date, leaving DDK an understudied kinase.Here, we describe a two-pronged mass spectrometry-based approach and define the nuclear DDK-dependent phosphoproteome, which consists of approximately 400 phosphorylation events. Within this network, we found that DDK directly phosphorylates the Arp8 subunit of the multi-subunit chromatin remodeler complex INO80. Arp8 phosphorylation stabilises INO80’s intramolecular complex integrity, which finetunes its nucleosome spacing activity at replication origins. This adjustment of origin chromatin architecture stimulates replication and is important for the response to replication stress. Our results represent a significant advance in our understanding of the molecular mechanisms underlying the regulation of replication origins.
Experience-dependent predictions of feedforward and contextual information in mouse visual cortex
Authors: Seignette Koen , de Kraker Leander , Papale Paolo , Petro Lucy S. , Hobo Barbara , Montijn Jorrit S. , Self Matthew W. , Larkum Matthew E. , Roelfsema Pieter R. , Muckli Lars , Levelt Christiaan N. 
Published: June 2024

ABSTRACTNeurons in primary visual cortex are driven by feedforward visual inputs and top-down contextual inputs. The nature of this contextual information is difficult to study, as responses to feedforward and top-down inputs overlap in time and are difficult to disentangle experimentally. To address this issue, we measured responses to natural images and partially occluded versions of these images in the visual cortex of mice. Assessing neuronal responses before and after familiarizing mice with the non-occluded images allowed us to study experience-dependent and stimulus-specific contextual responses in pyramidal cells (PyCs) in cortical layers 2/3 and 5 in the absence of feedforward input. Surprisingly, in the same retinotopic region of cortex, we found that separate populations of PyCs in layer 2/3 responded to occluded and non-occluded images. Responses of PyCs selective for occluded images were strengthened upon familiarization and decoding analysis revealed they contained image-specific information, suggesting that they signaled the absence of predicted visual stimuli. Responses of PyCs selective for non-occluded scenes were weaker for familiarized images but stronger for unfamiliar images, suggesting that these neurons signaled the presence of unpredicted visual stimuli. Layer 5 also contained PyCs preferring either feedforward or contextual inputs, but their responses were more complex and strengthening of responses to occluded images required task engagement. The results show that visual experience decreases the activity of neurons responding to known feedforward inputs but increases the activity of neurons responding to contextual inputs tied to expected stimuli.
A minimally invasive thrombotic stroke model to study circadian rhythm in awake mice
Authors: Marks Kimberly , Ahn Sung-Ji , Rai Ninamma , Anfray Antoine , Iadecola Costantino , Anrather Josef 
Published: June 2024

AbstractExperimental stroke models in rodents are essential for mechanistic studies and therapeutic development. However, these models have several limitations negatively impacting their translational relevance. Here we aimed to develop a minimally invasive thrombotic stroke model through magnetic particle delivery that does not require craniotomy, is amenable to reperfusion therapy, can be combined with in vivo imaging modalities, and can be performed in awake mice. We found that the model results in reproducible cortical infarcts within the middle cerebral artery (MCA) with cytologic and immune changes similar to that observed with more invasive distal MCA occlusion models. Importantly, the injury produced by the model was ameliorated by tissue plasminogen activator (tPA) administration. We also show that MCA occlusion in awake animals results in bigger ischemic lesions independent of day/night cycle. Magnetic particle delivery had no overt effects on physiologic parameters and systemic immune biomarkers. In conclusion, we developed a novel stroke model in mice that fulfills many requirements for modeling human stroke.
Activity-Dependent Remodeling of Corticostriatal Axonal Boutons During Motor Learning
Authors: Sheng Mengjun , Lu Di , Sheng Kaiwen , Ding Jun B 
Published: June 2024

AbstractMotor skill learning induces long-lasting synaptic plasticity at not only the inputs, such as dendritic spines1–4, but also at the outputs to the striatum of motor cortical neurons5,6. However, very little is known about the activity and structural plasticity of corticostriatal axons during learning in the adult brain. Here, we used longitudinal in vivo two-photon imaging to monitor the activity and structure of thousands of corticostriatal axonal boutons in the dorsolateral striatum in awake mice. We found that learning a new motor skill induces dynamic regulation of axonal boutons. The activities of motor corticostriatal axonal boutons exhibited selectivity for rewarded movements (RM) and un-rewarded movements (UM). Strikingly, boutons on the same axonal branches showed diverse responses during behavior. Motor learning significantly increased the fraction of RM boutons and reduced the heterogeneity of bouton activities. Moreover, motor learning-induced profound structural dynamism in boutons. By combining structural and functional imaging, we identified that newly formed axonal boutons are more likely to exhibit selectivity for RM and are stabilized during motor learning, while UM boutons are selectively eliminated. Our results highlight a novel form of plasticity at corticostriatal axons induced by motor learning, indicating that motor corticostriatal axonal boutons undergo dynamic reorganization that facilitates the acquisition and execution of motor skills.
Does prosperity pay? Unraveling the relationship between economic performance and life expectancy across a large number of European regions, 2008-2019
Authors: Sauerberg Markus , Cilek Laura Ann , Mühlichen Michael , Bonnet Florian , Alliger Ina , Camarda Carlo Giovanni 
Published: June 2024

AbstractUnderstanding the relationship between life expectancy at birth (e0) and the gross domestic product per capita (GDPpc) is relevant for cohesion policies in the European Union (EU), because it might imply that economic convergence (or divergence) is accompanied by narrowing (or widening) health gaps. Previous studies have studied the association between GDPpc ande0almost exclusively based on national data. However, it is certainly relevant to add a subnational dimension, because levels and trends in bothe0and GDPpc vary substantially across Europe’s regions. Accordingly, the aim of our study is examining whether the economic performance of a region is correlated to theire0level. To do so, we collected official mortality and population counts from national statistical offices and information on GDPpc from the Eurostat database for 506 regions in 21 European countries from 2008 to 2019. Using this data, we built Preston curves from regression models. Our results suggest that there is indeed a positive association between GDPpc ande0. Similarly to Preston’s original analysis, we observe an upward shift in the curve, indicating that factors exogenous to a region’s GDPpc level also play an important role in explaininge0gains. Yet, the relationship differs between geographical areas, and we also find examples, such as women in Germany, Austria, Poland, and the Netherlands, where the relationship/pattern does not seem to hold.
A scalable and modular computational pipeline for axonal connectomics: automated tracing and assembly of axons across serial sections
Authors: Torres Russel , Takasaki Kevin , Gliko Olga , Laughland Connor , Yu Wan-Qing , Turschak Emily , Hellevik Ayana , Balaram Pooja , Perlman Eric , Sümbül Uygar , Reid R. Clay 
Published: June 2024

AbstractProgress in histological methods and in microscope technology has enabled dense staining and imaging of axons over large brain volumes, but tracing axons over such volumes requires new computational tools for 3D reconstruction of data acquired from serial sections. We have developed a computational pipeline for automated tracing and volume assembly of densely stained axons imaged over serial sections, which leverages machine learning-based segmentation to enable stitching and alignment with the axon traces themselves. We validated this segmentation-driven approach to volume assembly and alignment of individual axons over centimeter-scale serial sections and show the application of the output traces for analysis of local orientation and for proofreading over aligned volumes. The pipeline is scalable, and combined with recent advances in experimental approaches, should enable new studies of mesoscale connectivity and function over the whole human brain.
Epidemiological Study Of Foot And Mouth Diseases Through Serological And Molecular Investigation In Cattle Of Selected Districts, Jimma Zone, Southwest Ethiopia
Authors: Tegegne Hailehizeb , Ababulgu Seid , Ejigu Eyoel 
Published: June 2024

ABSTRACTFoot and mouth disease is highly contagious and notifiable transboundary disease of cattle that can cause a huge cattle productivity and production loss. A cross-sectional study was performed to estimate sero prevalence, assess associated risk factors and molecular detection of FMDV in cattle. Cluster sampling technique was employed for the selection of sampling units for the seroprevalence study. A total of 245 blood samples were collected using plain vacutainer tubes and the obtained sera were tested by 3ABC-Ab ELISA at the Animal Health institute. Twenty nine (29) epithelial tissue and vesicular fluid samples were collected purposively from outbreak cases for the molecular detection of FMDV. Kebeles and individual cattle were randomly selected, while households were designated using systematic random sampling method. An overall prevalence of 22.45% (95%, CI=17.22%-27.67%) was recorded. Multivariable logistic regression analysis indicated that herd size, age, new animal introduction into the herd and management system were the major risk factors, significantly associated with FMD sero positivity (P<0.05). The large herd size had 4-times (OR=3.97; P=0.000) more odds of FMD sero-positivity compared to the small herd sizes. The FMD seropositivity decreases 0.11013 as the Cattle age increases by 5years with the (coefficient=-0.11; P=0.172). The animals from herd to which new animals was introduced had nearly 9-times more odds (OR=9.40; P=0.000) of sero positivity than the animals sampled from no new animal introduction. Likewise, cattle those reared under extensive management system were 4-times (OR=4.10; P=0.009) at higher chance of being sero-positive compared to the intensive one. From outbreak cases, 27 (93.1%) were identified positive for FMDV serotype SAT 2. A total of 124 individuals were interviewed, and the majority responded that there is no practice of reporting disease outbreak, free animal movement, free rangeland grazing and they use traditional case management as a means of controlling the disease. The finding of FMD virus antibodies in cattle from all study areas indicate endemic circulation of the virus. The implementation of regular vaccination could minimize the occurrence and further molecular characterization should be needed to identify other serotypes of FMD virus that could inform to supply an appropriate vaccine to the area.
Selecting applications to increase the efficiency of distance learning in architectural design
Authors: Sidhom Girges , Attia Sahar , Zayed Mohammed A. 
Published: June 2024

PurposeIn light of the technological advancements and impact of the COVID-19 pandemic on educational systems, universities worldwide had to find new methods to ensure that the educational process continued. In many countries, including Egypt, it has become a priority to direct their institutions toward digital transformation, using electronic means in the educational process. A set of challenges emerged in the educational process, especially in architectural learning, focusing on the design studio; problems intensified and some professors rejected the idea of distance learning, announcing their strong adherence to traditional face-to-face learning. This research aims to find a methodology that informs the choice of digital technology in architectural design courses.Design/methodology/approachThe researchers used both qualitative and quantitative methodology based on inductive, analytical, interview-questionnaire and empirical studies in Egypt.FindingsResults show that many criteria affect the selection of proper applications. Also, using multiple applications in architecture design course helps students understand the material. However, hybrid learning is crucial in teaching architectural design since it cannot be effectively conveyed solely through distance learning.Originality/valueThe results of the research will help improve and develop the distance learning system in architectural education by proposing a methodology for choosing suitable electronic tools for architecture studio courses. These courses enhance the effectiveness of students' understanding and comprehension during the distance learning process to increase motivation for thinning development, imagination and educational skills.