bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular pathways associated with Kallikrein 6 overexpression in colorectal cancer
Authors: Pandey Ritu , Zhou Muhan , Chen Yuliang , Darmoul Dalila , Kisiel Conner C. , Nfonsam Valentine N. , Ignatenko Natalia A. 
Published: December 2020

AbstractColorectal cancer (CRC) remains one of leading causes of cancer-related death worldwide. The high mortality of CRC is related to its ability to metastasize to distant organs. Current management of the CRC disease is limited due to the need of more extensive molecular characterization of tumor biomarkers. Kallikrein 6 (KLK6) is a member of the fifteen-gene family of kallikrein-related peptidases. KLK6 is overexpressed in CRC and contributes to cancer cell invasion through its proteolytic degradation of the extracellular matrix and recently discovered regulation of metastasis signaling pathways.The goal of this study was to evaluate the clinical features, CRC molecular subtypes, mutational and gene expression patterns of the CRC tumors with overexpressed KLK6 in order to identify KLK6-associated markers for the CRC prognosis and treatment. RNA-Seq data from the CRC patients with a significantly elevated KLK6 transcript levels (KLK6-high group) (Z-score higher than-1.96) were identified in the Cancer Genome Atlas (TCGA) database and processed for clinical, molecular evaluation and bioinformatic analysis, using Gene Ontology (GO), Phenotype and Reactome enrichment and protein interaction methods. KLK6-high cases had a distinct spectrum of mutations in titin (TTN), APC, K-RAS and MUC 16 genes. Differentially expressed genes (DEGs) unique to KLK6-high group were clustered to regulatory pathways controlling the cell signaling, extracellular matrix organization, and cell communication regulation. The members of kallikrein family (KLK7, KLK8, KLK10), keratins (KRT6A, 6B, 15, 16, 19, 80), extracellular matrix proteins (integrin 4B), small proline rich repeat proteins (SPRRs), S100A families, protein trafficking genes (SYL1) and signaling genes within TGF-β, FOS and Ser/Thr protein kinase pathways were recognized as the top KLK6-interaction partners. Expression of selected KLK6-associated genes was validated in a subset of paired normal and tumor CRC patient-derived organoid cultures.The performed analyses identified KLK6 itself and a set of genes, which are co-expressed with KLK6, as potential clinical biomarkers for the management of the CRC disease.
How long do nursing staff take to measure and record patients’ vital signs observations in hospital? A time-and-motion study
Authors: Dall’Ora Chiara , Griffiths Peter , Hope Joanna , Briggs Jim , Jones Jeremy , Gerry Stephen , Redfern Oliver 
Published: December 2020

ABSTRACTIntroductionMonitoring vital signs in hospital is an important part of safe patient care. However, there are no robust estimates of the workload it generates for nursing staff. This makes it difficult to plan adequate staffing to ensure current monitoring protocols can be delivered.ObjectiveTo estimate the time taken to measure and record one set of patient’s vital signs observations; and to identify factors associated with time to measure and record one set of patient’s vital signs observations.MethodsWe undertook a time-and-motion study of 16 acute medical or surgical wards across four hospitals in England. One hospital recorded vital signs on paper, while three recorded measurements on electronic devices. Two trained observers followed a standard operating procedure to record the time taken to measure and record vital sign observations. We used mixed-effects models to estimate the mean time using whole observation rounds, which included preparation time, or time spent taking observations at the bedside. We tested whether our estimates were influenced by nurse, ward and hospital factors.ResultsAfter excluding non-vital signs related interruptions, dividing the length of an observation round by the number of observations in that round yielded an estimated time per observation set of 5 minutes and 1 second (95% Confidence Interval (CI) = 4:39-5:24). If interruptions within the round were included, the estimated time was 6:26 (95% CI = 6:01-6:50). If only time taking each patient’s observations at the bedside was considered, after excluding non-vital signs related interruptions the estimated time was 3:45 (95% CI = 3:32-3:58). We found no substantial differences by hospital, ward or nurse characteristics, despite different systems for recording observations being used across the hospitals.DiscussionThe time taken to observe and record a patient’s vital signs is considerable, so changes to recommended observation frequency could have major workload implications. Variation in estimates derived from previous studies may, in part, arise from a lack of clarity about what was included in the reported times. We found no evidence that nurses save time when using electronic vital signs recording, or that the grade of staff taking the observation influenced the time taken.ConclusionsTaking and recording vital signs observations is time consuming and the impact of interruptions and preparation away from the bedside is considerable. When considering the nursing workload around vital signs observations, no assumption of relative efficiency should be made if different technologies or staff groups are deployed.
Contacts and behaviours of university students during the COVID-19 pandemic at the start of the 2020/21 academic year
Authors: Nixon Emily , Trickey Adam , Christensen Hannah , Finn Adam , Thomas Amy , Relton Caroline , Montgomery Clara , Hemani Gibran , Metz Jane , Walker Josephine G. , Turner Katy , Kwiatkowska Rachel , Sauchelli Sarah , Danon Leon , Brooks-Pollock Ellen 
Published: December 2020

AbstractCONQUEST (COroNavirus QUESTionnaire) is an online survey of contacts, behaviour, and COVID-19 symptoms for University of Bristol (UoB) staff/students. We analysed survey results from the start of the 2020/2021 academic year, prior to the second national lockdown (14/09/2020-01/11/2020), where COVID-19 outbreaks led to lockdown of some student halls of residence. The aim of these analyses was to enhance knowledge of student contact patterns to inform infection disease mathematical modelling approaches.Responses captured information on demographics, contacts on the previous day, symptoms and self-isolation during the prior week, and COVID-19 status.740 students provided 1261 unique records. Of 42 (3%) students testing positive in the prior fortnight, 99% had been self-isolating. The median number of contacts on the previous day was 2 (interquartile range: 1-5), mode: 1, mean: 6.1; 8% had ≥20 contacts. 57% of student contacts were other UoB students/staff.Most students reported few daily contacts but there was heterogeneity, and some reported many. Around 40% of student contacts were with individuals not affiliated with UoB, indicating potential for transmission to non-students/staff.
COVID-19 vaccine confidence and hesitancy among healthcare workers: a cross-sectional survey from a MERS-CoV experienced nation
Authors: Barry Mazin , Temsah Mohamad-Hani , Alhuzaimi Abdullah , Alamro Nurah , Al-Eyadhy Ayman , Aljamaan Fadi , Saddik Basema , Alhaboob Ali , Alsohime Fahad , Alhasan Khalid , Alrabiaah Abdulkarim , Alaraj Ali , Halwani Rabih , Jamal Amr , Alsubaie Sarah , Al-Shahrani Fatimah S. , Memish Ziad A. , Al-Tawfiq Jaffar A. 
Published: December 2020

AbstractObjectivesThis study aimed to identify COVID-19 vaccine perception, acceptance, confidence, hesitancy, and barriers among healthcare workers (HCW).MethodsAn online national cross-sectional pilot-validated questionnaire was self-administered by HCW in Saudi Arabia, a nation with MERS-CoV experience. The main outcome variable was HCW’s acceptance of COVID-19 vaccine candidates. The associated factors of vaccination acceptance were identified through a logistic regression analysis and the level of anxiety using generalized anxiety disorder 7.ResultOut of 1512 HCWs who completed the study questionnaire—944 (62.4%) women and 568 (37.6%) men—1058 (70%) were willing to receive COVID-19 vaccines. Logistic regression analysis revealed that male HCWs (ORa=1.551, 95% CI: 1.122–2.144), HCWs who believe in vaccine safety (ORa=2.151; 95% CI:1.708–2.708), HCWs who believe that COVID vaccines are the most likely way to stop the pandemic (ORa=1.539; 95% CI: 1.259–1.881), and HCWs who rely on Centers for Disease Control and Prevention website for COVID 19 updates (ORa=1.505, 95% CI: 1.125–2.013) were significantly associated with reporting willingness to be vaccinated. However, HCWs who believed vaccines were rushed without evidence-informed testing were found to be 60% less inclined to accept COVID-19 vaccines (ORa=0.394, 95% CI: 0.298– 0.522).ConclusionMost HCWs are willing to receive COVID-19 vaccines once available; yet, satisfactoriness of COVID-19 vaccination among HCWs is crucial because health professionals’ knowledge and confidence toward vaccines are important determining factors for their own vaccine acceptance and recommendation to their patients.
Investigating the origin of the Belgian second SARS-CoV-2 wave by using (pre)admission screening samples
Authors: Naesens Reinout , Heireman Laura , Vandamme Sarah , Willems Philippe , Van Herendael Bruno , Verstrepen Walter , De Schouwer Pieter , Bruynseels Peggy 
Published: December 2020

AbstractThe goal of this study was to estimate rates of SARS-CoV-2 carriership and viral loads in the general Antwerp population and to compare the estimated prevalences and incidences with governmental data (numbers of detected positive cases, stringency measure index) in order to evaluate the dynamics leading to the second wave. We used (pre)admission screening results from the major Antwerp hospitals for estimating community prevalences and incidences. 43.545 samples were included (April – November 2020). High SARS-CoV-2 carriership rates (mean week prevalence of 1.3%) were found in the general Antwerp population. 35.4% of positive cases carried high viral loads. Only a small proportion (15.3%) of the viral circulation was detected by the nationally implemented testing policy. In the weeks before the second Belgian wave, increasing prevalences and incidences were found, together with country-wide easing of restriction measures. In our opinion these findings have led to origin of the second viral wave.
Heartbeats entrain breathing via baroreceptor-mediated modulation of expiratory activity
Authors: Barnett William H. , Baekey David M. , Paton Julian F. R. , Dick Thomas E. , Wehrwein Erica A. , Molkov Yaroslav I. 
Published: December 2020

AbstractCardio-ventilatory coupling refers to a heartbeat (HB) occurring at a preferred latency before the onset of the next breath. We hypothesized that the pressure pulse generated by a HB activates baroreceptors that modulates brainstem expiratory neuronal activity and delays the initiation of inspiration. In supine male subjects, we recorded ventilation, electrocardiogram, and blood pressure during 20-min epochs of baseline, slow-deep breathing, and recovery. Inin siturodent preparations, we recorded brainstem activity in response to pulses of perfusion pressure. We applied a well-established respiratory network model to interpret these data. In humans, the latency between HBs and onset of inspiration was consistent across different breathing patterns. Inin situpreparations, a transient pressure pulse during expiration activated a subpopulation of expiratory neurons normally active during post-inspiration; thus, delaying the next inspiration. In the model, baroreceptor input to post-inspiratory neurons accounted for the effect. These studies are consistent with baroreflex activation modulating respiration through a pauci-synaptic circuit from baroreceptors to onset of inspiration.
Cortical resonance selects coherent input
Authors: Lewis Christopher Murphy , Ni Jianguang , Wunderle Thomas , Jendritza Patrick , Lazar Andreea , Diester Ilka , Fries Pascal 
Published: December 2020

SummarySynchronization has been implicated in neuronal communication, but causal evidence remains indirect. We used optogenetics to generate depolarizing currents in pyramidal neurons of cat visual cortex, emulating excitatory synaptic inputs under precise temporal control, while measuring spike output. Cortex transformed constant excitation into strong gamma-band synchronization, revealing the well-known cortical resonance. Increasing excitation with ramps increased the strength and frequency of synchronization. Slow, symmetric excitation profiles revealed hysteresis of power and frequency. Crucially, white-noise input sequences enabled causal analysis of network transmission, establishing that cortical resonance selectively transmits coherent input components. Models composed of recurrently coupled excitatory and inhibitory units uncovered a crucial role of feedback inhibition and suggest that hysteresis can arise through spike-frequency adaptation. The presented approach provides a powerful means to investigate the resonance properties of local circuits and probe how these properties transform input and shape transmission.
In Vivo CRISPR Screens Identify E3 Ligase Cop1 as a Modulator of Macrophage Infiltration and Cancer Immunotherapy Target
Authors: Wang Xiaoqing , Tokheim Collin , Wang Binbin , Gu Shengqing Stan , Tang Qin , Li Yihao , Traugh Nicole , Zhang Yi , Li Ziyi , Zhang Boning , Fu Jingxin , Xiao Tengfei , Li Wei , Meyer Clifford A. , Chu Jun , Jiang Peng , Cejas Paloma , Lim Klothilda , Long Henry , Brown Myles , Liu X. Shirley 
Published: December 2020

SUMMARYDespite remarkable clinical efficacies of immune checkpoint blockade (ICB) in cancer treatment, ICB benefits in triple-negative breast cancer (TNBC) remain limited. Through pooled in vivo CRISPR knockout (KO) screens in syngeneic TNBC mouse models, we found that inhibition of the E3 ubiquitin ligase Cop1 in cancer cells decreases the secretion of macrophage-associated chemokines, reduces tumor macrophage infiltration, and shows synergy in anti-tumor immunity with ICB. Transcriptomics, epigenomics, and proteomics analyses revealed Cop1 functions through proteasomal degradation of the C/ebpδ protein. Cop1 substrate Trib2 functions as a scaffold linking Cop1 and C/ebpδ, which leads to polyubiquitination of C/ebpδ. Cop1 inhibition stabilizes C/ebpδ to suppress the expression of macrophage chemoattractant genes. Our integrated approach implicates Cop1 as a target for improving cancer immunotherapy efficacy by regulating chemokine secretion and macrophage levels in the TNBC tumor microenvironment.HighlightsLarge-scale in vivo CRISPR screens identify new immune targets regulating the tumor microenvironmentCop1 knockout in cancer cells enhances anti-tumor immunityCop1 modulates chemokine secretion and macrophage infiltration into tumorsCop1 targets C/ebpδ degradation via Trib2 and influences ICB response
Duck, duck, goose: Benchmark bird surveys help quantify counting errors and bias in a citizen-science database
Authors: Robinson W. Douglas , Hallman Tyler A. , Hutchinson Rebecca A. 
Published: December 2020

AbstractThe growth of biodiversity data sets generated by citizen scientists continues to accelerate. The availability of such data has greatly expanded the scale of questions researchers can address. Yet, error, bias, and noise continue to be serious concerns for analysts, particularly when data being contributed to these giant online data sets are difficult to verify. Counts of birds contributed to eBird, the world’s largest biodiversity online database, present a potentially useful resource for tracking trends over time and space in species’ abundances. We quantified counting errors in a sample of 1406 eBird checklists by comparing numbers contributed by birders (N=246) who visited a popular birding location in Oregon, USA, with numbers generated by a professional ornithologist engaged in a long-term study creating benchmark (reference) measurements of daily waterbird counts. We focused on waterbirds, which are easily visible at this site. We evaluated potential predictors of count differences, including characteristics of contributed checklists, of each species, and of time of day and year. Count differences were biased toward undercounts, with more than 75% of counts being below the daily benchmark value. When only checklists that actually reported a species known to be present were included, median count errors were −29.1% (range: 0 to −42.8 %; N=20 species). Model sets revealed an important influence of each species’ reference count, which varied seasonally as waterbird numbers fluctuated, and of percent of species known to be present each day that were included on each checklist. That is, checklists indicating a more thorough survey of the species richness at the site also had, on average, lower counting errors. However, even on checklists with the most thorough species lists, counts were biased low and exceptionally variable in their accuracy. To improve utility of such bird count data, we suggest three strategies to pursue in the future. One is to assess additional options for analytically determining how to select checklists that have the highest probability of including less biased count data, as well as exploring options for correcting bias during the analysis stage. Another is to add options for users to provide additional information that helps analysts choose checklists, such as an option for users to tag checklists where they focused on obtaining accurate counts. We also recommend exploration of opportunities to effectively calibrate citizen-science bird count data by establishing a formalized network of marquis sites where dedicated observers regularly contribute carefully collected benchmark data.
Analysis of Intermolt and Postmolt Transcriptomes Provides Insight into Molecular Mechanisms of the Red Swamp Crayfish,Procambarus ClarkiiMolting
Authors: Su Shengyan , Munganga Brian Pelekelo , Tian Can , Li JianLin , Yu Fan , Li Hongxia , Wang Meiyao , He Xinjin , Tang Yongkai 
Published: December 2020

AbstractIn the present study, we explored expression changes in the transcriptomes of two molting stages (post-molt (M) and Intermolt (NM)) of the red swamp crayfish. A total of 307608398 clean reads, with an average length of 145bp were obtained. Further clustering and assembly of the transcripts generated 139100 unigenes. The results were searched against the NCBI, NR, KEGG, Swissprot, and KOG databases, in order to annotate gene descriptions, associate them with gene ontology terms, and assign them to pathways. Several genes and other factors involved in a number of molecular events critical for molting, such as energy requirements, hormonal regulation, immune response, and exoskeleton formation were identified, evaluated, and characterized. The information presented here provides a basic understanding of the molecular mechanisms underlying the crayfish molting process, with respect to energy requirements, hormonal regulation, immune response, and skeletal related activities during post-molt stage and the intermolt stage.
MRI- and histologically derived neuroanatomical atlas of theAmbystoma mexicanum(axolotl)
Authors: Lazcano Iván , Cisneros-Mejorado Abraham , Concha Luis , Ortíz Retana Juan José , Garza-Villarreal Eduardo A. , Orozco Aurea 
Published: December 2020

AbstractAmphibians are an important vertebrate model system to understand anatomy, genetics and physiology. Importantly, the brain and spinal cord of adult urodels (salamanders) have an incredible regeneration capacity, contrary to anurans (frogs) and the rest of adult vertebrates. Among these amphibians, the axolotl (Ambystoma mexicanum) has gained most attention because of the surge in the understanding of CNS regeneration and the recent sequencing of its whole genome. However, a complete comprehension of the brain anatomy is not available. In the present study we created a magnetic resonance imaging atlas of thein vivoneuroanatomy of the juvenile axolotl brain. This is the first MRI atlas for this species and includes 3 levels: 1) 80 regions of interest (ROIs); 2) a division of the brain according to the embryological origin of the neural tube, and 3) left and right hemispheres. Additionally, we localized the myelin rich regions of the juvenile brain. The atlas, the template that the atlas was derived from, and a masking file, can be found on Zenodo at DOI: 10.5281/zenodo.4311937. This MRI brain atlas aims to be an important tool for future research of the axolotl brain and that of other amphibians.
Expanding the range of editable targets in the wheat genome using the variants of the Cas12a and Cas9 nucleases
Authors: Wang Wei , Tian Bin , Pan Qianli , Chen Yueying , He Fei , Bai Guihua , Akhunova Alina , Trick Harold N. , Akhunov Eduard 
Published: December 2020

AbstractThe development of CRISPR-based editors having different protospacer adjacent motif (PAM) recognition specificities, or guide RNA length/structure requirements broadens the range of possible genome editing applications. Here, we evaluated the natural and engineered variants of Cas12a (FnCas12a fromFrancisella novicidaand LbCas12a fromLachnospiraceae bacterium) and Cas9 for wheat genome editing efficiency and ability to induce heritable mutations in endogenous genes controlling important agronomic traits in wheat. Unlike FnCas12a, LbCas12a was able to induce mutations in the wheat genome in the current study, even though with a lower rate than that reported for SpCas9. The eight-fold improvement in the gene editing efficiency was achieved for LbCas12a by using the guide RNAs flanked by ribozymes and driven by the RNA polymerase II promoter from switchgrass. The efficiency of multiplexed genome editing (MGE) using LbCas12a was mostly similar to that obtained using the simplex RNA guides. A LbCas12a-MGE construct was successfully applied for generating heritable mutations in a gene controlling grain size and weight in wheat. We show that the range of editable loci in the wheat genome could be expanded by using the engineered variants of Cas12a (LbCas12a-RVR) and Cas9 (Cas9-NG and xCas9) that recognize the TATV and NG PAMs, respectively, with the Cas9-NG showing higher editing efficiency on the targets with atypical PAMs compared to xCas9. In conclusion, our study reports the set of validated natural and engineered variants of Cas12a and Cas9 editors for targeting loci in the wheat genome not amenable to Cas9-based modification.
Directed differentiation of Dental Pulp Pluripotent-like Stem Cells into Hepatocyte-like Cells
Authors: Gil-Recio Carlos , Montori Sheyla , Cámara Vallejo M , Demour Saddam Al , Ferrés-Padró Eduard , Barajas Miguel , Martin Carles , Madhoun Ashraf Al , Atari Maher 
Published: December 2020

AbstractLiver diseases are a major cause of morbidity and mortality. Dental pulp pluripotent-like stem cells (DPPSC) are a considerable promise in tissue engineering and regenerative medicine as a source of tissue-specific cells, therefore this study aims to demonstrate their ability to generate functional hepatocyte-like cellsin vitro. Cells were differentiated on a collagen scaffolds in serum free media supplemented with growth factors and cytokines to recapitulate liver development. At day 5, the differentiated DPPSC cells expressed the endodermal markers FOXA1 and FOXA2. Then, the cells were derived into the hepatic lineage generating hepatocyte-like cells. In addition to the associated morphological changes, the cells expressed the hepatic genes HNF6, AFP. The terminally differentiated hepatocyte-like cells expressed the liver functional proteins albumin and CYP3A4. In this study, we report an efficient serum-free protocol to differentiate DPPSCs into functional hepatocyte-like cells. Our approach promotes the use of DPPSCs as a new source of adult stem cells for prospective use in liver regenerative medicine.