bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of sensitive circulating tumor DNA monitoring on CT scan intervals during postoperative colorectal cancer surveillance
Authors: Sasaki Tomoko , Iwaya Takeshi , Yaegashi Mizunori , Idogawa Masashi , Hiraki Hayato , Abe Masakazu , Koizumi Yuka , Sasaki Noriyuki , Yashima-Abo Akiko , Fujisawa Ryosuke , Endo Fumitaka , Tange Shoichiro , Hirano Tomomi , Otsuka Koki , Sasaki Akira , Masuda Mari , Fujita Masashi , Nakagawa Hidewaki , Takahashi Fumiaki , Sasaki Yasushi , Tokino Takashi , Nishizuka Satoshi S. 
Published: September 2022

ObjectiveThis study investigated whether digital PCR (dPCR)-based circulating tumor DNA (ctDNA) monitoringcan allow longer intervals between computed tomography (CT) scans during postoperative surveillance of colorectal cancer (CRC).DesignThe longitudinal dynamics of ctDNA for 52 patients with CRC as measured by dPCR using probes targeting 87 individual tumor-specific mutations (1-5 per patient) were compared with results from conventional (i.e., clinical) surveillance using serum tumor markers and CT. A total of 382 CT procedures were carried out for the patient cohort (3.3/year per patient) and the median lead time from ctDNA relapse to clinical relapse was 182 days (range 0-376 days). If the CT interval was annual, potential delays in detection of clinical relapse would have occurred for 7 of the 10 patients who experienced clinical relapse (9 of 13 events), with a median delay of 164 days (range, 0-267 days). If annual CT surveillance was performed together with ctDNA monitoring, 218 (57.1%) CTs would not have been needed to detect the first clinical relapse. Nonetheless, ctDNA monitoring would still have provided a lead time of 339 days for detection of clinical relapse (range, 42-533 days).ConclusionOur findings suggest that the ctDNA monitoring as part of post-operative surveillance and clinical relapse detection for patients with CRC could allow the CT interval to be lengthened.
Statistical learning of large-scale genetic data: How to run a genome-wide association study of gene-expression data using the 1000 Genomes Project data
Authors: Sugolov Anton , Emmenegger Eric , Paterson Andrew D. , Sun Lei 
Published: September 2022

AbstractTeaching statistics through engaging applications to contemporary large-scale datasets is essential to attracting students to the field. To this end, we developed a hands-on, week-long workshop for senior high-school or junior undergraduate students, without prior knowledge in statistical genetics but with some basic knowledge in data science, to conduct their own genome-wide association studies (GWAS). The GWAS was performed for open source gene expression data, using publicly-available human genetics data. Assisted by a detailed instruction manual, students were able to obtain ∼1.4 million p-values from a real scientific study, within several days. This early motivation kept students engaged in learning the theories that support their results, including regression, data visualization, results interpretation, and large-scale multiple hypothesis testing. To further their learning motivation by emphasizing the personal connection to this type of data analysis, students were encouraged to make short presentations about how GWAS has provided insights into the genetic basis of diseases that are present in their friends and/or families. The appended open source, step-by-step instruction manual includes descriptions of the datasets used, the software needed, and results from the workshop. Additionally, scripts used in the workshop are archived on Zenodo to further enhance reproducible research and training.
Survival rate of dental implants installed by residents attending an implantology Program in Brazil: a 52-month retrospective analysis
Authors: Kang Myungjin , Neto Henrique Smanio , Pelegrine André Antonio , Turssi Cecilia Pedroso , Clemente-Napimoga Juliana Trindade , Napimoga Marcelo Henrique 
Published: September 2022

AbstractThe aim of this study was to identify any associations between predictor variables, mainly risk factors and dental implant outcome. Dental records were reviewed from January 1, 2018, to December 31, 2020. The inclusion criteria was all implant surgery made using Intraoss brand. Data collected from the patients’ medical charts included: implant loss, gender, diabetes, smoking, continuous use of medication, type of implant connection system, implant position (maxilla or mandible), previous bone grafting and type of prosthetic provisioning (temporary prosthesis, immediate prosthesis or permanent prosthesis). It was evaluated the cumulative survival rate of 1,164 dental implants made by residents attending an implantology residency in a university setting. One thousand forty-eight dental implants were placed on 471 patients seen by residents. The cumulative survival rate was 2.5%. Furthemore, the association of implant losses to the variables tested using the chi-square and G tests showed no statistically significant association. Based on Kaplan-Meier curve analysis, with a 95% confidence interval up to 52 months of implant placement, it revealed that the overall survival rate was 90.5%. Therefore, this study showed high survival rates of implants installed by residents of implantology at Faculdade São Leopoldo Mandic using Intraoss implants. The implant failure was not correlated with any of the variables tested.
Savanna chimpanzees (Pan troglodytes verus) in Senegal react to deadly snakes and other reptiles: Testing the snake detection hypothesis
Authors: Pruetz Jill D. , LaDuke Thomas C. , Dobson K. 
Published: September 2022

AbstractThe hypothesis that dangerous snakes served as evolutionary selective pressures on traits characterizing the Order Primates (Snake Detection Hypothesis, SDH), specifically vision and aspects of the brain, has received recent attention. We provide data on 52 encounters between chimpanzees (Pan troglodytes verus) in a savanna landscape and snakes and other large reptiles at the Fongoli site in Senegal, over the course of eight years. These encounters yielded data on 178 interactions between identified individual chimpanzees and reptiles. The majority of encounters with identified reptiles (62%) involved potentially deadly snakes. Constrictors of the family Pythonidae were encountered more frequently than any other reptile. Chimpanzees exhibited a variety of reactions to reptiles, ranging from attacking with objects to ignoring them. Even reptiles other than snakes were met with some degree of alarm when they were in water or moving quickly. We assessed variables that may affect apes’ reactions, as well as the age-sex class of chimpanzees. As a test of Isbell’s snake detection hypothesis, we examined chimpanzees’ reaction intensity to venomous versus constricting snakes but found no difference. We did find significant age-sex differences in chimpanzees’ reactions to snakes, with adolescent males exhibiting higher-intensity reactions than adult males and females and adolescent female chimpanzees. Chimpanzees reacted at significantly higher intensities when snakes were arboreal in location, but reptile species, size, and activity did not significantly influence individuals’ reactions to snakes. We also report one inferred encounter between an adult female chimpanzee and a venomous snake, which led to her death. Our data suggest that snakes are significant threats to chimpanzees in savanna environments and support the hypothesis that danger from snakes could have exerted significant evolutionary pressure on the Order Primates.
Sea lamprey nests promote the diversity of benthic macroinvertebrate assemblages
Authors: Dhamelincourt Marius , Rives Jacques , Pons Marie , Larrañaga Aitor , Tentelier Cédric , Elosegi Arturo 
Published: September 2022

AbstractThe habitat heterogeneity hypothesis states that increased habitat heterogeneity promotes species diversity through increased availability of ecological niches. We aimed at describing the local-scale effects of nests of the sea lamprey (Petromyzon marinus L.) as ecosystem engineer on macroinvertebrate assemblages. We hypothesized that increased streambed physical heterogeneity caused by sea lamprey spawning would modify invertebrate assemblages and specific biologic traits and promote reach-scale diversity. We sampled thirty lamprey nests of the Nive River in three zones: the unmodified riverbed (control) and zones corresponding to the nest: the area excavated (pit) and the downstream accumulation of pebbles and cobbles (mound). The increased habitat heterogeneity created by lamprey was traduced by biological heterogeneity with a reduced density of invertebrates (1160 to 6540 individuals per m2 in control, 680 to 6460 individuals per m2 in pit and 1980 to 6240 individuals per m2 in mound) and number of taxa (23.5 ± 3.9 taxa for control, 18.6 ± 3.9 taxa in pit and 21.2 ± 4.5 taxa for mound) in the pit compared to other zones. However the overall taxa diversity in nest increased with 82 ± 14 taxa compared to the 69 ± 8 taxa estimated in control zone. Diversity indices were consistent with the previous results indicating a loss of α diversity in pit but a higher β diversity between a pit and a mound than between two control zones, especially considering Morisita index accounting for taxa abundance. Trait analysis showed high functional diversity within zones with a reduced proportion of collectors, scrapers, shredders, litter/mud preference and small invertebrates in mound, while the proportion of “slabs, blocks, stones and pebbles” preference and largest invertebrates increased. Pit presented the opposite trend, while control had globally intermediate trait proportions. Our results highlight important effects on species and functional diversity due to habitat heterogeneity created by a nest-building species, what can ultimately influence food webs and nutrient processes in river ecosystems.
Advanced Care Planning (ACP) in the early phase of COVID-19: A rapid review of the practice and policy lessons learned
Authors: Younan Sarah , Cardona Magnolia , Sahay Ashlyn , Willis Eileen , Chroinin Danielle Ni 
Published: September 2022

AbstractThis rapid review of quantitative and qualitative publications of any design indexed in PUBMED between January 2020-April 2021 investigates barriers and enablers of advancecare planning (ACP) worldwide in the early stages of the life-threatening COVID-19 pandemic. Seventy-four papers were included: 35 primary research studies (cohorts, reviews, case studies, and cross-sectional designs) and 39 commentaries. Publications from hospitals, outpatient services, aged care and community indicated widespread interest in accelerating ACP documentation to facilitate management decisions and goal-aligned care. Enablers of ACP included targeted public awareness, availability of telehealth, access to online tools and a person-centered approaches. Barriers included uncertainty regarding clinical outcomes, cultural or communication difficulties, legal and ethical considerations, infection control restrictions, lack of time, and limited resources and support systems. The opportunities for rapid implementation of ACP offered by the social distancing restrictions and high demand for health services are valuable in informing future policy and practice.What this paper addsOur study adds to existing evidence by identifying emerging barriers and creative ways of overcoming them in response to a global crisisDiscussions on death prospects and care of the dying were feasible and a step towards normalisation of advance care planningDespite new and overwhelming challenges, policies and practices could be rapidly implemented to satisfy clinicians and families in need of advance care planningApplications of study findingsThe lessons learnt can be incorporated in future health service planning since the threat of other pandemics is realA formal evaluation of effectiveness of some of the emerging strategies would be a valuable addition to the evidence
AHoJ: rapid, tailored search and retrieval of apo and holo protein structures for user-defined ligands
Authors: Feidakis Christos P. , Krivak Radoslav , Hoksza David , Novotny Marian 
Published: September 2022

AbstractUnderstanding the mechanism of action of a protein or designing better ligands for it often requires access to a bound (holo) and an unbound (apo) state of the protein. Resources for the quick and easy retrieval of such conformations are severely limited.Apo-Holo Juxtaposition (AHoJ) is a web application for retrieving apo-holo structure pairs for user-defined ligands. Given a query structure and one or more defined ligands, it retrieves all other structures of the same protein that feature the same binding sites(s), aligns them, and examines the superimposed binding sites to determine whether each structure is apo or holo, in reference to the query. The resulting superimposed datasets of apo-holo pairs can be visualized and downloaded for further analysis. AHoJ accepts multiple input queries, allowing the creation of customized apo-holo datasets. To demonstrate AHoJ’s functionality, we present a newly constructed dataset of apo-holo pairs featuring 13 ion ligands, by complimenting an existing database of biologically relevant holo interactions (BioLiP).Availability and ImplementationFreely available for non-commercial use at http://apoholo.cz.Graphical abstract
The cytidine deaminase APOBEC3G drives cancer mutagenesis and clonal evolution in bladder cancer
Authors: Liu Weisi , Newhall Kevin P. , Khani Francesca , Barlow LaMont , Nguyen Duy , Gu Lilly , Eng Ken , Bhinder Bhavneet , Uppal Manik , Récapet Charlotte , Sboner Andrea , Ross Susan R. , Elemento Olivier , Chelico Linda , Faltas Bishoy M. 
Published: September 2022

AbstractMutagenic processes leave distinct signatures in cancer genomes. The mutational signatures attributed to APOBEC3 cytidine deaminases are pervasive in human cancers. However, data linking individual APOBEC3 proteins to cancer mutagenesis in vivo are limited. Here, we show that transgenic expression of human APOBEC3G promotes mutagenesis, genomic instability, and kataegis, leading to shorter survival in a murine bladder cancer model. Acting as mutagenic fuel, APOBEC3G increases the clonal diversity of bladder cancers, driving divergent cancer evolution. We characterize the single base substitution signature induced by APOBEC3G in vivo, showing the induction of a mutational signature different from that caused by APOBEC3A and APOBEC3B. Analysis of thousands of human cancers reveals the contribution of APOBEC3G to the mutational profiles of multiple cancer types, including bladder cancer. Our findings define the role of APOBEC3G in cancer mutagenesis and clonal heterogeneity. These results potentially inform future therapeutic efforts that restrict tumor evolution.
Acquisition of hybrid E/M phenotype associated with increased migration, drug resistance and stemness is mediated by reduced miR-18a levels in ER-negative breast cancer
Authors: Nair Madhumathy G , Apoorva D , Chandrakala M , Snijesh VP , Anupama CE , Rajarajan Savitha , Sahoo Sarthak , Mohan Gayathri , Jayakumar Vishnu Sunil , Ramesh Rakesh S , Srinath BS , Jolly Mohit Kumar , Maliekal Tessy Thomas , Prabhu Jyothi S 
Published: September 2022

AbstractThe complexity of the ER-negative subtype of breast cancer arises due to the heterogeneous nature of the disease rendering them more aggressive and this poses a challenge to effective treatment and eventually the prognosis of the patients. We have explored the miRNA regulation of altered molecular signatures and the effect on tumour progression in ER-negative breast cancer. Using breast tumour specimens, gene expression data from public datasets and in-vitro and in-vivo model systems we have shown that low-levels of miR-18a in ER-negative tumours drives enrichment of hybrid Epithelial/Mesenchymal (E/M) cells with luminal attributes. On inhibition of miR-18a in ER-negative breast cancer cell lines, the cells showed traits of increased migration, stemness and drug-resistance. miR-18a/low tumours were also associated with increased expression of genes associated with EMT, stemness, drug resistance and immune-suppression. Further analysis of the miR-18a targets pointed out at a possible HIF-1α mediated signalling in these tumours. HIF-1α inhibition reduced the enrichment of the hybrid E/M cells and decreased the migratory ability of miR-18a/low cells. Our study reports for the first time a dual role of miR-18a in breast cancer that is subtype specific based on hormone receptor expression and a novel association of low miR-18a levels and enrichment of hybrid E/M cells. The results highlight the possibility of stratifying the ER-negative disease into clinically relevant groups by analysing epigenetic signatures.
BBB-on-a-chip with Integrated micro-TEER for permeability evaluation of multi-functionalized gold nanorods against Alzheimer’s disease
Authors: Palma-Florez Sujey , López-Canosa Adrián , Morales-Zavala Francisco , Castaño Oscar , Kogan M.J. , Samitier Josep , Lagunas Anna , Mir Mónica 
Published: September 2022

ABSTRACTBackgroundThe lack of predictive models that mimic the blood-brain barrier (BBB) hinders the development of effective drugs for neurodegenerative diseases. Animal models behave differently from humans, are expensive and have ethical constraints. Organ-on-a-chip (OoC) platforms offer several advantages to resembling physiological and pathological conditions in a versatile, reproducible, and animal-free manner. In addition, OoC give us the possibility to incorporate sensors to determine cell culture features such as trans-endothelial electrical resistance (TEER). Here, we developed a BBB-on-a-chip (BBB-oC) platform with a TEER measurement system in close distance to the barrier used for the first time for the evaluation of the permeability performance of GNR-PEG-Ang2/D1 for Alzheimer’s disease. GNR-PEG-Ang2/D1 is a therapeutic nanosystem previously developed by us consisting of gold nanorods (GNR) functionalized with polyethylene glycol (PEG), angiopep-2 peptide (Ang2) to overcome the BBB and the D1 peptide as beta amyloid fibrillation inhibitor, finally obtaining GNR-PEG-Ang2/D1 which showed to be useful for disaggregation of the amyloid inin vitroandin vivomodels. In this work, we evaluated its cytotoxicity, permeability, and some indications of its impact on the brain endothelium by employing an animal-free device based on neurovascular human cells.ResultsIn this work, we fabricated a BBB-oC with human astrocytes, pericytes and endothelial cells and a TEER measuring system (TEER-BBB-oC) integrated at a micrometric distance of the endothelial barrier. The characterization displayed a neurovascular network and the expression of tight junctions in the endothelium. We produced GNR-PEG-Ang2/D1 and determined its non-cytotoxic range (0,05–0,4 nM) for plated cells included in the BBB-oC and confirmed its harmless effect at the highest concentration (0.4 nM) in the microfluidic device. The permeability assays revealed that GNR-PEG-Ang2/D1 cross the BBB and this entry is facilitated by Ang2 peptide. Parallel to the permeability analysis of GNR-PEG-Ang2/D1, an interesting behavior of the TJs expression was observed after its administration probably related to the ligands on the nanoparticle surface.ConclusionBBB-oC with TEER integrated setup was proven as a functional and throughput platform to evaluate the brain permeability performance of nanotherapeutics in a physiological environment with human cells, putting forward a viable alternative to animal experimentation.
Membrane Targeted Azobenzene Drives Optical Modulation of Bacterial Membrane Potential
Authors: de Souza-Guerreiro Tailise Carlina , Bondelli Gaia , Grobas Iago , Donini Stefano , Sesti Valentina , Bertarelli Chiara , Lanzani Guglielmo , Asally Munehiro , Paternò Giuseppe Maria 
Published: September 2022

AbstractRecent studies have shown that bacterial membrane potential is dynamic and plays signalling roles. Yet, little is still known about the mechanisms of bacterial membrane potential regulation –owing in part to a scarcity of appropriate research tools. Optical modulation of bacterial membrane potential could fill this gap and provide a new approach to studying and controlling bacterial physiology and electrical signalling. Here, we show that a membrane-targeted azobenzene (Ziapin2) can be used to photo-modulate the membrane potential in cells of the Gram-positive bacterium Bacillus subtilis. We found that upon exposure to blue-green light (λ = 470 nm), isomerization of Ziapin2 in the bacteria membrane induces hyperpolarisation of the potential. In order to investigate the origin of this phenomenon we examined ion-channel-deletion strains and ion channel blockers. We found that in presence of the chloride channel blocker idanyloxyacetic acid-94 (IAA-94) or in absence of KtrAB potassium transporter, the hyperpolarisation response is attenuated. These results reveal that the Ziapin2 isomerization can induce ion channel opening in the bacterial membrane, and suggest that Ziapin2 can be used for studying and controlling bacterial electrical signalling. This new optical tool can contribute to better understand microbial phenomena, such as biofilm electric signalling and antimicrobial resistance.
The Tripod neuron: a minimal structural reduction of the dendritic tree
Authors: Quaresima Alessio , Fitz Hartmut , Duarte Renato , van den Broek Dick , Hagoort Peter , Petersson Karl Magnus 
Published: September 2022

AbstractNeuron models with explicit dendritic dynamics have shed light on mechanisms for coincidence detection, pathway selection, and temporal filtering. However, it is still unclear which morphological and physiological features are required to capture these phenomena. In this work, we introduce the Tripod neuron model and propose a minimal structural reduction of the dendritic tree that is able to reproduce these dendritic computations. The Tripod is a three-compartment model consisting of two segregated passive dendrites and a somatic compartment modeled as an adaptive, exponential integrate-and-fire neuron. It incorporates dendritic geometry, membrane physiology, and receptor dynamics as measured in human pyramidal cells. We characterize the response of the Tripod to glutamatergic and GABAergic inputs and identify parameters that support supra-linear integration, coincidence-detection, and pathway-specific gating through shunting inhibition. Following NMDA spikes, the Tripod neuron generates plateau potentials whose duration depends on the dendritic length and the strength of synaptic input. When fitted with distal compartments, the Tripod neuron encodes previous activity into a dendritic depolarized state. This dendritic memory allows the neuron to perform temporal binding and we show that the neuron solves transition and sequence detection tasks on which a single-compartment model fails. Thus, the Tripod neuron can account for dendritic computations previously explained only with more detailed neuron models or neural networks. Due to its simplicity, the Tripod model can be used efficiently in simulations of larger cortical circuits.