bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of molecular heterogeneity of colorectal cancer among Bangladeshi population by targeted next generation sequencing
Authors: Kamruzzaman Mohammad , Rahman Aura , Karmakar Aparna R , Alam A B M Khurshid , Kader Kazi Monzur , Jamal A B M , Hossain Maqsud 
Published: November 2022

AbstractBackgroundSince the Sanger sequencing procedure was invented, scientists all over the world have been working to improve and further develop this cutting-edge technology. Next-generation sequencing (NGS) is a game-changing advancement and the ability to profile genetic changes in cancer in great detail has been made possible by recent advances in sequencing technology.Several studies produced high-quality data in terms of mutation identification, particularly in the areas of actionable or rarely mutated genes, epigenetics, and transcriptomics. The goal of this project is to look at genetic heterogeneity in Bangladeshi colorectal cancer patients so that cost-effective precision medicine can be developed applied in Bangladesh.MethodsThe mutational characteristics of 24 colorectal tumor samples from Bangladeshi patients were investigated using targeted next generation sequencing to explore the association of mutations with clinical aspects. A total of 50 genes were sequenced with an average target depth of 675X.ResultsThe left-sided tumors had higher mutation frequencies in TP53, APC, and ATM, while the right-sided tumors had higher mutation frequencies in EZH2, HNF1A, HRAS, and PIK3CA. Almost all of the samples in this study had a mutation in FGFR3. Deleterious mutations in the APC gene (94%) provided a selective advantage to the nascent intestinal tumor cell via constitutional stimulation of the Wnt signal transduction pathway and chromosomal instability. CDKN2A nonsynonymous mutations were found in almost all patient samples, with the exception of one. In a different patient with three unique mutations, 17 samples (71%) had a mutation in SMAD4 located in exon5 (p.P223N) synonymous and nonsynonymous mutations (two in NGRI04, and one in NGRI10). Several genes, including ATM, CDH1, ERBB4, and FBXW7, have been identified as being significantly affected by TNM stages.Except for a few key colorectal cancer genes, a comparison of mutational characteristics with subjects from other countries’ independent data re vealed that the identified mutational characteristics are largely Bangladesh-specific.ConclusionIn Bangladesh, precision medicine development and use in colorectal cancer are poorly addressed. The pilot study will serve as a starting point for genomics research into colon cancer in poor-resource settings like Bangladesh. The relationship between metastasis and genomic markers will aid in the identification of prospective intervention markers and the development of therapeutic options at the individual level, resulting in the development of precision medicine.
Proteomic analysis of circulating immune cells identifies novel cellular phenotypes associated with COVID-19 severity
Authors: Potts Martin , Fletcher-Etherington Alice , Nightingale Katie , Mescia Federica , Bergamaschi Laura , Calero-Nieto Fernando J. , Antrobus Robin , Williamson James ,   Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration, Kingston Nathalie , Göttgens Berthold , Bradley John R , Lehner Paul J , Matheson Nicholas J , Smith Kenneth G.C. , Wills Mark R , Lyons Paul A , Weekes Michael P 
Published: November 2022

SummaryCertain serum proteins, including CRP and D-dimer, have prognostic value in patients with SARS-CoV-2 infection. Nonetheless, these factors are non-specific, and provide limited mechanistic insight into the peripheral blood mononuclear cell (PBMC) populations which drive the pathogenesis of severe COVID-19. To identify novel cellular phenotypes associated with disease progression, we here describe a comprehensive, unbiased analysis of the total and plasma membrane proteomes of PBMCs from a cohort of 40 unvaccinated individuals with SARS-CoV-2 infection, spanning the whole spectrum of disease severity. Combined with RNA-seq and flow cytometry data from the same donors, we define a comprehensive multi-omic profile for each severity level, revealing cumulative immune cell dysregulation in progressive disease. In particular, the cell surface proteins CEACAMs1, 6 and 8, CD177, CD63 and CD89 are strongly associated with severe COVID-19, corresponding to the emergence of atypical CD3+CD4+CD177+and CD16+CEACAM1/6/8+mononuclear cells. Utilisation of these markers may facilitate real-time patient assessment by flow cytometry, and identify immune cell populations that could be targeted to ameliorate immunopathology.
The CANDID Study: impact of COVID-19 on critical care nurses and organisational outcomes: implications for the delivery of critical care services. A questionnaire study before and during the pandemic
Authors: McCallum Louise , Rattray Janice , Pollard Beth , Miller Jordan , Hull Alastair , Ramsay Pam , Salisbury Lisa , Scott Teresa , Cole Stephen , Dixon Diane 
Published: November 2022

AbstractObjectiveTo use a model of occupational stress to quantify and explain the impact of working in critical care during the Covid-19 pandemic on critical care nurses and organisational outcomes.ParticipantsCritical care nurses (CCNs) who worked in the UK NHS between January to November 2021 (n=461).MethodsA self-reported survey measured the components of the Job-Demand Reward model of occupational stress. Job-demands, job-resources, health impairment (mental health (GHQ-12), burnout (MBI), PTSD symptoms (PCL-5)), work engagement and six organisational outcomes (commitment, job satisfaction, changing jobs, certainty about the future, quality of care, patient safety) were measured. Data were compared to baseline data (n=557) collected between April to October 2018. Regression analyses identified predictors of health impairment, work engagement and organisational outcomes.FindingsCompared to 2018, CCNs were at elevated risk of probable psychological distress (GHQ-12, OR 6.03 [95% C.I. 4.75 to 7.95]; burnout emotional exhaustion, OR 4.02 [3.07 to 5.26]; burnout depersonalisation, OR 3.18 [1.99 to 5.07]; burnout accomplishment, OR 1.53 [1.18 to 1.97]). A third of CCNs reported probable PTSD. Job demands predicted psychological distress and job demands increased during the pandemic. Resources reduced the negative impact of job demands on psychological distress, but this moderating effect of resources was not observed at higher levels of demand. CCNs were less engaged in their work. Job and personal resources predicted work engagement and were reduced during the pandemic. All six organisational outcomes were impaired. Lack of resources, especially reduced learning opportunities, lack of focus on staff wellbeing, and reduced focus on quality predicted worse organisational outcomes.ConclusionsThe NHS needs to prioritise the welfare of CCNs, implement workplace change/planning, and support them to recover from the pandemic. The NHS is struggling to retain CCNs and, unless staff welfare is improved, quality of care and patient safety will likely decline.
The genomic footprint of social stratification in admixing American populations
Authors: Mas-Sandoval Alex , Mathieson Sara , Fumagalli Matteo 
Published: November 2022

AbstractCultural and socioeconomic differences stratify human societies and shape their genetic structure beyond the sole effect of geography. Despite mating being limited by the permeability of sociocultural stratification, most demographic models in population genetics often assume random mating. Taking advantage of the correlation between sociocultural stratification and the proportion of genetic ancestry in admixed populations, we sought to infer the former process in the Americas. To this aim, we define a mating model where the individual proportions of the genome inherited from Native American, European and sub-Saharan African ancestral populations constrain the mating probabilities through ancestry-related assortative mating and sex bias parameters. We simulate a wide range of admixture scenarios under this model. Then, we train a deep neural network and retrieve good performance in predicting mating parameters from genomic data. Our results show how population stratification shaped by racial and gender hierarchies have constrained the admixture processes in the Americas since the European colonisation and the subsequent Atlantic slave trade.
Maximizing the reliability and the number of species assignments in metabarcoding studies
Authors: Bourret Audrey , Nozères Claude , Parent Eric , Parent Geneviève J. 
Published: November 2022

AbstractThe use of environmental DNA (eDNA) for biodiversity assessments has increased rapidly over the last decade. However, the reliability of taxonomic assignments in metabarcoding studies is variable, and affected by the reference databases and the assignment methods used. Species level assignments are usually considered as reliable using regional libraries but unreliable using public repositories. In this study, we aimed to test this assumption for metazoan species detected in the Gulf of St. Lawrence, in the Northwest Atlantic. We first created a regional library with COI barcode sequences including a reliability ranking system for species assignments. We then estimated the accuracy of the public repository NCBI-nt for species assignments using sequences from the regional library, and contrasted assigned species and their reliability using NCBI-nt or the regional library with a metabarcoding dataset and popular assignment methods. With NCBI-nt and sequences from the regional library, Blast-LCA was the most accurate method for species assignments but the proportions of accurate species assignments were higher with Blast-TopHit (>80 % overall taxa, between 70 and 90 % amongst taxonomic groups). With the metabarcoding dataset, the reliability of species assignments was greater using the GSL-rl compared to NCBI-nt. However, we also observed that the total number of reliable species assignments could be maximized using both GSL-rl and NCBI-nt, and their optimal assignment methods, which differed. The use of a two-step approach in species assignments, using a regional library and a public repository, could improve the reliability and the number of detected species in metabarcoding studies.
Therapy-induced senescence upregulates antigen presentation machinery and triggers anti-tumor immunity in Acute Myeloid Leukemia
Authors: Gilioli Diego , Fusco Simona , Tavella Teresa , Giannetti Kety , Conti Anastasia , Santoro Antonella , Carsana Edoardo , Beretta Stefano , Schönlein Martin , Gambacorta Valentina , Aletti Federico Mario , Carrabba Matteo Giovanni , Bonini Chiara , Ciceri Fabio , Merelli Ivan , Vago Luca , Schmitt Clemens , Di Micco Raffaella 
Published: November 2022

ABSTRACTAcute myeloid leukemia (AML) is an aggressive hematological malignancy often curable only by using intensive chemotherapy. Nonetheless, resistance/early relapses are frequent, underscoring the need to investigate the molecular events occurring shortly after chemotherapy. Therapy-induced senescence (TIS) is a fail-safe tumor suppressive mechanism that may elicit immune-mediated responses contributing to senescent cell clearance. Yet, TIS functional role in AML eradication and immune surveillance early post-chemotherapy remains ill-defined. By combining transcriptional and cellular-based evaluation of senescence markers in AML patient samples, we found upregulation of senescence-associated genes and interferon gene categories with concomitant induction of HLA class I and class II molecules, pointing to a causal link between TIS and leukemia immunogenicity. Consistently, senescence-competent AML samples activated autologous CD4+and CD8+T cells and improved leukemia recognition by both T-cell subsets. Lastly, the anti-leukemic activity of Immune Checkpoint Blockades (ICBs) was enhanced upon senescence engagement in AML. Altogether, our results identify senescence as a potent immune-related anti-leukemic mechanism that may rapidly translate into innovative senescence-based strategies to prevent AML relapse.STATEMENT OF SIGNIFICANCEOur findings uncover a novel link between senescence induction and leukemia immune recognition by T cells via upregulation of antigen presentation machinery components, providing the basis for conceptually novel senescence-based targeted immunotherapeutic regimens for AML patients.
Transcriptional analysis in bacteriophage Fc02 ofPseudomonas aeruginosarevealed two overlapping genes with exclusion activity
Authors: Ramírez-Sánchez Irais , Magos-Castro Marco , Guarneros Gabriel 
Published: November 2022

AbstractLittle is known about the gene expression program during transition from lysogenic to lytic cycles of temperate bacteriophages inPseudomonas aeruginosa. To investigate this issue, we developed a thermo-sensitive repressor mutant in a lysogen and analyzed the phage transcriptional program by strand-specific RNA-Seq before and after thermo-induction. As expected, the repressor gene located on the phage DNA forward strand, is transcribed in the lysogen at the permissive temperature of 30°C. Upstream the promoter gene, we noticed the presence of two overlapped ORFs apparently in the same transcript, one ORF is a gene that encodes a protein of 7.9 kDa mediating exclusion of various super-infecting phages. The other ORF, placed in an alternate reading frame, with a possible AUG initiation codon at 25 n downstream the AUG of the first gene, is expected to encode a 20.7 kDa polypeptide of yet unknown function. Upon lifting repression at 40°C, starts transcription of an operon, involved in the lytic cycle from a promoter on the reverse phage DNA strand. The first gene in the operon is a homolog of the antirepresorner, a common gene in the lysis-lysogeny regulation region of other phages. Interestingly, the next gene afterneris gene10 that on the reverse strand, overlaps the overlapped geneolg1on the forward strand. Curiously, gene 10 expression also shows superinfection exclusion. Strand-specific RNA-Seq also has uncover the transcription succession of gene modules expressed during the phage lytic stage.
Improved Neutralization of Omicron BA.4/5, BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1 with Bivalent BA.4/5 Vaccine
Authors: Zou Jing , Kurhade Chaitanya , Patel Sohil , Kitchin Nicholas , Tompkins Kristin , Cutler Mark , Cooper David , Yang Qi , Cai Hui , Muik Alexander , Zhang Ying , Lee Dung-Yang , Sahin Ugur , Anderson Annaliesa S. , Gruber William C. , Xie Xuping , Swanson Kena A. , Shi Pei-Yong 
Published: November 2022

AbstractThe BNT162b2 bivalent BA.4/5 COVID-19 vaccine has been authorized to mitigate COVID-19 due to current Omicron and potentially future variants. New sublineages of SARS-CoV-2 Omicron continue to emerge and have acquired additional mutations, particularly in the spike protein, that may lead to improved viral fitness and immune evasion. The present study characterized neutralization activities against new Omicron sublineages BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1 after a 4thdose (following three doses of BNT162b2) of either the original monovalent BNT162b2 or the bivalent BA.4/5 booster in individuals >55 years of age. For all participants, the 4thdose of monovalent BNT162b2 vaccine induced a 3.0×, 2.9×, 2.3×, 2.1×, 1.8×, and 1.5× geometric mean neutralizing titer fold rise (GMFR) against USA/WA1-2020 (a strain isolated in January 2020), BA.4/5, BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1, respectively; the bivalent vaccine induced 5.8×, 13.0×, 11.1×, 6.7×, 8.7×, and 4.8× GMFRs. For individuals without SARS-CoV-2 infection history, BNT162b2 monovalent induced 4.4×, 3.0×, 2.5×, 2.0×, 1.5×, and 1.3× GMFRs, respectively; the bivalent vaccine induced 9.9×, 26.4×, 22.2×, 8.4×, 12.6×, and 4.7× GMFRs. These data suggest the bivalent BA.4/5 vaccine is more immunogenic than the original BNT162b2 monovalent vaccine against circulating Omicron sublineages, including BQ.1.1 that is becoming prevalent globally.
Sleep deprivation detected by voice analysis
Authors: Thoret Etienne , Andrillon Thomas , Gauriau Caroline , Léger Damien , Pressnitzer Daniel 
Published: November 2022

AbstractSleep deprivation has an ever-increasing impact on individuals and societies. Yet, to date, there is no quick and objective test for sleep deprivation. Here, we used automated acoustic analyses of the voice to detect sleep deprivation. Building on current machine-learning approaches, we focused on interpretability by introducing two novel ideas: the use of a fully generic auditory representation as input feature space, combined with an interpretation technique based on reverse correlation. The auditory representation consisted of a spectro-temporal modulation analysis derived from neurophysiology. The interpretation method aimed to reveal the regions of the auditory representation that supported the classifiers’ decisions. Results showed that generic auditory features could be used to detect sleep deprivation successfully, with an accuracy comparable to state-of-the-art speech features. Furthermore, the interpretation revealed two distinct effects of sleep deprivation on the voice: a change in prosody and a change in timbre. Importantly, the relative balance of the two effects varied widely across individuals, even though the amount of sleep deprivation was controlled, thus confirming the need to characterize sleep deprivation at the individual level. Moreover, while the prosody factor correlated with subjective sleepiness reports, the timbre factor did not, consistent with the presence of both explicit and implicit consequences of sleep deprivation. Overall, the findings show that individual effects of sleep deprivation may be observed in vocal biomarkers. Future investigations correlating such markers with objective physiological measures of sleep deprivation could enable “sleep stethoscopes” for the cost-effective diagnosis of the individual effects of sleep deprivation.Author summarySleep deprivation has an ever-increasing impact on individuals and societies, from accidents to chronic conditions costing billions to health systems. Yet, to date, there is no quick and objective test for sleep deprivation. We show that sleep deprivation can be detected at the individual level with voice recordings. Importantly, we focused on interpretability, which allowed us to identify two independent effects of sleep deprivation on the voice: a change in prosody and a change in timbre. The results also revealed a striking variability in individual reactions to the same deprivation, further confirming the need to consider the effects of sleep deprivation at the individual level. Vocal markers could be correlated to specific underlying physiological factors in future studies, outlining possible cost-effective and non-invasive “sleep stethoscopes”.
Assigning functionality to cysteines by base editing of cancer dependency genes
Authors: Li Haoxin , Remsberg Jarrett R. , Won Sang Joon , Zhao Kevin T. , Huang Tony P. , Lu Bingwen , Simon Gabriel M. , Liu David R. , Cravatt Benjamin F. 
Published: November 2022

ABSTRACTChemical probes are lacking for most human proteins. Covalent chemistry represents an attractive strategy for expanding the ligandability of the proteome, and chemical proteomics has revealed numerous electrophile-reactive cysteines on diverse proteins. Determining which of these covalent binding events impact protein function, however, remains challenging. Here, we describe a base-editing strategy to infer the functionality of cysteines by quantifying the impact of their missense mutation on cell proliferation. We show that the resulting atlas, which covers >13,800 cysteines on >1,750 cancer dependency proteins, correctly predicts the essentiality of cysteines targeted by cancer therapeutics and, when integrated with chemical proteomic data, identifies essential, ligandable cysteines on >110 cancer dependency proteins. We further demonstrate how measurements of reactivity in native versus denatured proteomes can discriminate essential cysteines amenable to chemical modification from those buried in protein structures, providing a valuable resource to prioritize the pursuit of small-molecule probes with high function-perturbing potential.
Quadratic computations maintain neural specificity to natural stimuli across stages of visual processing
Authors: Rowekamp Ryan J. , Sharpee Tatyana 
Published: November 2022

AbstractDespite recent successes in machine vision, artificial recognition systems continue to be less robust than biological systems. The brittleness of artificial recognition system has been attributed to the linearity of the core operation that matches inputs to target patterns at each stage of the system. Here we analyze responses of neurons from the visual areas V1, V2, and V4 of the brain using the framework that incorporates quadratic computations into multi-stage models. These quadratic computations make it possible to capture local recurrent computation, and in particular, nonlinear suppressive interactions between visual features. We find that incorporating quadratic computation not only strongly improved predictive power of the resulting model, but also revealed several computation motifs that increased the selectivity of neural responses to natural stimuli. These motifs included the organization of excitatory and suppressive features along mutually exclusive hypotheses about incoming stimuli, such as orthogonal orientations or opposing motion directions. The balance between excitatory and suppressive features was largely maintained across brain regions. These results emphasize the importance and properties of quadratic computations that are necessary for achieving robust object recognition.
The effect of context congruency on fMRI repetition suppression for objects
Authors: Li Chenglin , Ficco Linda , Trapp Sabrina , Rostalski Sophie-Marie , Korn Lukas , Kovács Gyula 
Published: November 2022

AbstractThe recognition of objects is strongly facilitated when they are presented in the context of other objects (Biederman, 1972). Such contexts facilitate perception and induce expectations of context-congruent objects (Trapp & Bar, 2015). The neural mechanisms underlying these facilitatory effects of context on object processing, however, are not yet fully understood. In the present study, we investigate how context-induced expectations affect subsequent object processing. We used functional magnetic resonance imaging and measured repetition suppression, a proxy for prediction error processing, for pairs of alternating or repeated object images, preceded by context-congruent, context-incongruent or neutral cues. We found a stronger repetition suppression in congruent as compared to incongruent or neutral cues in the object sensitive lateral occipital cortex. Interestingly, this effect was driven by enhanced responses to alternating stimulus pairs in the congruent contexts. In addition, in the congruency condition, we discovered significant functional connectivity between object-responsive and frontal cortical regions, as well as between object-responsive regions and the fusiform gyrus. Our findings unravel the neural mechanisms underlying context facilitation.