bluuebunny/crossref_metadata_2025_split huggingface dataset:
Limitations of models for guiding policy in the COVID-19 pandemic
Authors: McKeigue Paul M , Wood Simon N 
Published: April 2023

AbstractAt the outset of the COVID-19 epidemic in the UK, infectious disease modellers advised the government that unless a lockdown was imposed, most of the population would be infected within a few months and critical care capacity would be overwhelmed. This paper investigates the quantitative arguments underlying these predictions, and draws lessons for future policy.The modellers assumed that within age bands all individuals were equally susceptible and equally connected, leading to predictions that more than 80% of the population would be infected in the first wave of an unmitigated epidemic. Models that relax this unrealistic assumption to allow for selective removal of the most susceptible and connected individuals predict much smaller epidemic sizes. In most European countries no more than 10% of the population was infected in the first wave, irrespective of what restrictions were imposed. The modellers assumed that about 2% of those infected would require critical care, far higher than the proportion who entered critical care in the first wave, and failed to identify the key role of nosocomial transmission in overloading health systems. Model-based forecasts that only a lockdown could suppress the epidemic relied on a survey of contact rates in 2006, with no information on the types of contact most relevant to aerosol transmission or on heterogeneity of contact rates.In future epidemics, modellers should communicate the uncertainties associated with their assumptions and data, especially when these models are used to recommend policies that have high societal costs and are hard to reverse. Recognition of the gap between models and reality also implies a need to rebalance in favour of greater reliance on rapid studies of real-world transmission, robust model criticism, and acceptance that when measurements contradict model predictions it is the model that needs to be changed.
EGR1 regulates oral epithelial cell responses toCandida albicansvia the EGFR- ERK1/2 pathway
Authors: Dickenson Ruth E. , Pellon Aize , Ponde Nicole O. , Hepworth Olivia , Daniels Gatward Lydia F. , Naglik Julian R. , Moyes David L. 
Published: April 2023

ABSTRACTCandida albicansis a fungal pathobiont colonising mucosal surfaces of the human body, including the oral cavity. Under certain predisposing conditions,C. albicansinvades mucosal tissues activating EGFR-MAPK signalling pathways in epithelial cells via the action of its peptide toxin candidalysin. However, our knowledge of the epithelial mechanisms involved duringC. albicanscolonisation is rudimentary. Here, we describe the role of the transcription factor early growth response protein 1 (EGR1) in human oral epithelial cells (OECs) in response toC. albicans. EGR1 expression increases in OECs when exposed toC. albicansindependently of fungal viability, morphology, or candidalysin release, suggesting EGR1 is involved in the fundamental recognition ofC. albicans, rather than in response to invasion or ‘pathogenesis’. Upregulation of EGR1 is mediated by EGFR via Raf1, ERK1/2 and NF-κB signalling but not PI3K/mTOR signalling. Notably, EGR1 mRNA silencing impacts on anti-C. albicansimmunity, reducing GM-CSF, IL-1α and IL-1β release, and increasing IL-6 and IL-8 production. These findings identify an important role for EGR1 in priming epithelial cells to respond to subsequent invasive infection byC. albicansand elucidate the regulation circuit of this transcription factor after contact.
Cross sectional study of knowledge, attitude and practice among general population towards COVID19 vaccines in Duhok province, Kurdistan region of Iraq
Authors: Elyas Ramis Imad , Abdulrahman Halima Adil , Ismaeel Rozan Sagvan 
Published: April 2023

AbstractBackgroundVaccines are immunization against diseases and leads to saving millions of lives every year. However, after the availability of COVID-19 vaccines, little information is available on the public knowledge and attitudes towards the COVID-19 vaccines in Kurdistan-Iraq.AimThis study aimed to investigate the knowledge, attitude and practice toward the COVID-19 vaccines among general population at Duhok province, Kurdistan region, Iraq.MethodsThe cross-sectional study was done between November 1st, 2022 and march 1st, 2023 at Duhok province, Kurdistan region, Iraq including Duhok City, Zakho, Semel and surrounding area) toward COVID-19 vaccines. It included 759 randomly selected participants answering a structured questionnaire who were interviewed face-to-face by the authors. The participants ages ranged from 18 to 75 years. The survey questionnaire was divided into three parts, the first part was sociodemographic characteristics. The second part was composed of eight questions of knowledge regarding the COVID-19 vaccine and third part was 6 statements about Attitudes toward COVID-19 vaccines.FindingsThe mean age of the respondents was 32.95 years (SD±12) and more than half of them (52.3%) were males. About 55% of the respondents reported that they had infected with COVID-19. About 25.3% of the subjects were employed and only 18.3% had chronic diseases. Around 55% of the participants reported that they have previously infected with COVID-19. The majority of the participants (99.60%) had heard of COVID-19 vaccine, almost (68%) of the participants trusted COVID-19 vaccine and reported that the vaccine is safe. Almost three-quarters (74.04%) of the participants were strongly agreed that it is important to get a vaccine to protect the people from COVID-19. According to the survey results, a significant proportion of the participants, specifically 62.58%, believed that COVID-19 vaccines offer protection against the disease. It was notable that a high percentage of the participants, approximately 86.17%, were aware of the potential side effects associated with the vaccine. Moreover, an overwhelming majority of the participants, nearly 96.31%, were knowledgeable that the vaccination process would require two or more doses.ConclusionsThe history of chronic disease, source of vaccine knowledge, education level, occupation, and employment states were factors that affected the willingness to accept the vaccine. The most trusted sources of information on COVID-19 vaccines were social media. Therefore, the willingness to take the COVID-19 vaccine can be supported by utilizing social media and television to spread awareness about the vaccine’s safety and efficacy.
Opto-lipidomics of tissues
Authors: Jensen Magnus , Liu Shiyue , Stepula Elzbieta , Martella Davide , Birjandi Anahid A. , Farrell-Dillon Keith , Chan Ka Lung Andrew , Parsons Maddy , Chiappini Ciro , Chapple Sarah J. , Mann Giovanni E. , Vercauteren Tom , Abbate Vincenzo , Bergholt Mads S. 
Published: April 2023

AbstractLipid metabolism and signalling play pivotal functions in biology and disease development. Despite this, there is currently no optical technique available that can directly visualise the lipidome in tissues. In this study, we introduce opto-lipidomics, a new approach to optical molecular tissue imaging. We expand the capability of vibrational Raman spectroscopy to identify individual lipids in complex tissue matrices through correlation with desorption electrospray ionisation (DESI) - mass spectrometry imaging in an integrated instrument. A computational pipeline of inter-modality regression analysis is established to extract lipidomic information from optical vibrational spectra. Opto-lipidomic imaging of transient cerebral ischemia-reperfusion injury in a murine model of ischemic stroke demonstrates the visualisation and identification of lipids in disease with unprecedented molecular specificity using light. Furthermore, we deploy opto-lipidomics in a handheld fiber-optic Raman probe and demonstrate real-time classification of bulk brain tissues based on specific lipid abundances. Opto-lipidomics opens a host of opportunities to study lipid biomarkers for diagnostics, prognostics, and novel therapeutic targets.
Blocking Interleukin-1β transiently limits left ventricular dilation and modulates cardiac lymphangiogenesis in a mouse pressure-overload model
Authors: Heron C. , Lemarcis T. , Laguerre O. , Valet M. , Michel JB. , Mulder P. , Tardif V. , Brakenhielm E. 
Published: April 2023

AbstractBlocking inflammatory pathways, such as the inflammasome or IL-1β, is a promising therapeutic target in both ischemic and non-ischemic heart failure (HF). We hypothesize that IL-1β may stimulate cardiac lymphangiogenesis, driven by left ventricular dilation in HF. Thus, blocking IL-1β signaling may reduce lymphangiogenesis, which could delay resolution of myocardial edema and inflammation, aggravate cardiac fibrosis, and accelerate HF development.Here, we investigated the effects ofearlyversuslateanti-IL-1β treatment during pressure-overload induced by transaortic constriction (TAC) in Balb/c mice prone to left ventricular (LV) dilation. We also investigated links between perivascular lymphatics and fibrosis in ischemic versus dilated cardiomyopathy (DCM) HF patients.We found thatearlytreatment transiently delayed LV dilation, but did not alter cardiac hypertrophy or dysfunction at 8 weeks post-TAC.Latetreatment reduced cardiac lymphangiogenesis and lymphatic CCL21 gradients. Surprisingly, cardiac inflammation, fibrosis and dysfunction were not aggravated despite reduced lymphatic density. Further, similar as in mice, increased perivascular lymphatic density in HF patients was associated with less perivascular fibrosis.In conclusion, we found limited functional cardiac benefit of IL-1β blockage when initiated before onset of lymphangiogenesis post-TAC in Balb/c mice. In contrast,latetreatment reduced cardiac lymphangiogenesis. HF onset was however not significantly accelerated, likely reflecting lymphatic transport dysfunction post-TAC. Taken together, the therapeutic window for anti-IL-1β treatment appears crucial, as initiation of treatment during the lymphangiogenic response, induced by LV dilation, may limit the potential cardiac benefit in HF patients. Further, our data indicate that IL-1β-independent perivascular lymphangiogenesis may limit perivascular fibrosis.
Tamoxifen Response at Single Cell Resolution in Estrogen Receptor-Positive Primary Human Breast Tumors
Authors: Kim Hyunsoo , Whitman Austin A. , Wisniewska Kamila , Kakati Rasha T. , Garcia-Recio Susana , Calhoun Benjamin C. , Franco Hector L. , Perou Charles M. , Spanheimer Philip M. 
Published: April 2023

ABSTRACTIn ER+/HER2- breast cancer, multiple measures of intra-tumor heterogeneity are associated with worse response to endocrine therapy. To investigate heterogeneity in response to treatment, we developed an operating room-to-laboratory pipeline for the collection of live human tumors and normal breast specimens immediately after surgical resection for processing into single-cell workflows for experimentation and genomic analyses. We demonstrate differences in tamoxifen response by cell type and identify distinctly responsive and resistant subpopulations within the malignant cell compartment of human tumors. Tamoxifen resistance signatures from 3 distinct resistant subpopulations are prognostic in large cohorts of ER+ breast cancer patients and enriched in endocrine therapy resistant tumors. This novel ex vivo model system now provides a foundation to define responsive and resistant sub-populations within heterogeneous tumors, to develop precise single cell-based predictors of response to therapy, and to identify genes and pathways driving resistance to therapy.
Circular RNAs in the human brain are tailored to neuron identity and neuropsychiatric disease
Authors: Dong Xianjun , Bai Yunfei , Liao Zhixiang , Gritsch David , Liu Xiaoli , Wang Tao , Borges-Monroy Rebeca , Ehrlich Alyssa , Serano Geidy E. , Feany Mel B. , Beach Thomas G. , Scherzer Clemens R. 
Published: April 2023

AbstractLittle is known about circular RNAs (circRNAs) in specific brain cells and human neuropsychiatric disease. Here, we systematically identified over 11,039 circRNAs expressed in vulnerable dopamine and pyramidal neurons laser-captured from 190 human brains and non-neuronal cells using ultra-deep, total RNA sequencing. 1,526 and 3,308 circRNAs were custom-tailored to the cell identity of dopamine and pyramidal neurons and enriched in synapse pathways. 88% of Parkinson’s and 80% of Alzheimer’s disease-associated genes produced circRNAs.circDNAJC6,produced from a juvenile-onset Parkinson’s gene, was already dysregulated during prodromal, onset stages of common Parkinson’s disease neuropathology. Globally, addiction-associated genes preferentially produced circRNAs in dopamine neurons, autism-associated genes in pyramidal neurons, and cancers in non-neuronal cells. This study shows that circular RNAs in the human brain are tailored to neuron identity and implicate circRNA- regulated synaptic specialization in neuropsychiatric diseases.
Slide-tags: scalable, single-nucleus barcoding for multi-modal spatial genomics
Authors: Russell Andrew J. C. , Weir Jackson A. , Nadaf Naeem M. , Shabet Matthew , Kumar Vipin , Kambhampati Sandeep , Raichur Ruth , Marrero Giovanni J. , Liu Sophia , Balderrama Karol S. , Vanderburg Charles R. , Shanmugam Vignesh , Tian Luyi , Wu Catherine J. , Yoon Charles H. , Macosko Evan Z. , Chen Fei 
Published: April 2023

AbstractRecent technological innovations have enabled the high-throughput quantification of gene expression and epigenetic regulation within individual cells, transforming our understanding of how complex tissues are constructed. Missing from these measurements, however, is the ability to routinely and easily spatially localise these profiled cells. We developed a strategy, Slide-tags, in which single nuclei within an intact tissue section are ‘tagged’ with spatial barcode oligonucleotides derived from DNA-barcoded beads with known positions. These tagged nuclei can then be used as input into a wide variety of single-nucleus profiling assays. Application of Slide-tags to the mouse hippocampus positioned nuclei at less than 10 micron spatial resolution, and delivered whole-transcriptome data that was indistinguishable in quality from ordinary snRNA-seq. To demonstrate that Slide-tags can be applied to a wide variety of human tissues, we performed the assay on brain, tonsil, and melanoma. We revealed cell-type-specific spatially varying gene expression across cortical layers and spatially contextualised receptor-ligand interactions driving B-cell maturation in lymphoid tissue. A major benefit of Slide-tags is that it is easily adaptable to virtually any single-cell measurement technology. As proof of principle, we performed multiomic measurements of open chromatin, RNA, and T-cell receptor sequences in the same cells from metastatic melanoma. We identified spatially distinct tumour subpopulations to be differentially infiltrated by an expanded T-cell clone and undergoing cell state transition driven by spatially clustered accessible transcription factor motifs. Slide-tags offers a universal platform for importing the compendium of established single-cell measurements into the spatial genomics repertoire.
The re-emergence of influenza following the COVID-19 pandemic in Victoria, Australia
Authors: Pendrey Catherine GA , Strachan Janet , Peck Heidi , Aziz Ammar , Moselen Jean , Moss Rob , Rahaman Md Rezanur , Barr Ian G. , Subbarao Kanta , Sullivan Sheena G. 
Published: April 2023

Abstract textBackgroundCOVID-19 pandemic mitigation measures, including travel restrictions, effectively limited global circulation of influenza viruses. In Australia, travel bans for non-residents and quarantine requirements for returned travellers were eased in November 2021, providing pathways for influenza viruses to be re-introduced.MethodsFrom 1 November 2021 to 30 April 2022 we conducted an epidemiological study to investigate the re-establishment of influenza in Victoria, Australia. We analyzed case notification data from the Victorian Department of Health to describe case demographics, interviewed the first 200 cases to establish probable routes of virus reintroduction, and examined phylogenetic and antigenic data to understand virus diversity and susceptibility to current vaccines.ResultsOverall, 1598 notifications and 1064 positive specimens were analyzed. The majority of cases occurred in the 15-34 year age group. Case interviews revealed a higher incidence of international travel exposure during the first month of case detections and high levels of transmission in university residential colleges associated with the return to campus. Influenza A(H3N2) was the dominant subtype, with a single lineage predominating despite multiple importations.ConclusionsEnhanced testing for respiratory viruses during the COVID-19 pandemic provided a more complete picture of influenza virus transmission compared to previous seasons. Returned international travellers were important drivers of the re-emergence of influenza, as were young adults, a group whose role has previously been under-recognised in the establishment of seasonal influenza epidemics. Targeting interventions, including vaccination, to these groups could reduce influenza transmission in the future.
Modelling the effect of migration on the localisation and spread of a gene drive
Authors: Camm Benjamin , Fournier-Level Alexandre 
Published: April 2023

AbstractGene drives have the potential to address pressing ecological issues. Through the super-Mendelian inheritance of a gene drive, a trait can be spread through a population even in spite of a fitness cost. This ability to spread is both its greatest quality and detractor. We may not want a gene drive to spread universally. If a gene drive were designed to cause the collapse of a pest population, it may inadvertently cause the collapse of the entire species. Migration is the mechanism through which a gene drive can spread to distant populations. Understanding its effect on the progression of a gene drive is crucial to our ability to control a gene drive. While migration can spread the gene drive to other populations, equally it can bring in other alleles to the population that may disrupt the progression of the gene drive. Through our deterministic migration gene drive model we can assess the conditions in which a gene drive is likely to spread to unintended populations, and if a gene drive is likely to be displaced by incoming alleles.
Longitudinal Analysis of Humoral and Cellular Immune Response Following SARS-CoV-2 Vaccination Supports Utilizing Point-Of-Care Tests to Enhance COVID-19 Booster Uptake
Authors: Mallory Michael , Munt Jennifer E. , Narowski Tara M. , Castillo Izabella , Cuadra Edwing , Pisanic Nora , Fields Paul , Powers John M. , Dickson Alexandria , Harris Rohan , Wargowsky Richard , Moran Seamus , Allabban Ahmed , Raphel Kristin , McCaffrey Timothy A. , Brien James D. , Heaney Christopher D. , Lafleur John E. , Baric Ralph S. , Premkumar Lakshmanane 
Published: April 2023

AbstractIndividuals with weaker neutralizing responses show reduced protection with SARS-CoV-2 variants. Booster vaccines are recommended for vaccinated individuals, but the uptake is low. We present the feasibility of utilizing point-of-care tests (POCT) to support evidence-based decision-making around COVID-19 booster vaccinations. Using infectious virus neutralization, ACE2 blocking, spike binding, and TCR sequencing assays, we investigated the dynamics of changes in the breadth and depth of blood and salivary antibodies as well as T-cell clonal response following mRNA vaccination in a cohort of healthcare providers. We evaluated the accuracy of two POCTs utilizing either blood or saliva to identify those in whom humoral immunity was inadequate. >4 months after two doses of mRNA vaccine, SARS-CoV-2 binding and neutralizing Abs (nAbs) and T-cell clones declined 40-80%, and 2/3rd lacked Omicron nAbs. After the third mRNA booster, binding and neutralizing Abs increased overall in the systemic compartment; notably, individuals with previously weak nAbs gained sharply. The third dose failed to stimulate secretory IgA, but salivary IgG closely tracked systemic IgG levels. Vaccine boosting increased Ab breadth against a divergent bat sarbecovirus, SHC014, although the TCR-beta sequence breadth was unchanged. Post 3rd booster dose, Ab avidity increased for the Wuhan and Delta strains, while avidity against Omicron and SHC014 increased to levels seen for Wuhan after the second dose. Negative results on POCTs strongly correlated with a lack of functional humoral immunity. The third booster dose helps vaccinees gain depth and breadth of systemic Abs against evolving SARS-CoV-2 and related viruses. Our findings show that POCTs are useful and easy-to-access tools to inform inadequate humoral immunity accurately. POCTs designed to match the circulating variants can help individuals with booster vaccine decisions and could serve as a population-level screening platform to preserve herd immunity.One Sentence SummarySARS-CoV-2 point-of-care antibody tests are valuable and easy-to-access tools to inform inadequate humoral immunity and to support informed decision-making regarding the current and future booster vaccination.
Improved Performance of ChatGPT-4 on the OKAP Exam: A Comparative Study with ChatGPT-3.5
Authors: Teebagy Sean , Colwell Lauren , Wood Emma , Yaghy Antonio , Faustina Misha 
Published: April 2023

AbstractThis study aims to evaluate the performance of ChatGPT-4, an advanced Artificial Intelligence (AI) language model, on the Ophthalmology Knowledge Assessment Program (OKAP) examination compared to its predecessor, ChatGPT-3.5. Both models were tested on 180 OKAP practice questions covering various ophthalmology subject categories. Results showed that ChatGPT-4 significantly outperformed ChatGPT-3.5 (81% vs. 57%; p<0.001), indicating improvements in medical knowledge assessment. The superior performance of ChatGPT-4 suggests potential applicability in ophthalmologic education and clinical decision support systems. Future research should focus on refining AI models, ensuring a balanced representation of fundamental and specialized knowledge, and determining the optimal method of integrating AI into medical education and practice.