bluuebunny/crossref_metadata_2025 huggingface dataset:
Preventive small-quantity lipid-based nutrient supplements reduce severe wasting and severe stunting among young children: an individual participant data meta-analysis of randomized controlled trials
Authors: Dewey Kathryn G. , Arnold Charles D. , Wessells K. Ryan , Prado Elizabeth L. , Abbeddou Souheila , Adu-Afarwuah Seth , Ali Hasmot , Arnold Benjamin F. , Ashorn Per , Ashorn Ulla , Ashraf Sania , Becquey Elodie , Brown Kenneth H. , Christian Parul , Colford John M. , Dulience Sherlie J. L. , Fernald Lia C.H. , Galasso Emanuela , Hallamaa Lotta , Hess Sonja Y. , Humphrey Jean H. , Huybregts Lieven , Iannotti Lora L. , Jannat Kaniz , Lartey Anna , Port Agnes Le , Leroy Jef L. , Luby Stephen P. , Maleta Kenneth , Matias Susana L. , Mbuya Mduduzi NN , Mridha Malay K. , Nkhoma Minyanga , Null Clair , Paul Rina R. , Okronipa Harriet , Ouédraogo Jean-Bosco , Pickering Amy J. , Prendergast Andrew J. , Ruel Marie , Shaikh Saijuddin , Weber Ann M. , Wolff Patricia , Zongrone Amanda , Stewart Christine P.
Published: April 2023

Background

Meta-analyses show that small-quantity lipid-based nutrient supplements (SQ- LNS) reduce child wasting and stunting. There is little information regarding effects on severe wasting or stunting.

Objective

We aimed to identify the effect of SQ-LNS on severe wasting (weight-for-length z- score < −3) and severe stunting (length-for-age z-score < −3).

Methods

We conducted a two-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNS provided to children 6 to 24 mo of age. We generated study-specific and subgroup estimates of SQ-LNS vs. control and pooled the estimates using fixed-effects models. We used random effects meta-regression to examine study-level effect modifiers. In sensitivity analyses, we examined whether results differed depending on study arm inclusion criteria and types of comparisons.

Results

Q-LNS provision led to a relative reduction of 31% in severe wasting (Prevalence Ratio, PR 0.69 (0.55, 0.86), n=34,373) and 17% in severe stunting (PR 0.83 (95% CI: 0.78, 0.90), n=36,795). Results were similar in most of the sensitivity analyses but somewhat attenuated when comparisons using passive control arms were excluded: PR 0.74 (0.57, 0.96), n=26,327 for severe wasting and PR 0.88 (0.81, 0.95), n=28,742 for severe stunting. Study-level characteristics generally did not significantly modify the effects of SQ-LNS, but results suggested greater effects of SQ-LNS in sites with greater burdens of wasting or stunting, or with poorer water quality or sanitation.

Conclusions

Including SQ-LNS in preventive interventions to promote healthy child growth and development is likely to reduce rates of severe wasting and stunting. Registered atwww.crd.york.ac.uk/PROSPEROas CRD42019146592.
Nanopore Fingerprinting of Supramolecular DNA Nanostructures
Authors: Confederat Samuel , Sandei Ilaria , Mohanan Gayathri , Wälti Christoph , Actis Paolo
Published: April 2023

DNA nanotechnology has paved the way for new generations of programmable nanomaterials. Utilising the DNA origami technique, various DNA constructs can be designed, ranging from single tiles to the self-assembly of large-scale complex multi-tile arrays. These DNA nanostructures have enabled new applications in biosensing, drug delivery and other multifunctional materials. In this study, we demonstrate real-time, non-destructive and label-free fingerprinting of higher-order assemblies of DNA origami nanostructures using solid-state nanopores. Using this approach, we quantify the assembly yields for each DNA origami nanostructure with single-entity resolution using the nanostructure-induced charge introduced in the nanopore as a discriminant. We compare the assembly yield of the supramolecular DNA nanostructures obtained with the nanopore with agarose gel electrophoresis and AFM imaging and demonstrate that the nanopore system can provide enhanced information about the nanostructures. We envision that this nanopore detection platform can be applied to a range of nanomaterial designs and enable the analysis and manipulation of large DNA assemblies in real-time with single-molecule resolution.

STATEMENT OF SIGNIFICANCE

We demonstrate a single molecule high-throughput approach for the analysis of higher-order DNA origami assemblies with a crowded nanopore. The technique enables the characterisation of DNA origami nanostructures at statistically relevant numbers in real-time and at single-molecule resolution while being non-destructive and label-free, and without the requirement of lengthy sample preparations or use of expensive reagents. We exemplify the technique by demonstrating the quantification of the assembly yield of DNA origami nanostructures based on their equivalent charge surplus computed from the ion current signals recorded. Compared to the standard analysis methods of AFM and agarose gel electrophoresis, the nanopore measurements provides enhanced information about the nanostructures.
Detailed profiling with MaChIAto reveals various genomic and epigenomic features affecting the efficacy of knock-out, short homology-based knock-in and Prime Editing
Authors: Nakamae Kazuki , Takenaga Mitsumasa , Nakade Shota , Awazu Akinori , Sakamoto Naoaki , Yamamoto Takashi , Sakuma Tetsushi
Published: April 2023

Highly efficient gene knock-out and knock-in have been achieved by harnessing CRISPR-Cas9 and its advanced technologies such as Prime Editor. In addition, various bioinformatics resources have become available to quantify and qualify the efficiency and accuracy of CRISPR edits, which significantly increased the user-friendliness of the general next-generation sequencing (NGS) analysis in the context of genome editing. However, there is no specialized and integrated software for investigating the preference in the genomic context involved in the efficiency and accuracy of genome editing using CRISPR-Cas9 and beyond. Here, we address this issue by establishing a novel analysis platform of NGS data for profiling the outcome of template-free knock- out and short homology-based editing, named MaChIAto (Microhomology-associatedChromosomalIntegration/editingAnalysistools) (https://github.com/KazukiNakamae/MaChIAto). MaChIAto accommodates the classification and profiling of the NGS reads to uncover the tendency of the corresponding method of genome editing. In the profiling function, MaChIAto can summarize the mutation patterns along with the editing efficiency, and > 70 kinds of feature analysis, e.g., correlation analysis with thermodynamics and secondary structure parameters, are available. Additionally, the classifying function of MaChIAto is based on, but much stricter than, that of the existing tool, which is achieved by implementing a novel method of parameter adaptation utilizing Bayesian optimization. To demonstrate the functionality of MaChIAto, we analyzed the NGS data of knock- out, short homology-based knock-in, and Prime Editing. We confirmed that some features of (epi-)genomic context affected the efficiency and accuracy. These results show that MaChIAto is a helpful tool for understanding the best design for CRISPR edits. More importantly, it is the first tool for discovering features in the short homology-based knock-in outcomes. MaChIAto would help researchers profile editing data and generate prediction models for CRISPR edits, further contributing to revealing a “black box” process to produce a variety of CRISPR and Prime Editing outcomes.
Limitations of models for guiding policy in the COVID-19 pandemic
Authors: McKeigue Paul M , Wood Simon N
Published: April 2023

At 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.
High changing curvature regions detect chromatin enrichment in single cell data
Authors: Amici Giulia , Papale Andrea , Lando David , Boucher Wayne , Holcman D.
Published: April 2023

Chromatin organization is nowadays accessible from population and single cell Hi-C data in the form of large contact matrices. Yet reconstructing the three-dimensional chromatin structure remains challenging and relies on polymer models and numerical simulations to account for these Hi-C data. Here we propose a novel optimization algorithm to identify cross-linker ensemble reproducing the experimental contact matrix. Furthermore, based on the polymer configurations extracted from the optimization procedure, we identify high changing curvature (HCC) regions in the chromatin, detected both in population and in single cell Hi-C, that we also compare to Topological Associated Domains (TADs). We report here that the HCC regions correlate with gene expression and CTCF high density distribution. Interestingly, the HCC region locations are heterogeneous across one cell repeats, revealing cell-to-cell variability. To conclude, HCC regions appear both in single and population Hi-C polymer reconstruction and can provide a possible unit for gene regulation.
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

Candida 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

Background

Vaccines 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.

Aim

This study aimed to investigate the knowledge, attitude and practice toward the COVID-19 vaccines among general population at Duhok province, Kurdistan region, Iraq.

Methods

The 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.

Findings

The 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.

Conclusions

The 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

Lipid 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

Blocking 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

In 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

Little 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

Recent 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 text

Background

COVID-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.

Methods

From 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.

Results

Overall, 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.

Conclusions

Enhanced 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

Gene 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

Individuals 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 Summary

SARS-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.
Early Treatment with Hydroxychloroquine and Azithromycin: A ‘Real-World’ Monocentric Retrospective Cohort Study of 30,423 COVID-19 Patients
Authors: Million Matthieu , Cortaredona Sébastien , Delorme Léa , Colson Philippe , Levasseur Anthony , Tissot-Dupont Hervé , Cassir Nadim , Bendamardji Karim , Lahouel Salima , Scola Bernard La , Camoin-Jau Laurence , Fenollar Florence , Gautret Philippe , Parola Philippe , Lagier Jean-Christophe , Gentile Stéphanie , BRouqui Philippe , Raoult Didier
Published: April 2023

The authors have withdrawn this manuscript because analytic strategies for this project have changed. Therefore, the authors do not wish this work to be cited as reference for the project.
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

This 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.
Colopathy Associated with Pentosan Polysulfate Use
Authors: Jung Emily H. , Zheng Wei , Weiss Ryan J. , Mathew Namita E. , Meyer Benjamin I. , Nizam Azhar , Iskandar Heba , Jain Nieraj
Published: April 2023

Introduction

We describe a novel colopathy associated with pentosan polysulfate (PPS) use and measure the strength of the drug-disease association.

Methods

Two-part investigation. In the cohort study of individuals with a history of prior long-term PPS use, case histories were obtained and gastrointestinal disease course was followed with review of endoscopy records and histopathology specimens. Findings were summarized with descriptive statistics. In the cross-sectional study of individuals with interstitial cystitis, drug exposure and medical histories were obtained for patients seen at a single clinical center. Strength of association between PPS use and diagnoses of inflammatory bowel disease (IBD) and/or irritable bowel syndrome (IBS) was measured with multivariate logistic regression.

Results

In the cohort study of 13 participants, median PPS exposure was 2.04 kg (0.99–2.54). Eleven (84.6%) developed symptoms suggestive of IBD and/or IBS after initiation of PPS therapy. Of the 10 participants whose endoscopic and histopathologic findings we reviewed, six had abnormal-appearing colonic mucosa on endoscopy and all 10 had abnormal mucosal changes on histology. Clinical and histologic improvement was observed after PPS cessation. In the cross-sectional study of 219 subjects with interstitial cystitis, PPS use was a statistically significant predictor of both the IBD [adjusted odds ratio=3.3 (95% confidence interval, 1.2–8.8, p=0.02)] and the composite IBD+IBS [adjusted odds ratio=3.3 (95% confidence interval, 1.5–7.3, p=0.002)] outcomes.

Discussion

We describe a strong association between PPS use and a clinical diagnosis of IBD and/or IBS. Histopathologic findings suggest a novel drug-associated colopathy, with some subjects requiring colectomy for dysplasia.
Social support improves nurses’ resilience: a cross-sectional study in Greece
Authors: Galanis Petros , Katsiroumpa Aglaia , Vraka Irene , Siskou Olga , Konstantakopoulou Olympia , Katsoulas Theodoros , Gallos Parisis , Kaitelidou Daphne
Published: April 2023

Background

Since nursing job is perceived as personally and professionally demanding, internal resources such as resilience and coping skills are essential to improve nurses’ health and wellbeing and therefore work productivity and quality of patient care.

Objective

To assess the effect of social support on nurses’ resilience. Moreover, we investigated the impact of demographic characteristics of nurses on their resilience.

Methods

We conducted an on-line cross-sectional study in Greece. Data were collected during October 2022. We used the Multidimensional Scale of Perceived Social Support to measure social support, and the Brief Resilience Scale to measure resilience. We measured the following demographic characteristics of nurses: gender, age, self-perceived health status, COVID-19 diagnosis, MSc/PhD diploma, and clinical experience.

Results

Study population included 963 nurses with a mean age of 37.9 years. Nurses experienced moderate levels of resilience and high levels of social support. Multivariable linear regression analysis identified that increased significant others support and increased friends support were associated with increased resilience. Moreover, we found a positive relationship between age and resilience. Also, nurses with good/very good health had higher levels of resilience compared to nurses with very poor/poor/moderate health. Finally, resilience was higher among nurses with MSc/PhD diploma.

Conclusions

We found a positive relationship between social support and resilience among nurses. Understanding of factors that influence nurses’ resilience can add invaluable knowledge to develop and establish tailored programs. Peer support is essential to improve nurses’ resilience and promote patient healthcare.
Automated identification of abnormal infant movements from smart phone videos
Authors: Passmore E. , Kwong A. L. , Greenstein S. , Olsen J. E. , Eeles A. L. , Cheong J. L. Y. , Spittle A. J. , Ball G.
Published: April 2023

Cerebral palsy (CP) is the most common cause of physical disability during childhood. Early diagnosis is essential to improve functional outcomes of children with CP. The General Movements Assessment (GMA) is a strong predictor of CP, but access is limited by the need for trained GMA assessors. Using 503 infant movement videos acquired at 12-18 weeks’ term-corrected age, we developed a framework to automate the GMA using smartphone videos acquired at home. We trained a deep learning model to label and track 18 key body points, implemented a custom pipeline to adjust for camera movement and infant size and trained a convolutional neural network to predict GMA. Our model achieved an area under the curve (mean ± S.D.) of 0.80 ± 0.08 in unseen test data for predicting expert GMA classification. This work highlights the potential for automated GMA screening programs for infants.
SARS-CoV-2 infection and post-acute risk of non-Covid-19 infectious disease hospitalizations: a nationwide cohort study of Danish adults aged ≥50 years
Authors: Andersson Niklas Worm , Thiesson Emilia Myrup , Lassaunière Ria , Hansen Jørgen Vinsløv , Hviid Anders
Published: April 2023

Reports suggest that the potential long-lasting health consequences of SARS-CoV-2 infection may involve persistent dysregulation of some immune populations, but the potential clinical implications are unknown. In a nationwide cohort of 2,430,694 50+-year-olds, we compared the rates of non-Covid-19 infectious disease inpatient hospitalizations (of ≥5 hours) following the acute phase of SARS-CoV-2 infection in 930,071 individuals with rates among SARS-CoV-2 uninfected from 1 January 2021 to 10 December 2022. The post-acute phase of SARS-CoV-2 infection was associated with an incidence rate ratio of 0.90 (95% confidence interval 0.88-0.92) for any infectious disease hospitalization. Findings were similar for upper- (1.08, 0.97-1.20), lower respiratory tract (0.90, 0.87-0.93), influenza (1.04, 0.94-1.15), gastrointestinal (1.28, 0.78-2.09), skin (0.98, 0.93-1.03), urinary tract (1.01, 0.96-1.08), certain invasive bacterial (0.96, 0.91-0.1.01), and other (0.96, 0.92-1.00) infectious disease hospitalizations and in subgroups. Our study does not support an increased susceptibility to non-Covid-19 infectious disease hospitalization following SARS-CoV-2 infection.
Effective concentration of marine nanoflagellates with a microfluidic device
Authors: Hamilton Bryan R. , Hunter-Cevera Kristen R.
Published: April 2023

Protist cells are typically manipulated through either centrifugation or membrane filtration, which can damage these fragile cell types. Use of microfluidic devices could greatly aid in the separation and concentration of protist cells with significantly less damage. Recent developments have enabled passive cell separation and consequent concentration based only on cell size. We utilize these advances to show that a passive spiral microfluidic device can effectively concentrate marine nanoflagellates within the 3-20 micron size range without harm to cells, while reducing background bacteria levels. The ability to concentrate these cell types appears only dependent on cell size, despite complicated cell surface geometries and motility. We anticipate that this approach will greatly aid researchers who require an ability to manipulate fragile cell types as well as reduce bacteria concentrations for experimental setups and cell isolation.
Distributable, Metabolic PET Reporting of Tuberculosis
Authors: Khan R.M. Naseer , Ahn Yong-Mo , Marriner Gwendolyn A. , Via Laura E. , D’Hooge Francois , Lee Seung Seo , Yang Nan , Basuli Falguni , White Alexander G. , Tomko Jaime A. , Frye L. James , Scanga Charles A. , Weiner Danielle M. , Sutphen Michelle L. , Schimel Daniel M. , Dayao Emmanuel , Piazza Michaela K. , Gomez Felipe , Dieckmann William , Herscovitch Peter , Mason N. Scott , Swenson Rolf , Kiesewetter Dale O. , Backus Keriann M. , Geng Yiqun , Raj Ritu , Anthony Daniel C. , Flynn JoAnne L. , Barry Clifton E. , Davis Benjamin G.
Published: April 2023

Tuberculosis remains a large global disease burden for which treatment regimens are protracted and monitoring of disease activity difficult. Existing detection methods rely almost exclusively on bacterial culture from sputum which limits sampling to organisms on the pulmonary surface. Advances in monitoring tuberculous lesions have utilized the common glucoside [18F]FDG, yet lack specificity to the causative pathogenMycobacterium tuberculosis(Mtb) and so do not directly correlate with pathogen viability. Here we show that a close mimic that is also positron-emitting of the non-mammalianMtbdisaccharide trehalose – 2-[18F]fluoro-2-deoxytrehalose ([18F]FDT) – can act as a mechanism-based enzyme reporter in vivo. Use of [18F]FDT in the imaging ofMtbin diverse models of disease, including non-human primates, successfully co-optsMtb-specific processing of trehalose to allow the specific imaging of TB-associated lesions and to monitor the effects of treatment. A pyrogen-free, direct enzyme-catalyzed process for its radiochemical synthesis allows the ready production of [18F]FDT from the most globally-abundant organic18F-containing molecule, [18F]FDG. The full, pre-clinical validation of both production method and [18F]FDT now creates a new, bacterium-specific, clinical diagnostic candidate. We anticipate that this distributable technology to generate clinical-grade [18F]FDT directly from the widely-available clinical reagent [18F]FDG, without need for either bespoke radioisotope generation or specialist chemical methods and/or facilities, could now usher in global, democratized access to a TB-specific PET tracer.
Rapid and continuing regional decline of butterflies in eastern Denmark 1993-2019
Authors: Bjerregård Emil Blicher , Baastrup-Spohr Lars , Markussen Bo , Bruun Hans Henrik
Published: April 2023

Many butterfly populations respond negatively to land-use intensification in human-dominated landscapes. However, networks of protected sites have been established with the aim to halt species loss.

We undertook annual surveys of all populations of 22 uncommon butterfly species in eastern Denmark during the period 2014-2019 and compared to a systematic atlas survey done 1989-1993, in order to assess trends in regional occupancy of species.

Three out of 22 species went regionally extinct between 1993 and 2015. One species sustained a single population through the study period. Logistic regression for the remaining 18 species showed 10 to be in strong decline from 1993 to 2015, two showed a declining trend and six had stable trends. For all species except one, the declining trend continued 2015-2019. For five species, a sustained strong decline was evident.

In 1993, the total count of populations for all 22 butterfly species was 565, which by 2019 had declined to 158 populations (a 72 % loss over 26 years). From 2015 to 2019, the total count of populations further shrank from 200 to 158 (a 21 % decline over just four years).

Legal protection of areas (Natura 2000 and Danish Nature Protection Act §3) was, unexpectedly, not associated with lower probability of local extinction for butterfly population. The observed sustained decline across species suggests an overall low efficiency of the network of protected sites, probably due to a combination of misguided management regimes and payment of extinction debts from the past.
Piezo inhibition preventsandrescues scarring by targeting the adipocyte to fibroblast transition
Authors: Griffin Michelle F. , Talbott Heather E. , Guardino Nicholas J. , Guo Jason L. , Spielman Amanda F. , Chen Kellen , Parker Jennifer B.L. , Mascharak Shamik , Henn Dominic , Liang Norah , King Megan , Cotterell Asha C. , Bauer-Rowe Khristian E. , Abbas Darren B. , Diaz Deleon Nestor M. , Sivaraj Dharshan , Fahy Evan J. , Downer Mauricio , Akras Deena , Berry Charlotte , Cook Jessica , Quarto Natalina , Klein Ophir D. , Lorenz H. Peter , Gurtner Geoffrey C. , Januszyk Michael , Wan Derrick C. , Longaker Michael T.
Published: April 2023

While past studies have suggested that plasticity exists between dermal fibroblasts and adipocytes, it remains unknown whether fat actively contributes to fibrosis in scarring. We show that adipocytes convert to scar-forming fibroblasts in response toPiezo-mediated mechanosensing to drive wound fibrosis. We establish that mechanics alone are sufficient to drive adipocyte-to- fibroblast conversion. By leveraging clonal-lineage-tracing in combination with scRNA-seq, Visium, and CODEX, we define a “mechanically naïve” fibroblast-subpopulation that represents a transcriptionally intermediate state between adipocytes and scar-fibroblasts. Finally, we show thatPiezo1orPiezo2-inhibition yields regenerative healing by preventing adipocytes’ activation to fibroblasts, in both mouse-wounds and a novel human-xenograft-wound model. Importantly,Piezo1-inhibition induced wound regeneration even inpre-existingestablished scars, a finding that suggests a role for adipocyte-to-fibroblast transition in wound remodeling, the least-understood phase of wound healing. Adipocyte-to-fibroblast transition may thus represent a therapeutic target for minimizing fibrosis viaPiezo-inhibition in organs where fat contributes to fibrosis.
Experimentally induced active and quiet sleep engage non-overlapping transcriptional programs inDrosophila
Authors: Anthoney Niki , Tainton-Heap Lucy A.L. , Luong Hang , Notaras Eleni , Kewin Amber B. , Zhao Qiongyi , Perry Trent , Batterham Philip , Shaw Paul J. , van Swinderen Bruno
Published: April 2023

Sleep in mammals can be broadly classified into two different physiological categories: rapid eye movement (REM) sleep and slow wave sleep (SWS), and accordingly REM and SWS are thought to achieve a different set of functions. The fruit flyDrosophila melanogasteris increasingly being used as a model to understand sleep functions, although it remains unclear if the fly brain also engages in different kinds of sleep as well. Here, we compare two commonly used approaches for studying sleep experimentally inDrosophila: optogenetic activation of sleep-promoting neurons and provision of a sleep-promoting drug, Gaboxadol. We find that these different sleep-induction methods have similar effects on increasing sleep duration, but divergent effects on brain activity. Transcriptomic analysis reveals that drug-induced deep sleep (‘quiet’ sleep) mostly downregulates metabolism genes, whereas optogenetic ‘active’ sleep upregulates a wide range of genes relevant to normal waking functions. This suggests that optogenetics and pharmacological induction of sleep inDrosophilapromote different features of sleep, which engage different sets of genes to achieve their respective functions.