bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fully automated histological classification of cell types and tissue regions of celiac disease is feasible and correlates with the Marsh score
Authors: Griffin Michael , Gruver Aaron M. , Shah Chintan , Wani Qasim , Fahy Darren , Khosla Archit , Kirkup Christian , Borders Daniel , Brosnan-Cashman Jacqueline A. , Fulford Angie D. , Credille Kelly M. , Jayson Christina , Najdawi Fedaa , Gottlieb Klaus 
Published: December 2023

ABSTRACTAimsHistological assessment is essential for the diagnosis and management of celiac disease. Current scoring systems, including modified Marsh (Marsh–Oberhuber) score, lack inter-pathologist agreement. To address this unmet need, we aimed to develop a fully automated, quantitative approach for histology characterisation of celiac disease.MethodsConvolutional neural network models were trained using pathologist annotations of haematoxylin and eosin-stained biopsies of celiac disease mucosa and normal duodenum to identify cells, tissue and artifact regions. Human interpretable features were extracted and the strength of their correlation with Marsh scores were calculated using Spearman rank correlations.ResultsOur model accurately identified cells, tissue regions and artifacts, including distinguishing intraepithelial lymphocytes and differentiating villous epithelium from crypt epithelium. Proportional area measurements representing villous atrophy negatively correlated with Marsh scores (r=−0.79), while measurements indicative of crypt hyperplasia and intraepithelial lymphocytosis positively correlated (r=0.71 and r=0.44, respectively). Furthermore, features distinguishing celiac disease from normal colon were identified.ConclusionsOur novel model provides an explainable and fully automated approach for histology characterisation of celiac disease that correlates with modified Marsh scores, facilitating diagnosis, prognosis, clinical trials and treatment response monitoring.KEY MESSAGESWhat is already known on this topic➢Prior research has utilised machine learning (ML) techniques to detect celiac disease and evaluate disease severity based on Marsh scores.➢However, existing approaches lack the capability to provide fully explainable tissue segmentation and cell classifications across whole slide images in celiac disease histology.➢The need for a more comprehensive and interpretable ML-based method for celiac disease diagnosis and characterisation is evident from the limitations of currently available scoring systems as well as inter-pathologist variability.What this study adds➢This study is the first to introduce an explainable ML-based approach that provides comprehensive, objective celiac disease histology characterisation, overcoming inter-observer variability and offering a scalable tool for assessing disease severity and monitoring treatment response.How this study might affect research, practice or policy➢This study’s fully automated and ML-based histological analysis, including the correlation of Marsh scores, has the potential to enable more precise disease severity measurement, risk assessment and clinical trial endpoint evaluation, ultimately improving patient care.
Four years of PrEP use; sexual behaviour and STIs in the AMPrEP demonstration project cohort among men who have sex with men in Amsterdam, the Netherlands
Authors: Van Den Elshout Mark A.M. , Wijstma Eline , Boyd Anders , Jongen Vita , Coyer Liza , Anderson Peter L. , Davidovich Udi , De Vries Henry J.C. , Prins Maria , Schim Van Der Loeff Maarten F. , Hoornenborg Elske 
Published: December 2023

AbstractBackgroundAn increasing number of countries are currently implementing or scaling-up HIV pre-exposure prophylaxis (PrEP) care. With the introduction of PrEP, there was apprehension about possible risk compensation, particularly on the long term. To inform sexual health counselling and STI screening programmes, we aimed to study sexual behaviour and STI incidence among men who have sex with men (MSM) and transgender women who use long-term daily or event-driven PrEP.MethodsThe Amsterdam PrEP demonstration project (AMPrEP) provided oral daily PrEP and event-driven PrEP to MSM and transgender women in 2015-2020. Participants could choose their PrEP regimen, and could switch at each three-monthly visit. STI testing occurred at and, upon request, in-between 3-monthly study visits. We assessed changes in number of sex partners and condomless anal sex acts over time with casual partners (CAS) using negative binomial regression. We assessed changes in incidence rates (IR) of any STI (i.e., chlamydia, gonorrhoea, or infectious syphilis), individual STIs, and HIV over time using Poisson regression.Findings367 participants (365 MSM) commenced PrEP and were followed for a median 3.9 years (IQR=3.4-4.0). The number of sex partners decreased over time (adjusted rate ratio [aRR]=0.89/year, 95%CI=0.86-0.92), while the number of CAS acts with casual partners remained stable (aRR=0.98/year, 95%CI=0.94-1.01). IR of any STI was 87/100 person years (PY) (95%CI=82-93) and did not change over time for both daily PrEP or event-driven PrEP users. However, IRs of chlamydia and gonorrhoea decreased slightly in daily PrEP users. Two daily PrEP users, and no event-driven PrEP users, were diagnosed with HIV during their first year on PrEP.ConclusionWith no increase in the number of casual sex partners nor of CAS acts, we found no indication of possible risk compensation during the first four years of PrEP use. Although the STI incidence was high, it did not increase over time.FundingZonMw, RIVM, GGD, H-TEAM, Gilead.
SARS-CoV-2 infection risk in COVISHIELD (AstraZeneca-SII) Vaccinated Healthcare Workers in a Tertiary Cancer Care Centre of North-East India
Authors: Sarma Dhruba Jyoti , Das Biki Chandra , Rai Avdhesh Kumar , Sarma Pallavi , Baruah Priyanki , Deka Kamalika Bhandari , Bhattacharyya Mouchumee , Sarma Anupam , Barman Debanjana , Kataki Amal Chandra , Das Sawmik , Barman Rashmisnata 
Published: December 2023

ABSTRACTCOVID-19 vaccination of Healthcare workers and vulnerable groups remain priority in containing the spread of SARS-CoV-2 infection and health complications arising post COVID-19. In India, COVISHIELD is the major part of COVID-19 vaccination drive. post-vaccination SARS-CoV-2 infection risk and its impact on severity as well as mortality need to be assessed in vaccinated population. The study included 350 COVISHIELD vaccinated HCWs in tertiary cancer care centre of North-East India. A total of 16 symptomatic HCWs (4.57%) were confirmed as SARS-CoV-2 positive. Among SARS-CoV-2 positive FV HCWs none were positive within 14 days, 13.33 % within 15 to 30 days, 53.33% within 30 to 45 days, and 33.33% after 45 or more days. None of the SARS-CoV-2 positive HCWs required oxygen support or hospitalisation. We also found that 66.67% FV HCWs (n=10) had Ct values below 20, 20% (n=3) had Ct values in between 20-25 and 13.33% (n=2) had Ct values in between 30 to 35. In North-East India COVISHIELD FV HCWs HCW,SARS-CoV-2 infection and COVID-19 symptoms were mild. Majority of FV HCWs have RT-PCR COVID-19 positive Ct Value was below 20. SARS-CoV-2 infection occurred mostly after 15 days to 45 days or more post vaccination.
Analyses using multiple imputation need to consider missing data in auxiliary variables
Authors: Madley-Dowd Paul , Curnow Elinor , Hughes Rachael A. , Cornish Rosie , Tilling Kate , Heron Jon 
Published: December 2023

AbstractAuxiliary variables are used in multiple imputation (MI) to reduce bias and increase efficiency. These variables may often themselves be incomplete. We explored how missing data in auxiliary variables influenced estimates obtained from MI. We implemented a simulation study with three different missing data mechanisms for the outcome. We then examined the impact of increasing proportions of missing data and different missingness mechanisms for the auxiliary variable on bias of an unadjusted linear regression coefficient and the fraction of missing information. We illustrate our findings with an applied example in the Avon Longitudinal Study of Parents and Children. We found that where complete records analyses were biased, increasing proportions of missing data in auxiliary variables, under any missing data mechanism, reduced the ability of MI including the auxiliary variable to mitigate this bias. Where there was no bias in the complete records analysis, inclusion of a missing not at random auxiliary variable in MI introduced bias of potentially important magnitude (up to 17% of the effect size in our simulation). Careful consideration of the quantity and nature of missing data in auxiliary variables needs to be made when selecting them for use in MI models.
GWAS from Spoken Phenotypic Descriptions: A Proof of Concept from Maize Field Studies
Authors: Yanarella Colleen F. , Fattel Leila , Lawrence-Dill Carolyn J. 
Published: December 2023

ABSTRACTWe present a novel approach to Genome-Wide Association Studies (GWAS) by leveraging unstructured, spoken phenotypic descriptions to identify genomic regions associated with maize traits. Utilizing the Wisconsin Diversity panel, we collected spoken descriptions ofZea maysssp.maystraits, converting these qualitative observations into quantitative data amenable to GWAS analysis. First, we determined that visually striking phenotypes could be detected from unstructrured spoken phenotypic descriptions. Next, we developed two methods to process the same descriptions to derive the trait plant height, a well-characterized phenotypic feature in maize: (1) a semantic similarity metric that assigns a score based on the resemblance of each observation to the concept of ‘tallness,’ and (2) a manual scoring system that categorizes and assigns values to phrases related to plant height. Our analysis successfully corroborated known genomic associations and uncovered novel candidate genes potentially linked to plant height. Some of these genes are associated with gene ontology terms that suggest a plausible involvement in determining plant stature. This proof-of-concept demonstrates the viability of spoken phenotypic descriptions in GWAS and introduces a scalable framework for incorporating unstructured language data into genetic association studies. This methodology has the potential not only to enrich the phenotypic data used in GWAS and to enhance the discovery of genetic elements linked to complex traits, but also to expand the repertoire of phenotype data collection methods available for use in the field environment.
Engineering Planar Gram-Negative Outer Membrane Mimics Using Bacterial Outer Membrane Vesicles
Authors: Singh Aarshi N. , Wu Meishan , Ye Tiffany T. , Brown Angela C. , Wittenberg Nathan J. 
Published: December 2023

AbstractAntibiotic resistance is a major challenge in modern medicine. The unique double membrane structure of gram-negative bacteria limits the efficacy of many existing antibiotics and adds complexity to antibiotic development by limiting transport of antibiotics to the bacterial cytosol. New methods to mimic this barrier would enable high-throughput studies for antibiotic development. In this study, we introduce an innovative approach to modify outer membrane vesicles (OMVs) fromAggregatibacter actinomycetemcomitans,to generate planar supported lipid bilayer membranes. Our method first involves the incorporation of synthetic lipids into OMVs using a rapid freeze-thaw technique to form outer membrane hybrid vesicles (OM-Hybrids). Subsequently, these OM-Hybrids can spontaneously rupture when in contact with SiO2surfaces to form a planar outer membrane supported bilayer (OM-SB). We assessed the formation of OM-Hybrids using dynamic light scattering and a fluorescence quenching assay. To analyze the formation of OM-SBs from OM-Hybrids we used quartz crystal microbalance with dissipation monitoring (QCM-D) and fluorescence recovery after photobleaching (FRAP). Additionally, we conducted assays to detect surface-associated DNA and proteins on OM-SBs. The interaction of an antimicrobial peptide, polymyxin B, with the OM-SBs was also assessed. These findings emphasize the capability of our platform to produce planar surfaces of bacterial outer membranes, which in turn, could function as a valuable tool for streamlining the development of antibiotics.
Multimodal Mitigations for Cybersickness in Motion Base Simulators
Authors: Weech Séamas , Lamontagne Anouk 
Published: December 2023

1.AbstractBackgroundVirtual reality (VR) technologies that integrate with motion-base simulators (MBS) have the potential to accelerate personnel training and enhance workplace safety. Motion sickness on an MBS is a widespread problem with vast individual differences that are likely related to idiosyncrasies in estimates of head, body, and vehicle motions. When combined with head-mounted VR, we term the emergent symptoms ‘cybersickness’.MethodsWe conducted two experiments that evaluated cybersickness mitigations in an MBS. In Experiment 1 (N = 8), we tested the effectiveness of a light-touch body harness attached to a mobile-elevated work platform (MEWP) simulator during two nauseogenic VR tasks. In Experiment 2 (N = 14, 7 of whom completed Experiment 1), we tested the effectiveness of a dynamic field-of-view (dFOV) modifier that adaptively restricted the FOV for vehicle rotations in the same VR tasks. We gathered subjective sickness data and qualitative evaluations of the mitigations after the fact.ResultsWe observed a reduced level of sickness in both Experiment 1 and 2 when mitigations were applied. In Experiment 1, the use of a harness led to a mild decrease in total cybersickness of between 3-11%, which was only significant for the nausea dimension. In Experiment 2, the use of dFOV imparted a large benefit to comfort, up to a 45% improvement. Both mitigations primarily improved comfort in a bumpy trench traversal task.ConclusionsCybersickness mitigations can help to deliver VR training for longer, and to more users. The type of content undertaken should be considered when employing new mitigations.
VARIABILITY IN THERMAL SENSITIVITY OF ADULT REPRODUCTIVE DIAPAUSE IN THE SPRUCE BEETLE, DENDROCTONUS RUFIPENNIS
Authors: Davenport Marianne E. , Bentz Barbara J. , Hansen E. Matthew , Ragland Gregory J. 
Published: December 2023

AbstractDiapause induction and termination, which regulate seasonal insect life cycles, can be highly variable within and among populations because these traits are often genetically variable and sensitive to environmental fluctuations. Both types of variation may influence how insect populations respond plastically or evolutionarily to changing climates. In this study we assessed variability in the expression of reproductive diapause in spruce beetles (Dendroctonus rufipennis), a major forest pest whose life cycle timing is regulated by both a prepupal and adult reproductive diapause. Prepupal diapause is facultative and dependent on temperature in the field, whereas previous studies suggest that adult reproductive diapause is effectively obligate. We tested for variability in adult reproductive diapause termination within and between two populations of spruce bark beetle collected from sites in Colorado and Wyoming and reared under warm, summer-like conditions in the laboratory. We also sampled beetles from under tree bark during the fall and spring to estimate how reproductive diapause might terminate naturally in the field. We present evidence that though most beetles induce and do not terminate diapause under constant warm conditions, a small proportion of females from both populations developed mature ovaries and successfully reproduced under warm conditions in the lab. Previous studies have suggested that most beetles require exposure to relatively low temperatures for several weeks to months to terminate diapause in the lab. We found that most female beetles sampled in the field had mature ovaries relatively early in the fall, suggesting that exposure to transiently low temperatures in the field may rapidly terminate adult reproductive diapause. Thus, adult reproductive arrest may primarily act as a block to prevent offspring production prior to winter and appears unnecessary for survival overwinter. Overall, our data do not suggest that major shifts in spruce beetle life cycles as mediated by adult reproductive diapause are immediately imminent with changing climates but, if the variability that we observed is heritable, adult reproductive diapause may have some capacity to evolve in both populations.** Note **all figures/tables designated with ‘S’ are supplemental figures/tables that will appear only in the supplement in the published version. They are provided here alongside the main figures/tables, in-line in the order that they appear in the text for convenience.
Evaluation of recombination rate of microhaplotypes based on the 1000 Genomes Project family data
Authors: Wei Yifan , Li Xi , Shan Tiantian , Wang Haoyu , Dai Xuan , Zhu Qiang , Wang Yufang , Zhang Ji 
Published: December 2023

AbstractMicrohaplotype, a kind of multi-allelic genetic marker that contains two or more SNPs in the range of hundreds of base pairs, has emerged as an important genetic marker in forensic genetics. However, the recombination within the microhaplotype, which has been neglected in most studies, leads to changes in its alleles during inheritance, producing alleles that are not identical to parental alleles and affecting the likelihood ratio calculation of the MH in forensic DNA analysis involving kinship. We constructed a highly dense and extensive MH set in the human genome based on the expanded 1000 Genomes Project (GRCh38). Using the pedigree data contained in 18 populations and a total of 1204 meioses in the GRCh38 dataset, we scanned and confirmed the recombination events that occurred within the above MH loci, to clarify the relationship between recombination and MH polymorphisms. We investigated the average incidence of MH recombinant alleles and the average recombination rate of genome-wide MHs in the hope of providing a reference for the correction of the likelihood ratio in the MH system of future kinship analysis.
Revisiting Alpha Resting State Dynamics Underlying Hallucinatory Vulnerability: Insights from Hidden Semi-Markov Modeling
Authors: Honcamp H. , Schwartze M. , Amorim M. , Linden D.E.J. , Pinheiro A.P. , Kotz S.A. 
Published: December 2023

AbstractResting state (RS) brain activity is inherently non-stationary. Hidden Semi-Markov Models (HsMM) can characterize the continuous RS data as a sequence of recurring and distinct brain states along with their spatio-temporal dynamics. Recent explorations suggest that EEG brain state dynamics in the alpha frequency link to auditory hallucination proneness (HP) in non-clinical individuals. The present study aims to replicate these findings to elucidate robust neural correlates of hallucinatory vulnerability. Specifically, we aimed to investigate the reproducibility of HsMM states across different data sets and within-data set variants as well as the replicability of the association between alpha brain state dynamics and HP. We found that most brain states are reproducible in different data sets, confirming that the HsMM characterized robust and generalizable EEG RS dynamics. Brain state topographies and temporal dynamics of different within-data set variants showed substantial similarities and were robust against reduced data length and number of electrodes. However, the association with HP was not directly reproducible across data sets. These results indicate that the sensitivity of brain state dynamics to capture individual variability in HP may depend on the data recording characteristics and individual variability in RS cognition, such as mind wandering. We suggest that the order in which eyes-open and eyes-closed RS data are acquired directly influences an individual’s attentional state and generation of spontaneous thoughts, and thereby might mediate the link to hallucinatory vulnerability.
A transient burst of mutations occurs during the normal development of yeast colonies
Authors: Agier Nicolas , Vittorelli Nina , Chaux Frédéric , Gillet-Markowska Alexandre , O’Donnell Samuel , Fischer Gilles , Delmas Stéphane 
Published: December 2023

AbstractCharacterizing the pace of mutation accumulation is crucial for understanding how populations adapt to their environment and for unraveling the intricate dynamics between gradual processes and more sudden burst-like events occurring during cancer development. We engineered the genome ofSaccharomyces cerevisiaeto measure the rates of single and double mutations, including point mutations, segmental duplications and reciprocal translocations. We found that during the development of wild-type yeast colonies, double mutations occur at rates that are up to 17-fold higher than those expected on the basis of single mutation rates. We found that this excess of double mutations is partially dependent on theELG1/ATAD5clamp unloader. Additionally, the double mutants retain wild-type mutation rates, suggesting that they originated from genetically wild-type cells that transiently expressed a mutator phenotype. Numerical simulations based on the experimentally measured mutation rates, confirmed that the excess of double mutations can be accounted for by subpopulations of transient mutators within the colony. These subpopulations would be limited to less than a few thousand cells and temporarily adopt mutation rates multiplied by hundreds or thousands for less than five generations. We found that the majority of double mutations would accumulate sequentially in different cell cycles. The simultaneous acquisition of both mutations during the same cell cycle would be rare and possibly associated with systemic genomic instability. In conclusion, our results suggest that transient hypermutators play a major role in genomic instability and contribute significantly to the mutational load naturally accumulating during the growth of isogenic cell populations.Significance statementUnderstanding the pace at which mutations accumulate is of paramount importance in the field of genome dynamics and evolution. In our study, we unveiled a surprising burst of mutations within growing yeast colonies, occurring independently of external stressors. This discovery indicates that, during short intervals, a small subset of cells within the colonies undergoes a mutational overdrive. Notably, these mutator cells do not represent genetically stable mutators with mutations in genes associated with genome stability. Instead, they stem from a strong mutator phenotype that was transiently expressed in genetically wild-type cells. This phenomenon, previously underestimated or even overlooked, holds significant importance and may have far-reaching implications, particularly in the context of cancer development.