bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrasonic Artificial Intelligence Shows Statistically Equivalent Performance for Thyroid Nodule Diagnosis to Fine Needle Aspiration Cytopathology and BRAFV600E Mutation Analysis Combined
Authors: Zhou Tianhan , Xu Lei , Shi Jingjing , Zhang Yu , Hu Tao , Xu Rujun , Xie Lesi , Sun Lijuan , Li Dandan , Zhang Wenhua , Chen Chuanghua , Wang Wei , Xu Chenke , Kong Fanlei , Xun Yanping , Yu Lingying , Zhang Shirong , Ding Jinwang , Wu Fan , Tang Tian , Zhan Siqi , Zhang Jiaoping , Kong Dexing , Luo Dingcun 
Published: May 2022

AbstractObjectiveTo investigate the difference between an artificial intelligence (AI) system, fine-needle aspiration (FNA) cytopathology, BRAFV600E mutation analysis and combined method of the latter two in thyroid nodule diagnosis.MethodsUltrasound images of 490 thyroid nodules (378 patients) with postsurgical pathology or twice of consistent combined FNA examination outcomes with a half-year interval, which were considered as gold standard, were collected and analyzed. The diagnostic efficacies of an AI diagnostic system and FNA-based methods were evaluated in terms of sensitivity, specificity, accuracy, κ coefficient compared to the gold standard.ResultsThe malignancy threshold of 0.53 for an AI system was selected according to the optimization of Youden index based on a retrospective cohort of 346 nodules and then applied for a prospective cohort of 144 nodules. The combined method of FNA cytopathology according to Bethesda risk stratification system and BRAFV600E mutation analysis showed no significant difference in comparison with the AI diagnostic system in accuracy for both the retrospective and prospective cohort in our single center study. Besides, for the 33 indeterministic Bethesda system category III and IV nodules included in our study, the AI system showed no significant difference in comparison with the BRAFV600E mutation analysis.ConclusionThe evaluated AI diagnostic system showed similar diagnostic performance to FNA cytopathology combined with and BRAFV600E mutation analysis. Given its advantages in ease of operation, time efficiency, and noninvasiveness for thyroid nodule screening as well as the wide availability of ultrasonography, it can be widely applied in all levels of hospitals and clinics to assist radiologists for thyroid nodule diagnosis and is expected to reduce the need for relatively invasive FNA biopsies and thereby reducing the associated risks and side effects as well as to shorten the diagnostic time.
Acute exercise induces natural killer cell mobilization but not infiltration into prostate cancer tissue in humans
Authors: Schenk A , Esser T , Belen S , Gunasekara N , Joisten N , Winker M , Weike L , Bloch W , Heidenreich A , Herden J , Löser H , Oganesian S , Theurich S , Watzl C , Zimmer P 
Published: May 2022

AbstractThe mobilization and activation of natural killer (NK) cells have been proposed as key mechanisms promoting anti oncogenic effects of physical exercise. Although mouse models have proven that physical exercise recruits NK cells to tumor tissue and inhibits tumor growth, this preclinical finding has not been transferred to the clinical setting yet. In this first-in-human study, we found that physical exercise mobilizes and redistributes NK cells, especially those with a cytotoxic phenotype, in line with preclinical models. However, physical exercise did not increase NK cell tumor infiltrates. Future studies should carefully distinguish between acute and chronic exercise modalities and should be encouraged to investigate more immune responsive tumor entities.
Artificial Intelligence Enables Quantitative Assessment of Ulcerative Colitis Histology
Authors: Najdawi Fedaa , Sucipto Kathleen , Mistry Pratik , Hennek Stephanie , Jayson Christina , Lin Mary , Fahy Darren , Kinsey Shawn , Wapinski Ilan , Beck Andrew H. , Resnick Murray B. , Khosla Archit , Drage Michael G. 
Published: May 2022

AbstractUlcerative colitis (UC) is a chronic inflammatory bowel disease that is characterized by a relapsing and remitting course. Appropriate assessment of disease activity is critical for adequate treatment decisions. In addition to endoscopic mucosal healing, histologic remission is emerging as a treatment target and a key factor in the evaluation of disease activity and therapeutic efficacy. However, there is no standardized definition of histologic remission, limiting the utility of histologic scoring, and manual pathologist evaluation is subject to intra-and inter-observer variability. Machine learning approaches are increasingly being developed to aid pathologists in accurate and reproducible scoring of histology, and can enable sensitive assessment of clinically relevant features. Here we report a proof-of-concept study using the PathAI platform to develop ML models for identification and quantification of UC histological features directly from hematoxylin and eosin (H&E)-stained whole slide images. Model-predicted histological features were used to quantify tissue area proportions and cell count proportions and densities, which correlated with disease severity and pathologist-assigned Nancy Histological Index (NHI) scores. Moreover, using multivariate analysis based on selected model-predicted histological features, we were able to accurately predict NHI scores, with a weighted kappa (k=0.93) and Spearman correlation (ρ=0.93, p<0.001) when compared to manual pathologist consensus NHI scores. We were also able to predict histological remission, based on the resolution of active inflammation, with high accuracy of 0.94. These results demonstrate the accuracy of ML models in quantifying histologic features of UC and predicting NHI scores, and highlight the potential of this approach to enable standardized and robust assessment of histologic remission for improved evaluation of disease activity and prognosis.
Differences in epidemiology of enteropathogens in children pre- and post-rotavirus vaccine introduction in Kilifi, coastal Kenya
Authors: Agoti Charles N. , Curran Martin D. , Murunga Nickson , Ngari Moses , Muthumbi Ester , Lambisia Arnold , Frost Simon DW , Blacklaws Barbara , Nokes D. James , Drumright Lydia N 
Published: May 2022

ABSTRACTBackgroundIn July 2014, Kenya introduced the Rotarix® vaccine into its national immunization program. The impact of this vaccination programme on the local epidemiology of enteropathogens is unclear.MethodsThe TaqMan Array Card (TAC) was used for screening for 28 different enteropathogens in 718 stools from children less than 13 years of age who presented with diarrhea and were admitted to Kilifi County Hospital, coastal Kenya, in 2013 (before vaccine introduction) and in 2016-2018 (after vaccine introduction). The differences between pre- and post-Rotarix® vaccination periods were examined using univariate and multivariable logistic regressions.ResultsIn 665 specimens (92.6%), one or more enteropathogens were detected, while in 323 specimens (48.6%), three or more enteropathogens were detected. There was a significant increase in the proportion of samples containing enteroaggregative Escherichia coli (35.7% vs 45.3%, p=0.014), cytomegalovirus (4.2% vs 9.9%, p=0.008), Vibrio cholerae (0.0% vs 2.3%, p=0.019), Strongyloides species (0.8% vs 3.6%, p=0.048) and Dientamoeba fragilis (2.1% vs 7.8%, p=0.004) post-vaccine introduction. Sapovirus detection decreased significantly (7.6% vs 4.0%, p=0.030) post-vaccine introduction. The proportion of samples that tested positive for rotavirus group A did not statistically differ between the pre- and post-vaccine periods (27.4% vs. 23.5%, p=0.253).ConclusionsIn this setting, the burden of childhood enteropathogen infection was high both pre- and post-rotavirus vaccination introduction, with some specific changes in the burden of enteropathogens in hospitalized children after rotavirus vaccination introduction.
A Solution to the Kermack and McKendrick Integro-Differential Equations
Authors: Duclos Ted , Reichert Tom 
Published: May 2022

AbstractIn this manuscript, we derive a closed form solution to the full Kermack and McKendrick integro-differential equations (Kermack and McKendrick 1927) which we call the KMES. We demonstrate the veracity of the KMES using independent data from the Covid 19 pandemic and derive many previously unknown and useful analytical expressions for characterizing and managing an epidemic. These include expressions for the viral load, the final size, the effective reproduction number, and the time to the peak in infections. The KMES can also be cast in the form of a step function response to the input of new infections; and that response is the time series of total infections.Since the publication of Kermack and McKendrick’s seminal paper (1927), thousands of authors have utilized the Susceptible, Infected, and Recovered (SIR) approximations; expressions putatively derived from the integro-differential equations to model epidemic dynamics. Implicit in the use of the SIR approximation are the beliefs that there is no closed form solution to the more complex integro-differential equations, that the approximation adequately reproduces the dynamics of the integro-differential equations, and that herd immunity always exists. However, the KMES demonstrates that the SIR models are not adequate representations of the integro-differential equations, and herd immunity is not guaranteed. We suggest that the KMES obsoletes the need for the SIR approximations; and provides a new level of understanding of epidemic dynamics.
Evidence for the presence and diagnostic utility of SPM in human peripheral blood
Authors: Dalli Jesmond , Gomez Esteban A , Serhan Charles N 
Published: May 2022

SummaryWe thank O’Donnell et al, for their comments on our contribution and are grateful to be afforded this opportunity to formally respond to their critique24.We are surprised by the author’s assertion relating to the biological relevance of SPM because a simple literature search for related terms such as ‘resolvin’ in PubMed yields an abundance (>1,420 publications) of evidence supporting the potent biological activities and the diagnostic potential of some of these mediators. Several co-authors of the O’Donnell’s et al manuscript, have published on the resolvins and SPMs, including some publications within recent weeks. Importantly, O’Donnell et al, misreport as well as mis-apply criteria for peak identification reported in the Gomez et al, publication which lead to the flawed analysis they performed.In this response therefore, we provide a step-by-step clarification of the methodologies used in Gomez et al, and a side-by-side comparison of the underlying data to clarify any confusion. We also demonstrate that using the orthogonal criteria discussed by O’Donnell et al, we obtain essentially identical results thus providing additional validation of our techniques and support the conclusions.
Polycomb-lamina antagonism partitions heterochromatin at the nuclear periphery
Authors: Siegenfeld Allison P. , Roseman Shelby A. , Roh Heejin , Lue Nicholas Z. , Wagen Corin C. , Zhou Eric , Johnstone Sarah E. , Aryee Martin J. , Liau Brian B. 
Published: May 2022

AbstractThe genome can be divided into two spatially segregated compartments, A and B,1,2 which broadly partition active and inactive chromatin states, respectively. Constitutive heterochromatin is predominantly located within the B compartment and comprises chromatin that is in close contact with the nuclear lamina.3–5 By contrast, facultative heterochromatin marked by H3K27me3 can span both compartments.2–5 How epigenetic modifications, A/B compartmentalization, and lamina association collectively maintain heterochromatin architecture and function remains unclear.6,7 Here we developed an approach termed Lamina-Inducible Methylation and Hi-C (LIMe-Hi-C) that jointly measures chromosome conformation, DNA methylation, and nuclear lamina positioning. Through this approach, we identified topologically distinct A/B sub-compartments characterized by high levels of H3K27me3 and differing degrees of lamina association. To study the regulation of these sub-compartments, we inhibited Polycomb repressive complex 2 (PRC2), revealing that H3K27me3 is an essential factor in sub-compartment segregation. Unexpectedly, PRC2 inhibition also elicited broad gains in lamina association and constitutive heterochromatin spreading into H3K27me3-marked B sub-compartment regions. Consistent with repositioning to the lamina, genes originally marked with H3K27me3 in the B compartment, but not in the A compartment, remained largely repressed, suggesting that constitutive heterochromatin spreading can compensate for loss of H3K27me3 at a transcriptional level. These findings demonstrate that Polycomb sub-compartments and their antagonism with nuclear lamina association are fundamental organizational features of genome structure. More broadly, by jointly measuring nuclear position and Hi-C contacts, our study demonstrates how dynamic changes in compartmentalization and nuclear lamina association represent distinct but interdependent modes of heterochromatin regulation.
A chromosome-length genome assembly and annotation of blackberry (Rubus argutus, cv. ‘Hillquist’)
Authors: Brůna Tomáš , Aryal Rishi , Dudchenko Olga , Sargent Daniel James , Mead Daniel , Buti Matteo , Cavallini Andrea , Hytönen Timo , Andrés Javier , Pham Melanie , Weisz David , Mascagni Flavia , Usai Gabriele , Natali Lucia , Bassil Nahla , Fernandez Gina E. , Lomsadze Alexandre , Armour Mitchell , Olukolu Bode , Poorten Thomas , Britton Caitlin , Davik Jahn , Ashrafi Hamid , Aiden Erez Lieberman , Borodovsky Mark , Worthington Margaret 
Published: May 2022

AbstractBackgroundBlackberries (Rubus spp.) are the fourth most economically important berry crop worldwide. Genome assemblies and annotations have been developed for Rubus species in subgenus Idaeobatus, including black raspberry (R. occidentalis), red raspberry (R. idaeus), and R. chingii, but very few genomic resources exist for blackberries and their relatives in subgenus Rubus.FindingsHere we present a chromosome-length assembly and annotation of the diploid blackberry germplasm accession ‘Hillquist’ (R. argutus). ‘Hillquist’ is the only known source of primocane-fruiting (annual-fruiting) in tetraploid fresh-market blackberry breeding programs and is represented in the pedigree of many important cultivars worldwide. The ‘Hillquist’ assembly, generated using PacBio long reads scaffolded with Hi-C sequencing, consisted of 298 Mb, of which 270 Mb (90%) was placed on seven chromosome-length scaffolds with an average length of 38.6 Mb. Approximately 52.8% of the genome was composed of repetitive elements. The genome sequence was highly collinear with a novel maternal haplotype-resolved linkage map of the tetraploid blackberry selection A-2551TN and genome assemblies of R. chingii and red raspberry. A total of 38,503 protein-coding genes were predicted using the assembly and Iso-Seq and RNA-seq data, of which 72% were functionally annotated.ConclusionsThe utility of the ‘Hillquist’ genome has been demonstrated here by the development of the first genotyping-by-sequencing based linkage map of tetraploid blackberry and the identification of several possible candidate genes for primocane-fruiting within the previously mapped locus. This chromosome-length assembly will facilitate future studies in Rubus biology, genetics, and genomics and strengthen applied breeding programs.
Chemical screen of Arabidopsis zygote and proteomics in tobacco BY-2 cells identify general plant cell division inhibitors
Authors: Kimata Yusuke , Yamada Moé , Murata Takashi , Kuwata Keiko , Sato Ayato , Suzuki Takamasa , Kurihara Daisuke , Hasebe Mitsuyasu , Higashiyama Tetsuya , Ueda Minako 
Published: May 2022

AbstractCell division is essential for growth and development and involves events such as spindle assembly, chromosome separation, and cell plate formation. In plants, the tools used to control these events at the desired time are still poor because the genetic approach is ineffective owing to a high redundancy and lethality, as well as harmful side effects. Accordingly, we screened cell division-affecting compounds, with a focus on Arabidopsis thaliana zygotes, which individually develop in maternal ovules; the cell division was reliably traceable without time-lapse observations. We then identified the target events of the identified compounds using tobacco BY-2 cells for live-cell imaging and proteomics. As a result, we isolated two compounds, PD-180970 and PP2. PD-180970 disrupts microtubule (MT) organization and, thus, nuclear separation, presumably by inhibiting MT-associated proteins (MAP70). PP2 affected class II Kinesin-12 localization at the phragmoplast emerging site and impaired cytokinesis. Moreover, neither chemical caused irreversible damage to viability but they were effective in multiple plant species such as cucumber (Cucumis sativus) and moss (Physcomitrium patens). We propose that the combination of chemical screening based on Arabidopsis zygotes and target event specification focusing on tobacco BY-2 cells can be used to effectively identify novel tools and transiently control specific cell division events that are conserved in diverse plant species.
Benchmark of tools for in silico prediction of MHC class I and class II genotypes from NGS data
Authors: Claeys Arne , Staut Jasper , Merseburger Peter , Marchal Kathleen , Van den Eynden Jimmy 
Published: May 2022

AbstractThe Human Leukocyte Antigen (HLA) genes are a group of highly polymorphic genes that are located in the Major Histocompatibility Complex (MHC) region on chromosome 6. The HLA genotype affects the presentability of tumour antigens to the immune system. While knowledge of these genotypes is of utmost importance to study differences in immune responses between cancer patients, gold standard, PCR-derived genotypes are rarely available in large Next Generation Sequencing (NGS) datasets. Therefore, a variety of methods for in silico NGS-based HLA genotyping have been developed, bypassing the need to determine these genotypes with separate experiments. However, there is currently no consensus on the best performing tool. Here, we compiled a list of 13 HLA callers and evaluated their accuracy on three different datasets. Based on these results, best-practice guidelines were constructed, and consensus HLA allele predictions were made for DNA and RNA samples from The Cancer Genome Atlas (TCGA).
The Repeating, Modular Architecture of the HtrA Proteases
Authors: Merski Matthew , Macedo-Ribeiro Sandra , Wieczorek Rafal M. , Górna Maria W. 
Published: May 2022

AbstractA conserved, 26 residue sequence [AA(X2)[A/G][G/L](X2)GDV[I/L](X2)[V/L]NGE(X1)V(X6)] and corresponding structure repeating module was identified within the HtrA protease family using a non-redundant set (N=20) of publically available structures. While the repeats themselves were far from sequence perfect they had notable conservation to a statistically significant level with three or more repetitions identified within one protein at a level that would be expected to randomly occur only once per 1031 residues. This sequence repeat was associated with a six stranded antiparallel β-barrel module, two of which are present in the core of the structures of the PA clan of serine proteases, while a modified version of this module could be identified in the PDZ-like domains. Automated structural alignment methods had difficulties in superimposing these β-barrels but use of a target human HtrA2 structure showed that these modules had an average RMSD across the set of structures of less than 2 Å (mean and median). Our findings support Dayhoff’s hypothesis that complex proteins arose through duplication of simpler peptide motifs and domains.
Systematic analysis of alternative splicing in time course data using Spycone
Authors: Lio Chit Tong , Louadi Zakaria , Fenn Amit , Baumbach Jan , Kacprowski Tim , List Markus , Tsoy Olga 
Published: May 2022

AbstractDuring disease progression or organism development, alternative splicing (AS) may lead to isoform switches (IS) that demonstrate similar temporal patterns and reflect the AS co-regulation of such genes. Tools for dynamic process analysis usually neglect AS. Here we propose Spycone (https://github.com/yollct/spycone), a splicing-aware framework for time course data analysis. Spycone exploits a novel IS detection algorithm and offers downstream analysis such as network and gene set enrichment. We demonstrate the performance of Spycone using simulated and real-world data of SARS-CoV-2 infection.
Pre-T cell receptor Self-MHC Sampling Restricts Thymocyte Dedifferentiation
Authors: Duke-Cohan Jonathan S. , Akitsu Aoi , Mallis Robert J. , Messier Cameron M. , Lizotte Patrick H. , Hwang Wonmuk , Lang Matthew J. , Reinherz Ellis L. 
Published: May 2022

Summary paragraphProgramming T lymphocytes to distinguish self from non-self is a vital, multi-step process arising in the thymus1–4. Signalling through the pre-T cell receptor (preTCR), a CD3-associated heterodimer comprising an invariant pTα chain and a clone-specific β chain, constitutes a critical early checkpoint in thymocyte development within the αβ T-cell lineage5, 6. Recent work demonstrates that preTCRs arrayed on double negative (DN) thymocytes, like αβ TCRs appearing on double positive (DP) thymocytes, ligate peptides bound to MHC molecules (pMHC) on thymic stroma but via a different molecular docking strategy7–10. Here we show the consequences of those distinctive interactions for thymocyte progression, using synchronized fetal thymic progenitor cultures differing in the presence or absence of pMHC on support stroma, determining single cell transcriptomes at key thymocyte developmental transitions. Although MHC negative stroma fosters αβ T lymphocyte differentiation, the absence of pMHC-preTCR interplay leads to deviant thymocyte transcriptional programming associated with de-differentiation. Highly proliferative DN and DP subsets with antecedent characteristics of T cell lymphoblastic and myeloid malignancies emerge. Thus, at least in vitro, beyond fostering β chain repertoire broadening for subsequent αβ TCR utilization, preTCR-pMHC interaction limits cellular plasticity to facilitate normal thymocyte differentiation and proliferation that, if absent, introduces significant developmental vulnerabilities.