Miracle-dz/UniFAR-FTUs huggingface dataset:
Corpus Construction of Precision Medicine

[Background]For advancing biomedical text-mining research, formal evaluations and manually annotated text corpus are critically important. In terms of biomedical corpus construction, in order to meet different needs, many scholars have built different biomedical corpus with different emphasis. Through horizontal observation and vertical comparison of existing biomedical corpus, it is found that most of the entities of biomedical corpus are roughly classified and have narrow coverage. Most of the classification and sub-classification of entities only includes genes, proteins, drugs, diseases and other entities, while the classification of pathways, mutations and other entities is rarely involved. The exploration of the relationship between entities is not enough in depth and the relationship type is uncomprehensive. Therefore, we have developed our own precise medical corpus to store more comprehensive medical knowledge and enrich the biomedical corpus. [Methods]Through repeated iteration the process of article selection, systematic evaluation, manual annotation, formulating consensus of annotation, cross validation, submission assessment to form a more comprehensive and authoritative text corpus, which is also of great significance to promote biomedical text mining research. [Results]At present, a total of 6000 articles have been auto and manual annotated. Each 1000 PubMed English articles of cardiovascular diseases (circulatory system) intestinal neoplasm and liver neoplasm (digestive system) metabolic diseases; 1500 articles of lung neoplasm (respiratory system) and 500 articles of neurological diseases. (but in this issue, we only had a detailed illustration of the lung neoplasm.[Conclusion]A high-quality precise medical corpus was constructed, which promotes the research process of biomedical data mining. At present, some resources of the corpus have been opened to the public, welcome scholars to use and put forward valuable suggestions. (Database URL:http://111.198.139.89/corpus/)
Management of hunger strike: A medical, ethical and legal conundrum

Hunger strike is a protest where an informed person refuses essential nourishment with the intention of accomplishing a specific goal. Hunger strikes conflict with medical, ethical, humanitarian and legal values. A multidisciplinary approach is important when dealing with hunger strike patients. On one hand, there is the wish to preserve life, and on the other to respect the strikers’ autonomy and their wishes, values and advanced directives (or living will). Most hunger strikes are short-lived, but in complex and prolonged circumstances, legal advice must be sought from health service solicitors and a doctor’s medical indemnity organisation. There is an emergent need to have defined guidelines for the management of these hunger strikes to be followed.
Measuring ligand-cell surface receptor affinities with axial line-scanning fluorescence correlation spectroscopy

Development and homeostasis of multicellular organisms is largely controlled by complex cell-cell signaling networks that rely on specific binding of secreted ligands to cell surface receptors. The Wnt signaling network, as an example, involves multiple ligands and receptors to elicit specific cellular responses. To understand the mechanisms of such a network, ligand-receptor interactions should be characterized quantitatively, ideally in live cells or tissues. Such measurements are possible using fluorescence microscopy yet challenging due to sample movement, low signal-to-background ratio and photobleaching. Here, we present a robust approach based on fluorescence correlation spectroscopy with ultra-high speed axial line scanning, yielding precise equilibrium dissociation coefficients of interactions in the Wnt signaling pathway. Using CRISPR/Cas9 editing to endogenously tag receptors with fluorescent proteins, we demonstrate that the method delivers precise results even with low, near-native amounts of receptors.
Colour Doppler ultrasound of temporal arteries for the diagnosis of giant cell arteritis: a multicentre deep learning study.

OBJECTIVES Giant cell arteritis (GCA) is the most common systemic vasculitis in adults. In recent years, colour Doppler ultrasound of the temporal arteries (CDU) has proven to be a powerful non-invasive diagnostic tool, but its place in the diagnosis of GCA remains to be defined. A limitation of the CDU is the inter-operator reproducibility. Image analysis from a different perspective is now possible with the development of artificial intelligence algorithms. We propose to assess this technology for the detection of the halo sign on CDU images. METHODS Three public hospitals retrospectively collected data from 137 patients suspected of having GCA between January 2017 and April 2019. CDU images (n=1,311) were labelled with the VIA software. Three sets (training, validation and test) were created and analysed with a semantic segmentation technique using a U-Net convolutional neural network. RESULTS The area under the curve (AUC) was 0.931 and 0.835 on the validation and test set, respectively. An image positivity threshold was determined by focusing on the specificity. With this threshold, a specificity of 95% and a sensitivity of 60% were obtained for the test set. The analysis of the false interpretation showed that the acquisition modalities and the presence of thrombus caused confusion for the algorithm. CONCLUSIONS We propose an automated image analysis tool for GCA diagnosis. The 2018 EULAR guidelines for image acquisition must be respected before generalising this algorithm. After external validation, this tool could be used as an aid for diagnosis, staff training and student education.
Prevalence of Themes Linked to Delayed Presentation of Breast Cancer in Africa: A Meta-Analysis of Patient-Reported Studies

PURPOSE The prevalence of themes linked to delay in presentation of breast cancer (BC) and their underlying factors vary considerably throughout Africa. Regional differences and trends are largely unreported. The purpose of this research was to provide summary estimates of the prevalence and distribution of the themes and underlying factors linked to delay in the presentation of BC, regional variation, and trends in an effort to identify targets for intervention. DESIGN We screened articles found through PubMed/Medline, African Journal OnLine, Science Direct, Google/Google Scholar, and ResearchGate. We included patient-reported surveys on the reasons linked to delayed presentation under 6 previously identified themes: symptom misinterpretation, fear, preference for alternative care, social influence, hospital-related factors, and access factors. The meta-analytical procedure in MetaXL used the quality-effect model. RESULTS Twelve of the 236 identified articles were eligible for this review. The overall summary estimate of late presentation (> 90 days) was 54% (95% CI, 23 to 85) and was worst in the eastern and central regions. Symptom misinterpretation was the most common theme (50%; 95% CI, 21 to 56), followed by fear (17%; 95% CI, 3 to 27), hospital-related theme (11%; 95% CI, 1 to 21), preference for alternative care (10%; 95% CI, 0 to 21), social influence (7%; 95% CI, 0 to 14), and access-related theme (6%; 95% CI, 0 to 13). The most common factor underlying symptom misinterpretation was mischaracterizing the breast lesion as benign (60%; 95% CI, 4 to 100) which surpassed lack of awareness in the last decade. Misdiagnosis and failure to refer were the dominant hospital-related factors. CONCLUSION Modifiable factors such as mischaracterizing malignant masses as benign, fear, misdiagnosis, and failure to refer were the prevalent factors contributing to delays throughout Africa. These factors are promising targets for intervention.
Nanoparticle contrast agents for X-ray imaging applications.

X-ray imaging is the most widely used diagnostic imaging method in modern medicine and several advanced forms of this technology have recently emerged. Iodinated molecules and barium sulfate suspensions are clinically approved X-ray contrast agents and are widely used. However, these existing contrast agents provide limited information, are suboptimal for new X-ray imaging techniques and are developing safety concerns. Thus, over the past 15 years, there has been a rapid growth in the development of nanoparticles as X-ray contrast agents. Nanoparticles have several desirable features such as high contrast payloads, the potential for long circulation times, and tunable physicochemical properties. Nanoparticles have also been used in a range of biomedical applications such as disease treatment, targeted imaging, and cell tracking. In this review, we discuss the principles behind X-ray contrast generation and introduce new types of X-ray imaging modalities, as well as potential elements and chemical compositions that are suitable for novel contrast agent development. We focus on the progress in nanoparticle X-ray contrast agents developed to be renally clearable, long circulating, theranostic, targeted, or for cell tracking. We feature agents that are used in conjunction with the newly developed multi-energy computed tomography and mammographic imaging technologies. Finally, we offer perspectives on current limitations and emerging research topics as well as expectations for the future development of the field. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.
Detection of Fusarium oxysporum f.sp. vasinfectum in cotton tissue by polymerase chain reaction

A polymerase chain reaction assay was developed for the detection of Fusariumoxysporum f.sp. vasinfectum (FOV), a serious wilt pathogen of cotton in many parts of the world. Based on small nucleotide differences in internal transcribed spacer sequences between 18S, 5.8S and 28S ribosomal DNAs, primers Fov1 (5′-CCCCTGTGAACATACCTTACT-3′) and Fov 2 (5′-ACCAGTAACGAGGGTTTTACT-3′) were selected. These primers unambiguously amplified a 400-bp DNA fragment of all the FOV isolates tested (from Angola, Brazil, China and the USA) but did not amplify any other isolates of mycoflora associated with cotton, such as F. moniliforme, Verticillium albo-atrum, V. dahliae, Aspergillus sp. , F. oxysporum, F. sambucinum or F. solani. A control PCR assay was developed employing the universal primer pair ITS1 and ITS2 which amplified a fragment of approximately 220 bp from all isolates tested. This control assay demonstrated that all fungal DNAs were readily amplifiable, thus confirming that the lack of amplification with Fov1 and Fov2 primers was a result of primer specificity and not of other possible causes, such as DNA degradation or the presence of PCR inhibitors. The assay was effective on samples from the stems, leaves, roots and calli, and from plant tissues both with and without symptoms. This detection system proved to be accurate and sensitive and could aid not only diagnosis but also disease monitoring and forecasting.
Genetic overlap and causal inferences between kidney function and cerebrovascular disease

Objective Leveraging large-scale genetic data, we aimed to identify shared pathogenic mechanisms and causal relationships between impaired kidney function and cerebrovascular disease phenotypes. Methods We used summary statistics from genome-wide association studies (GWAS) of kidney function traits (chronic kidney disease diagnosis, estimated glomerular filtration rate [eGFR], and urinary albumin-to-creatinine ratio [UACR]) and cerebrovascular disease phenotypes (ischemic stroke and its subtypes, intracerebral hemorrhage [ICH], and white matter hyperintensities [WMH] on brain MRI). We (1) tested the genetic overlap between them with polygenic risk scores (PRS), (2) searched for common pleiotropic loci with pairwise GWAS analyses, and (3) explored causal associations by employing 2-sample Mendelian randomization. Results A PRS for lower eGFR was associated with higher large artery stroke (LAS) risk (p = 1 × 10−4). Multiple pleiotropic loci were identified between kidney function traits and cerebrovascular disease phenotypes, with 12q24 associated with eGFR and both LAS and small vessel stroke (SVS), and 2q33 associated with UACR and both SVS and WMH. Mendelian randomization revealed associations of both lower eGFR (odds ratio [OR] per 1-log decrement, 2.10; 95% confidence interval [CI], 1.38–3.21) and higher UACR (OR per 1-log increment, 2.35; 95% CI, 1.12–4.94) with a higher risk of LAS, as well as between higher UACR and higher risk of ICH. Conclusions Impaired kidney function, as assessed by decreased eGFR and increased UACR, may be causally involved in the pathogenesis of LAS. Increased UACR, previously proposed as a marker of systemic small vessel disease, is involved in ICH risk and shares a genetic risk factor at 2q33 with manifestations of cerebral small vessel disease.
Starch-to-sugar conversion in wood parenchyma of field-growing Laurus nobilis plants: a component of the signal pathway for embolism repair?

The ability of stems of Laurus nobilis (L.) to refill embolised xylem conduits was studied in plants both at optimal water supply (W) and under conditions of soil drought inducing xylem pressures (Px) of -1.54 (S1) and -2.35 MPa (S2). Starch depolymerisation in wood parenchyma was measured as percentage of cells 'with high starch content' (HSC-cells) counted under a microscope. HSC-cells decreased during embolism and increased again in refilled stems. A direct relationship was found between percentage of HSC-cells and Px, with HSC-cells between 65 and 75% of the total at Px ≥ -0.6 MPa, at which recovery from PLC was recorded. At low transpiration, starch re-appeared in wood parenchyma cells but only in plants that showed diurnal stomatal opening (W- and S1-plants). In S2-plants showing diurnal stomatal closure and nocturnal opening with Px between -1.2 to -2.4 MPa, HSC-cells were only 25% and plants did not recover from PLC. This finding suggests that (i) the Px threshold for embolism repair was ≥ -0.6 MPa, and (ii) impeded phloem loading limits starch content in wood parenchyma and embolism repair. We conclude that starch depolymerisation acts as a signal to phloem unloading sugars to embolised conduits thus generating the necessary osmotic gradients driving refilling.
Ineffectiveness of Apistan® treatment against the mite Varroa jacobsoni Oud in several districts of Lombardy (Italy)

Dans plusieurs regions d'Italie on signale depuis quelques annees de fortes mortalites d'abeilles dues a la varroose dans des colonies traitees a l'Apistan®. Afin d'etudier ce phenomene, 78 colonies reparties en 8 localites de Lombardie (fig 1) ont ete traitees a l'Apistan® durant 22 j. Lors du traitement on a procede a un blocage de la ponte en encageant les reines. Les acariens tombes sur les plaques de depistage ont ete denombres tous les 8 j. Deux j apres le retrait des lanieres d'Apistan® un traitement de controle au Perizin® a ete effectue. La faible efficacite generale du traitement (tableau I) et les grandes differences entre ruchers mais aussi entre ruches d'un meme rucher (fig 2) prouvent la presence de souches de V jacobsoni resistantes a l'Apistan® et leur diffusion au sein des populations de Lombardie
COVID-19–associated Diffuse Leukoencephalopathy and Microhemorrhages

Diffuse leukoencephalopathy and juxtacortical and/or callosal microhemorrhages were brain imaging features in critically ill patients with coronavirus disease 2019. Coronavirus disease 2019 (COVID-19) has been reported in association with a variety of brain imaging findings such as ischemic infarct, hemorrhage, and acute hemorrhagic necrotizing encephalopathy. Herein, the authors report brain imaging features in 11 critically ill patients with COVID-19 with persistently diminished mental status who underwent MRI between April 5 and April 25, 2020. These imaging features include (a) confluent T2 hyperintensity and mild restricted diffusion in bilateral supratentorial deep and subcortical white matter (in 10 of 11 patients) and (b) multiple punctate microhemorrhages in juxtacortical and callosal white matter (in seven of 11 patients). The authors also discuss potential pathogeneses. © RSNA, 2020 Online supplemental material is available for this article.
The moment-to-moment pitch dynamics of child-directed speech shape toddlers' attention and learning.

Young children have an overall preference for child-directed speech (CDS) over adult-directed speech (ADS), and its structural features are thought to facilitate language learning. Many studies have supported these findings, but less is known about processing of CDS at short, sub-second timescales. How do the moment-to-moment dynamics of CDS influence children's attention and learning? In Study 1, we used hierarchical clustering to characterize patterns of pitch variability in a natural CDS corpus, which uncovered four main word-level contour shapes: 'fall', 'rise', 'hill', and 'valley'. In Study 2, we adapted a measure from adult attention research - pupil size synchrony - to quantify real-time attention to speech across participants and found that toddlers showed higher synchrony to the dynamics of CDS than to ADS. Importantly, there were consistent differences in toddlers' attention when listening to the four word-level contour types. In Study 3, we found that pupil size synchrony during exposure to novel words predicted toddlers' learning at test. This suggests that the dynamics of pitch in CDS not only shape toddlers' attention but guide their learning of new words. By revealing a physiological response to the real-time dynamics of CDS, this investigation yields a new sub-second framework for understanding young children's engagement with one of the most important signals in their environment.
StressFoot: Uncovering the Potential of the Foot for Acute Stress Sensing in Sitting Posture

Stress is a naturally occurring psychological response and identifiable by several body signs. We propose a novel way to discriminate acute stress and relaxation, using movement and posture characteristics of the foot. Based on data collected from 23 participants performing tasks that induced stress and relaxation, we developed several machine learning models to construct the validity of our method. We tested our models in another study with 11 additional participants. The results demonstrated replicability with an overall accuracy of 87%. To also demonstrate external validity, we conducted a field study with 10 participants, performing their usual everyday office tasks over a working day. The results showed substantial robustness. We describe ten significant features in detail to enable an easy replication of our models.
Failed Genetic Protection: Type 1 Diabetes in the Presence of HLA-DQB1*06:02

Certain HLA class II genes increase the risk for type 1 diabetes (T1D) development while others provide protection from disease development. HLA class II alleles encode MHC proteins on antigen-presenting cells, which function to present peptides and activate CD4 T cells. The DRB1*15:01 (DR15)-DQA1*01:02-DQB1*06:02 (DQ6) haplotype provides dominant protection across all stages of T1D and is a common haplotype found in Caucasians. However, it is present in <1% of people with T1D. Knowing which metabolic, immunologic, and genetic features are unique to individuals who fail genetic protection and develop T1D is important for defining the underlying mechanisms of DQB1*06:02-mediated protection. We describe a T1D cohort with DQB1*06:02 (n = 50) and compare them to individuals with T1D and without DQB1*06:02 (n = 2,759) who were identified over the last 26 years at the Barbara Davis Center for Diabetes. The age at diagnosis was similar between the cohorts and normally distributed throughout childhood and early adulthood. The average hemoglobin A1c was 10.8 ± 2.8% (95 ± 7 mmol/mol) at diagnosis in those DQB1*06:02 positive. The majority of T1D DQB1*06:02+ individuals were positive for one or more islet autoantibodies; however, there was a greater proportion who were islet autoantibody negative compared with those T1D DQB1*06:02− individuals. Interestingly, DQB1*03:02, which confers significant T1D risk, was present in only those DQB1*06:02+ individuals with islet autoantibodies. This is one of the largest studies examining patients presenting with clinical T1D in the presence of DQB1*06:02, which provides a population to study the mechanisms of failed genetic protection against T1D.
scTPA: A web tool for single-cell transcriptome analysis of pathway activation signatures

The most fundamental challenge in current single-cell RNA-seq data analysis is functional interpretation and annotation of cell clusters. The biological pathways in distinct cell types have different activation patterns, which facilitates understanding cell functions in single-cell transcriptomics. However, no effective web tool has been implemented for single-cell transcriptomic data analysis based on prior biological pathway knowledge. Here, we introduce scTPA (http://sctpa.bio-data.cn/sctpa), which is a web-based platform providing pathway-based analysis of single-cell RNA-seq data in human and mouse. scTPA incorporates four widely-used gene set enrichment methods to estimate the pathway activation scores of single cells based on a collection of available biological pathways with different functional and taxonomic classifications. The clustering analysis and cell-type-specific activation pathway identification were provided for the functional interpretation of cell types from pathway-oriented perspective. An intuitive interface allows users to conveniently visualize and download single-cell pathway signatures. Together, scTPA is a comprehensive tool to identify pathway activation signatures for dissecting single cell heterogeneity.
Relationship between sleep characteristics and markers of inflammation in Swedish women from the general population

Systemic inflammation is thought to mediate the link between sleep and cardiovascular outcomes, but previous studies on sleep habits and inflammation markers have found inconsistent results. This study investigated the relationship between sleep characteristics and C‐reactive protein (CRP), interleukin‐6 (IL‐6) and tumor necrosis factor α (TNFα). A representative sample of 319 Swedish women was randomly selected from the general population for in‐home polysomnography, sleep questionnaire and blood samples. As variables were highly correlated, principal component analysis was used to reduce the number of original variables. Linear regression with log‐transformation of the outcomes (lnCRP, lnIL‐6 and lnTNFα) and quantile regression were fitted to estimate cross‐sectional relationships. Multivariable linear regression models suggested a significant association of insomnia symptoms (self‐reported) with higher lnCRP levels (β = 0.11; 95% confidence interval [CI] = 0.02; 0.21), but not with lnIL‐6 and lnTNFα. From quantile regression analysis we found that a high non‐restorative index (subjective) and insomnia symptoms (self‐reported) were associated with higher values of CRP, especially in the highest quantiles of the CRP distribution (90th percentile: β = 0.71; 95% CI = 0.17; 1.24. β = 1.23; 95% CI = 0.44; 2.02, respectively). Additionally, higher amounts of rapid eye movement (REM) sleep were associated with lower CRP values (90th percentile: β = −0.80; 95% CI = −0.14; −1.46). In conclusion, sleep disturbances (self‐reported), specifically difficulties maintaining sleep and early morning awakenings, but not sleep duration (neither subjective nor objective), were associated with higher CRP levels. No association was found with IL‐6 or TNFα. Elevated REM sleep was associated with lower CRP levels. The results suggest that inflammation might be an intermediate mechanism linking sleep and health in women.