Miracle-dz/UniFAR-FTUs huggingface dataset:
Spatial Architecture and Arrangement of Tumor-Infiltrating Lymphocytes for Predicting Likelihood of Recurrence in Early-Stage Non–Small Cell Lung Cancer

Purpose: The presence of a high degree of tumor-infiltrating lymphocytes (TIL) has been proven to be associated with outcome in patients with non–small cell lung cancer (NSCLC). However, recent evidence indicates that tissue architecture is also prognostic of disease-specific survival and recurrence. We show a set of descriptors (spatial TIL, SpaTIL) that capture density, and spatial colocalization of TILs and tumor cells across digital images that can predict likelihood of recurrence in early-stage NSCLC. Experimental Design: The association between recurrence in early-stage NSCLC and SpaTIL features was explored on 301 patients across four different cohorts. Cohort D1 (n = 70) was used to identify the most prognostic SpaTIL features and to train a classifier to predict the likelihood of recurrence. The classifier performance was evaluated in cohorts D2 (n = 119), D3 (n = 112), and D4 (n = 112). Two pathologists graded each sample of D1 and D2; intraobserver agreement and association between manual grading and likelihood of recurrence were analyzed. Results: SpaTIL was associated with likelihood of recurrence in all test sets (log-rank P < 0.02). A multivariate Cox proportional hazards analysis revealed an HR of 3.08 (95% confidence interval, 2.1–4.5, P = 7.3 × 10−5). In contrast, agreement among expert pathologists using tumor grade was moderate (Kappa = 0.5), and the manual TIL grading was only prognostic for one reader in D2 (P = 8.0 × 10−3). Conclusions: A set of features related to density and spatial architecture of TILs was found to be associated with a likelihood of recurrence of early-stage NSCLC. This information could potentially be used for helping in treatment planning and management of early-stage NSCLC. See related commentary by Peled et al., p. 1449
Soft Coral Dendronephthya puetteri Extract Ameliorates Inflammations by Suppressing Inflammatory Mediators and Oxidative Stress in LPS-Stimulated Zebrafish

Marine-derived extract and/or bioactive compounds have attracted increasing demand due to their unique and potential uses as cures for various inflammation-based diseases. Several studies revealed anti-inflammatory candidates found in soft corals. However, the effects of soft corals on inflammation in an in vivo model remain to be determined. Therefore, the extract of soft coral Dendronephthya puetteri (DPE) was investigated for an in vivo anti-inflammatory effect in a lipopolysaccharide (LPS)-stimulated zebrafish model to determine its potential use as a natural anti-inflammatory agent. We also investigated whether DPE has toxic effects in a zebrafish model. No significant changes were observed in terms of survival, heart beat rate, or developmental abnormalities in the zebrafish embryos exposed to a concentration below 100 µg/mL of DPE. Treating the zebrafish model with LPS-treatment significantly increased the ROS, NO generation, and cell death. However, DPE inhibited this LPS-stimulated ROS, NO generation, and cell death in a dose-dependent manner. In addition, DPE significantly reduced the mRNA expression of both iNOS and COX-2 and markedly suppressed the expression levels of the proinflammatory cytokines, TNF-α and IL-6, in an LPS-stimulated zebrafish model. These findings demonstrate that DPE has profound anti-inflammatory effect in vivo, suggesting that DPE might be a strong natural anti-inflammatory agent.
Center-Reported Adherence to Nutrition Standards of the Child and Adult Care Food Program.

BACKGROUND The Child and Adult Care Food Program (CACFP) sets nutrition standards for foods served in participating settings. Licensing regulations in many states, including Connecticut (CT), extend these rules to nonparticipating facilities. This study evaluates the food environment for preschool-age children in CT child care centers and describes center-reported adherence to the CACFP nutrition regulations. METHODS We surveyed directors of licensed CACFP-participating and non-CACFP centers that served meals and/or snacks. Food served, caregiver feeding behavior, nutrition practices and policies, and CACFP knowledge were reported by 256 non-CACFP and 87 CACFP centers. We conducted bivariate analyses to describe adherence to the CACFP regulations as reported by CACFP and nonparticipating centers. Data were collected in 2015-2016 and analyzed in 2017. RESULTS CACFP centers reported more engagement in recommended feeding and nutrition practices than non-CACFP centers, including serving more fresh fruit and whole grains at snack time, serving low-fat milk for meals/snacks, and use of family style dining and positive caregiver behaviors. No center reported serving soda, only a few had fruit drinks, and the majority prohibited parents from sending in sugary drinks. Despite the licensing regulations about compliance with the CACFP nutrition standards, 52% of non-CACFP centers had never heard of CACFP and only 21% received information about following the CACFP standards and practices. CONCLUSIONS CACFP participation is associated with better center-reported adherence to the CACFP nutrition standards and feeding practices. Poor awareness about CACFP among nonparticipating centers needs to be addressed to improve compliance with the CACFP nutrition standards.
Force Increase in a Repetitive Motor Task Inducing Motor Fatigue

Abstract To evaluate task induced motor fatigue in a well-established finger tapping task, we analyzed tapping parameters and included the time course of measures of force. We hypothesized that a decline in tapping force would reflect task induced motor fatigue, defined by a lengthening of inter-tap intervals (ITI). A secondary aim was to investigate the reliability of tapping data acquisition with the force sensor. Results show that, as expected, tapping speed decreased linearly over time, due to both an increase of ITI and tap duration. In contrast, tapping force increased non-linearly over time and was uncorrelated to changes in tapping speed. Force data could serve as a measure to characterize task induced motor fatigue. Force sensors can assess a decline in tapping speed as well as an independent increase of tapping force. We argue that the increase of force reflects central compensation, i.e. perception of fatigue, due to an increase in task effort and difficulty.
Oxidant Signaling Mediated by Nox2 in Neutrophils Promotes Regenerative Myelopoiesis and Tissue Recovery following Ischemic Damage

Ischemic tissue damage activates hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (BM)-generating myeloid cells, and persistent HSPC activity may drive chronic inflammation and impair tissue recovery. Although increased reactive oxygen species in the BM regulate HSPC functions, their roles in myelopoiesis of activated HSPCs and subsequent tissue recovery during ischemic damage are not well understood. In this paper, we report that deletion of Nox2 NADPH oxidase in mice results in persistent elevations in BM HSPC activity and levels of inflammatory monocytes/macrophages in BM and ischemic tissue in a model of hindlimb ischemia. Ischemic tissue damage induces oxidants in BM such as elevations of hydrogen peroxide and oxidized phospholipids, which activate redox-sensitive Lyn kinase in a Nox2-dependent manner. Moreover, during tissue recovery after ischemic injury, this Nox2-ROS–Lyn kinase axis is induced by Nox2 in neutrophils that home to the BM, which inhibits HSPC activity and inflammatory monocyte generation and promotes tissue regeneration after ischemic damage. Thus, oxidant signaling in the BM mediated by Nox2 in neutrophils regulates myelopoiesis of HSPCs to promote regeneration of damaged tissue.
Prognostic Genes of Breast Cancer Identified by Gene Co-expression Network Analysis

Background Breast cancer is the mostly diagnosed malignance in female worldwide. However, the mechanisms of its pathogenesis remain largely unknown. Methods In this study, we used weighted gene co-expression network analysis (WGCNA) to identify novel biomarkers associated with the prognosis of breast cancer. Gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. Results A total of 5 modules were identified via the average linkage hierarchical clustering. And a module significantly with the pathological grade was screened out. 33 genes with high connectivity in the clinically significant module were identified as hub genes. Among them, CASC5 and RAD51 were negatively associated with the overall survival and disease-specific survival. Similar results were observed in the validation dataset. Protein levels of CACS5 and RAD51 were also significantly higher in tumor tissues compared with normal tissues based on the analysis of the Human Protein Atlas. Convincingly, qRT-PCR analysis of breast cancer tissues and matched paracancerous tissue demonstrated that CACS5 and RAD51 were significantly upregulated in in breast cancer compared to paracancerous tissues. Further cell proliferation assay indicated that CACS5 and RAD51 depletion decreased cell proliferation capability. Conclusion In conclusion, our findings suggested that CASC5 and RAD51 could serve as biomarkers related to the prognosis of breast cancer and may be helpful for revealing pathogenic mechanism and developing further research.
Monomeric C-Reactive Protein and Cerebral Hemorrhage: From Bench to Bedside

C-reactive protein (CRP) is an important mediator and a hallmark of the acute-phase response to inflammation. High-sensitivity assays that accurately measure levels of CRP have been recommended for use in risk assessment in ischemic stroke patients. Elevation of CRP during the acute-phase response in intracerebral hemorrhage (ICH) is also associated with the outcomes such as death and vascular complications. However, no association has been found with the increased risk of ICH. The aim of this review is to synthesize the published literature on the associations of CRP with acute ICH both as a risk biomarker and predictor of short- and long-term outcomes as well as its role as a pathogenic determinant. We believe before any clinical utility, a critical appraisal of the strengths and deficiencies of the accumulated evidence is required both to evaluate the current state of knowledge and to improve the design of future clinical studies.
The Interplay of Relational and Non-relational Processes in Sentence Production: The Case of Relative Clause Planning in Japanese and Spanish

Speech planning involves different steps in order to transform a conceptual message into speech. These include establishing structural relations among constituents (i.e., relational information), and selecting the appropriate lexical items to convey the intended message (non-relational elements). However, the precise way relational and non-relational information are computed when undertaking linguistic encoding is not clear. This paper explores how the pre-linguistic message undergoes linguistic encoding, and what kind of information (relational or non-relational) is prioritized in doing so. We analyze the production planning of Relative Clauses in Spanish (a head-initial language) and Japanese (a head-final language) by monolingual speakers, by means of the eye-tracking method while participants described colored pictures. Although in both Spanish and Japanese the structure under study is the same (with the same syntactic configuration), word order is entirely opposite between both languages. In Japanese, the head noun is not uttered until the end of the clause, thus making it possible to explore sentence planning in a structure where the syntactically most dominant element (the head noun, HN) is not the first element. Variables tested were type of relative clause, with either the agent or the patient as head noun, and the animacy of the agent and the patient of the event, the latter allowing the manipulation of the conceptual saliency of the elements involved. Results showed Japanese speakers focus extensively on the HN before directing their gazes to the element they are going to utter first, suggesting a speech planning process that prioritizes relational information, that is, structural scaffolding. Spanish monolinguals, in turn, showed a pattern in which both structural and linear information appear to be more closely related from the beginning. In both languages, the animacy of isolated elements had little effect on gaze patterns. Results point to a planning process that prioritizes structural relations over access to lexical elements in order in the planning of complex structures, with room for flexibility when the grammar of the language allows so.
Big Data in traumatic brain injury; promise and challenges

Traumatic brain injury (TBI) is a spectrum disease of overwhelming complexity, the research of which generates enormous amounts of structured, semi-structured and unstructured data. This resulting big data has tremendous potential to be mined for valuable information regarding the “most complex disease of the most complex organ”. Big data analyses require specialized big data analytics applications, machine learning and artificial intelligence platforms to reveal associations, trends, correlations and patterns not otherwise realized by current analytical approaches. The intersection of potential data sources between experimental TBI and clinical TBI research presents inherent challenges for setting parameters for the generation of common data elements and to mine existing legacy data that would allow highly translatable big data analyses. In order to successfully utilize big data analyses in TBI, we must be willing to accept the messiness of data, collect and store all data and give up causation for correlation. In this context, coupling the big data approach to established clinical and pre-clinical data sources will transform current practices for triage, diagnosis, treatment and prognosis into highly integrated evidence-based patient care.
xSense: Learning Sense-Separated Sparse Representations and Textual Definitions for Explainable Word Sense Networks

Despite the success achieved on various natural language processing tasks, word embeddings are difficult to interpret due to the dense vector representations. This paper focuses on interpreting the embeddings for various aspects, including sense separation in the vector dimensions and definition generation. Specifically, given a context together with a target word, our algorithm first projects the target word embedding to a high-dimensional sparse vector and picks the specific dimensions that can best explain the semantic meaning of the target word by the encoded contextual information, where the sense of the target word can be indirectly inferred. Finally, our algorithm applies an RNN to generate the textual definition of the target word in the human readable form, which enables direct interpretation of the corresponding word embedding. This paper also introduces a large and high-quality context-definition dataset that consists of sense definitions together with multiple example sentences per polysemous word, which is a valuable resource for definition modeling and word sense disambiguation. The conducted experiments show the superior performance in BLEU score and the human evaluation test.
Human inner ear blood supply revisited: the Uppsala collection of temporal bone—an international resource of education and collaboration

Abstract Background: The Uppsala collection of human temporal bones and molds is a unique resource for education and international research collaboration. Micro-computerized tomography (micro-CT) and synchrotron imaging are used to investigate the complex anatomy of the inner ear. Impaired microcirculation is etiologically linked to various inner ear disorders, and recent developments in inner ear surgery promote examination of the vascular system. Here, for the first time, we present three-dimensional (3D) data from investigations of the major vascular pathways and corresponding bone channels. Methods: We used the archival Uppsala collection of temporal bones and molds consisting of 324 inner ear casts and 113 macerated temporal bones. Micro-CT was used to investigate vascular bone channels, and 26 fresh human temporal bones underwent synchrotron radiation phase contrast imaging (SR-PCI). Data were processed by volume-rendering software to create 3D reconstructions allowing orthogonal sectioning, cropping, and soft tissue analyses. Results: Micro-CT with 3D rendering was superior in reproducing the anatomy of the vascular bone channels, while SR-PCI replicated soft tissues. Arterial bone channels were traced from scala vestibuli (SV) arterioles to the fundus, cochlea, and vestibular apparatus. Drainage routes along the aqueducts were examined. Conclusion: Human inner ear vessels are difficult to study due to the adjoining hard bone. Micro-CT and SR-PCI with 3D reconstructions revealed large portions of the micro-vascular system in un-decalcified specimens. The results increase our understanding of the organization of the vascular system in humans and how altered microcirculation may relate to inner ear disorders. The findings may also have surgical implications.
Altered Nucleus Basalis Connectivity Predicts Treatment Response in Mild Cognitive Impairment

Purpose To determine whether functional connectivity (FC) mapping of nucleus basalis of Meynert (NBM) cholinergic network (hereafter, NBM FC) could provide a biomarker of central cholinergic deficits with predictive potential for response to cholinesterase inhibitor (ChEI) treatment. Materials and Methods The Alzheimer’s Disease Neuroimaging Initiative (ADNI) was approved by the institutional review boards of all participating sites. All participants and their representatives gave written informed consent prior to data collection. NBM FC was examined in 33 healthy control participants, 102 patients with mild cognitive impairment (MCI), and 33 patients with AD by using resting-state functional MRI data from the ADNI database. NBM FC was compared between groups before and after 6 months of ChEI treatment in MCI. Associations between baseline NBM FC and baseline cognitive performance as well as cognitive outcomes after treatment were investigated. Results Compared with the healthy control group, NBM FC was decreased in patients with untreated MCI and increased in patients with AD treated with ChEI (corrected P ˂ .05). Global cognition (Alzheimer’s Disease Assessment Scale-Cognitive subscale score) was associated with NBM FC (r = −0.349; P ˂ .001). NBM FC was higher 6 months after ChEI compared with before ChEI in treated MCI (corrected P ˂ .05), but did not change at 6 months in patients with untreated MCI (corrected P ˂ .05). Baseline NBM FC in MCI strongly predicted cognitive outcomes 6 months after ChEI (R2 = 0.458; P = .001). Conclusion Functional dissociation of the nucleus basalis of Meynert from a cortical network may explain the cognitive deficits in dementia and allow for the selection of individuals who are more likely to respond to cholinesterase inhibitors at early disease stages. Published under a CC BY-NC-ND 4.0 license. Online supplemental material is available for this article.
Investigation of schema modes currently activated in patients with psychiatric disorders

Abstract Objectives: To investigate schema modes currently activated in individuals with psychiatric disorders and to attain a greater understanding of healthy and dysfunctional schema modes in this population. Furthermore, we wish to ascertain if individuals who fulfil criteria for clinical (psychiatric) disorders with the Minnesota Multiphasic Personality Inventory (MMPI), also manifest dysfunctional modes and weaker healthy modes on the Schema Mode Inventory (SMI). Method: Fifty individuals were administered the MMPI and SMI during routine psychological assessments between September 2008 and June 2010. Results: Both healthy schema modes (Happy Child (HC) and dysfunctional schema modes (Compliant Surrender (CS), Detached Self-soother (DSS) and Demanding Parent (DP)) were evident in this population. Positive correlations were noted between several dysfunctional schema modes from the Child, Maladaptive Coping and Maladaptive Parent domains of the SMI and several scales of the MMPI including: Depression (D), Psychopathic deviate (Pd), Masculine feminine (Mf), Paranoia (Pa), Psychasthenia (Ps), Mania (Ma), Schizophrenia (Sc), and Social introversion (Si) (p < 0.001). A negative correlation (p < 0.001) was found between the Healthy Adult (HA) and Happy Child (HC) schema modes of the SMI and the Hypochondriasis (Hs), Depression (D), Psychopathic deviate (Pd), Psychasthenia (Pt), and Social introversion (Si) scales of MMPI. Conclusion: This study demonstrates the presence of several dysfunctional schema modes in individuals with a wide range of clinical (psychiatric) disorders and a strong correlation between dysfunctional schema modes and clinical disorders of the MMPI. The SMI can aid in the assessment and understanding of individuals with a wide range of psychiatric disorders and can also form the basis for Schema Focused Therapy (SFT), a therapy showing promise for a number of clinical conditions, particularly borderline personality disorder.
Biomarkers of exposure among "dual users" of tobacco cigarettes and electronic cigarettes in Canada.

Introduction "Dual use" refers to the concurrent use of tobacco cigarettes (smoking) and e-cigarettes (vaping). Although dual use is common among e-cigarette users, there is little evidence regarding biomarkers of exposure among dual users and how these change under different conditions of product use. Methods A non-blinded within-subjects cross-over experiment was conducted with adult daily dual users (n=48) in Ontario, Canada. Participants completed three consecutive seven-day periods in which the use of tobacco cigarettes and e-cigarettes was experimentally manipulated, resulting in four study conditions: dual use, exclusive smoking, exclusive vaping, and no product use. Repeated measures models were used to examine changes in product use and biomarkers of exposure. Results Compared to dual use, cotinine remained stable when participants exclusively smoked (p=0.524), but significantly decreased when they exclusively vaped (p=0.027), despite significant increases in e-cigarette consumption (p=0.001). Biomarkers of exposure to toxicants, including carbon monoxide (CO), 1-hydroxypyrene (1-HOP), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) were significantly lower when participants exclusively vaped, as compared to when they engaged in dual use (CO: -41%, p<0.001; 1-HOP: -31%, p=0.025; NNAL: -30%, p=0.017). Similar findings were observed among participants abstaining from both products, as compared to dual use (CO: -26%, p<0.001; 1-HOP: -14% (ns); NNAL: -35%, p=0.016). In contrast, exposure biomarkers increased when participants exclusively smoked as compared to dual use (CO: +21%, p=0.029; 1-HOP: +23%, p=0.048; NNAL: +8% (ns)). Conclusions Although dual use may reduce exposure to tobacco smoke constituents to some extent, abstaining from smoking is the most effective way to reduce such exposure. Implications Public health authorities should clearly communicate the relative risk of e-cigarettes and tobacco cigarettes to the general public, focusing on two salient points: 1) e-cigarettes are not harmless, but they are less harmful than smoking tobacco cigarettes; and 2) using e-cigarettes while smoking may not necessarily reduce health risks; therefore, consumers should stop smoking completely to maximize potential health benefits.