bluuebunny/crossref_metadata_2025_split huggingface dataset:
Word embeddings trained on published case reports are lightweight, effective for clinical tasks, and free of protected health information
Authors: Flamholz Zachary N. , Ungar Lyle H. , Weissman Gary E. 
Published: December 2019

AbstractRationaleWord embeddings are used to create vector representations of text data but not all embeddings appropriately capture clinical information, are free of protected health information, and are computationally accessible to most researchers.MethodsWe trained word embeddings on published case reports because their language mimics that of clinical notes, the manuscripts are already de-identified by virtue of being published, and the corpus is much smaller than those trained on large, publicly available datasets. We tested the performance of these embeddings across five clinically relevant tasks and compared the results to embeddings trained on a large Wikipedia corpus, all publicly available manuscripts, notes from the MIMIC-III database using fastText, GloVe, and word2vec, and using different dimensions. Tasks included clinical applications of lexicographic coverage, semantic similarity, clustering purity, linguistic regularity, and mortality prediction.ResultsThe embeddings trained using the published case reports performed as well as if not better on most tasks than those using other corpora. The embeddings trained using all published manuscripts had the most consistent performance across all tasks and required a corpus with 100 times as many tokens as the corpus comprised of only case reports. Embeddings trained on the MIMIC-III dataset had small but marginally better scores on the clustering tasks which was also based on clinical notes from the MIMIC-III dataset. Embeddings trained on the Wikipedia corpus, although containing almost twice as many tokens as all available published manuscripts, performed poorly compared to those trained on medical and clinical corpora.ConclusionWord embeddings trained on freely available published case reports performed well for most clinical task, are free of protected health information, and are small compared to commonly used embeddings trained on larger clinical and non-clinical corpora. The optimal corpus, dimension size, and which embedding model to use for a given task involves tradeoffs in privacy, reproducibility, performance, and computational resources.
Severe volcanic SO2 exposure and respiratory morbidities in the Icelandic population – a register study
Authors: Carlsen Hanne Krage , Valdimarsdóttir Unnur , Briem Haraldur , Dominici Francesca , Finnbjornsdottir Ragnhildur Gudrun , Jóhannsson Thorsteinn , Aspelund Thor , Gislason Thorarinn , Gudnason Thorolfur 
Published: December 2019

AbstractBackgroundThe Holuhraun volcanic eruption September 2014 to February 2015 emitted large amounts of sulfur dioxide (SO2).ObjectivesThe aim of this study was to determine the association between volcanic SO2 gases on general population respiratory health in the Icelandic capital area some 250 km from the eruption site.MethodsRespiratory health outcomes were: asthma medication dispensing (AMD) from the Icelandic Medicines Register, medical doctor consultations in primary care (PCMD) and hospital emergency department visits (HED) in Reykjavík (population: 215 000) for respiratory disease from 1 January 2010 to 31 December 2014. The associations between daily counts of health events,and daily mean SO2 concentration and high SO2 levels (24-hour mean SO2>125µg/m3) were analyzed using generalized additive models.ResultsAfter the eruption began, AMD was higher than before (129.4 vs. 158.4 individuals per day, p<0.05). Increases in SO2 concentration were associated with an estimated increase in AMD by 1.05% (95% CI 0.48 - 1.62%) per 10 µg/m3 at lag 0-2, 1.51% (95% CI 0.63 – 2.40%) increase in individuals under 18 years of age. PCMD for respiratory causes increased by 1.52% (95% CI 1.04 -2.00%) per 10 µg/m3 SO2 at lag 0-2. For HED, only effect estimated for individuals aged 64 years and older were significantly increased, by 1.541% (95% CI 0.02-3.07%) per 10 µg/m3 SO2 at lag 0-2. Following days with SO2 levels above 125 µg/m3, AMD and PCMD were increased in all age groups, in AMD mostly so in individuals under 18 by 20.4%(95%CI 4.8 – 23.4%), and adult PCMD visits by 24.1%(95%CI 16.8 – 31.3%). HED was significantly increased in elderly by 26.3% (95%CI 5.56-47.0).DiscussionHigh levels of volcanic SO2 are associated with increases in dispensing of AMD, and health care utilization in primary and tertiary care. Individuals with prevalent respiratory disease may be particularly susceptible.FundingThe study was funded by the Icelandic Ministry of Health.
Predictors of health related quality of life among diabetic patients on follow up at Nekemte Specialized Hospital, Western Ethiopia: A cross sectional study
Authors: Feyisa Bikila Regassa , Yilma Mekdes Tigistu , Tolessa Belachew Etana 
Published: December 2019

AbstractObjectiveTo assess health related quality of life (HRQoL) and its predictors among diabetic patients on follow up at Nekemte Specialized Hospital (NSH) in Western Ethiopia.Design, setting and participantsThis facility based cross sectional study was conducted among 224 diabetic patients on follow up at one of the public hospitals in western Ethiopia.Main outcome measuredHRQoL was measured by using the Medical Outcome Study 36-item Short Form Health Survey from 15th April to 5th June. Structured questionnaire was used for data the collection from participants selected by systematic random sampling. Multiple linear regression was used for final model.ResultA total of 215 diabetic patients were involved in the study with the response rate of 96%. The mean score of the overall HRQoL of the study participants was found to be 50.30 ± 18.08 with highest mean score in physical functioning and lowest mean score in general health domain. Age, education status, history of smoking, feeling of stigmatized and Body mass index (BMI) were inversely associated while being male, being married, absence of co morbidity and absence of chronic complications related to diabetes mellitus were found to be positively associated with overall HRQoL.ConclusionThe overall HRQoL of diabetic patients on follow up at the study area was found to be moderate. General health, mental health, bodily pain and vitality were the most affected domains. Both the mental and physical components need to be considered when caring the diabetic patients on follow up beyond provision of treatment.Strength and limitations of this studyThe study was the first of its kind in assessing the predictors of health-related quality of life (HRQoL) among both diabetes mellitus type I and type II in Ethiopia.The tools used was validated across different culturesEight domains of HRQoL and two component summary scores were used to make the measurement more specific.The cross sectional nature of the study design made the result of the study difficult to identify either the cause or the effect comes first.
Null effect of circulating sphingomyelins on risk for breast cancer: a Mendelian randomization report using Breast Cancer Association Consortium (BCAC) data
Authors: Adams Charleen D. 
Published: December 2019

AbstractBackgroundChanges in cellular metabolism are a hallmark of cancer and are linked with sphingolipid synthesis. Due to immense interest in how sphingolipids influence chemoresistance, more is known about the impact of sphingolipids during cancer treatment and progression than about the potential role of sphingolipids in the induction of tumors in humans.MethodsBecause estrogen triggers sphingolipid signaling cascades, the causal role of circulating levels of sphingomyelin (a type of sphingolipid) on breast cancer was investigated with a well-powered Mendelian randomization design.ResultsThe results reveal a null effect (OR = 0.94; 95% CI = 0.85, 1.05; P = 0.30).ConclusionDespite the role sphingomyelins play during chemoresistance and cancer progression, circulating sphingomyelins do not appear to initiate or protect from breast cancer.ImpactThis finding comprises the first causal report in humans that sphingomyelins on breast cancer initiation is null. Future investigations of risk in other cancer types are needed to further explore the potential role of sphingolipid biology in cancer etiology.
The genetic and clinical landscape of nanophthalmos in an Australian cohort
Authors: Siggs Owen M , Awadalla Mona S , Souzeau Emmanuelle , Staffieri Sandra E , Kearns Lisa S , Laurie Kate , Kuot Abraham , Qassim Ayub , Edwards Thomas L , Coote Michael A , Mancel Erica , Walland Mark J , Dondey Joanne , Galanopoulous Anna , Casson Robert J , Mills Richard A , MacArthur Daniel G , Ruddle Jonathan B , Burdon Kathryn P , Craig Jamie E 
Published: December 2019

AbstractPurposeRefractive error is caused by a disparity between the axial length and focusing power of the eye. Nanophthalmos is a rare ocular abnormality in which both eyes are abnormally small, typically causing extreme hyperopic refractive error, and associated with an increased risk of angle-closure glaucoma.MethodsA cohort of 40 individuals from 13 unrelated nanophthalmos kindreds were recruited, with 11 probands subjected to exome sequencing.ResultsNine probands (69.2%) were assigned a genetic diagnosis, with variants in PRSS56 (4), MFRP (3), and previously reported variants in TMEM98 (1) and MYRF (1). Two of the four PRSS56 probands harboured the previously described c.1066dupC frameshift variant implicated in over half of all reported PRSS56 kindreds, with surrounding haplotypes distinct from each other, and from a previously reported Tunisian c.1066dupC haplotype. Individuals with a genetic diagnosis had shorter mean axial lengths (P=7.22×10−9) and more extreme hyperopia (P=0.0005) than those without a genetic diagnosis, with recessive forms associated with the shortest axial lengths and highest hyperopia. All individuals with an axial length below 18 mm in their smaller eye (17/17) were assigned a genetic diagnosis.ConclusionsThese findings detail the genetic architecture of nanophthalmos in an Australian cohort of predominantly European ancestry, their relative clinical phenotypes, and highlight the shared genetic architecture of rare and common disorders of refractive error.
Measuring Tibial Forces is More Useful than Varus-Valgus Laxities for Identifying and Correcting Overstuffing in Kinematically Aligned Total Knee Arthroplasty
Authors: Roth Joshua D. , Howell Stephen M. , Hull Maury L. 
Published: December 2019

AbstractIdentifying and correcting varus-valgus (V-V) malalignment of the tibial component is important when balancing a kinematically aligned total knee arthroplasty (TKA). Accordingly, the primary objective was to determine whether the tibial forces or V-V laxities are more sensitive to, and thus more useful for identifying and correcting, V-V malalignments of the tibial component that overstuff a compartment. Calipered kinematically aligned TKA was performed on nine human cadaveric knees. Medial and lateral tibial forces and V-V laxities were measured from 0° to 120° flexion with an unmodified reference tibial component and modified tibial components that introduced ±1° and ±2° V-V malalignments from the reference component to overstuff either the medial or lateral compartment. Changes in the tibial forces were most sensitive to V-V malalignments at 0° flexion (medial = 118±34 N/deg valgus malalignment and lateral = 79±20 N/deg varus malalignment). The varus and valgus laxities were most sensitive to V-V malalignments at 30° flexion (−0.6±0.1 deg/deg varus malalignment) and 120° flexion (−0.4±0.2 deg/deg valgus malalignment), respectively. The maximum average signal-to-noise ratios of the sensitivities to changes in tibial forces and V-V laxities were 8.4 deg-1 and 0.9 deg-1, respectively, based on reported measurement errors (i.e., noise) using current intraoperative technologies (14 N and 0.7°). Because of the greater signal-to-noise ratios, measuring tibial forces is more useful than V-V laxities for identifying and correcting V-V malalignments of the tibial component that overstuff a compartment.Clinical SignificanceThe sensitivities of tibial forces provide objective guidance to surgeons performing V-V recuts of the tibia.
Sporadic activation of an oxidative stress-dependent NRF2–p53 signaling network in breast epithelial spheroids and premalignancies
Authors: Pereira Elizabeth J. , Burns Joseph S. , Lee Christina Y. , Marohl Taylor , Calderon Delia , Wang Lixin , Atkins Kristen A. , Wang Chun-Chao , Janes Kevin A. 
Published: December 2019

ABSTRACTBreast–mammary epithelial cells experience different local environments during tissue development and tumorigenesis. Microenvironmental heterogeneity gives rise to distinct cell-regulatory states whose identity and importance are just beginning to be appreciated. Cellular states diversify when clonal 3D spheroids are cultured in basement membrane, and prior transcriptomic analyses identified a state associated with stress tolerance and poor response to anticancer therapeutics. Here, we examined the regulation of this state and found that it is jointly coordinated by the NRF2 and p53 pathways, which are co-stabilized by spontaneous oxidative stress within the 3D cultures. Inhibition of NRF2 or p53 individually disrupts some of the transcripts defining the regulatory state but does not yield a notable phenotype in nontransformed breast epithelial cells. In contrast, combined perturbation prevents 3D growth in an oxidative stress-dependent manner. By integrating systems models of NRF2 and p53 signaling together as a single oxidative-stress network, we recapitulate these observations and make predictions about oxidative stress profiles during 3D growth. Similar coordination of NRF2 and p53 signaling is observed in normal breast epithelial tissue and hormone-negative ductal carcinoma in situ lesions. However, the pathways are uncoupled in triple-negative breast cancer, a subtype in which p53 is usually mutated. Using the integrated model, we reconcile the different NRF2-knockdown phenotypes of triple-negative cancer lines with their inferred handling of oxidative stress. Our results point to an oxidative stress-tolerance network that is important for single cells during glandular development and the early stages of breast cancer.One Sentence SummaryReactive oxygen species co-stabilize a non-oncogene and a tumor suppressor for triple-negative breast cancer when cells are surrounded by basement-membrane ECM.
Investigating the Role of Hypoxia-Induced Migration in Glioblastoma Growth Rates
Authors: Curtin Lee , Hawkins-Daarud Andrea , van der Zee Kristoffer G. , Swanson Kristin R. , Owen Markus R. 
Published: December 2019

AbstractWe analyze the wave-speed of the Proliferation Invasion Hypoxia Necrosis Angiogenesis (PIHNA) model that was previously created and applied to simulate the growth and spread of glioblastoma (GBM), a particularly aggressive primary brain tumor. We extend the PIHNA model by allowing for different hypoxic and normoxic cell migration rates and study the impact of these differences on the wave-speed dynamics. Through this analysis, we find key variables that drive the outward growth of the simulated GBM. We find a minimum tumor wave-speed for the model; this depends on the migration and proliferation rates of the normoxic cells and is achieved under certain conditions on the migration rates of the normoxic and hypoxic cells. If the hypoxic cell migration rate is greater than the normoxic cell migration rate above a threshold, the wave-speed increases above the predicted minimum. This increase in wave-speed is explored through an eigenvalue and eigenvector analysis of the linearized PIHNA model, which yields an expression for this threshold. The PIHNA model suggests that an inherently faster-diffusing hypoxic cell population can drive the outward growth of a GBM as a whole, and that this effect is more prominent for faster proliferating tumors that recover relatively slowly from a hypoxic phenotype.
Measurement and models accounting for cell death capture hidden variation in compound response
Authors: Bae Song Yi , Guan Ning , Yan Rui , Warner Katrina , Meyer Aaron S 
Published: December 2019

AbstractCancer cell sensitivity or resistance is almost universally quantified through a direct or surrogate measure of cell number. However, compound responses can occur through many distinct phenotypic outcomes including changes in cell growth, apoptosis, and non-apoptotic cell death. These outcomes have distinct effects on the tumor microenvironment, immune responses, and resistance mechanisms. Here, we show that quantifying cell viability alone is insufficient to distinguish between these compound responses. Using an alternative assay and drug response analysis amenable to high-throughput measurement, we find that compounds with identical viability outcomes can have very different effects on cell growth and death. Moreover, compound pairs with additive cell growth and death effects can appear synergistic when only assessed by viability. Overall, these results demonstrate an approach to incorporating measurements of cell death when characterizing a pharmacologic response.Summary PointsMeasurements of solely live cell numbers mask important differences in compound effects.Additive effects on growth and death rates can appear synergistic when analyzed solely via live cell number.Automated imaging can provide reasonable throughput to analyze cell response in terms of cell growth and death, and endpoint analysis is similarly informative.
EpitoCore: mining conserved epitope vaccine candidates in the core proteome of multiple bacteria strains
Authors: Fiuza T.S. , Lima J.P.M.S. , de Souza G.A. 
Published: December 2019

ABSTRACTIn reverse vaccinology approaches, complete proteomes of bacteria are submitted to multiple computational prediction steps in order to filter proteins that are possible vaccine candidates. Most available tools perform such analysis only in a single strain, or a very limited number of strains. But the vast amount of genomic data had shown that most bacteria contain pangenomes, i.e. their genomic information contains core, conserved genes, and random accessory genes specific to each strain. Therefore, it is of the utmost importance to define core proteins, and also core epitopes, in reverse vaccinology methods. EpitoCore is a decision-tree pipeline developed to fulfill that need. It provides surfaceome prediction of proteins from related strains, defines clusters of core proteins within those, calculate the immunogenicity of such clusters, predicts epitopes for a given set of MHC alleles defined by the user, and then reports if epitopes are located extracellularly and if they are conserved among the core homologues. Pipeline performance is illustrated by mining peptide vaccine candidates inMycobacterium avium hominissuisstrains. From a total proteome of approximately 4,800 proteins per strain, EpitoCore mined 103 highly immunogenic core homologues located at cell surface, many of those related to virulence and drug resistance. Conserved epitopes identified among these homologues allows the users to define sets of peptides with potential to immunize the largest coverage of tested HLA alleles using peptide-based vaccines. Therefore, EpitoCore is able to provide automated identification of conserved epitopes in bacterial pangenomic datasets.
Pay to know me in your eyes: A computational account and oxytocin modulation of social evaluation
Authors: Wang Danyang , Ma Yina 
Published: December 2019

AbstractPeople are eager to know and recast the self in the eyes of others, even at a personal cost. However, it remains unknown what drives people to pursue costly evaluations of the self. Here, we propose that the evaluation of the self is valuable and that such subjective value placed on evaluation drives the costly-to-know behavior. By measuring the amount of money that individuals would forgo for the opportunity to know evaluations from other people (social evaluation) or a computer program (non-social evaluation), we quantified the subjective value individuals assigned to the evaluation on the self. The results from 5 studies (n= 375) lent cognitive and computational support for this hypothesis. Furthermore, the subjective value was modulated by the source and valence of the evaluation. Participants equally valued positive and negative non-social evaluations, characterized by a shared unknown aversion computation. However, individuals computed independent unknown aversion towards positive and negative social evaluations and placed a higher value on the opportunity to know another person’s evaluation on positive than negative aspects. Such a valence-dependent valuation of the social evaluation was facilitated by oxytocin, a neuropeptide linked to linked to social feedback learning and valuation processes, which decreased the value ascribed to negative social evaluation. Taken together, the current study reveals the psychological and computational processes underlying self-image formation and updating and suggests a role of oxytocin in modulating the value of social evaluation.
End-to-end multitask learning, from protein language to protein features without alignments
Authors: Elnaggar Ahmed , Heinzinger Michael , Dallago Christian , Rost Burkhard 
Published: December 2019

AbstractCorrectly predicting features of protein structure and function from amino acid sequence alone remains a supreme challenge for computational biology. For almost three decades, state-of-the-art approaches combined machine learning and evolutionary information from multiple sequence alignments. Exponentially growing sequence databases make it infeasible to gather evolutionary information for entire microbiomes or meta-proteomics. On top, for many important proteins (e.g. dark proteome and intrinsically disordered proteins) evolutionary information remains limited. Here, we introduced a novel approach combining recent advances of Language Models (LMs) with multi-task learning to successfully predict aspects of protein structure (secondary structure) and function (cellular component or subcellular localization) without using any evolutionary information from alignments. Our approach fused self-supervised pre-training LMs on an unlabeled big dataset (UniRef50, corresponding to 9.6 billion words) with supervised training on labelled high-quality data in one single end-to-end network. We provided a proof-of-principle for the novel concept through the semi-successful per-residue prediction of protein secondary structure and through per-protein predictions of localization (Q10=69%) and the distinction between integral membrane and water-soluble proteins (Q2=89%). Although these results did not reach the levels obtained by the best available methods using evolutionary information from alignments, these less accurate multi-task predictions have the advantage of speed: they are 300-3000 times faster (where HHblits needs 30-300 seconds on average, our method needed 0.045 seconds). These new results push the boundaries of predictability towards grayer and darker areas of the protein space, allowing to make reliable predictions for proteins which were not accessible by previous methods. On top, our method remains scalable as it removes the necessity to search sequence databases for evolutionary related proteins.