bluuebunny/crossref_metadata_2025_split huggingface dataset:
A representation model for biological entities by fusing structured axioms with unstructured texts
Authors: Lou Peiliang , Dong YuXin , Jimeno Yepes Antonio , Li Chen 
Published: October 2020

Abstract

Motivation
Structured semantic resources, for example, biological knowledge bases and ontologies, formally define biological concepts, entities and their semantic relationships, manifested as structured axioms and unstructured texts (e.g. textual definitions). The resources contain accurate expressions of biological reality and have been used by machine-learning models to assist intelligent applications like knowledge discovery. The current methods use both the axioms and definitions as plain texts in representation learning (RL). However, since the axioms are machine-readable while the natural language is human-understandable, difference in meaning of token and structure impedes the representations to encode desirable biological knowledge.

Results
We propose ERBK, a RL model of bio-entities. Instead of using the axioms and definitions as a textual corpus, our method uses knowledge graph embedding method and deep convolutional neural models to encode the axioms and definitions respectively. The representations could not only encode more underlying biological knowledge but also be further applied to zero-shot circumstance where existing approaches fall short. Experimental evaluations show that ERBK outperforms the existing methods for predicting protein–protein interactions and gene–disease associations. Moreover, it shows that ERBK still maintains promising performance under the zero-shot circumstance. We believe the representations and the method have certain generality and could extend to other types of bio-relation.

Availability and implementation
The source code is available at the gitlab repository https://gitlab.com/BioAI/erbk.

Supplementary information
Supplementary data are available at Bioinformatics online.
Rethinking how Technologies Harm
Authors: Wood Mark A 
Published: October 2020

AbstractUnderstanding how technologies contribute to social harms is a perennial issue, animating debate within and well beyond criminology. This article contributes to these debates in two ways. First, it critically examines five of the key approaches criminologists have used to think through how technologies contribute to harms. Second, it proposes a new approach to understanding ‘technology–harm relations’. Bringing the theory of critical realism, Simondon and Floridi into conversation, the proposed approach offers a stratigraphy of harm that enables us to excavate the different layers of human–technology and technology–harm relations. In doing so, it enables us to distinguish between four technology–harm relations that untangle the socio-technicality of harmful events: instrumental utility harms, generative utility harms, instrumental technicity harms and generative technicity harms.
Neuregulin-1 beta 1 is implicated in pathogenesis of multiple sclerosis
Authors: Kataria Hardeep , Hart Christopher G , Alizadeh Arsalan , Cossoy Michael , Kaushik Deepak K , Bernstein Charles N , Marrie Ruth Ann , Yong V Wee , Karimi-Abdolrezaee Soheila 
Published: October 2020

AbstractMultiple sclerosis is characterized by immune mediated neurodegeneration that results in progressive, life-long neurological and cognitive impairments. Yet, the endogenous mechanisms underlying multiple sclerosis pathophysiology are not fully understood. Here, we provide compelling evidence that associates dysregulation of neuregulin-1 beta 1 (Nrg-1β1) with multiple sclerosis pathogenesis and progression. In the experimental autoimmune encephalomyelitis model of multiple sclerosis, we demonstrate that Nrg-1β1 levels are abated within spinal cord lesions and peripherally in the plasma and spleen during presymptomatic, onset and progressive course of the disease. We demonstrate that plasma levels of Nrg-1β1 are also significantly reduced in individuals with early multiple sclerosis and is positively associated with progression to relapsing-remitting multiple sclerosis. The functional impact of Nrg-1β1 downregulation preceded disease onset and progression, and its systemic restoration was sufficient to delay experimental autoimmune encephalomyelitis symptoms and alleviate disease burden. Intriguingly, Nrg-1β1 therapy exhibited a desirable and extended therapeutic time window of efficacy when administered prophylactically, symptomatically, acutely or chronically. Using in vivo and in vitro assessments, we identified that Nrg-1β1 treatment mediates its beneficial effects in EAE by providing a more balanced immune response. Mechanistically, Nrg-1β1 moderated monocyte infiltration at the blood-CNS interface by attenuating chondroitin sulphate proteoglycans and MMP9. Moreover, Nrg-1β1 fostered a regulatory and reparative phenotype in macrophages, T helper type 1 (Th1) cells and microglia in the spinal cord lesions of EAE mice. Taken together, our new findings in multiple sclerosis and experimental autoimmune encephalomyelitis have uncovered a novel regulatory role for Nrg-1β1 early in the disease course and suggest its potential as a specific therapeutic target to ameliorate disease progression and severity.
Bufalin inhibits human diffuse large B-cell lymphoma tumorigenesis by inducing cell death through the Ca2+/NFATC1/cMYC pathway
Authors: Song Jincheng , Zou Dan , Zhao Xiaoxuan , Chen Yang , Lv Fei , Wang Song , Sui Dan , Han Qiuyue , Yang Chunjiao , Wang Ximing , Liu Bofang , Deng Mingming , Zhang Ye 
Published: October 2020

Abstract
The 5-year survival rate of diffuse large B-cell lymphoma (DLBCL) can reach 60%. However, nearly half of patients undergo relapse/refractory issues with a survival period of less than 2 years. New therapeutic approaches are therefore needed to improve chemotherapy efficacy and patient survival. Bufalin (BF), isolated from the traditional Chinese medicine Chansu, has been reported to play an anticancer role in multiple cancer cell types. However, there are few reports of the effects of BF on the growth of DLBCL. In the present study, we demonstrated that BF exerts antitumor activity in DLBCL cells, both in vitro and in vivo. Treatment of DLBCL cells with BF resulted in increased proliferation and apoptosis in a dose- and time-dependent manner. Daily intraperitoneal injection of 1.5 mg/kg BF significantly delayed DLBCL xenograft growth in NOD/SCID mice without affecting body weight. Bioinformatics analysis showed that BF may regulate NFATC1 protein and affect expression of its downstream gene, cMYC. Our results suggest that BF can attenuate NFATC1 translocation by reducing the intracellular calcium concentration; BF may also have a low synergistic effect with cyclosporin A. In conclusion, we demonstrated that BF exerts antitumor activity that is mediated at least in part by the Ca2+/NFATC1/cMYC pathway. Our findings suggest that BF can be effectively applied as a novel potential therapeutic agent for DLBCL.
Elimination of NF-κB signaling in Vimentin+ stromal cells attenuates tumorigenesis in a mouse model of Barrett’s Esophagus
Authors: Anand Akanksha , Fang Hsin-Yu , Mohammad-Shahi Donja , Ingermann Jonas , Baumeister Theresa , Strangmann Julia , Schmid Roland M , Wang Timothy C , Quante Michael 
Published: October 2020

Abstract
Chronic inflammation induces Barrett’s Esophagus (BE) which can advance to esophageal adenocarcinoma. Elevated levels of interleukin (IL)-1b, IL-6 and IL-8 together with activated nuclear factor-kappaB (NF-κB), have been identified as important mediators of tumorigenesis. The inflammatory milieu apart from cancer cells and infiltrating immune cells contains myofibroblasts (MFs) that express aSMA and Vimentin. As we observed that increased NF-κB activation and inflammation correlates with increased MF recruitment and an accelerated phenotype we here analyze the role of NF-κB in MF during esophageal carcinogenesis in our L2-IL-1B mouse model. To analyze the effect of NF-κB signaling in MFs, we crossed L2-IL-1B mice to tamoxifen inducible Vim-Cre (Vim-CreTm) mice and floxed RelA (p65fl/fl) mice to specifically eliminate NF-κB signaling in MF (IL-1b.Vim-CreTm.p65fl/fl). The interaction of epithelial cells and stromal cells was further analyzed in mouse BE organoids and patient-derived human organoids. Histological scoring of IL-1b.Vim-CreTm.p65fl/fl mice showed a significantly attenuated phenotype compared with L2-IL-1B mice, with mild inflammation, decreased metaplasia and no dysplasia. This correlated with decreased proliferation and increased differentiation in cardia tissue of IL-1b.Vim-CreTm.p65fl/fl compared with L2-IL-1B mice. Distinct changes of cytokines and chemokines within the local microenvironment in IL-1b.Vim-CreTm.p65fl/fl mice reflected the histopathological abrogated phenotype. Co-cultured NF-κB inhibitor treated MF with mouse BE organoids demonstrated NF-κB-dependent growth and migration. MFs are essential to form an inflammatory and procarcinogenic microenvironment and NF-κB signaling in stromal cells emerges as an important driver of esophageal carcinogenesis. Our data suggest anti-inflammatory approaches as preventive strategies during surveillance of BE patients.
Reconsidering the Border between the Visual and Posterior Parietal Cortex of Mice
Authors: Gilissen Sara R J , Farrow Karl , Bonin Vincent , Arckens Lutgarde 
Published: October 2020

AbstractThe posterior parietal cortex (PPC) contributes to multisensory and sensory-motor integration, as well as spatial navigation. Based on primate studies, the PPC is composed of several subdivisions with differing connection patterns, including areas that exhibit retinotopy. In mice the composition of the PPC is still under debate. We propose a revised anatomical delineation in which we classify the higher order visual areas rostrolateral area (RL), anteromedial area (AM), and Medio-Medial-Anterior cortex (MMA) as subregions of the mouse PPC. Retrograde and anterograde tracing revealed connectivity, characteristic for primate PPC, with sensory, retrosplenial, orbitofrontal, cingulate and motor cortex, as well as with several thalamic nuclei and the superior colliculus in the mouse. Regarding cortical input, RL receives major input from the somatosensory barrel field, while AM receives more input from the trunk, whereas MMA receives strong inputs from retrosplenial, cingulate, and orbitofrontal cortices. These input differences suggest that each posterior PPC subregion may have a distinct function. Summarized, we put forward a refined cortical map, including a mouse PPC that contains at least 6 subregions, RL, AM, MMA and PtP, MPta, LPta/A. These anatomical results set the stage for a more detailed understanding about the role that the PPC and its subdivisions play in multisensory integration-based behavior in mice.
NECAB1 and NECAB2 are Prevalent Calcium-Binding Proteins of CB1/CCK-Positive GABAergic Interneurons
Authors: Miczán Vivien , Kelemen Krisztina , Glavinics Judit R , László Zsófia I , Barti Benjámin , Kenesei Kata , Kisfali Máté , Katona István 
Published: October 2020

AbstractThe molecular repertoire of the “Ca2+-signaling toolkit” supports the specific kinetic requirements of Ca2+-dependent processes in different neuronal types. A well-known example is the unique expression pattern of calcium-binding proteins, such as parvalbumin, calbindin, and calretinin. These cytosolic Ca2+-buffers control presynaptic and somatodendritic processes in a cell-type-specific manner and have been used as neurochemical markers of GABAergic interneuron types for decades. Surprisingly, to date no typifying calcium-binding proteins have been found in CB1 cannabinoid receptor/cholecystokinin (CB1/CCK)-positive interneurons that represent a large population of GABAergic cells in cortical circuits. Because CB1/CCK-positive interneurons display disparate presynaptic and somatodendritic Ca2+-transients compared with other interneurons, we tested the hypothesis that they express alternative calcium-binding proteins. By in silico data mining in mouse single-cell RNA-seq databases, we identified high expression of Necab1 and Necab2 genes encoding N-terminal EF-hand calcium-binding proteins 1 and 2, respectively, in CB1/CCK-positive interneurons. Fluorescent in situ hybridization and immunostaining revealed cell-type-specific distribution of NECAB1 and NECAB2 throughout the isocortex, hippocampal formation, and basolateral amygdala complex. Combination of patch-clamp electrophysiology, confocal, and STORM super-resolution microscopy uncovered subcellular nanoscale differences indicating functional division of labor between the two calcium-binding proteins. These findings highlight NECAB1 and NECAB2 as predominant calcium-binding proteins in CB1/CCK-positive interneurons.
Impact of Screening and Treatment ofUreaplasmaspecies on Hyperammonemia Syndrome in Lung Transplant Recipients: A Single Center Experience
Authors: Roberts Scott C , Bharat Ankit , Kurihara Chitaru , Tomic Rade , Ison Michael G 
Published: October 2020

AbstractBackgroundInfection with Ureaplasma species (spp) has been linked to fatal hyperammonemia syndrome (HS) in lung transplant recipients. We sought to characterize the epidemiology of Ureaplasma spp in candidates and donors and describe outcomes of antimicrobial therapy in preventing and treating HS.MethodsCandidate testing for Ureaplasma spp was performed with urine culture and polymerase chain reaction (PCR) pretransplant. Positive candidates were treated with levofloxacin. Donor testing was performed with bronchoalveolar lavage (BAL) culture and PCR intraoperatively. From 7/2014 to 2/2017 patients were treated according to results; from 2/2017 to 10/2018 recipients received empiric levofloxacin and azithromycin at transplant until testing returned negative. HS was defined as new onset altered mental status after transplant with ammonia &gt; 200 µmol/L.ResultsIn total, 60 patients who underwent lung transplant were included. And 80% (n = 48) of patients had negative screening tests in donor and candidate pre-lung transplant, 8.3% (n = 5) of recipients had positive Ureaplasma spp testing in urine pre-transplant, and 13.3% (n = 8) had positive donor BAL testing at the time of lung transplant. Three patients developed HS a median of 7 days posttransplant; 2 died of HS. Recipients of organs with Ureaplasma spp who received empiric therapy did not develop HS. Donors with Ureaplasma spp were younger and more sexually active.ConclusionsDonor-derived Ureaplasma spp in lung transplant was associated with HS. Screening lung donors for Ureaplasma spp might allow for targeted therapy to reduce risk for development of HS, but future confirmatory studies are needed.
The Vitamin D Metabolite Ratio Is Independent of Vitamin D Binding Protein Concentration
Authors: Ginsberg Charles , Hoofnagle Andrew N , Katz Ronit , Becker Jessica O , Kritchevsky Stephen B , Shlipak Michael G , Sarnak Mark J , Ix Joachim H 
Published: October 2020

Abstract

Background
25-Hydroxyvitamin D [25(OH)D] may be a poor marker of vitamin D status as it reflects differences in vitamin D binding protein (VDBP) between individuals. The vitamin D metabolite ratio [VMR, ratio of 24,25(OH)2D3 to 25(OH)D3] is a marker of vitamin D status that has been hypothesized to be independent of variability in VDBP. This hypothesis has not been directly evaluated.

Methods
We measured 25(OH)D3, 24,25(OH)2D3, 1,25(OH)2D3, and VDBP in 377 community-dwelling older adults that participated in the Health Aging and Body Composition Study. 24,25(OH)2D3 and 25(OH)D3 were used to calculate the VMR. We used linear regression to assess the relationship between VDBP with the VMR, 24,25(OH)2D3, 25(OH)D3, and 1,25(OH)2D3.

Results
Participants had mean age 75 ± 3 years, 52% were female, 40% were black, and 24% had chronic kidney disease. VDBP concentrations were associated with sex, serum albumin, and VDBP phenotype in multivariable models. In fully adjusted models, each 1% higher VDBP was associated with a 0.92%[95% CI(0.37,1.49%)], 0.76% (0.39, 1.13%), and 0.57% (0.29, 0.85%), higher 24,25(OH)2D3, 25(OH)D3, and 1,25(OH)2D3. The VMR was independent of VDBP concentration, [0.16%(-0.11, 0.44) higher VMR per 1% higher VDBP, P = .25].

Conclusions
The VMR was independent of VDBP concentration, whereas VDBP was strongly directly associated with the individual vitamin D metabolite concentrations. Prior studies evaluating only 25(OH)D3 may have been confounded by absence of data on VDBP status. The VMR may serve as an important biomarker of vitamin D status and clinical outcomes that can be utilized in populations with a large spectrum of VDBP concentrations.
SDVoIP—A Software-Defined VoIP Framework For SIP And Dynamic QoS
Authors: Gandotra Rahil , Perigo Levi 
Published: October 2020

AbstractSoftware-defined networking (SDN) allows for the decoupling of the control and data planes, enabling more programmability and a global view of the network. Previous research indicates that traditional applications recreated using SDN principles allow for more granularity and customization. In this research, we extend the insights behind SDN to develop a Voice over Internet Protocol (VoIP) framework with the objective to enhance traditional Session Initiation Protocol (SIP) operation and quality of service (QoS) approaches. The contributions of this research are 2-fold: first, an SIP control application is implemented, which communicates with an SDN controller to provide VoIP call registration and call routing capabilities, thereby eliminating the need for specialized SIP proxy hardware devices; second, a dynamic QoS application is developed that provides the ability to make network-wide QoS decisions based on real-time network measurements of latency, bandwidth and packet loss. Functional validation of the framework is performed to verify its operation. The experiment results indicate that the proposed framework allows for enhancements to traditional QoS implementations.
CCA-Almost-Full Anonymous Group Signature with Verifier Local Revocation in the Standard Model
Authors: Ma Sha , Huang Qiong 
Published: October 2020

Abstract
Group signature (GS) allows each member in a group to do signatures anonymously on behalf of the group under management of a group authority. Membership revocation has been a central issue in GS and widely studied so far. The mechanism of verifier local revocation for GS, first formalized by Boneh and Shacham, has an advantage of making the signers free from fetching the up-to-date information of the revoked users and practicality in the scenario of periodically update in the large population of group users. Most of work related to group signature with verifier-local revocation either can only achieve selfless anonymity or have inefficient constructions due to complicate primitives. Aiming to a recent chosen ciphertext attack-almost-full anonymous notion for GS, this paper presents an efficient GS with verifier local revocation in the standard model by adding a new primitive plaintext searchable encryption into Groth’s GS under Canard et al.’s framework. We prove that it has backward unlinkability to ensure that all signatures generated by the user before the revocation remain anonymous, even if it is revoked later.
Spatio-Temporal Model for Predicting Spring Hatch of the Spotted Lanternfly (Hemiptera: Fulgoridae)
Authors: Smyers Erica C , Urban Julie M , Dechaine Andrew C , Pfeiffer Douglas G , Crawford Stephen R , Calvin Dennis D 
Published: October 2020

Abstract
The effect of temperature on the rate of spotted lanternfly, Lycorma delicatula (White) (Hemiptera: Fulgoridae), egg development was investigated for a population in Pennsylvania. Mean developmental duration (days ± SE) for egg hatch was evaluated at five constant temperatures of 19.9, 24.2, 25.1, 26.7, and 30°C using egg masses laid during the fall of 2018 and collected in 2019 from Berks Co., Pennsylvania. Base temperature thresholds for egg development were estimated using intercept and slope parameters by fitting a linear relationship between average temperature and developmental rate for the Pennsylvania study, two Korean studies, and the combined data sets. The base threshold estimates were then used to calculate seasonal accumulated degree-days (ADD) and construct logistic equations for predicting cumulative proportion of hatch in the spring. The fitted logistic prediction equations were then graphed against the egg hatch observations from field sites in Pennsylvania (2017) and Virginia (2019). When base temperature estimates from the three studies and combined studies were used to calculate ADD, the logistic models predicted similar timing for seasonal egg hatch. Because the slopes and intercepts for these four data sets were not statistically different, a base temperature threshold of 10.4°C derived from the combined model is a good estimate for computing ADD to predict spotted lanternfly spring emergence across a spatio-temporal scale. The combined model was linked with open source weather database and mapping programs to provide spatiotemporal prediction maps to aid pest surveillance and management efforts for spotted lanternfly.
Left ventricular segmental strain and the prediction of cancer therapy-related cardiac dysfunction
Authors: Demissei Biniyam G , Fan Yong , Qian Yiwen , Cheng Henry G , Smith Amanda M , Shimamoto Kelsey , Vedage Natasha , Narayan Hari K , Scherrer-Crosbie Marielle , Davatzikos Christos , Ky Bonnie 
Published: October 2020

Abstract

Aims
We aimed to determine the early changes and predictive value of left ventricular (LV) segmental strain measures in women with breast cancer receiving doxorubicin.

Methods and results
In a cohort of 237 women with breast cancer receiving doxorubicin with or without trastuzumab, 1151 echocardiograms were prospectively acquired over a median (Q1–Q3) of 7 (2–24) months. LV ejection fraction (LVEF) and 36 segmental strain measures were core lab quantified. A supervised machine learning (ML) model was then developed using random forest regression to identify segmental strain measures predictive of nadir LVEF post-doxorubicin completion. Cancer therapy-related cardiac dysfunction (CTRCD) was defined as a ≥10% absolute LVEF decline pre-treatment to a value &lt;50%. Median (Q1–Q3) baseline age was 48 (41–57) years. Thirty-five women developed CTRCD, and eight of these developed symptomatic heart failure. From pre-treatment to doxorubicin completion, longitudinal strain worsened across the basal and mid-LV segments but not in the apical segments; circumferential strain worsened primarily in the septum; radial strain worsened uniformly and transverse strain remained unchanged across all LV segments. In the ML model, anterolateral and inferoseptal circumferential strain were the most predictive features; longitudinal and transverse strain in the basal inferoseptal, anterior, basal anterolateral, and apical lateral segments were also top predictive features. The addition of predictive segmental strain measures to a model including age, cancer therapy regimen, hypertension, and LVEF increased the area under the curve (AUC) from 0.70 (95% confidence interval (CI) 0.60–0.80) to 0.87 (95% CI 0.81–0.92), ΔAUC = 0.18 (95% CI 0.08–0.27) for the prediction of CTRCD.

Conclusion
Our findings suggest that segmental strain measures can enhance cardiotoxicity risk prediction in women with breast cancer receiving doxorubicin.