bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic rewiring of the human interactome by interferon signaling
Authors: Kerr Craig H. , Skinnider Michael A. , Andrews Daniel D. T. , Madero Angel M. , Chan Queenie W. T. , Stacey R. Greg , Stoynov Nikolay , Jan Eric , Foster Leonard J. 
Published: June 2020

Abstract
Background
The type I interferon (IFN) response is an ancient pathway that protects cells against viral pathogens by inducing the transcription of hundreds of IFN-stimulated genes. Comprehensive catalogs of IFN-stimulated genes have been established across species and cell types by transcriptomic and biochemical approaches, but their antiviral mechanisms remain incompletely characterized. Here, we apply a combination of quantitative proteomic approaches to describe the effects of IFN signaling on the human proteome, and apply protein correlation profiling to map IFN-induced rearrangements in the human protein-protein interaction network.

Results
We identify > 26,000 protein interactions in IFN-stimulated and unstimulated cells, many of which involve proteins associated with human disease and are observed exclusively within the IFN-stimulated network. Differential network analysis reveals interaction rewiring across a surprisingly broad spectrum of cellular pathways in the antiviral response. We identify IFN-dependent protein-protein interactions mediating novel regulatory mechanisms at the transcriptional and translational levels, with one such interaction modulating the transcriptional activity of STAT1. Moreover, we reveal IFN-dependent changes in ribosomal composition that act to buffer IFN-stimulated gene protein synthesis.

Conclusions
Our map of the IFN interactome provides a global view of the complex cellular networks activated during the antiviral response, placing IFN-stimulated genes in a functional context, and serves as a framework to understand how these networks are dysregulated in autoimmune or inflammatory disease.
Efficacy, safety, and economic assessment of hominis placental pharmacopuncture for chronic temporomandibular disorder: a protocol for a multicentre randomised controlled trial
Authors: Kim Jongho , Park Kyoung Sun , Lee Yoon Jae , Kim Koh-Woon , Cho Jae-Heung , Ha In-Hyuk 
Published: June 2020

AbstractBackgroundTemporomandibular disorder (TMD) is a condition encompassing clinical symptoms of the temporomandibular joint, masseter muscle, and surrounding structures. Hominis placental pharmacopuncture (HPP), consisting of human placental extract, has been reported as effective for treating chronic musculoskeletal disorders, but a lack of well-designed randomised controlled trial s (RCTs) mean there is insufficient evidence to prove the efficacy of HPP.MethodsThis study is a two-arm parallel, assessor-blinded, multi-centre, randomised controlled trial. We will enrol 82 chronic TMD patients from rwo Korean Medicine hospitals in Axis 1, Group I according to RDC/TMD diagnostic criteria, and randomly allocate 41 patients each to an HPP group and a physical therapy (PT) group. Treatment will be administered in 10 rounds, after which there will be four follow-up visits 6, 9, 13, and 25 weeks from baseline. The primary end point is 6 weeks after baseline, and the primary outcome is the difference in Visual Analogue Scale (VAS) score for temporomandibular pain between baseline and week 6. Secondary outcomes will be Numeric Rating Scale (NRS) scores for temporomandibular pain and discomfort, temporomandibular joint range of motion, the Korean version of Beck’s Depression Index-II (K-BDI-II), Jaw Functional Limitation Scale (JFLS), Patient Global Impression of Change (PGIC) scores, and quality of life. Using data on adverse events and cost-effectiveness in the two groups, we will perform a safety assessment and a cost-effectiveness analysis (economic assessment).DiscussionThis study will assess the efficacy and safety of HPP for chronic TMD compared with PT. This RCT will provide evidence for the efficacy, safety, and economics of HPP.Trial registrationclinicaTrials.gov(NCT04087005) / Clinical Research Information Service (CRIS) (KCT0004437) / IRB (JASENG 2017–09–002-002, KHNMCOH 2019–08-002) / Ministry of Food and Drug Safety (No. 31886).
Engineering Pichia pastoris with surface-display minicellulosomes for carboxymethyl cellulose hydrolysis and ethanol production
Authors: Dong Ce , Qiao Jie , Wang Xinping , Sun Wenli , Chen Lixia , Li Shuntang , Wu Ke , Ma Lixin , Liu Yi 
Published: June 2020

AbstractBackgroundsEngineering yeast as a consolidated bioprocessing (CBP) microorganism by surface assembly of cellulosomes has been aggressively utilized for cellulosic ethanol production. However, most of the previous studies focused onSaccharomyces cerevisiae, achieving efficient conversion of phosphoric acid-swollen cellulose (PASC) or microcrystalline cellulose (Avicel) but not carboxymethyl cellulose (CMC) to ethanol, with an average titer below 2 g/L.ResultsHarnessing an ultra-high-affinity IM7/CL7 protein pair, here we describe a method to engineerPichia pastoriswith minicellulosomes by in vitro assembly of three recombinant cellulases including an endoglucanase (EG), an exoglucanase (CBH) and a β-glucosidase (BGL), as well as a carbohydrate-binding module (CBM) on the cell surface. For the first time, the engineered yeasts enable efficient and direct conversion of CMC to bioethanol, observing an impressive ethanol titer of 5.1 g/L.ConclusionsThe research promotes the application ofP. pastorisas a CBP cell factory in cellulosic ethanol production and provides a promising platform for screening the cellulases from different species to construct surface-assembly celluosome.
Favorable efficacy of rituximab in ANCA-associated vasculitis patients with excessive B cell differentiation
Authors: Miyazaki Yusuke , Nakayamada Shingo , Kubo Satoshi , Ishikawa Yuichi , Yoshikawa Maiko , Sakata Kei , Iwata Shigeru , Miyagawa Ippei , Nakano Kazuhisa , Tanaka Yoshiya 
Published: June 2020

Abstract
Objectives
B cell depletion by rituximab (RTX) is an effective treatment for anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). However, peripheral B cell phenotypes and the selection criteria for RTX therapy in AAV remain unclear.

Methods
Phenotypic characterization of circulating B cells was performed by 8-color flow cytometric analysis in 54 newly diagnosed AAV patients (20 granulomatosis with polyangiitis and 34 microscopic polyangiitis). Patients were considered eligible to receive intravenous cyclophosphamide pulse (IV-CY) or RTX. All patients also received high-dose glucocorticoids (GC). We assessed circulating B cell phenotypes and evaluated the efficacy after 6 months of treatment.

Results
There were no significant differences in the rate of clinical improvement, relapses, or serious adverse events between patients receiving RTX and IV-CY. The rate of Birmingham Vasculitis Activity Score (BVAS) improvement at 6 months tended to be higher in the RTX group than in the IV-CY group. The proportion of effector or class-switched memory B cells increased in 24 out of 54 patients (44%). The proportions of peripheral T and B cell phenotypes did not correlate with BVAS at baseline. However, among peripheral B cells, the proportion of class-switched memory B cells negatively correlated with the rate of improvement in BVAS at 6 months after treatment initiation (r = − 0.28, p = 0.04). Patients with excessive B cell differentiation were defined as those in whom the proportion of class-switched memory B cells or IgD−CD27− B cells among all B cells was > 2 SDs higher than the mean in the HCs. The rate of BVAS remission in patients with excessive B cell differentiation was significantly lower than that in patients without. In patients with excessive B cell differentiation, the survival rate, the rate of BVAS-remission, and dose reduction of GC were significantly improved in the RTX group compared to those in the IV-CY group after 6 months of treatment.

Conclusions
The presence of excessive B cell differentiation was associated with treatment resistance. However, in patients with circulating B cell abnormality, RTX was effective and increased survival compared to IV-CY. The results suggest that multi-color flow cytometry may be useful to determine the selection criteria for RTX therapy in AAV patients.
Application of median lethal concentration (LC50) of pathogenic microorganisms and their antigens in vaccine development
Authors: Saganuwan Saganuwan Alhaji 
Published: June 2020

Abstract
Objective
Lack of ideal mathematical models to qualify and quantify both pathogenicity, and virulence is a dreadful setback in development of new antimicrobials and vaccines against resistance pathogenic microorganisms. Hence, the modified arithmetical formula of Reed and Muench has been integrated with other formulas and used to determine bacterial colony forming unit/viral concentration, virulence and immunogenicity.

Results
Microorganisms’ antigens tested are Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa in mice and rat, Edwardsiella ictaluri, Aeromonas hydrophila, Aeromonas veronii in fish, New Castle Disease virus in chicken, Sheep Pox virus, Foot-and-Mouth Disease virus and Hepatitis A virus in vitro, respectively. The LC50s for the pathogens using different routes of administrations are 1.93 × 103(sheep poxvirus) and 1.75 × 1010 for Staphylococcus aureus (ATCC29213) in rat, respectively. Titer index (TI) equals N log10 LC50 and provides protection against lethal dose in graded fashion which translates to protection index. N is the number of vaccine dose that could neutralize the LC50. Hence, parasite inoculum of 103 to 1011 may be used as basis for determination of LC50 and median bacterial concentrations (BC50).Pathogenic dose for immune stimulation should be sought at concentration about LC10.
Methylome profiling of young adults with depression supports a link with immune response and psoriasis
Authors: Lapsley Coral R. , Irwin Rachelle , McLafferty Margaret , Thursby Sara Jayne , O’Neill Siobhan M. , Bjourson Anthony J. , Walsh Colum P. , Murray Elaine K. 
Published: June 2020

Abstract
Background
Currently the leading cause of global disability, clinical depression is a heterogeneous condition characterised by low mood, anhedonia and cognitive impairments. Its growing incidence among young people, often co-occurring with self-harm, is of particular concern. We recently reported very high rates of depression among first year university students in Northern Ireland, with over 25% meeting the clinical criteria, based on DSM IV. However, the causes of depression in such groups remain unclear, and diagnosis is hampered by a lack of biological markers. The aim of this exploratory study was to examine DNA methylation patterns in saliva samples from individuals with a history of depression and matched healthy controls.

Results
From our student subjects who showed evidence of a total lifetime major depressive event (MDE, n = 186) we identified a small but distinct subgroup (n = 30) with higher risk scores on the basis of co-occurrence of self-harm and attempted suicide. Factors conferring elevated risk included being female or non-heterosexual, and intrinsic factors such as emotional suppression and impulsiveness. Saliva samples were collected and a closely matched set of high-risk cases (n = 16) and healthy controls (n = 16) similar in age, gender and smoking status were compared. These showed substantial differences in DNA methylation marks across the genome, specifically in the late cornified envelope (LCE) gene cluster. Gene ontology analysis showed highly significant enrichment for immune response, and in particular genes associated with the inflammatory skin condition psoriasis, which we confirmed using a second bioinformatics approach. We then verified methylation gains at the LCE gene cluster at the epidermal differentiation complex and at MIR4520A/B in our cases in the laboratory, using pyrosequencing. Additionally, we found loss of methylation at the PSORSC13 locus on chromosome 6 by array and pyrosequencing, validating recent findings in brain tissue from people who had died by suicide. Finally, we could show that similar changes in immune gene methylation preceded the onset of depression in an independent cohort of adolescent females.

Conclusions
Our data suggests an immune component to the aetiology of depression in at least a small subgroup of cases, consistent with the accumulating evidence supporting a relationship between inflammation and depression. Additionally, DNA methylation changes at key loci, detected in saliva, may represent a valuable tool for identifying at-risk subjects.
Anaphylaxis to three humanized antibodies for severe asthma: a case study
Authors: Jingo Koichi , Harada Norihiro , Nishioki Toshihiko , Torasawa Masahiro , Yamada Tomoko , Asao Tetsuhiko , Takagi Haruhi , Takeshige Tomohito , Ito Jun , Takahashi Kazuhisa 
Published: June 2020

Abstract
Background
Omalizumab, mepolizumab, benralizumab, and dupilumab are the currently available biologics used to treat asthma in Japan. Anaphylaxis following treatment with mepolizumab or benralizumab is considered rare.

Case presentation
We report the case of a 35-year-old woman with severe asthma, who experienced anaphylaxis following the administration of benralizumab, mepolizumab, and omalizumab, separately. The therapy with biologics was chosen to avoid the repeated use of systemic corticosteroids for asthma exacerbations. The mechanisms underlying anaphylaxis caused by these three biologics remain unclear. The patient’s asthma symptoms and lung function improved after treatment with bronchial thermoplasty.

Conclusions
To our knowledge, this is the first report of an asthmatic patient developing anaphylaxis after commencement of benralizumab, mepolizumab, and omalizumab therapy. These three biologics should be administered carefully, and patients should be monitored for anaphylaxis.
Defining clusters of young autistic and typically developing children based on loudness-dependent auditory electrophysiological responses
Authors: Dwyer Patrick , Wang Xiaodong , De Meo-Monteil Rosanna , Hsieh Fushing , Saron Clifford D. , Rivera Susan M. 
Published: June 2020

Abstract
Background
Autistic individuals exhibit atypical patterns of sensory processing that are known to be related to quality of life, but which are also highly heterogeneous. Previous investigations of this heterogeneity have ordinarily used questionnaires and have rarely investigated sensory processing in typical development (TD) alongside autism spectrum development (ASD).

Methods
The present study used hierarchical clustering in a large sample to identify subgroups of young autistic and typically developing children based on the normalized global field power (GFP) of their event-related potentials (ERPs) to auditory stimuli of four different loudness intensities (50, 60, 70, 80 dB SPL): that is, based on an index of the relative strengths of their neural responses across these loudness conditions.

Results
Four clusters of participants were defined. Normalized GFP responses to sounds of different intensities differed strongly across clusters. There was considerable overlap in cluster assignments of autistic and typically developing participants, but autistic participants were more likely to display a pattern of relatively linear increases in response strength accompanied by a disproportionately strong response to 70 dB stimuli. Autistic participants displaying this pattern trended towards obtaining higher scores on assessments of cognitive abilities. There was also a trend for typically developing participants to disproportionately fall into a cluster characterized by disproportionately/nonlinearly strong 60 dB responses. Greater auditory distractibility was reported among autistic participants in a cluster characterized by disproportionately strong responses to the loudest (80 dB) sounds, and furthermore, relatively strong responses to loud sounds were correlated with auditory distractibility. This appears to provide evidence of coinciding behavioral and neural sensory atypicalities.

Limitations
Replication may be needed to verify exploratory results. This analysis does not address variability related to classical ERP latencies and topographies. The sensory questionnaire employed was not specifically designed for use in autism. Hearing acuity was not measured. Variability in sensory responses unrelated to loudness is not addressed, leaving room for additional research.

Conclusions
Taken together, these data demonstrate the broader benefits of using electrophysiology to explore individual differences. They illuminate different neural response patterns and suggest relationships between sensory neural responses and sensory behaviors, cognitive abilities, and autism diagnostic status.
Methods to assess binocular rivalry with periodic stimuli
Authors: Darki Farzaneh , Rankin James 
Published: June 2020

AbstractBinocular rivalry occurs when the two eyes are presented with incompatible stimuli and perception alternates between these two stimuli. This phenomenon has been investigated in two types of experiments: (1) Traditional experiments where the stimulus is fixed, (2) eye-swap experiments in which the stimulus periodically swaps between eyes many times per second (Logothetis et al. in Nature 380(6575):621–624, 1996). In spite of the rapid swapping between eyes, perception can be stable for many seconds with specific stimulus parameter configurations. Wilson introduced a two-stage, hierarchical model to explain both types of experiments (Wilson in Proc. Natl. Acad. Sci. 100(24):14499–14503, 2003). Wilson’s model and other rivalry models have been only studied with bifurcation analysis for fixed inputs and different types of dynamical behavior that can occur with periodically forcing inputs have not been investigated. Here we report (1) a more complete description of the complex dynamics in the unforced Wilson model, (2) a bifurcation analysis with periodic forcing. Previously, bifurcation analysis of the Wilson model with fixed inputs has revealed three main types of dynamical behaviors: Winner-takes-all (WTA), Rivalry oscillations (RIV), Simultaneous activity (SIM). Our results have revealed richer dynamics including mixed-mode oscillations (MMOs) and a period-doubling cascade, which corresponds to low-amplitude WTA (LAWTA) oscillations. On the other hand, studying rivalry models with numerical continuation shows that periodic forcing with high frequency (e.g. 18 Hz, known as flicker) modulates the three main types of behaviors that occur with fixed inputs with forcing frequency (WTA-Mod, RIV-Mod, SIM-Mod). However, dynamical behavior will be different with low frequency periodic forcing (around 1.5 Hz, so-called swap). In addition to WTA-Mod and SIM-Mod, cycle skipping, multi-cycle skipping and chaotic dynamics are found. This research provides a framework for either assessing binocular rivalry models to check consistency with empirical results, or for better understanding neural dynamics and mechanisms necessary to implement a minimal binocular rivalry model.
Comparison of regional flortaucipir PET with quantitative tau immunohistochemistry in three subjects with Alzheimer’s disease pathology: a clinicopathological study
Authors: Pontecorvo Michael J. , Keene C. Dirk , Beach Thomas G. , Montine Thomas J. , Arora Anupa K. , Devous Michael D. , Navitsky Michael , Kennedy Ian , Joshi Abhinay D. , Lu Ming , Serrano Geidy E. , Sue Lucia I. , Intorcia Anthony J. , Rose Shannon E. , Wilson Angela , Hellstern Leanne , Coleman Natalie , Flitter Matthew , Aldea Patricia , Fleisher Adam S. , Mintun Mark A. , Siderowf Andrew 
Published: June 2020

Abstract
Background
The objective of this study was to make a quantitative comparison of flortaucipir PET retention with pathological tau and β-amyloid across a range of brain regions at autopsy.

Methods
Patients with dementia (two with clinical diagnosis of AD, one undetermined), nearing the end of life, underwent 20-min PET, beginning 80 min after an injection of ~370 mBq flortaucipir [18F]. Neocortical, basal ganglia, and limbic tissue samples were obtained bilaterally from 19 regions at autopsy and subject-specific PET regions of interest corresponding to the 19 sampled target tissue regions in each hemisphere were hand drawn on the PET images. SUVr values were calculated for each region using a cerebellar reference region. Abnormally phosphorylated tau (Ptau) and amyloid-β (Aβ) tissue concentrations were measured for each tissue region with an antibody capture assay (Histelide) using AT8 and H31L21 antibodies respectively.

Results
The imaging-to-autopsy interval ranged from 4–29 days. All three subjects had intermediate to high levels of AD neuropathologic change at autopsy. Mean cortical SUVr averaged across all three subjects correlated significantly with the Ptau immunoassay (Pearson r = 0.81; p < 0.0001). When Ptau and Aβ1-42 were both included in the model, the Ptau correlation with flortaucipir SUVr was preserved but there was no correlation of Aβ1-42 with flortaucipir. There was also a modest correlation between limbic (hippocampal/entorhinal and amygdala) flortaucipir SUVr and Ptau (Pearson r = 0.52; p < 0.080). There was no significant correlation between SUVr and Ptau in basal ganglia.

Conclusions
The results of this pilot study support a quantitative relationship between cortical flortaucipir SUVr values and quantitative measures of Ptau at autopsy. Additional research including more cases is needed to confirm the generalizability of these results.
Trial registration, NIH Clinicaltrials.gov NCT # 02516046. Registered August 27, 2015. https://clinicaltrials.gov/ct2/show/NCT02516046?term=02516046&draw=2&rank=1
Cerenkov luminescence imaging is an effective preclinical tool for assessing colorectal cancer PD-L1 levels in vivo
Authors: Zhao Sheng , Pan Wenbin , Jiang Huijie , Zhang Rongjun , Jiang Hao , Liang Zonghui , Hu Hongbo 
Published: June 2020

Abstract
Background
Preclinical and clinical studies have demonstrated that immunotherapy has effectively delayed tumor progression, and the clinical outcomes of anti-PD-1/PD-L1 therapy were related to PD-L1 expression level in the tumors. A 131I-labeled anti-PD-L1 monoclonal antibody tracer, 131I-PD-L1-Mab, was developed to study the target ability of noninvasive Cerenkov luminescence imaging in colorectal cancer xenograft mice.

Method
Anti-PD-L1 monoclonal antibody labeled with 131I (131I-PD-L1-Mab), and in vitro binding assays were used to evaluate the affinity of 131I-PD-L1-Mab to PD-L1 and their binding level to different colorectal cancer cells, and compared with flow cytometry, Western blot analysis, and immunofluorescence staining. The clinical application value of 131I-PD-L1-Mab was evaluated through biodistribution and Cerenkov luminescence imaging, and different tumor-bearing models expressing PD-L1 were evaluated.

Results
131I-PD-L1-Mab showed high affinity to PD-L1, and the equilibrium dissociation constant was 1.069 × 10-9 M. The competitive inhibition assay further confirmed the specific binding ability of 131I-PD-L1-Mab. In four different tumor-bearing models with different PD-L1 expression, the biodistribution and Cerenkov luminescence imaging showed that the RKO tumors demonstrated the highest uptake of the tracer 131I-PD-L1-Mab, with a maximum uptake of 1.613 ± 0.738% IA/g at 48 h.

Conclusions
There is a great potential for 131I-PD-L1-Mab noninvasive Cerenkov luminescence imaging to assess the status of tumor PD-L1 expression and select patients for anti-PD-L1 targeted therapy.
Positive solutions for a system of Riemann–Liouville fractional boundary value problems with p-Laplacian operators
Authors: Tudorache Alexandru , Luca Rodica 
Published: June 2020

AbstractWe study the existence and nonexistence of positive solutions for a system of Riemann–Liouville fractional differential equations with p-Laplacian operators, nonnegative nonlinearities and positive parameters, subject to coupled nonlocal boundary conditions which contain Riemann–Stieltjes integrals and various fractional derivatives. We use the Guo–Krasnosel’skii fixed point theorem in the proof of the main existence results.