bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of subclinical skin manifestation in patients with psoriasis and psoriatic arthritis by fluorescence optical imaging
Authors: Schmidt A. , Glimm A. M. , Haugen I. K. , Hoff P. , Schmittat G. , Burmester G. R. , Klotsche J. , Ohrndorf S. 
Published: August 2020

Abstract
Objectives
To investigate the frequency of subclinical skin inflammation in both hands by fluorescence optical imaging (FOI) in patients with psoriasis/psoriatic arthritis (Pso/PsA) vs. rheumatoid arthritis (RA) and healthy individuals, and to correlate these findings with cardiovascular (CV) risk factors.

Patients and methods
The FOI scans were analyzed retrospectively to detect clinically invisible skin enhancement (0–3 scale) in both hands without relationship to underlying joints or blood vessels. We further characterized the FOI patterns and sorted the scans into groups based on the assumed diagnosis (Pso/PsA, RA, and healthy controls), which was compared with the physician’s diagnosis. Furthermore, the associations between CV risk factors and imaging findings were investigated by regression analyses.

Results
We included FOI scans of patients with Pso/PsA (n = 80), RA (n = 78), and healthy controls (n = 25). Subclinical skin enhancement on the back of their hands was more common in Pso/PsA (72.5%) than in RA patients (20.5%) and healthy individuals (28.0%) (p < 0.001). Based on the FOI pattern, the majority of patients with Pso/PsA (72.5%), RA (76.9%), and healthy controls (68.0%) were classified correctly using the physician-based diagnosis as reference (overall agreement of 74%, kappa = 0.57). No CV risk factors except body weight (kg) were associated with subclinical skin enhancement (OR 1.04, 95% CI 1.02–1.06; p < 0.001).

Conclusion
Subclinical subdermal skin inflammation was common in Pso/PsA patients using FOI. Based on the FOI pattern, most patients with Pso/PsA and were classified with the correct diagnosis. We demonstrated an important influence of the body weight on our FOI results. FOI may be a helpful novel tool to study microcirculation in rheumatic diseases with skin involvement.
Assessment of the association of baseline anti-CarbV and anti-MCV antibodies with response to treatment and radiographic progression in an RA population treated with either methotrexate or baricitinib: post-hoc analyses from RA-BEGIN
Authors: López-Romero Pedro , Martinez-Gamboa Lorena , Bang Holger , de la Torre Inmaculada , Holzkämper Thorsten , Feist Eugen 
Published: August 2020

Abstract
Background
The development of autoantibodies in patients with rheumatoid arthritis (RA) has potential as a marker of treatment response. This analysis assessed the association of an autoantibody response to carbamylated vimentin (anti-CarbV) and to vimentin modified by citrullination (anti-MCV) with response to treatment and structural damage progression in the phase III study RA-BEGIN.

Methods
Data from patients in the modified intent-to-treat population of RA-BEGIN were included for analysis; these patients received methotrexate (MTX), baricitinib 4 mg once daily, or baricitinib plus MTX during the 52-week study period. Endpoints analyzed were clinical response to treatment, assessed using change from baseline (CFB) in Simplified Disease Activity Index (SDAI) and Disease Activity Score for 28-joint count with serum high-sensitivity C-reactive protein (DAS28-hsCRP), and structural damage progression, assessed using CFB greater than the smallest detectable change in the van der Heijde-modified Total Sharp Score. The anti-CarbV and anti-MCV isotypes assessed were immunoglobulin (Ig) A, IgG, and IgM. Multivariable mixed-effect models for repeated measures (MMRMs) were used for the longitudinal analysis of treatment response, and multivariable logistic regression models were used for the analysis of structural damage progression at week 52.

Results
Analysis of the association between autoantibodies and treatment response showed that high titers of anti-CarbV (IgA and IgG) were associated with a greater clinical response as measured by SDAI and DAS28-hsCRP. Anti-CarbV IgA and IgG, but not IgM, demonstrated an association after adjustment for other factors included in the MMRMs. High titers of anti-CarbV IgM were associated with a poor response to MTX monotherapy, whereas a nonsignificant trend toward a better response to baricitinib and baricitinib plus MTX was observed. There was no association between anti-MCV antibodies and treatment response. High titers of anti-CarbV IgA were associated with a greater probability of radiographic progression, but no association between anti-MCV antibodies and radiographic progression was observed.

Conclusions
High titers of anti-CarbV IgA and IgG isotypes, but not anti-MCV isotypes, may be useful prognostic biomarkers for identifying the likelihood of the response to treatment and structural damage progression in patients with RA.
Recent progress on the role of miR-140 in cartilage matrix remodelling and its implications for osteoarthritis treatment
Authors: Duan Li , Liang Yujie , Xu Xiao , Xiao Yin , Wang Daping 
Published: August 2020

AbstractCartilage matrix remodelling homeostasis is a crucial factor in maintaining cartilage integrity. Loss of cartilage integrity is a typical characteristic of osteoarthritis (OA). Strategies aimed at maintaining cartilage integrity have attracted considerable attention in the OA research field. Recently, a series of studies have suggested dual functions of microRNA-140 (miR-140) in cartilage matrix remodelling. Here, we discuss the significance of miR-140 in promoting cartilage formation and inhibiting degeneration. Additionally, we focused on the role of miR-140 in the chondrogenesis of mesenchymal stem cells (MSCs). Of note, we carefully reviewed recent advances in MSC exosomes for miRNA delivery in OA treatment.
Beyond just “flattening the curve”: Optimal control of epidemics with purely non-pharmaceutical interventions
Authors: Kantner Markus , Koprucki Thomas 
Published: August 2020

AbstractWhen effective medical treatment and vaccination are not available, non-pharmaceutical interventions such as social distancing, home quarantine and far-reaching shutdown of public life are the only available strategies to prevent the spread of epidemics. Based on an extended SEIR (susceptible-exposed-infectious-recovered) model and continuous-time optimal control theory, we compute the optimal non-pharmaceutical intervention strategy for the case that a vaccine is never found and complete containment (eradication of the epidemic) is impossible. In this case, the optimal control must meet competing requirements: First, the minimization of disease-related deaths, and, second, the establishment of a sufficient degree of natural immunity at the end of the measures, in order to exclude a second wave. Moreover, the socio-economic costs of the intervention shall be kept at a minimum. The numerically computed optimal control strategy is a single-intervention scenario that goes beyond heuristically motivated interventions and simple “flattening of the curve”. Careful analysis of the computed control strategy reveals, however, that the obtained solution is in fact a tightrope walk close to the stability boundary of the system, where socio-economic costs and the risk of a new outbreak must be constantly balanced against one another. The model system is calibrated to reproduce the initial exponential growth phase of the COVID-19 pandemic in Germany.
Neurally plausible mechanisms for learning selective and invariant representations
Authors: Anselmi Fabio , Patel Ankit , Rosasco Lorenzo 
Published: August 2020

AbstractCoding for visual stimuli in the ventral stream is known to be invariant to object identity preserving nuisance transformations. Indeed, much recent theoretical and experimental work suggests that the main challenge for the visual cortex is to build up such nuisance invariant representations. Recently, artificial convolutional networks have succeeded in both learning such invariant properties and, surprisingly, predicting cortical responses in macaque and mouse visual cortex with unprecedented accuracy. However, some of the key ingredients that enable such success—supervised learning and the backpropagation algorithm—are neurally implausible. This makes it difficult to relate advances in understanding convolutional networks to the brain. In contrast, many of the existing neurally plausible theories of invariant representations in the brain involve unsupervised learning, and have been strongly tied to specific plasticity rules. To close this gap, we study an instantiation of simple-complex cell model and show, for a broad class of unsupervised learning rules (including Hebbian learning), that we can learn object representations that are invariant to nuisance transformations belonging to a finite orthogonal group. These findings may have implications for developing neurally plausible theories and models of how the visual cortex or artificial neural networks build selectivity for discriminating objects and invariance to real-world nuisance transformations.
The tail domain of PRRSV NSP2 plays a key role in aggrephagy by interacting with 14-3-3ε
Authors: Cao Shengliang , Liu Jiaqi , Ding Guofei , Shao Qingyuan , Wang Bin , Li Yingchao , Feng Jian , Zhao Yuzhong , Liu Sidang , Xiao Yihong 
Published: August 2020

AbstractPorcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV) is one of the most severe swine diseases that affects almost all swine-breeding countries. Nonstructural protein 2 (NSP2) is one of the most important viral proteins in the PRRSV life cycle. Our previous study showed that PRRSV NSP2 could induce the formation of aggresomes. In this study we explored the effects of aggresome formation on cells and found that NSP2 could induce autophagy, which depended on aggresome formation to activate aggrephagy. The transmembrane and tail domains of NSP2 contributed to aggrephagy and the cellular protein 14-3-3ε played an important role in NSP2-induced autophagy by binding the tail domain of NSP2. These findings provide information on the function of the C-terminal domain of NSP2, which will help uncover the function of NSP2 during PRRSV infection.
Mukonal exerts anticancer effects on the human breast cancer cells by inducing autophagy and apoptosis and inhibits the tumor growth in vivo
Authors: Wang Wenbiao , Zhou Zhengui , Zhou Xiaohong , Chen Limin , Bie Shuang , Jing Zhengjun 
Published: August 2020

AbstractMukonal is an active member of carbazole alkaloids isolated from Murraya koenigii. It has been shown to possess remarkable biological and pharmacological activities including anticancer activity. Therefore, the aim of current investigation was to explore anti-breast cancer activity of mukonal and to explore the underlying mechanism. Results indicate that mukonal has potential to induce antiproliferative effects against MDA-MB-231 and SK-BR-3 cells with an IC50 of 7.5 µM. No significant toxicity of mukonal was observed in case of normal breast cells. The antiproliferative effects of mukonal were found to proceed via apoptosis, which was further supported by increased cleavage of PARP and caspase-3 and reduced expression of Bcl-2. Mukonal induced autophagic cells death in breast cancer cells as was evidenced by formation of autophagosomes and enhanced expressions of Beclin-1, LC3B-I and LC3B-II proteins. In vivo examination of anti-breast cancer property of mukonal indicated that it could potentially reduce tumor weight and volume in xenografted mice models. In conclusion, mukonal has a remarkable potential of inhibiting breast cancer via induction of apoptosis and autophagy. Mukonal also inhibited xenografted tumors models in a dose-dependent manner. Therefore, mukonal may prove lead molecule in breast cancer drug discovery and treatment provided further investigations are recommended.
A novel technique to prevent SQL injection and cross-site scripting attacks using Knuth-Morris-Pratt string match algorithm
Authors: Abikoye Oluwakemi Christiana , Abubakar Abdullahi , Dokoro Ahmed Haruna , Akande Oluwatobi Noah , Kayode Aderonke Anthonia 
Published: August 2020

AbstractStructured Query Language (SQL) injection and cross-site scripting remain a major threat to data-driven web applications. Instances where hackers obtain unrestricted access to back-end database of web applications so as to steal, edit, and destroy confidential data are increasing. Therefore, measures must be put in place to curtail the growing threats of SQL injection and XSS attacks. This study presents a technique for detecting and preventing these threats using Knuth-Morris-Pratt (KMP) string matching algorithm. The algorithm was used to match user’s input string with the stored pattern of the injection string in order to detect any malicious code. The implementation was carried out using PHP scripting language and Apache XAMPP Server. The security level of the technique was measured using different test cases of SQL injection, cross-site scripting (XSS), and encoded injection attacks. Results obtained revealed that the proposed technique was able to successfully detect and prevent the attacks, log the attack entry in the database, block the system using its mac address, and also generate a warning message. Therefore, the proposed technique proved to be more effective in detecting and preventing SQL injection and XSS attacks
What can primary care services do to help First Nations people with unhealthy alcohol use? A systematic review: Australia, New Zealand, USA and Canada
Authors: Purcell-Khodr Gemma C. , Lee K. S. Kylie , Conigrave James H. , Webster Emma , Conigrave Katherine M. 
Published: August 2020

Abstract
Background
First Nations peoples of Australia, New Zealand, the United States of America (USA) and Canada are more likely to be non-drinkers than other people in these countries. However, those who do drink may be at greater risk of alcohol-related harms (at a population level) due to the ongoing impacts from colonisation and associated oppression. Addressing unhealthy drinking (drinking above recommended limits including alcohol use disorders) in primary care settings is one important way to increase accessibility of treatment.

Methods
This systematic review identifies peer-reviewed studies of alcohol treatments delivered in primary care or other non-residential settings for First Nations peoples of Australia, New Zealand, USA and Canada. Literature searches were conducted in seven academic databases from their inception until March, 2020. We assessed evidence of treatment or implementation effectiveness, perceived acceptability or accessibility, and the study quality as assessed by the AXIS tool and by a measure of community participation in the research process.

Results
Twenty-eight studies were included, published between 1968 and 2018. Studies reported on a range of alcohol treatments, from brief intervention to ambulatory withdrawal management, relapse prevention medicines, and cultural therapies. Brief intervention was the most studied approach. Cultural healing practices and bicultural approaches were a key theme amongst several studies. Four studies measured treatment effectiveness, including one randomised controlled trial (naltrexone vs naltrexone plus sertraline vs placebo) and two uncontrolled trials of disulfiram. Of the six implementation studies, three were (hybrid) effectiveness-implementation designs. Most of the remaining studies (n = 21) focused on treatment accessibility or acceptability. Community participation in the research process was poorly reported in most studies.

Conclusions
Research evidence on how best to care for First Nations peoples with unhealthy alcohol use is limited. Trials of naltrexone and disulfiram presented promising results. Cultural and bicultural care were perceived as highly important to clinical staff and clients in several studies. More effectiveness studies on the full scope of alcohol treatments are needed. Greater community participation in research and more transparent reporting of this in study methods will be key to producing quality research that combines scientific rigour with cultural appropriateness.
The stability of carbapenems before and after admixture to PMMA-cement used for replacement surgery caused by Gram-negative bacteria
Authors: Schmid Matthias , Steiner Oliver , Fasshold Lisa , Goessler Walter , Holl Anna-Maria , Kühn Klaus-Dieter 
Published: August 2020

Abstract
Background
Prosthetic joint infection (PJI) is a serious complication of orthopedic implant surgery. Treatment often includes the use of an antibiotic-loaded Polymethyl methacrylate (PMMA) bone cement spacer. Several antibiotics are commonly used for the preparation of these spacers, but due to the increasing number of infections with resistant Gram-negative bacteria, there is a need for the use of carbapenem antibiotics such as meropenem and imipenem as drugs of last resort. Unfortunately, the reaction heat generated during the preparation of the bone cement can be a major problem for the stability of these antibiotics. In the present study, the stability of meropenem and imipenem was tested before and after the admixture to PMMA bone cements.

Methods
High-performance liquid chromatography with ion-pairing reversed-phase separation and spectrophotometric detection was used for analysis. Stability tests with meropenem and imipenem were performed with antibiotics in solution and solid form at different temperatures (37 °C, 45 °C, 60 °C, 90 °C) and times (30 min, 60 min, 120 min). To test the stability of both antibiotics in PMMA after exposure to the reaction heat during polymerization, three different bone cements were used to generate specimens that contained defined amounts of antibiotics. Reaction heat was measured. The form bodies were mechanically crushed and aliquots were dissolved in ethyl acetate. Samples were prepared for HPLC DAD analysis.

Results
Meropenem and imipenem showed the highest degradation levels after heat stressed in solution, with maximum levels of 75% and 95%, respectively. In solid form, degradation levels decreased dramatically for meropenem (5%) and imipenem (13%). Stability tests of both carbapenems in bone cement showed that they remained largely stable during PMMA polymerization, with retrieved amounts of about 70% in Palacos® R and Copal® G+V, and between 80 and 90% in Copal® spacem.

Conclusions
In contrast to the results of meropenem and imipenem in solution, both antibiotics remain stable in solid form and mostly stable in the cement after PMMA polymerization. The low degradation levels of both antibiotics after exposure to temperatures > 100 °C allow the conclusion that they can potentially be used for an application in PMMA cements.
Spatial modeling of erosion hotspots using GIS-RUSLE interface in Omo-Gibe river basin, Southern Ethiopia: implication for soil and water conservation planning
Authors: Girma Rediet , Gebre Eshetu 
Published: August 2020

Abstract
Soil degradation due to soil erosion is one of the major environmental threats in developing countries. In resource limited conditions, computing the spatial distribution of soil erosion risk has become an essential and practical mechanism to implement soil conservation measures. This study aimed to assess the spatial distribution of soil loss in Omo-Gibe river basin using the integration of computer-based RUSLE and ArcGIS 10.7.1 to identify areas that require erosion prevention priority. Once raster layer of the input parameters was created, overlay analysis was carried to assess the spatial distribution of soil loss. The estimated annual soil loss varies from 0–279 t ha−1 yr−1 with a mean annual soil loss of 69 t ha−1 yr−1. The empirical analysis also confirmed that the basin losses a total of about 89.6 Mt of soil annually. Out of the total area; 7% was in very sever class, 4.8% was found in the sever and 8.7% was categorized in very high range. The remaining area were ranging from low to high erosion risk class. The influence of the combined LS factor for soil loss is significant. It was observed that small area of the Omo-Gibe basin contributed for the significant amount of soil loss. The finding of this study is in a good agreement with previous studies. Compared to the country permissible soil loss rate, 26% of the entire basin significantly exceeds the country threshold value (TSL = 18 t ha−1 yr−1). As a result, precedence and immediate attention should be given to those erosion prone areas. The study output could deliver watershed management experts and policy makers for better management implementation and resource allocation based on the local context.
Single-cell mass cytometry reveals complex myeloid cell composition in active lesions of progressive multiple sclerosis
Authors: Böttcher Chotima , van der Poel Marlijn , Fernández-Zapata Camila , Schlickeiser Stephan , Leman Julia K. H. , Hsiao Cheng-Chih , Mizee Mark R. , Adelia  , Vincenten Maria C. J. , Kunkel Desiree , Huitinga Inge , Hamann Jörg , Priller Josef 
Published: August 2020

AbstractMyeloid cells contribute to inflammation and demyelination in the early stages of multiple sclerosis (MS), but it is still unclear to what extent these cells are involved in active lesion formation in progressive MS (PMS). Here, we have harnessed the power of single-cell mass cytometry (CyTOF) to compare myeloid cell phenotypes in active lesions of PMS donors with those in normal-appearing white matter from the same donors and control white matter from non-MS donors. CyTOF measurements of a total of 74 targeted proteins revealed a decreased abundance of homeostatic and TNFhimicroglia, and an increase in highly phagocytic and activated microglia states in active lesions of PMS donors. Interestingly, in contrast to results obtained from studies of the inflammatory early disease stages of MS, infiltrating monocyte-derived macrophages were scarce in active lesions of PMS, suggesting fundamental differences of myeloid cell composition in advanced stages of PMS.
Tau reduction in aged mice does not impact Microangiopathy
Authors: Bennett Rachel E. , Hu Miwei , Fernandes Analiese , Perez-Rando Marta , Robbins Ashley , Kamath Tarun , Dujardin Simon , Hyman Bradley T. 
Published: August 2020

AbstractMicroangiopathy, including proliferation of small diameter capillaries, increasing vessel tortuosity, and increased capillary blockage by leukocytes, was previously observed in the aged rTg4510 mouse model. Similar gene expression changes related to angiogenesis were observed in both rTg4510 and Alzheimer’s disease (AD). It is uncertain if tau is directly responsible for these vascular changes by interacting directly with microvessels, and/or if it contributes indirectly via neurodegeneration and concurrent neuronal loss and inflammation. To better understand the nature of tau-related microangiopathy in human AD and in tau mice, we isolated capillaries and observed that bioactive soluble tau protein could be readily detected in association with vasculature. To examine whether this soluble tau is directly responsible for the microangiopathic changes, we made use of the tetracycline-repressible gene expression cassette in the rTg4510 mouse model and measured vascular pathology following tau reduction. These data suggest that reduction of tau is insufficient to alter established microvascular complications including morphological alterations, enhanced expression of inflammatory genes involved in leukocyte adherence, and blood brain barrier compromise. These data imply that 1) soluble bioactive tau surprisingly accumulates at the blood brain barrier in human brain and in mouse models, and 2) the morphological and molecular phenotype of microvascular disturbance does not resolve with reduction of whole brain soluble tau. Additional consideration of vascular-directed therapies and strategies that target tau in the vascular space may be required to restore normal function in neurodegenerative disease.