bluuebunny/crossref_metadata_2025_split huggingface dataset:
CT imaging-based machine learning model: a potential modality for predicting low-risk and high-risk groups of thymoma: “Impact of surgical modality choice”
Authors: Kayi Cangir Ayten , Orhan Kaan , Kahya Yusuf , Özakıncı Hilal , Kazak Betül Bahar , Konuk Balcı Buse Mine , Karasoy Duru , Uzun Çağlar 
Published: May 2021

Abstract
Introduction
Radiomics methods are used to analyze various medical images, including computed tomography (CT), magnetic resonance, and positron emission tomography to provide information regarding the diagnosis, patient outcome, tumor phenotype, and the gene-protein signatures of various diseases. In low-risk group, complete surgical resection is typically sufficient, whereas in high-risk thymoma, adjuvant therapy is usually required. Therefore, it is important to distinguish between both.
This study evaluated the CT radiomics features of thymomas to discriminate between low- and high-risk thymoma groups.

Materials and methods
In total, 83 patients with thymoma were included in this study between 2004 and 2019. We used the Radcloud platform (Huiying Medical Technology Co., Ltd.) to manage the imaging and clinical data and perform the radiomics statistical analysis. The training and validation datasets were separated by a random method with a ratio of 2:8 and 502 random seeds. The histopathological diagnosis was noted from the pathology report.

Results
Four machine-learning radiomics features were identified to differentiate a low-risk thymoma group from a high-risk thymoma group. The radiomics feature names were Energy, Zone Entropy, Long Run Low Gray Level Emphasis, and Large Dependence Low Gray Level Emphasis.

Conclusions
The results demonstrated that a machine-learning model and a multilayer perceptron classifier analysis can be used on CT images to predict low- and high-risk thymomas. This combination could be a useful preoperative method to determine the surgical approach for thymoma.
The effect of dipeptidyl peptidase IV on disease-associated microglia phenotypic transformation in epilepsy
Authors: Zheng Zhicheng , Liang Peiyu , Hou Baohua , Lu Xin , Ma Qianwen , Yu Xiaomin , Han Song , Peng Biwen , Chen Taoxiang , Liu Wanhong , Yin Jun , He Xiaohua 
Published: May 2021

Abstract
Background
Accumulating evidence suggests that disease-associated microglia (DAM), a recently discovered subset of microglia, plays a protective role in neurological diseases. Targeting DAM phenotypic transformation may provide new therapeutic options. However, the relationship between DAM and epilepsy remains unknown.

Methods
Analysis of public RNA-sequencing data revealed predisposing factors (such as dipeptidyl peptidase IV; DPP4) for epilepsy related to DAM conversion. Anti-epileptic effect was assessed by electroencephalogram recordings and immunohistochemistry in a kainic acid (KA)-induced mouse model of epilepsy. The phenotype, morphology and function of microglia were assessed by qPCR, western blotting and microscopic imaging.

Results
Our results demonstrated that DPP4 participated in DAM conversion and epilepsy. The treatment of sitagliptin (a DPP4 inhibitor) attenuated KA-induced epilepsy and promoted the expression of DAM markers (Itgax and Axl) in both mouse epilepsy model in vivo and microglial inflammatory model in vitro. With sitagliptin treatment, microglial cells did not display an inflammatory activation state (enlarged cell bodies). Furthermore, these microglia exhibited complicated intersections, longer processes and wider coverage of parenchyma. In addition, sitagliptin reduced the activation of NF-κB signaling pathway and inhibited the expression of iNOS, IL-1β, IL-6 and the proinflammatory DAM subset gene CD44.

Conclusion
The present results highlight that the DPP4 inhibitor sitagliptin can attenuate epilepsy and promote DAM phenotypic transformation. These DAM exhibit unique morphological features, greater migration ability and better surveillance capability. The possible underlying mechanism is that sitagliptin can reduce the activation of NF-κB signaling pathway and suppress the inflammatory response mediated by microglia. Thus, we propose DPP4 may act as an attractive direction for DAM research and a potential therapeutic target for epilepsy.
IL-9-triggered lncRNA Gm13568 regulates Notch1 in astrocytes through interaction with CBP/P300: contribute to the pathogenesis of experimental autoimmune encephalomyelitis
Authors: Liu Xiaomei , Zhou Feng , Wang Weixiao , Chen Guofang , Zhang Qingxiu , Lv Ruixue , Zhao Zijun , Li Xiangyang , Yu Qian , Meves Jessica M. , Hua Hui , Li Xiaocui , Wang Xiaotian , Sun Hong , Gao Dianshuai 
Published: May 2021

Abstract
Background
Interleukin 9 (IL-9), produced mainly by T helper 9 (Th9) cells, has been recognized as an important regulator in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Astrocytes respond to IL-9 and reactive astrocytes always associate with blood-brain barrier damage, immune cell infiltration, and spinal injury in MS and EAE. Several long non-coding RNAs (lncRNAs) with aberrant expression have been identified in the pathogenesis of MS. Here, we examined the effects of lncRNA Gm13568 (a co-upregulated lncRNA both in EAE mice and in mouse primary astrocytes activated by IL-9) on the activation of astrocytes and the process of EAE.

Methods
In vitro, shRNA-recombinant lentivirus with glial fibrillary acidic protein (GFAP) promoter were performed to determine the relative gene expression and proinflammatory cytokines production in IL-9 treated-astrocytes using Western blot, real-time PCR, and Cytometric Bead Array, respectively. RIP and ChIP assays were analyzed for the mechanism of lncRNA Gm13568 regulating gene expression. Immunofluorescence assays was performed to measure the protein expression in astrocytes. In vivo, H&E staining and LFB staining were applied to detect the inflammatory cells infiltrations and the medullary sheath damage in spinal cords of EAE mice infected by the recombinant lentivirus. Results were analyzed by one-way ANOVA or Student’s t test, as appropriate.

Results
Knockdown of the endogenous lncRNA Gm13568 remarkably inhibits the Notch1 expression, astrocytosis, and the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) as well as the production of inflammatory cytokines and chemokines (IL-6, TNF-α, IP-10) in IL-9-activated astrocytes, in which Gm13568 associates with the transcriptional co-activators CBP/P300 which are enriched in the promoter of Notch1 genes. More importantly, inhibiting Gm13568 with lentiviral vector in astrocytes ameliorates significantly inflammation and demyelination in EAE mice, therefore delaying the EAE process.

Conclusions
These findings uncover that Gm13568 regulates the production of inflammatory cytokines in active astrocytes and affects the pathogenesis of EAE through the Notch1/STAT3 pathway. LncRNA Gm13568 may be a promising target for treating MS and demyelinating diseases.
Optimized workflow for digitalized FISH analysis in pathology
Authors: Chea Vira , Pleiner Valerie , Schweizer Viviane , Herzog Benjamin , Bode Beata , Tinguely Marianne 
Published: May 2021

Abstract
Background
Effective workflow management in a diagnostic pathology laboratory is critical to achieve rapid turnover while maintaining high quality. Fluorescence in situ hybridization analysis (FISH) is the preferred technique for detecting single chromosomal aberrations in diagnostic surgical pathology.

Material and methods
FISH analysis applying a rapid hybridization protocol and using an automated whole-slide fluorescence scanning device (3DHISTECH, Sysmex, Switzerland) were implemented in our workflow. By analyzing 42 diagnostic cases, effects of two different scanning profiles on scanning time, and device memory usage were investigated. Manual signal counting (CaseViewer) and software based signal counting (FISHQuant) were compared.

Results
The two scanning profiles, both including a Z-stack function, differed in their exposure time and digital gain. The “low profile” setting (LP) resulted in a significantly shorter scanning time and lower storage volume compared to the “high profile” (HP) setting, making the LP ideal for routine applications. Both signal counting methods (manual versus software based) provided similar cut-offs on a test-cohort of 13 samples.

Conclusion
Scanning FISH slides provides good picture quality, reduces the analysis time and allows easy picture archiving and facilitates remote diagnostics, allowing an effective workflow.
On the optimistic performance evaluation of newly introduced bioinformatic methods
Authors: Buchka Stefan , Hapfelmeier Alexander , Gardner Paul P. , Wilson Rory , Boulesteix Anne-Laure 
Published: May 2021

AbstractMost research articles presenting new data analysis methods claim that “the new method performs better than existing methods,” but the veracity of such statements is questionable. Our manuscript discusses and illustrates consequences of the optimistic bias occurring during the evaluation of novel data analysis methods, that is, all biases resulting from, for example, selection of datasets or competing methods, better ability to fix bugs in a preferred method, and selective reporting of method variants. We quantitatively investigate this bias using an example from epigenetic analysis: normalization methods for data generated by the Illumina HumanMethylation450K BeadChip microarray.
Improving the performance of a radio-frequency localization system in adverse outdoor applications
Authors: de Sousa Marcelo N. , Sant’Ana Ricardo , Fernandes Rigel P. , Duarte Julio Cesar , Apolinário José A. , Thomä Reiner S. 
Published: May 2021

AbstractIn outdoor RF localization systems, particularly where line of sight can not be guaranteed or where multipath effects are severe, information about the terrain may improve the position estimate’s performance. Given the difficulties in obtaining real data, a ray-tracing fingerprint is a viable option. Nevertheless, although presenting good simulation results, the performance of systems trained with simulated features only suffer degradation when employed to process real-life data. This work intends to improve the localization accuracy when using ray-tracing fingerprints and a few field data obtained from an adverse environment where a large number of measurements is not an option. We employ a machine learning (ML) algorithm to explore the multipath information. We selected algorithms random forest and gradient boosting; both considered efficient tools in the literature. In a strict simulation scenario (simulated data for training, validating, and testing), we obtained the same good results found in the literature (error around 2 m). In a real-world system (simulated data for training, real data for validating and testing), both ML algorithms resulted in a mean positioning error around 100 ,m. We have also obtained experimental results for noisy (artificially added Gaussian noise) and mismatched (with a null subset of) features. From the simulations carried out in this work, our study revealed that enhancing the ML model with a few real-world data improves localization’s overall performance. From the machine ML algorithms employed herein, we also observed that, under noisy conditions, the random forest algorithm achieved a slightly better result than the gradient boosting algorithm. However, they achieved similar results in a mismatch experiment. This work’s practical implication is that multipath information, once rejected in old localization techniques, now represents a significant source of information whenever we have prior knowledge to train the ML algorithm.
Conducting national burden of disease studies in small countries in Europe– a feasible challenge?
Authors: Cuschieri Sarah , Pallari Elena , Terzic Natasa , Alkerwi Ala’a , Sigurvinsdottir Rannveig , Sigfusdottir Inga Dora , Devleesschauwer Brecht 
Published: May 2021

Abstract
Background
Burden of Disease (BoD) studies use disability-adjusted life years (DALYs) as a population health metric to quantify the years of life lost due to morbidity and premature mortality for diseases, injuries and risk factors occurring in a region or a country. Small countries usually face a number of challenges to conduct epidemiological studies, such as national BoD studies, due to the lack of specific expertise and resources or absence of adequate data. Considering Europe’s small countries of Cyprus, Iceland, Luxembourg, Malta and Montenegro, the aim was to assess whether the various national data sources identified are appropriate to perform national BoD studies.

Main body
The five small countries have a well-established mortality registers following the ICD10 classification, which makes calculation of years of life lost (YLL) feasible. A number of health information data sources were identified in each country, which can provide prevalence data for the calculation of years lived with disability (YLD) for various conditions. These sources include disease-specific registers, hospital discharge data, primary health care data and epidemiological studies, provided by different organisations such as health directorates, institutes of public health, statistical offices and other bodies. Hence, DALYs can be estimated at a national level through the combination of the YLL and YLD information.
On the other hand, small countries face unique challenges such as difficulty to ensure sample representativeness, variations in prevalence estimates especially for rarer diseases, existence of a substantial proportion of non-residents affiliated to healthcare systems and potential exclusion from some European or international initiatives.
Recently established BoD networks may provide a platform for small countries to share experiences, expertise, and engage with countries and institutions that have long-standing experience with BoD assessment.

Conclusion
Apart from mortality registries, adequate health data sources, notably for cancer, are potentially available at the small states to perform national BoD studies. Investing in sharing expert knowledge through engagement of researchers in BoD networks can enable the conduct of country specific BoD studies and the establishment of more accurate DALYs estimates. Such estimates can enable local policymakers to reflect on the relative burden of the different conditions that are contributing to morbidity and mortality at a country level.
Chronic political instability and HIV/AIDS response in Guinea-Bissau: a qualitative study
Authors: Galjour Joshua , Havik Philip J. , Aaby Peter , Rodrigues Amabelia , Hoemeke Laura , Deml Michael J. , Zhao Jinkou , Mpinga Emmanuel Kabengele 
Published: May 2021

AbstractBackgroundThe Republic of Guinea-Bissau in West Africa has a high HIV/AIDS disease burden and has experienced political instability in the recent past. Our study used qualitative methods to better understand key stakeholders’ perceptions of the effects of chronic political instability on the HIV/AIDS response in Guinea-Bissau from 2000 to 2015 and lessons learned for overcoming them.MethodsSeventeen semi-structured in-depth key informant interviews were conducted in Bissau, Guinea-Bissau in 2018. Interviews were recorded and transcribed verbatim, coded thematically, and analyzed inductively.ResultsFour themes emerged: (1) constantly start over; (2) the effects of instability rippling from central level throughout the health pyramid; (3) vulnerable populations becoming more vulnerable; and (4) coping mechanisms.ConclusionsStakeholders from government, civil society, and donor organizations have recognized instability’s effects as a barrier to mounting an effective local response to HIV/AIDS in Guinea-Bissau. To mitigate the effects of the country’s political instability on the health sector, concerted efforts should be made to strengthen the capacities of health officials within the Ministry of Health to shield them from the effects of the country’s political instability.Graphic abstract
Real-time and on-line monitoring of ethanol fermentation process by viable cell sensor and electronic nose
Authors: Feng Yao , Tian Xiwei , Chen Yang , Wang Zeyu , Xia Jianye , Qian Jiangchao , Zhuang Yingping , Chu Ju 
Published: May 2021

AbstractIn this study, introduction of a viable cell sensor and electronic nose into ethanol fermentation was investigated, which could be used in real-time and on-line monitoring of the amount of living cells and product content, respectively. Compared to the conventional off-line biomass determination, the capacitance value exhibited a completely consistent trend with colony forming units, indicating that the capacitance value could reflect the living cells in the fermentation broth. On the other hand, in comparison to the results of off-line determination by high-performance liquid chromatography, the ethanol concentration measured by electronic nose presented an excellent consistency, so as to realize the on-line monitoring during the whole process. On this basis, a dynamic feeding strategy of glucose guided by the changes of living cells and ethanol content was developed. And consequently, the ethanol concentration, productivity and yield were enhanced by 15.4%, 15.9% and 9.0%, respectively. The advanced sensors adopted herein to monitor the key parameters of ethanol fermentation process could be readily extended to an industrial scale and other similar fermentation processes.
Perinatal exposure to tetracycline contributes to lasting developmental effects on offspring
Authors: Hill Elizabeth M. , Howard Christopher D. , Bale Tracy L. , Jašarević Eldin 
Published: May 2021

Abstract
Background
For more than 30 years, the tetracycline on/off system of inducible gene expression has been leveraged to study disease mechanisms across many research areas, especially that of metabolism and neuroscience. This system requires acute or chronic exposure to tetracycline derivatives, such as doxycycline, to manipulate gene expression in a temporal and tissue-specific manner, with exposure often being restricted to gestational and early developmental windows. Despite evidence showing that early life antibiotic exposure has adverse effects on gut microbiota, metabolism, physiology, immunity and behavior, little is known regarding the lasting impact of doxycycline treatment on relevant outcomes in experimental offspring.

Results
To examine the hypothesis that early life doxycycline exposure produces effects on offspring growth, behavior, and gut microbiota, we employed the most commonly used method for tetracycline on/off system by administering a low dose of doxycycline (0.5 mg/ml) in the drinking water to C57Bl/6J and C57BL/6J:129S1/SvImJ dams from embryonic day 15.5 to postnatal day 28. Developmental exposure to low dose doxycycline resulted in significant alterations to growth trajectories and body weight in both strains, which persisted beyond cessation of doxycycline exposure. Developmental doxycycline exposure influenced offspring bacterial community assembly in a temporal and sex-specific manner. Further, gut microbiota composition failed to recover by adulthood, suggesting a lasting imprint of developmental antibiotic exposure.

Conclusions
Our results demonstrated that early life doxycycline exposure shifts the homeostatic baseline of prior exposed animals that may subsequently impact responses to experimental manipulations. These results highlight the gut microbiota as an important factor to consider in systems requiring methods of chronic antibiotic administration during pregnancy and critical periods of postnatal development.
Differential gene expression analysis of ankylosing spondylitis shows deregulation of the HLA-DRB, HLA-DQB, ITM2A, and CTLA4 genes
Authors: AlEjielat Rowan , Khaleel Anas , Tarkhan Amneh H. 
Published: May 2021

Abstract
Background
Ankylosing spondylitis (AS) is a rare inflammatory disorder affecting the spinal joints. Although we know some of the genetic factors that are associated with the disease, the molecular basis of this illness has not yet been fully elucidated, and the genes involved in AS pathogenesis have not been entirely identified. The current study aimed at constructing a gene network that may serve as an AS gene signature and biomarker, both of which will help in disease diagnosis and the identification of therapeutic targets. Previously published gene expression profiles of 16 AS patients and 16 gender- and age-matched controls that were profiled on the Illumina HumanHT-12 V3.0 Expression BeadChip platform were mined. Patients were Portuguese, 21 to 64 years old, were diagnosed based on the modified New York criteria, and had Bath Ankylosing Spondylitis Disease Activity Index scores > 4 and Bath Ankylosing Spondylitis Functional Index scores > 4. All patients were receiving only NSAIDs and/or sulphasalazine. Functional enrichment and pathway analysis were performed to create an interaction network of differentially expressed genes.

Results
ITM2A, ICOS, VSIG10L, CD59, TRAC, and CTLA-4 were among the significantly differentially expressed genes in AS, but the most significantly downregulated genes were the HLA-DRB6, HLA-DRB5, HLA-DRB4, HLA-DRB3, HLA-DRB1, HLA-DQB1, ITM2A, and CTLA-4 genes. The genes in this study were mostly associated with the regulation of the immune system processes, parts of cell membrane, and signaling related to T cell receptor and antigen receptor, in addition to some overlaps related to the IL2 STAT signaling, as well as the androgen response. The most significantly over-represented pathways in the data set were associated with the “RUNX1 and FOXP3 which control the development of regulatory T lymphocytes (Tregs)” and the “GABA receptor activation” pathways.

Conclusions
Comprehensive gene analysis of differentially expressed genes in AS reveals a significant gene network that is involved in a multitude of important immune and inflammatory pathways. These pathways and networks might serve as biomarkers for AS and can potentially help in diagnosing the disease and identifying future targets for treatment.
Cone beam computed tomography for evaluation of mandibular lingual canal in an Egyptian subpopulation
Authors: Elmasry Rabab Amin , El-Fotouh Mona Mahmoud Abu , el Sadat Shaimaa Mohamed Abu , Aboelmaaty Wael 
Published: May 2021

Abstract
Background
A sample of three hundred cone beam computed tomography (CBCT) scans was evaluated. Median lingual canals (MLC) were identified and classified according to their anatomical location. Evaluation of the canal diameter, length, thickness of the buccal cortical plate, and the remaining bone above and below the canal was performed. The results were assessed twice with 2 weeks interval and statistically analyzed. The study was designed to evaluate MLC in an Egyptian subpopulation by the use of CBCT.

Results
Most of the scans presented with one MLC, with a maximum number of four canals, the mean diameter was 1.68± 1.27 mm, with a statistically significant difference in the length from the canal opening to the alveolar crest between females and males.

Conclusions
As the study detected a high prevalence of the MLC with a vast majority of the canals supra-spinosum, a vigilant examination is required using CBCT to avoid subsequent bleeding and airway obstruction.
Cogito, ergo praedico(I think, therefore I predict)
Authors: Lepping Peter 
Published: May 2021

SUMMARYI comment on a new overview of the treatment of delusional infestation. I focus on the challenges of communicating with a patient who has delusions and evaluate practical advice. I look at philosophical models to explain those communication problems as well as theories of delusional formation, and examine how these may help clinicians to understand and overcome those challenges.