bluuebunny/crossref_metadata_2025 huggingface dataset:
White Matter Integrity Predicts Electrical Stimulation (tDCS) and Language Therapy Effects in Primary Progressive Aphasia
Authors: Zhao Yi , Ficek Bronte , Webster Kimberly , Frangakis Constantine , Caffo Brian , Hillis Argye E. , Faria Andreia , Tsapkini Kyrana
Published: December 2020

Background

Transcranial direct current stimulation (tDCS), in conjunction with language therapy, improves language therapy outcomes in primary progressive aphasia (PPA). However, no studies show whether white matter integrity predicts language therapy or tDCS effects in PPA.

Objective

We aimed to determine whether white matter integrity, measured by diffusion tensor imaging (DTI), predicts written naming/spelling language therapy effects (letter accuracy on trained and untrained words) with and without tDCS over the left inferior frontal gyrus (IFG) in PPA.

Methods

Thirty-nine participants with PPA were randomly assigned to tDCS or sham condition, coupled with language therapy for 15 daily sessions. White matter integrity was measured by mean diffusivity (MD) and fractional anisotropy (FA) in DTI scans before therapy. Written naming outcomes were evaluated before, immediately after, 2 weeks, and 2 months posttherapy. To assess tDCS treatment effect, we used a mixed-effects model with treatment evaluation and time interaction. We considered a forward model selection approach to identify brain regions/fasciculi of which white matter integrity can predict improvement in performance of word naming.

Results

Both sham and tDCS groups significantly improved in trained items immediately after and at 2 months posttherapy. Improvement in the tDCS group was greater and generalized to untrained words. White matter integrity of ventral language pathways predicted tDCS effects in trained items whereas white matter integrity of dorsal language pathways predicted tDCS effects in untrained items.

Conclusions

White matter integrity influences both language therapy and tDCS effects. Thus, it holds promise as a biomarker for deciding which patients will benefit from language therapy and tDCS.
The Diagnostic Value of p16/Ki67 Dual Immunostaining for Anal Intraepithelial Neoplasia: A Meta-Analysis
Authors: Chen Cheng-Chieh , Hsueh Kuan-Chun , Shen Cheng-Huang , Bai Chyi-Huey , Wu Chia-Chang , Wang Yuan-Hung
Published: December 2020

The p16/Ki67 dual immunostaining was performed on anal cytology specimens; this is an anal cancer screening method. A literature search was performed in the BioMed Central, Cochrane Library, Embase, Google Scholar, and PubMed electronic databases for relevant articles. We included studies that discussed the efficacy of p16/Ki67 dual immunostaining for detecting anal intraepithelial neoplasia (AIN). Studies that calculated the diagnostic efficacy on a per-patient basis were included. We excluded review articles, case series, and studies that did not provide sufficient information. We extracted data on true positive, true negative, false positive, and false negative from the included studies to generate pooled sensitivity, specificity, and diagnostic odds ratio (DOR). All analyses were performed with a random-effects model using MetaDiSc 1.4 and MetaDTA. The meta-analysis produced a pooled sensitivity of 0.63 (95% CI: 0.34, 0.86) and specificity of 0.65 (95% CI: 0.46, 0.81) for p16/Ki67 dual immunostaining in detecting AIN. The pooled DOR was 3.26 (95% CI: −0.29, 6.82). A subgroup analysis of HIV-infected men who have sex with men (MSM) demonstrated a pooled sensitivity of 0.75 (95% CI: 0.28, 0.96). p16/Ki67 dual immunostaining might have a higher sensitivity for detecting AIN in HIV-infected MSM. p16/Ki67 dual immunostaining might be more sensitive in HIV-infected MSM and has higher specificity compared to human papillomavirus testing among this high-risk group. p16/Ki67 dual immunostaining might be an adjuvant and potential triage test for anal cytology in anal cancer screening.
Natural flat cocoon materials constructed by eri silkworm with high strength and excellent anti-ultraviolet performance
Authors: Zhou Bin , Wang Huiling , Zhou Hongtao , Wang Ke , Wang Shudong
Published: December 2020

Eri silkworm is easy to be raised and has high cocoon yield, the cocoon fails to be continuously reeled due to a loose structure, a large part of cocoon coat and an eclosion hole. In this work, a fifth instar larvae of eri silkworm was provided with only a flat cocooning place to spin to produce a flat cocoon, it was fed with the castor leaves sprayed with nano-TiO2 and graphene oxide (GO), Compared with the flat cocoon obtained without nanomaterials, the silk was not found to change in morphology and structure significantly. Nanomaterials promoted the transformation of the random coil/α-helix conformation of the silk to the β-sheet conformation to a certain extent, which formed a stable crystallization. Thus its strength value could increase by 15%–17%, the ultraviolet protection factor ( UPF) value of the flat cocoon with nanomaterials increased significantly, and the silk obtained made up for the lack of the strength in natural eri silkworm silk and poor resistance to sunlight. The flat cocoon features a stable structure, good formation, uniform thickness, and manual control. It can be directly used as raw material for processing flat textile products, which provides a feasible idea for the high-value utilization of the eri silkworm cocoon.
Evaluation for machine tool components importance based on improved LeaderRank
Authors: Zhang Yingzhi , Liang Shubin , Liu Jialin , Cao Peilong , Luan Lan
Published: December 2020

The existence of the failure transitivity of machine tool components makes the fault transfer probability of components demonstrate dynamic time-variability, which affects the importance of components and further affects the machine maintenance cycle. Therefore, studying fault transfer probability and the importance of machine tool components is necessary. In this article, the fault transfer probability of component is defined according to component fault propagation directed graph and component independent fault and related fault model based on time correlation. Assuming that the fault propagation follows the Markov process, the improved LeaderRank algorithm is applied to evaluate the importance of components by introducing background node and calculating failure impact degree of component on the basis of out-degree. Finally, the specific application is verified by taking the fault information of a certain type of machine as an example.
Can Injuries Have a Lasting Effect on the Perception of Pain in Young, Healthy Women and Men?
Authors: Maciejewska-Skrendo Agnieszka , Pawlak Maciej , Leońska-Duniec Agata , Jurewicz Alina , Kaczmarczyk Mariusz , Cięszczyk Paweł , Leźnicka Katarzyna
Published: December 2020

Background:

Pain is a characteristic, unpleasant sensory and emotional experience associated with actual or potential tissue damage. Pain is a subjective sensation, modulated by many factors such as age, sex, emotional state, national origin, or physical activity. Moreover, it is closely associated with intense physical activity, injuries, and traumas, which can significantly modulate pain tolerance.

Hypothesis:

We postulate that there are correlations between past injuries, physical activity, and intensity of pain perception (pain threshold and pain tolerance) in a population of healthy men and women.

Study Design:

Retrospective cohort study.

Level of Evidence:

Level 4.

Methods:

A total of 302 participants aged 18 to 32 years were included. The participants were divided into 2 groups (active and inactive individuals), in accordance with the scope of physical activity they had indicated. The test of pressure pain threshold and pressure pain tolerance was performed using an algometer.

Results:

Active women achieved significantly higher pain threshold and pain tolerance values in all measurements on the upper limb (except for the pain threshold on the left hand) compared with inactive women. In mediation analysis, the effect of injury remained significant only for the pressure pain tolerance in the dominant arm and the left hand in the female group. In the case of men, there were no significant differences in all measurements in view of the threshold and tolerance for pain between the groups of active and inactive and between men with injuries and without injuries.

Conclusion:

Intense, regular physical activity is a factor modulating the perception of pain. This was demonstrated as lowered sensitivity to pain stimuli in a population of healthy women.

Clinical Relevance:

Injuries should be treated as an important factor modulating the perception of pain. We recommend detailed monitoring of injuries during treatment and control of pain sensation.
Glucocorticoids in Graves’ orbitopathy: mechanisms of action and clinical application
Authors: Längericht Jan , Krämer Irene , Kahaly George J.
Published: December 2020

Background:

Graves’ orbitopathy (GO) is the most frequent extrathyroidal manifestation of the autoimmune Graves’ disease. GO significantly impacts quality of life and has a psycho-social morbidity. Inflammation and swelling of the orbital tissue often leads to proptosis, diplopia, and decrease of visual acuity. Due to the inflammatory background of the disease, glucocorticoids (GC) have been used as a first-line treatment for decades.

Methods:

PubMed and MeSH database were searched for original articles, clinical trials, reviews, and meta-analyses published between 1 January 2000 and 31 March 2020 and pertaining to both the mechanism of action and immunological effects of GC as well as to the treatment of GO by GC. The publications were evaluated according to their setting and study design.

Results:

GC act through genomic (trans-activation and trans-repression) and rapid non-genomic mechanisms. GC in general, and the intravenous (IV) administration of GC in particular, markedly decrease the activity and number of the most potent antigen-presenting dendritic cells. According to the internationally acknowledged European Thyroid Association Guidelines for the management of GO, weekly IVGC application over 12 weeks is recommended as first-line treatment for patients with active and severe GO. The daily and cumulative dose should be tailored according to clinical severity, for example, 4.5 g of IV methylprednisolone for the inflammatory component versus 7.5 g in the presence of diplopia and severe proptosis. Fast and significant improvements in orbital symptoms and signs are noted in 65–70% of patients. Long-term experience over decades, and worldwide availability at low cost, underline the clinical and therapeutic relevance of GC. Adverse events are rarely severe, dose-dependent, and usually reversible, hence easy to handle by medical investigators. Oral GC application on a daily basis is characterized by high bioavailability but reduced efficacy and increased toxicity.

Conclusion:

IVGC still represents the standard of care in active/severe GO. Innovative biologicals, like monoclonal antibodies targeting the thyrotropin/Insulin-like growth factor-1 receptors or pro-inflammatory cytokines (e.g., Interleukin-6) should be compared with standard GC treatment with respect to short- and long-term efficacy, safety, costs, and global availability.
Normal is not normative: Public relations indicators from a Spanish secondary political and economic region
Authors: Costa-Sánchez Carmen , Túñez-López Miguel , Míguez-González María-Isabel
Published: December 2020

The aim of this study is to analyze the state of communication in Galicia, as an example of a peripheral environment, and to determine to what extent it corresponds to the patterns indicated in different studies for the Spanish case and for the whole of Europe. A quantitative technique was used, consisting of the distribution of an online questionnaire, via e-mail, to three groups: communication officers from companies, communication managers from public institutions, and agencies offering communication and public relations services. Trends point to limited communication planning and to some impact of the economic crisis in terms of danger (budget cuts, especially in the case of agencies) and opportunity (increased need for measurements to justify investments). In addition, actions considered most needed within 5 years converge as a result of globalization: online communication and social media management are priority goals for diverse organizational profiles. However, the degree of awareness of strategic communication is higher in the institutional sector than in the corporate sector, since its use has been linked to the development of political communication management.
Adoption and Implementation of Clinical Legal Education Programmes in the Indonesian Legal Education System
Authors: Arifin Saru , Wedhatami Bayangsari , Alkadri Riska
Published: December 2020

Legal education in Indonesia has followed a traditional model, focusing on the rote transfer of legal doctrine. Students are taught legal theories and sources of law but not how to critically apply the law in concrete real-world scenarios. Consequently, law graduates tend to be unprepared for the workforce, which is a regular complaint of employers. To overcome this impediment, some law faculties in Indonesia adopted clinical legal education (CLE) as a ‘new method’ in the legal education system, whereby students not just learn theory but also gain practical legal experience. This article analyses the adoption of the model and methods of applying CLE to legal education in Indonesia. This study uses the doctrinal research method with a qualitative approach. It is found that the adoption of CLE in Indonesia is diverse; some programmes include it in the core curriculum, while others make it an extracurricular activity. CLE programmes generally use three of six methods, namely street law, advocacy and internship. The differences in the three methods of CLE directly influence their success, exposing participants to interaction with live clients, public speaking and networking. This article recommends that in order to achieve the optimal implementation of CLE, uniformity of the CLE adoption model in Indonesia’s legal education curriculum is needed.
FiberWire vs FiberTape: Comparison of Bacterial Adherence in a Murine Air Pouch Wound Model
Authors: Blumenthal Allison M. , Bou-akl Therese , Rossi Mario D. , Wu Bin , Ren Wei-Ping , Markel David C.
Published: December 2020

Background:

For high–tensile strength sutures, past research has largely focused on mechanical properties or bacterial adherence across various manufacturers.

Purpose:

This study investigated high-tensile strength sutures with different shapes but otherwise identical composition. The purpose was to evaluate the differences between high–tensile strength suture wire and suture tape relative to bacterial adherence and bacterial retention after washout.

Study Design:

Controlled laboratory study.

Methods:

Sutures were implanted in dorsal air pouches of 72 BALB/cJ mice. Experimental pouches were inoculated with Staphylococcus aureus; no bacteria were used in the control conditions. The mice were randomized into 3 groups: group 1 underwent suture extraction 7 days after implantation; group 2 underwent an irrigation procedure, followed by immediate suture extraction on day 7; and group 3 underwent an irrigation procedure on day 7, with delayed suture extraction on day 14 after implantation. The sutures were evaluated using confocal microscopy; electron microscopy; and spectrophotometry, through which optical density, as measured by the amount of scattered light, is directly correlated with the number of bacteria. Histological assessment was performed on the pouches.

Results:

Optical density (mean ± SD) was significantly higher for FiberTape sutures than for FiberWire sutures, respectively, at the 2-hour time point for all groups (group 1, 0.0550 ± 0.0081 vs 0.0162 ± 0.006 [ P = .0054]; group 2, 0.0225 ± 0.0049 vs 0.0056 ± 0.0006 [ P = .0045]; group 3, 0.055 ± 0.0222 vs 0.0043 ± 0.0005 [ P = .0103]). Additionally, groups 2 and 3 showed statistically significant results at the 4-hour time points (group 2, 0.0384 ± 0.0087 vs 0.0145 ± 0.0042 [ P = .0280]; group 3, 0.0532 ± 0.0159 vs 0.0101 ± 0.0025 [ P = .0058]). The wash fluid also demonstrated significantly greater optical density for the FiberTape than the FiberWire sutures, respectively, at the 2-hour time point for all groups (group 1, 0.1657 ± 0.0319 vs 0.0317 ± 0.008 [ P = .0063]; group 2, 0.0522 ± 0.0156 vs 0.0127 ± 0.0022 [ P = .0219]; group 3, 0.1707 ± 0.0205 vs 0.0191 ± 0.0053 [ P < .0001]). No bacterial growth occurred in the control conditions. Histological assessment revealed only mild inflammation in the control groups as compared with more severe responses in the experimental groups at all time points.

Conclusion:

FiberTape was associated with increased bacterial adhesion as well as retention as compared with FiberWire in an in vivo murine wound model.

Clinical Relevance:

This study demonstrates that suture design influences the occurrence of and ability to clear surgical infection and must be considered when selecting high-tensile strength sutures in a clinical setting.
Orphanage Trafficking and Child Protection in Emergencies in Nepal: A Comparative Analysis of the 2015 Earthquake and the 2020 COVID-19 Pandemic
Authors: Punaks Martin , Lama Samjyor
Published: December 2020

This article compares and contrasts two humanitarian emergencies and their impact on Nepal: these are the Nepal earthquake in 2015 and the COVID-19 pandemic in 2020. It explains how each emergency has impacted children without parental care or at risk of family separation, with specific reference to orphanage trafficking, voluntourism, child institutionalisation and family preservation. In relation to each emergency, the article considers the role of disaster preparedness; the roles of the Nepal government, the international community and civil society; and the significance of one emergency being localised, while the other is a global phenomenon. It also shows that while these emergencies have increased the risk of harm and exploitation for children and families, they have also driven forward innovation in child protection practices, particularly through the use of reintegration, case management and family preservation programmes.
The Role of Housing Finance Actors in Regenerating Delhi’s Unauthorised Colonies: An Examination of State–Citizen– Market Boundaries
Authors: Naik Mukta , Kunduri Eesha
Published: December 2020

Semi-formal settlements like Delhi’s unauthorised colonies (UACs), which await regularisation by the state, are characterised by aspirations for housing improvements and enhanced property values. Frustrated by the rigid regulatory frameworks that operate in the binaries of legal/illegal, formal/informal, planned/unplanned and having limited influence over processes of regularisation, UAC residents use ‘transversal logics’ (Caldeira, 2017) to negotiate planning regimes, credit markets and local politics to improve housing, which become their ‘action space’ to meet aspirations for social mobility. This article investigates the role of finance and networks of credit in autoconstruction, with a focus on the work of market actors in navigating market–citizen and market–state boundaries, foregrounded against the relatively well-studied politics of state–citizen relations. It finds that landowners and housing finance institutions, as well as actors within them, navigate regulatory boundaries through innovative partnerships and creative workarounds, and by strategically deploying collective and individual identities. Even as cities like Delhi endeavour to become planned world-class utopias, a multitude of actors continue to reshape the city’s peripheral landscapes through the assertion, dissolution and spanning of multiple boundaries—regulatory, individual–collective, state–citizen, citizen–market and state–market.
Male recombination map of the autosomal genome in German Holstein
Authors: Qanbari Saber , Wittenburg Dörte
Published: December 2020

Background

Recombination is a process by which chromosomes are broken and recombine to generate new combinations of alleles, therefore playing a major role in shaping genome variation. Recombination frequencies ($$\theta$$θ) between markers are used to construct genetic maps, which have important implications in genomic studies. Here, we report a recombination map for 44,696 autosomal single nucleotide polymorphisms (SNPs) according to the coordinates of the most recent bovine reference assembly. The recombination frequencies were estimated across 876 half-sib families with a minimum number of 39 and maximum number of 4236 progeny, comprising over 367 K genotyped German Holstein animals.

Results

Genome-wide, over 8.9 million paternal recombination events were identified by investigating adjacent markers. The recombination map spans 24.43 Morgan (M) for a chromosomal length of 2486 Mbp and an average of ~ 0.98 cM/Mbp, which concords with the available pedigree-based linkage maps. Furthermore, we identified 971 putative recombination hotspot intervals (defined as$$\theta$$θ > 2.5 standard deviations greater than the mean). The hotspot regions were non-uniformly distributed as sharp and narrow peaks, corresponding to ~ 5.8% of the recombination that has taken place in only ~ 2.4% of the genome. We verified genetic map length by applying a likelihood-based approach for the estimation of recombination rate between all intra-chromosomal marker pairs. This resulted in a longer autosomal genetic length for male cattle (25.35 cM) and in the localization of 51 putatively misplaced SNPs in the genome assembly.

Conclusions

Given the fact that this map is built on the coordinates of the ARS-UCD1.2 assembly, our results provide the most updated genetic map yet available for the cattle genome.
Analysis of readability and structural accuracy in SNOMED CT
Authors: Abad-Navarro Francisco , Quesada-Martínez Manuel , Duque-Ramos Astrid , Fernández-Breis Jesualdo Tomás
Published: December 2020

Background

The increasing adoption of ontologies in biomedical research and the growing number of ontologies available have made it necessary to assure the quality of these resources. Most of the well-established ontologies, such as the Gene Ontology or SNOMED CT, have their own quality assurance processes. These have demonstrated their usefulness for the maintenance of the resources but are unable to detect all of the modelling flaws in the ontologies. Consequently, the development of efficient and effective quality assurance methods is needed.

Methods

Here, we propose a series of quantitative metrics based on the processing of the lexical regularities existing in the content of the ontology, to analyse readability and structural accuracy. The readability metrics account for the ratio of labels, descriptions, and synonyms associated with the ontology entities. The structural accuracy metrics evaluate how two ontology modelling best practices are followed: (1) lexically suggest locally define (LSLD), that is, if what is expressed in natural language for humans is available as logical axioms for machines; and (2) systematic naming, which accounts for the amount of label content of the classes in a given taxonomy shared.

Results

We applied the metrics to different versions of SNOMED CT. Both readability and structural accuracy metrics remained stable in time but could capture some changes in the modelling decisions in SNOMED CT. The value of the LSLD metric increased from 0.27 to 0.31, and the value of the systematic naming metric was around 0.17. We analysed the readability and structural accuracy in the SNOMED CT July 2019 release. The results showed that the fulfilment of the structural accuracy criteria varied among the SNOMED CT hierarchies. The value of the metrics for the hierarchies was in the range of 0–0.92 (LSLD) and 0.08–1 (systematic naming). We also identified the cases that did not meet the best practices.

Conclusions

We generated useful information about the engineering of the ontology, making the following contributions: (1) a set of readability metrics, (2) the use of lexical regularities to define structural accuracy metrics, and (3) the generation of quality assurance information for SNOMED CT.
Modeling clinical activities based on multi-perspective declarative process mining with openEHR’s characteristic
Authors: Xu Haifeng , Pang Jianfei , Yang Xi , Yu Jinghui , Li Xuemeng , Zhao Dongsheng
Published: December 2020

Background

It is significant to model clinical activities for process mining, which assists in improving medical service quality. However, current process mining studies in healthcare pay more attention to the control flow of events, while the data properties and the time perspective are generally ignored. Moreover, classifying event attributes from the view of computers usually are difficult for medical experts. There are also problems of model sharing and reusing after it is generated.

Methods

In this paper, we presented a constraint-based method using multi-perspective declarative process mining, supporting healthcare personnel to model clinical processes by themselves. Inspired by openEHR, we classified event attributes into seven types, and each relationship between these types is represented in a Constrained Relationship Matrix. Finally, a conformance checking algorithm is designed.

Results

The method was verified in a retrospective observational case study, which consists of Electronic Medical Record (EMR) of 358 patients from a large general hospital in China. We take the ischemic stroke treatment process as an example to check compliance with clinical guidelines. Conformance checking results are analyzed and confirmed by medical experts.

Conclusions

This representation approach was applicable with the characteristic of easily understandable and expandable for modeling clinical activities, supporting to share the models created across different medical facilities.
A partial encryption algorithm for medical images based on quick response code and reversible data hiding technology
Authors: Li Jian , Zhang Zelin , Li Shengyu , Benton Ryan , Huang Yulong , Kasukurthi Mohan Vamsi , Li Dongqi , Lin Jingwei , Borchert Glen M. , Tan Shaobo , Li Gang , Ma Bin , Yang Meihong , Huang Jingshan
Published: December 2020

Background

Medical image data, like most patient information, have a strong requirement for privacy and confidentiality. This makes transmitting medical image data, within an open network, problematic, due to the aforementioned issues, along with the dangers of data/information leakage. Possible solutions in the past have included the utilization of information-hiding and image-encryption technologies; however, these methods can cause difficulties when attempting to recover the original images.

Methods

In this work, we developed an algorithm for protecting medical image key regions. Coefficient of variation is first employed to identify key regions, a.k.a. image lesion areas; then additional areas are processed as blocks and texture complexity is analyzed. Next, our novel reversible data-hiding algorithm embeds lesion area contents into a high-texture area, after which an Arnold transformation is utilized to protect the original lesion information. After this, we use image basic information ciphertext and decryption parameters to generate a quick response (QR) code used in place of original key regions.

Results

The approach presented here allows for the storage (and sending) of medical image data within open network environments, while ensuring only authorized personnel are able to recover sensitive patient information (both image and meta-data) without information loss.

Discussion

Peak signal to noise ratio and the Structural Similarity Index measures show that the algorithm presented in this work can encrypt and restore original images without information loss. Moreover, by adjusting the threshold and the Mean Squared Error, we can control the overall quality of the image: the higher the threshold, the better the quality and vice versa. This allows the encryptor to control the amount of degradation as, at appropriate amounts, degradation aids in the protection of the image.

Conclusions

As shown in the experimental results, the proposed method allows for (a) the safe transmission and storage of medical image data, (b) the full recovery (no information loss) of sensitive regions within the medical image following encryption, and (c) meta-data about the patient and image to be stored within and recovered from the public image.
Quality assurance and enrichment of biological and biomedical ontologies and terminologies
Authors: Agrawal Ankur , Cui Licong
Published: December 2020

Biological and biomedical ontologies and terminologies are used to organize and store various domain-specific knowledge to provide standardization of terminology usage and to improve interoperability. The growing number of such ontologies and terminologies and their increasing adoption in clinical, research and healthcare settings call for effective and efficient quality assurance and semantic enrichment techniques of these ontologies and terminologies. In this editorial, we provide an introductory summary of nine articles included in this supplement issue for quality assurance and enrichment of biological and biomedical ontologies and terminologies. The articles cover a range of standards including SNOMED CT, National Cancer Institute Thesaurus, Unified Medical Language System, North American Association of Central Cancer Registries and OBO Foundry Ontologies.
Exosomal miR-126 blocks the development of non-small cell lung cancer through the inhibition of ITGA6
Authors: Li Mingjun , Wang Qianqian , Zhang Xiaofei , Yan Ningning , Li Xingya
Published: December 2020

Background

Exosomes, emerging mediators of intercellular communication, are reported to transfer certain non-coding RNAs, such as microRNAs (miRNAs), which play a crucial role in cancer progression. The objective of this study was to determine the function of exosomal miR-126 and provide a novel mechanism of miR-126 action in NSCLC.

Methods

The morphology of exosomes was identified by transmission electron microscope (TEM), and the exosomal surface markers were quantified by western blot. The expression of miR-126 and integrin alpha-6 (ITGA6) mRNA was measured by quantitative real-time polymerase chain reaction (qRT-PCR), and ITGA6 protein expression was determined by western blot. For functional analyses, cell proliferation was assessed by colony formation assay and MTT assay. Cell cycle and cell apoptosis were monitored using flow cytometry assay. Cell migration and invasion were determined by transwell assay. ITGA6 was predicted as a target of miR-126 by bioinformatics analysis, which was verified by dual-luciferase reporter assay. The role of exosomal miR-126 in vivo was determined by Xenograft tumor models.

Results

NSCLC serum-derived exosomes harbored low expression of miR-126 and promoted NSCLC cell proliferation, cell cycle progression, cell migration and invasion. NSCLC serum-derived exosomes loaded with miR-126 mimic inhibits NSCLC cell proliferation, colony formation, migration and invasion but induced cell cycle arrest and apoptosis. Besides, exosomal miR-126 also blocked tumor growth in vivo. In mechanism, ITGA6 was a target of miR-126, and exosomal miR-126 weakened these NSCLC cell malignant behaviors and inhibited tumor growth by degrading the expression of ITGA6.

Conclusion

Exosomal miR-126 blocked the progression of NSCLC through the mediation of its target gene ITGA6, and exosomal miR-126 might be used as a promising biomarker for NSCLC therapy.
Coagulation abnormalities in SARS-CoV-2 infection: overexpression tissue factor
Authors: Eslamifar Zahra , Behzadifard Mahin , Soleimani Masoud , Behzadifard Saba
Published: December 2020

Among the pathways and mediators that may be dysregulated in COVID-19 infection, there are proinflammatory cytokines, lymphocyte apoptosis, and the coagulation cascade. Venous and arterial thromboembolisms also are frequent in COVID-19 patients with the increased risk of some life-threatening complications such as pulmonary embolism, myocardial infarction, and ischemic stroke. In this regard, overproduction of proinflammatory cytokines such as IL-6, IL-1β, and TNF-α induce cytokine storms, increase the risk of clot formation, platelet activation, and multiorgan failure that may eventually lead to death among these patients. Surface S protein of SARS-CoV-2 binds to its target transmembrane receptor, named as angiotensin converting enzyme 2 (ACE2(, on various cells such as lymphocyte, alveolar cells, monocytes/macrophages, and platelets. Notably, the activation of the coagulation cascade occurs through tissue factor (TF)/FVIIa-initiated hemostasis. Accordingly, TF plays the major role in the activation of coagulation system during viral infection. In viral infections, the related coagulopathy multiple factors such as inflammatory cytokines and viral specific TLRs are involved, which consequently induce TF expression aberrantly. SARS-COV-2 may directly infect monocytes/ macrophages. In addition, TF expression/release from these cells may play a critical role in the development of COVID-19 coagulopathy. In this regard, the use of TF- VIIa complex inhibitor may reduce the cytokine storm and mortality among COVID-19 patients.
Myeloid-derived suppressor cells therapy enhance immunoregulatory properties in acute graft versus host disease with combination of regulatory T cells
Authors: Park Min-Jung , Baek Jin-Ah , Kim Se-Young , Jung Kyung-Ah , Choi Jeong Won , Park Sung-Hwan , Kwok Seung‐Ki , Cho Mi-La
Published: December 2020

Background

Myeloid-derived suppressor cells (MDSCs) play a critical role in modulating the immune response and promoting immune tolerance in models of autoimmunity and transplantation. Regulatory T cells (Tregs) exert therapeutic potential due to their immunomodulatory properties, which have been demonstrated both in vitro and in clinical trials. Cell-based therapy for acute graft-versus-host disease (aGVHD) may enable induction of donor-specific tolerance in the preclinical setting.

Methods

We investigated whether the immunoregulatory activity of the combination of MDSCs and Tregs on T cell and B cell subset and alloreactive T cell response. We evaluated the therapeutic effects of combined cell therapy for a murine aGVHD model following MHC-mismatched bone marrow transplantation. We compared histologic analysis from the target tissues of each groups were and immune cell population by flow cytometric analysis.

Results

We report a novel approach to inducing immune tolerance using a combination of donor-derived MDSCs and Tregs. The combined cell-therapy modulated in vitro the proliferation of alloreactive T cells and the Treg/Th17 balance in mice and human system. Systemic infusion of MDSCs and Tregs ameliorated serverity and inflammation of aGVHD mouse model by reducing the populations of proinflammatory Th1/Th17 cells and the expression of proinflammatory cytokines in target tissue. The combined therapy promoted the differentiation of allogeneic T cells toward Foxp3 + Tregs and IL-10-producing regulatory B cells. The combination treatment control also activated human T and B cell subset.

Conclusions

Therefore, the combination of MDSCs and Tregs has immunomodulatory activity and induces immune tolerance to prevent of aGVHD severity. This could lead to the development of new clinical approaches to the prevent aGVHD.
Corticosteroid use in COVID-19 patients: a systematic review and meta-analysis on clinical outcomes
Authors: van Paassen Judith , Vos Jeroen S. , Hoekstra Eva M. , Neumann Katinka M. I. , Boot Pauline C. , Arbous Sesmu M.
Published: December 2020

Background

In the current SARS-CoV-2 pandemic, there has been worldwide debate on the use of corticosteroids in COVID-19. In the recent RECOVERY trial, evaluating the effect of dexamethasone, a reduced 28-day mortality in patients requiring oxygen therapy or mechanical ventilation was shown. Their results have led to considering amendments in guidelines or actually already recommending corticosteroids in COVID-19. However, the effectiveness and safety of corticosteroids still remain uncertain, and reliable data to further shed light on the benefit and harm are needed.

Objectives

The aim of this systematic review and meta-analysis was to evaluate the effectiveness and safety of corticosteroids in COVID-19.

Methods

A systematic literature search of RCTS and observational studies on adult patients was performed across Medline/PubMed, Embase and Web of Science from December 1, 2019, until October 1, 2020, according to the PRISMA guidelines. Primary outcomes were short-term mortality and viral clearance (based on RT-PCR in respiratory specimens). Secondary outcomes were: need for mechanical ventilation, need for other oxygen therapy, length of hospital stay and secondary infections.

Results

Forty-four studies were included, covering 20.197 patients. In twenty-two studies, the effect of corticosteroid use on mortality was quantified. The overall pooled estimate (observational studies and RCTs) showed a significant reduced mortality in the corticosteroid group (OR 0.72 (95%CI 0.57–0.87). Furthermore, viral clearance time ranged from 10 to 29 days in the corticosteroid group and from 8 to 24 days in the standard of care group. Fourteen studies reported a positive effect of corticosteroids on need for and duration of mechanical ventilation. A trend toward more infections and antibiotic use was present.

Conclusions

Our findings from both observational studies and RCTs confirm a beneficial effect of corticosteroids on short-term mortality and a reduction in need for mechanical ventilation. And although data in the studies were too sparse to draw any firm conclusions, there might be a signal of delayed viral clearance and an increase in secondary infections.
Nothobranchius annual killifishes
Authors: Terzibasi Tozzini Eva , Cellerino Alessandro
Published: December 2020

Annual fishes of the genus Nothobranchius inhabit ephemeral habitats in Eastern and Southeastern Africa. Their life cycle is characterized by very rapid maturation, a posthatch lifespan of a few weeks to months and embryonic diapause to survive the dry season. The speciesN. furzeriholds the record of the fastest-maturing vertebrate and of the vertebrate with the shortest captive lifespan and is emerging as model organism in biomedical research, evolutionary biology, and developmental biology. Extensive characterization of age-related phenotypes in the laboratory and of ecology, distribution, and demography in the wild are available. Species/populations from habitats differing in precipitation intensity show parallel evolution of lifespan and age-related traits that conform to the classical theories on aging. Genome sequencing and the establishment of CRISPR/Cas9 techniques made this species particularly attractive to investigate the effects genetic and non-genetic intervention on lifespan and aging-related phenotypes. At the same time, annual fishes are a very interesting subject for comparative approaches, including genomics, transcriptomics, and proteomics. TheN. furzericommunity is highly diverse and rapidly expanding and organizes a biannual meeting.
Quantum simulations of light-matter interactions in arbitrary coupling regimes
Authors: Lamata L.
Published: December 2020

Light-matter interactions are an established field that is experiencing a renaissance in recent years due to the introduction of exotic coupling regimes. These include the ultrastrong and deep-strong coupling regimes, where the coupling constant is smaller and of the order of the frequency of the light mode, or larger than this frequency, respectively. In the past few years, quantum simulations of light-matter interactions in all possible coupling regimes have been proposed and experimentally realized, in quantum platforms such as trapped ions, superconducting circuits, cold atoms, and quantum photonics. We review this fledgling field, illustrating the benefits and challenges of the quantum simulations of light-matter interactions with quantum technologies.
MorbiNet Study: Hypothyroidism Comorbidity Networks in the Adult General Population
Authors: Moratalla-Navarro Ferran , Moreno Victor , López-Simarro Flora , Aguado Alba
Published: December 2020

Purpose

Multimorbidity impacts quality of life. We constructed hypothyroidism comorbidity networks to identify positive and negative associations with other prevalent diseases.

Methods

We analyzed data of 285 342 patients with hypothyroidism from 3 135 948 adults with multimorbidity in a population-based study in Catalonia, Spain, (period: 2006-2017). We constructed hypothyroidism comorbidity networks using logistic regression models, adjusted by age and sex, and for men and women separately. We considered relevant associations those with odds ratios (OR) >1.2 or <0.8 and P value < 1e-5 to identify coexistence greater (or smaller) than the expected by the prevalence of diseases. Multivariate models considering comorbidities were used to further adjust OR values.

Results

The conditions associated included larynx cancer (adjusted OR: 2.48), congenital anomalies (2.26), thyroid cancer (2.13), hyperthyroidism (1.66), vitamin B12/folate deficiency anemia (1.57), and goiter (1.56). The network restricted to men had more connections (mental, cardiovascular, and neurological) and stronger associations with thyroid cancer (7.26 vs 2.55), congenital anomalies (5.11 vs 2.13), hyperthyroidism (4.46 vs 1.69), larynx cancer (3.55 vs 1.67), and goiter (3.94 vs 1.64). After adjustment for comorbidities, OR values were more similar in men and women. The strongest negative associations after adjusting for comorbidities were with HIV/AIDS (OR: 0.71) and tobacco abuse (0.77).

Conclusions

Networks show direct and indirect hypothyroidism multimorbidity associations. The strongest connections were thyroid and larynx cancer, congenital anomalies, hyperthyroidism, anemia, and goiter. Negative associations included HIV/AIDS and tobacco abuse. The network restricted to men had more and stronger associations, but not after adjusting for comorbidities, suggesting important indirect interactions.
Revisiting the Complexity of GLP-1 Action from Sites of Synthesis to Receptor Activation
Authors: McLean Brent A , Wong Chi Kin , Campbell Jonathan E , Hodson David J , Trapp Stefan , Drucker Daniel J
Published: December 2020

Glucagon-like peptide-1 (GLP-1) is produced in gut endocrine cells and in the brain, and acts through hormonal and neural pathways to regulate islet function, satiety, and gut motility, supporting development of GLP-1 receptor (GLP-1R) agonists for the treatment of diabetes and obesity. Classic notions of GLP-1 acting as a meal-stimulated hormone from the distal gut are challenged by data supporting production of GLP-1 in the endocrine pancreas, and by the importance of brain-derived GLP-1 in the control of neural activity. Moreover, attribution of direct vs indirect actions of GLP-1 is difficult, as many tissue and cellular targets of GLP-1 action do not exhibit robust or detectable GLP-1R expression. Furthermore, reliable detection of the GLP-1R is technically challenging, highly method dependent, and subject to misinterpretation. Here we revisit the actions of GLP-1, scrutinizing key concepts supporting gut vs extra-intestinal GLP-1 synthesis and secretion. We discuss new insights refining cellular localization of GLP-1R expression and integrate recent data to refine our understanding of how and where GLP-1 acts to control inflammation, cardiovascular function, islet hormone secretion, gastric emptying, appetite, and body weight. These findings update our knowledge of cell types and mechanisms linking endogenous vs pharmacological GLP-1 action to activation of the canonical GLP-1R, and the control of metabolic activity in multiple organs.
A nova cartografia abissal após a promulgação da Lei 13.465/2017: análise das modificações promovidas em matéria de regularização fundiária urbana de interesse social / The new abyssal cartography after the promulgation of Law No 13.465/2017: analysis of modifications promoted concerning urban land regularization of social interest
Authors: Almeida Marcos Felipe Lopes de , Rosa Waleska Marcy
Published: December 2020

ResumoO presente trabalho busca analisar as modificações promovidas pela Lei nº 13.465/2017 em comparação com a Lei revogada nº 11.977/2009, no que tange à regularização fundiária urbana de interesse social, cujos beneficiários são populações de baixa renda. Assim, a partir da metodologia de análise documental das referidas leis e da proposição teórica do pensamento abissal, cunhada por Boaventura de Sousa Santos, traçam-se inferências com objetivo de averiguar se a linha abissal jurídica ganhou uma nova configuração com a promulgação do referido diploma normativo. Além disso, abordam-se a composição do direito à moradia adequada, que não se resume à garantia de uma casa para morar, e sua compatibilidade com o novo paradigma de regularização fundiária urbana de interesse social. Por fim, verifica-se que a Lei 13.465/2017 priorizou a formalização da propriedade, em detrimento da urbanização e da oferta de serviços públicos, implicando em um aprofundamento da linha abissal. Portanto, a contribuição do trabalho reside, então, na compreensão da repercussão das mudanças legislativas no direito à moradia adequada e no enfrentamento às desigualdades sociais.Palavras-chave: Regularização fundiária; Direito à moradia adequada; Pensamento abissal;Legalização; Urbanização. AbstractThis paper seeks to analyze the modifications promoted by the law n. 13.465/2017 in comparison with the revoked law n. 11.977/2009, regarding the urban land regularization of social interest, whose beneficiaries are low-income communities. Using the documental analysis methodology on referred laws and the theoretical proposal of abyssal thinking, by Boaventura de Sousa Santos, inferences are built with the purpose to investigate if the law’s abyssal line got a different configuration after the promulgation of the new legal framework. Besides, the composition of the right to adequate housing, which is not limited to the guarantee of a house for living, and its compatibility with the new paradigm of urban land regularization of social interest are described. Finally, it is concluded that law n. 13.465/2017 prioritized the formalization of property, instead of the urbanization and the provision of public services, implying a deepening of the abyssal line. Therefore, the paper’s contribution is understanding the repercussion of legislative modifications in the right to adequate housing and in the confrontation of social inequalities.Keywords: Land regularization; Right to adequate housing; Abyssal thinking; Legalization; Urbanization.