bluuebunny/crossref_metadata_2025 huggingface dataset:
Incretin-Based Therapies Role in COVID-19 Era: Evolving Insights
Authors: Stoian Anca Pantea , Papanas Nikolaos , Prazny Martin , Rizvi Ali A. , Rizzo Manfredi
Published: July 2020

The current coronavirus disease 2019 (COVID-19) pandemic has led the scientific community to breach new frontiers in the understanding of human physiology and disease pathogenesis. It has been hypothesized that the human dipeptidyl peptidase 4 (DPP4) enzyme receptor may be a functional target for the spike proteins of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Since DPP4-inhibitors are currently used for the treatment of patients with type-2 diabetes (T2DM), there is currently high interest in the possibility that these agents, or incretin-based therapies (IBTs) in general, may be of benefit against the new coronavirus infection. Diabetes is associated with increased COVID-19 severity and mortality, and accumulating evidence suggests that IBTs may favorably alter the clinical course of SARS-CoV-2 infection due to their inherent mechanisms of action. Further research into prognostic variables associated with various antidiabetic treatment regimens, and in particular the IBT, in patients with T2DM affected by the COVID-19 pandemic is therefore warranted.
Model-free vibration control based on a virtual controlled object considering actuator uncertainty
Authors: Yonezawa Ansei , Kajiwara Itsuro , Yonezawa Heisei
Published: July 2020

The purpose of this research is to construct a simple and practical controller design method, considering the actuator’s parameter uncertainty, without using a model of controlled objects. In this method, a controller is designed with an actuator model including a single-degree-of-freedom virtual structure inserted between actuator and controlled object, resulting in a model-free controller design. Furthermore, an [Formula: see text] control problem is defined so that the actuator’s parameter uncertainty is compensated by satisfying a robust stability condition. Because the actuator model including the virtual controlled object is a simple low-order system, and the actuator’s parameter uncertainty is considered, a controller with high robustness to the actuator’s parameter uncertainty can be designed based on traditional model-based control theory. The effectiveness of the proposed method is verified by both simulation and experiment.
Toxicology Paradise: Sorting Out Adverse and Non-adverse Findings in Animal Toxicity Studies
Authors: Baldrick Paul , Cosenza Mary Ellen , Alapatt Tessie , Bolon Brad , Rhodes Melissa , Waterson Ian
Published: July 2020

A challenge for all toxicologists is defining what study findings are actually adverse versus non-adverse in animal toxicity studies, and which ones are relevant for generating a no observed adverse effect level (NOAEL) to assess human risk. This article presents views on this challenge presented by toxicologists, toxicologic pathologists, and regulatory reviewers at the 2019 annual meeting of the American College of Toxicology during a workshop entitled “Toxicology Paradise: Sorting Out Adverse and Non-adverse Findings.” The speakers noted that setting a NOAEL is not always straightforward, not only for small molecules but also for biopharmaceuticals, and that a “weight of evidence” approach often is more useful than a rigid threshold-setting algorithm. Regulators from the US Food and Drug Administration and European Union told how assessment of adverse nonclinical findings is undertaken to allow clinical studies to commence and drug marketing approvals to succeed, along with the process that allows successful dialogs with regulators. Nonclinical case studies of findings judged to be adverse versus non-adverse were presented in relation to the many factors that might halt or delay clinical development. The process of defining adverse findings and the NOAEL in final study reports was discussed, as well as who should be involved in the process.
Phacoemulsification in vitrectomized eyes: Maintaining the stability of the anterior chamber via a new technique
Authors: Li Xinxin , Li Qiumei , Bano Shazia , Li Shaowei
Published: July 2020

Fluctuating anterior chamber depth and reverse pupillary block are the most common problems encountered during phacoemulsification following pars plana vitrectomy in cases of cataracts. The sudden deepening of the anterior chamber makes the surgical procedure more cumbersome and increases the risk of intraoperative complications. To solve this problem, we describe a method of balancing the pressure of the anterior and posterior chamber by using a syringe with a flushing needle to inject balanced salt solution into the posterior chamber via the gap between the iris and the anterior capsule of the lens. This technique is especially suitable for complicated cataracts following previous pars plana vitrectomy and high myopia-complicated cataracts. This technique yielded promising results in reducing the difficulties that occur during surgical procedures, reduced the risk of intraoperative complications and simplified the intraocular lens implantation.
Microbiological spectrum of microbial keratitis in patients presenting with nasolacrimal duct obstruction
Authors: Sharma Supriya , Sahu Srikant K , Rath Suryasnata , Mallick Aparajita , Sharma Savitri , Das Sujata
Published: July 2020

Purpose:

To study the type of bacteria and their antibiotic susceptibility pattern from corneal scrapings of patients with infectious keratitis presenting with concurrent nasolacrimal duct obstruction.

Methods:

A retrospective analysis was carried out of patients with microbial keratitis and co-existing nasolacrimal duct obstruction during a 5-year period (January 2012 to December 2016). Antibiotic susceptibility profile data was collected from the microbiology records.

Results:

The study included 56 (M:F = 33:23; OD:OS = 34:22) eyes. The mean age of patients was 60.2 ± 12.3 years. Microscopic examination of corneal scrapings showed 52% of gram-positive ( n = 29/55) and 2% of multiple (>1; n = 1/55) bacteria. Streptococcus pneumoniae (32%, n = 18/56), coagulase-negative Staphylococcus (25%, n = 14/56), and Staphylococcus aureus (11%, n = 6/56) were the most common bacteria. Streptococcus pneumoniae was found to be susceptible to ciprofloxacin (72.2%), ofloxacin (94.4%), gatifloxacin (61.1%), and moxifloxacin (83.3%).

Conclusion:

Corneal infection associated with nasolacrimal duct obstruction is commonly caused by gram-positive-bacteria. Irrigation of nasolacrimal duct should be mandatory test in microbial keratitis. The gram-positive bacteria isolated showed maximum susceptibility to vancomycin and cefazolin. Early treatment by surgery and appropriate medical management is recommended for its control.
Experimental evaluation of the tensile bonding strength of the basalt fiber-reinforced polymer–concrete interface
Authors: Chhorn Buntheng , Jung WooYoung
Published: July 2020

The bonding performance of basalt fiber-reinforced polymer and concrete substrate has a significant effect on the reliability of externally strengthened existing concrete structure, due to being the most vulnerable element to failure in this fiber-reinforced polymer–concrete strengthening system. Its failure can result in the failure of the whole structure. Although many previous researchers have been interested in the tensile bonding strength of carbon fiber-reinforced polymer and glass fiber-reinforced polymer–concrete interface, that of basalt fiber-reinforced polymer–concrete interface has been very limited. Thus, the objective of this study is to experimentally assess the tensile bonding strength of the basalt fiber-reinforced polymer–concrete interface. The effects of high temperature, freezing–thawing cycles, type of resin, and concrete crack widths on the tensile bonding strength are also investigated. The pull-off experiment is conducted according to ASTM D7522/D7522M-15. A total of 205 core specimens of 50 mm diameter and 10 mm depth were taken from 41 concrete beams. The experimental results illustrate that both freezing–thawing and high-temperature condition have a substantial effect on the bonding strength of the basalt fiber-reinforced polymer–concrete interface. Bonding strength was decreased within the range of about 9%–30% when the number of freezing–thawing cycles increases from 100 to 300; likewise, it was decreased up to 30% when the exposure temperature rises to 200°C. Also, the specimens which were repaired to close their cracks by epoxy resin had no significant effect on the bonding strength of basalt fiber-reinforced polymer–concrete interface, when the specimens had crack width of less than 1.5 mm.
Attribution and attributional processes of organizations’ environmental messages
Authors: Shin Sumin , Ki Eyun-Jung
Published: July 2020

This experimental study, guided by attribution theory, investigated the impact of the substantiation and specificity of organizations’ environmental messages on perceived communication motivation and how this perception prompts audiences’ affective and cognitive responses. Findings showed that specific messages increased perceived intrinsic motivation, whereas vague messages increased perceived extrinsic motivation; in turn, perceived intrinsic motive positively influenced audiences’ message attitude, organization attitude, message credibility, organization credibility, and organization’s green image, whereas perceived extrinsic motive negatively influenced these aspects.
Does a comic style informed assent form improve comprehension for minors participating in clinical trials?
Authors: Ferrer-Albero Cristina , Díez-Domingo Javier
Published: July 2020

Background

Several authors have shown that children and adolescents have limited understanding of critical elements of the research studies in which they are participating. The inclusion of graphic elements is a promising approach to increase the understandability of assent forms of clinical trials.

Objectives

To design a new assent form in comic strip format for minors participating in clinical trials and to compare the comprehension of this new document with a traditional assent form.

Methods

This study included an assessment of the readability of standard informed assents, the evaluation of the comprehension of one of these documents, the development of a new (comic format) informed assent from the original document previously evaluated, and the analysis of readability and comprehension of the new informed assent. The readability of the documents was assessed using previously validated formulas, whereas comprehension analyses were performed through a questionnaire taken by two groups of 12-year-old students of secondary schools. Ethical considerations: All procedures involving human participants were in accordance with the ethical standards of the 1964 Helsinki Declaration and its later amendments.

Findings

Compared with the original document, the comic assent form improved the grammatical readability of the “Aims, Risks and Benefits and How to Get More Information” sections, the comprehension scores in the Aims and Procedure sections, the understanding of ideas, and the formation of macro-ideas. The benefits of the comic strip format were more noticeable among participants in the lower percentiles of the comprehension score.

Conclusions

Our results show that the comic assent form has high readability and comprehensibility compared with its original form, particularly in the domains of knowledge-based inferences and macro-ideas formation. The use of forms that combine text and comic strips may help the comprehension of minors participating of a clinical trial, supporting their autonomy in decision-making.
Impact of a Multimodal and Combination Therapy on Self-Regulation and Internal Coherence in German Breast Cancer Survivors With Chronic Cancer-Related Fatigue: A Mixed-Method Comprehensive Cohort Design Study
Authors: Mehl Annette , Reif Marcus , Zerm Roland , Pranga Danilo , Friemel Dorothea , Berger Bettina , Brinkhaus Benno , Gutenbrunner Christoph , Büssing Arndt , Kröz Matthias
Published: July 2020

Background: Recent studies have proved the relevance of salutogenetic variables for fatigue management in breast cancer survivors with cancer-related fatigue (CRF). This comprehensive cohort design study is the first to examine the impact of 2 multimodal therapies, multimodal therapy (MT) and combined therapy (CT), compared with standard aerobic training (AT) on salutogenetic variables (self-regulation and internal coherence) and distress in breast cancer survivors with CRF. Methods: A total of 105 patients started the therapies and n = 84 completed the Self-regulation Scale, the Internal Coherence Scale, the Cancer Fatigue Scale, and the Hospital Anxiety and Depression Scale at baseline, 10 weeks after treatment (T1) and n = 81 after 6 months (T2). Patient satisfaction and qualitative feedback regarding therapy quality was assessed at T1. A general linear model including allocation type, therapy arm (MT/CT/AT), and bias-adjusting propensity scores tested the superiority of both multimodal therapies versus AT for all questionnaires at T1 and T2. Results: MT and CT were superior to AT to improve self-regulation and patients’ satisfaction at T1. Additionally, CT showed superiority for self-regulation at T2 (all P < .05). Compared with AT, internal coherence was significantly higher for patients in the MT arms at T2, respectively (all P < .01). Pearson’s correlations between self-regulation, internal coherence, and CRF improved from baseline to T2 (Mean r = −0.60). Qualitative feedback confirmed patients’ benefits in several health-related categories. Conclusions: Self-regulation and internal coherence are manipulable variables with relevant CRF associations. They can be positively affected by multimodal therapies. Alongside patients’ satisfaction and qualitative feedback they help refine treatment.
Exosomes derived from synovial fibroblasts under hypoxia aggravate rheumatoid arthritis by regulating Treg/Th17 balance
Authors: Ding Yanjie , Wang Laifang , Wu Huiqiang , Zhao Qing , Wu Shufang
Published: July 2020

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic destructive joint disease. To date, the etiology and pathogenesis of RA have not been fully elucidated, but a large number of studies have indicated that hypoxia is an important feature of RA. Our study was designed to probe how hypoxia-induced exosome (exo) derived from synovial fibroblasts (SFs) affect RA. In this study, we found that hypoxic environment existed in synovial tissue of RA, and miR-424 expression was increased in RA, and exosome derived from synovial fibroblasts (SFs-exo) could significantly induce T cells differentiation, which Th17 cells increased and Treg cells decreased. Besides, SFs-exo affected the expression of related inflammatory cytokines. And, we also found that FOXP3 was a target gene of miR-424 and exo-miR-424 KD inhibited RA worsening. These results suggested that SFs-exo in hypoxia aggravates rheumatoid arthritis by regulating Treg/Th17 balance and thus may be a potential therapeutic target for RA.

Impact statement

A comparative study of osteoarthritis (OA) and RA mice was implemented to suggest that miR-424 expression was increased in RA, and exosome-miR-424 derived from synovial fibroblasts (SFs-exo) could significantly induce T cells differentiation in which Th17 cells increased and Treg cells decreased via targeting FOXP3. And thus, miR-424 may be a potential therapeutic target for RA.
Resistance to immune checkpoint inhibitors in non-small cell lung cancer: biomarkers and therapeutic strategies
Authors: Walsh Robert J. , Soo Ross A.
Published: July 2020

The treatment landscape for patients with advanced non-small cell lung cancer has evolved greatly with the advent of immune checkpoint inhibitors. However, many patients do not derive benefit from checkpoint blockade, developing either primary or secondary resistance, highlighting a need for alternative approaches to modulate immune function. In this review, we highlight the absence of a common definition of primary and secondary resistance and summarize their frequency and clinical characteristics. Furthermore, we provide an overview of the biomarkers and mechanisms of resistance involving the tumor, the tumor microenvironment and the host, and suggest treatment strategies to overcome these mechanisms and improve clinical outcomes.
Peak overpressure and impulse due to diffraction over a cylinder and/or multi-reflection of a shock wave in structural design- Part I
Authors: Hahn Andreas , Mensinger Martin , Rutner Marcus
Published: July 2020

The design and planning of structural components, such as columns, to resist blast loads is a complex task. Often standard free-field blast loads, specified in design codes or other literature, are used for the analysis of the object. These loads are then further increased or decreased depending on the topology of the surrounding geometry (Mach-Stem), the shape of the impacted object itself, and blast wave reflection. However, most of these research works focus purely on the assessment of the structural components itself, ignoring a complex fluid mechanics phenomenon such as diffraction, which is of particular interest when circular columns are standing next to each other or placed in front of a façade. The article addresses three main topics. First, the article answers the question whether the area behind the column is protected, meaning constituting a shadowed area. We present findings that the close area behind a column is subjected to higher pressure and impulse values as there would be without the column. Hence, the incident pressure sees significant pressure buildup due to diffraction. This pressure buildup is quantified using pressure increase factors and presented together with the accompanying impulse. Second, this pressure buildup is of relevance for realistic design of a façade behind the column, which is not covered in current design codes at all. We discuss relevant parameters in the design process. Third, directly coupled with the assessment of the pressure buildup behind the column due to diffraction is the assessment of pressure and impulse in the area behind the column due to multi-wave reflection at a façade, leading to a significant pressure and impulse scale-up, which might be relevant for design of a column and/or a façade. This article identifies gaps in understanding diffraction and subsequent multi-reflection of blast wave within a structural design framework and provides insights on how to establish safe design accounting for these effects.
Iliac May-Thurner syndrome coexisting with arteriovenous fistula treated by endovascular therapy
Authors: Shima Yuki , Shimada Takenobu , Tanaka Hiroyuki , Kadota Kazushige
Published: July 2020

An 82-year-old woman presented with persistent left leg swelling despite 3 months anticoagulation for deep vein thrombosis. Ultrasound showed venous blood flowing back into the toe. Enhanced computed tomography scans and angiography showed occlusion of the left common iliac vein and a large number of arteriovenous fistulas. We made a diagnosis of May-Thurner syndrome coexisting with arteriovenous fistulas and we performed endovascular therapy only for the common iliac vein. We considered embolization for arteriovenous fistulas, but it seemed to be difficult to perform because of the possibility of development of collateral circulation and a large number of arteriovenous fistulas. After percutaneous balloon angioplasty, antegrade venous blood flow was restored, and stent implantation was not performed. After the procedure, swelling of the leg gradually reduced. She had no symptoms for the following 1 year.
Gastrointestinal bleeding in patients with pancreatic cancer: Causes and haemostatic treatments
Authors: Aguilera Munoz Lina , de Mestier Louis , Lamallem Hanah , Jaïs Bénédicte , Maire Frédérique , Lévy Philippe , Rebours Vinciane , Hammel Pascal
Published: July 2020

Background

Gastrointestinal bleeding is a rare but severe complication of pancreatic ductal adenocarcinoma.

Objective

The purpose of this study was to describe the causes and treatments of non‐postoperative gastrointestinal bleeding in patients with pancreatic ductal adenocarcinoma, and explore the parameters associated with therapeutic effectiveness.

Methods

This was a single‐centre observational retrospective study (2000–2017) with data collected from the prospectively coded diagnostic hospital’s database system including patients with pancreatic ductal adenocarcinoma who had a gastrointestinal bleeding episode. Effectiveness of haemostatic treatment was assessed according to transfusion requirements and immediate and long‐term haemostatic efficacy; the latter defined as no bleeding recurrence.

Results

The population included 72 patients with pancreatic ductal adenocarcinoma who had 94 episodes of gastrointestinal bleeding. The main causes of gastrointestinal bleeding were gastroduodenal tumour invasion (56.4%) and oesophageal variceal bleeding due to left‐sided portal hypertension (19.1%). In cases of gastrointestinal bleeding caused by tumour invasion, the main treatment was therapeutic endoscopy (41.5%). Among patients who had gastrointestinal bleeding by tumour invasion treated by endoscopy or radiation therapy, haemostatic immediate efficacy rates were 70.6% and 100%, respectively. Bleeding recurrence rates were 35.3% and 25.0%, for patients treated by endoscopy or radiation therapy, respectively, for a first episode of gastrointestinal bleeding by tumour invasion. Transfusion requirements, before and after treatment, were not different in patients treated by haemostatic radiation therapy for gastrointestinal bleeding by tumour invasion compared to other treatments (odds ratio 0.3, 95% CI (0.06–1.59); p  = 0.16). The median survival after all‐cause gastrointestinal bleeding was 2.72 months (1.43–4.01).

Conclusion

Gastroduodenal tumour invasion was the main cause of gastrointestinal bleeding in patients with pancreatic ductal adenocarcinoma; haemostatic radiation therapy is a potential interesting option for gastrointestinal bleeding treatment in this context.
Sociodemographic Predictors of HIV Infection among Pregnant Women in Botswana: Cross-Sectional Study at 7 Health Facilities
Authors: Hamda Shimeles Genna , Tshikuka Jose Gaby , Joel Dipesalema , Monamodi Gotsileene , Masupe Tiny , Setlhare Vincent
Published: July 2020

Objectives:

To determine the prevalence and sociodemographic predictors of HIV among pregnant women in Botswana.

Methods:

This was a cross-sectional study of randomly enrolled women aged 18 to 49 years, attending 7 health facilities in Botswana. Data were gathered from November 2017 to March 2018 and analyzed using SPSS version 24.

Result:

Of the 429 women enrolled, 407 (96.4%) were included in the analysis. The HIV prevalence was 17%; 69 of 407 (95% CI: 13.4- 21.0). Women aged 35 to 49 years had higher HIV prevalence than those 18 to 24 years (adjusted odds ratio [AOR] = 6.2; 95% CI: 2.7-14.4). Illiterate and elementary school educated women had higher HIV prevalence than those with a tertiary education (AOR = 8.5; 95% CI: 1.8-39.1). Those with a history of alcohol intake had a higher HIV prevalence than those without (AOR = 2.6; 95% CI: 1.3-5.3).

Conclusion:

HIV prevalence was lower than it was in 2011. Age, level of education, and history of alcohol intake were strong predictors for HIV infection calling for targeted behavioral change interventions.
Naturally occurring hormones in foods and potential health effects
Authors: Palacios Orsolya M , Cortes Heather Nelson , Jenks Belinda H , Maki Kevin C
Published: July 2020

Hormones and hormone-like substances, for example, phytoestrogens, are food components that can be endogenously produced by a food source or occur secondary to farming practices. The hormone content of foods has been studied for decades, and safety evaluations in the United States and Europe indicate that naturally occurring hormones found in foods are safe for human consumption. More recent studies have focused on the role of certain hormones found in specific foods (e.g. dairy or soy) and their potential health effects. However, limited summaries exist on food content of hormones and hormone-like phytoestrogens in the context of a comprehensive US diet and implications, if any, of their daily consumption for overall health. This review provides an outline of hormone biosynthesis and functions in the body; discusses the more commonly studied, naturally occurring hormones in food and their biological role within food; estimates relative dietary contribution and when available, bioavailability, of naturally occurring food hormones; and summarizes the potential health associations of their intake in food. Based on the review of the scientific literature, the hormone content of typical serving sizes of commonly consumed foods is undetectable or in quantities that fall well within safety guidelines without any evidence for adverse effects on health.
Combination Antivascular Endothelial Growth Factor and Modified Panretinal Photocoagulation in Management of Proliferative Diabetic Retinopathy
Authors: Lu Amy Q. , Todorich Bozho
Published: July 2020

Purpose:

This work evaluates the effects of combined intravitreal antivascular endothelial growth factor (anti-VEGF) and modified panretinal photocoagulation (PRP) for management of proliferative diabetic retinopathy (PDR).

Methods:

This retrospective case series included 37 eyes of 33 patients with high-risk PDR. Anti-VEGF injections (≥ 2) were followed by modified, midperipheral PRP performed in 2 or more sessions. Visual and anatomic outcomes were tracked for 1 year after treatment. Regression analysis was performed for factors predictive of final outcomes.

Results:

Mean visual acuity (VA) at initial and final visit were 20/50 and 20/40 ( P = .22), respectively, over a mean follow-up duration of 341.4 days. Central foveal thickness decreased from 321.8 µm to 258.6 µm ( P = .01). Resolution of PDR was achieved in 94.6% of eyes, with 5.4% of eyes requiring additional anti-VEGF for persistent neovascularization. Final VA was significantly associated with baseline VA, VA at 1 month, and any adverse anatomical events. Treatment noncompliance was present in 24.3%; compliance decreased with increasing medical comorbidities, but was not significantly associated with final VA.

Conclusions:

Combination of anti-VEGF and modified PRP preserved VA and yielded PDR regression in the majority of eyes. This combination provides rapid PDR regression with anti-VEGF while achieving durable disease suppression in this real-world cohort without traditional PRP.
Breathing fresh air into respiratory research with single-cell RNA sequencing
Authors: Alexander Michael J. , Budinger G.R. Scott , Reyfman Paul A.
Published: July 2020

The complex cellular heterogeneity of the lung poses a unique challenge to researchers in the field. While the use of bulk RNA sequencing has become a ubiquitous technology in systems biology, the technique necessarily averages out individual contributions to the overall transcriptional landscape of a tissue. Single-cell RNA sequencing (scRNA-seq) provides a robust, unbiased survey of the transcriptome comparable to bulk RNA sequencing while preserving information on cellular heterogeneity. In just a few years since this technology was developed, scRNA-seq has already been adopted widely in respiratory research and has contributed to impressive advancements such as the discoveries of the pulmonary ionocyte and of a profibrotic macrophage population in pulmonary fibrosis. In this review, we discuss general technical considerations when considering the use of scRNA-seq and examine how leading investigators have applied the technology to gain novel insights into respiratory biology, from development to disease. In addition, we discuss the evolution of single-cell technologies with a focus on spatial and multi-omics approaches that promise to drive continued innovation in respiratory research.
Defining a role for exercise training in the management of asthma
Authors: Freeman Anna T. , Staples Karl J. , Wilkinson Tom M.A.
Published: July 2020

The prevalence of asthma remains high worldwide, with increasing awareness of the morbidity and mortality from asthma in low-income countries. In the UK, despite the development of biological treatments, many patients remain suboptimally controlled, and mortality rates have been static for decades. Therefore, new approaches are needed to treat asthma that are scalable at minimal cost. Exercise immunology is an expanding field, and there is growing evidence that exercise can modulate inflammatory and immune processes in asthma. Whilst exercise is encouraged in current treatment guidelines, there are no specific recommendations as to the intensity, frequency or duration of exercise exposure. Despite national and international guidance to increase exercise, patients with asthma are less likely to engage in physical activity. This review explores the disease modifying benefit of exercise in asthma. We also review the domains in which exercise exerts positive clinical effects in asthma, including the effects of exercise on symptom scores, quality of life, psychosocial health, and in the obese asthma phenotype. Finally, we review the barriers to exercise in asthma, given the benefits it confers. A better understanding of the mechanisms through which exercise exerts its positive effects in asthma may provide more accurate prescription of exercise training programmes as part of broader asthma management, with the potential of identification of new drug targets.
Evaluation of the effect of the mouth gag use on optic nerve sheath diameter of pediatric patients undergoing tonsillectomy or Adenotonsillectomy: An observational study
Authors: Altiparmak Başak , Korkmaz Toker Melike , Uysal Ali İhsan , Köseoğlu Sabri , Gümüş Demirbilek Semra
Published: July 2020

Background

A mouth gag is usually used during tonsillectomy and adenotonsillectomy surgeries, cleft palate repair, obstructive sleep apnea surgery, and intraoral tumor excision. The placement of the gag causes hemodynamic changes similar to laryngoscopy. The aim of this study was to evaluate the effect of mouth gag placement on the optic nerve sheath diameter (ONSD) of pediatric patients. The secondary aim was to assess the relationship between neck extension and changes in ONSD.

Methods

The trial was prospectively registered to the Australian New Zealand Clinical Trials Registry (Trial ID: ACTRN12618000551291) on 12.04.2018. This prospective, observational study was performed in a tertiary university hospital operating room between 01.05.2018–01.07.2018. Thirty-five children aged < 18 years, with ASA I status, who were scheduled for tonsillectomy and adenotonsillectomy surgeries were prospectively included in the study. Measurements of ONSD were performed (T0) after induction of anesthesia, (T1) after endotracheal intubation, (T2) after mouth gag placement, and (T3) 20 min after mouth gag placement. After the mouth gag was placed and the head was positioned for surgery, the degree of neck extension was calculated.

Results

All participants completed the study. There were significant differences in ONSD values at time points T1, T2, and T3 (p < 0.001, CI: − 0.09,-0.05; p < 0.001, CI: − 0.09,-0.05; p < 0.001, CI: − 0.05,-0.02; respectively). The maximum increase in ONSD was after intubation (0.69 ± 0.06 mm) and immediately after mouth gag placement (0.67 ± 0.07 mm). ONSD values continued to increase 20 min after gag placement (0.36 ± 0.04). There was no relation between the degree of neck extension and ONSD values (β = 0.63, p = 0.715).

Conclusions

The use of a mouth gag causes significant increases in ONSD measurements of children. Therefore, attention to the duration of mouth gag placement should be considered during surgery.

Trial registration

The trial was prospectively registered to the Australian New Zealand Clinical Trials Registry (Trial ID: ACTRN12618000551291) on 12.04.2018.
Vascular function and cardiovascular risk in a HIV infected and HIV free cohort of African ancestry: baseline profile, rationale and methods of the longitudinal EndoAfrica-NWU study
Authors: Fourie Carla M. T. , Botha-Le Roux Shani , Smith Wayne , Schutte Aletta E. , Breet Yolandi , Mels Carina M. C. , Gafane-Matemane Lebo F. , Lammertyn Leandi , Uys Lisa , Burger Adele , Joseph Jitcy S. , Goswami Nandu , De Boever Patrick , Strijdom Hans
Published: July 2020

Background

People living with the Human Immunodeficiency Virus (PLHIV) have an increased susceptibility to develop non-communicable diseases such as cardiovascular disease (CVD). Infection with HIV contributes to the development of CVD independent of traditional risk factors, with endothelial dysfunction being the central physiological mechanism. While HIV-related mortality is declining due to antiretroviral treatment (ART), the number of deaths due to CVD is rising in South Africa - the country with the highest number of PLHIV and the world’s largest ART programme.

The EndoAfrica study was developed to determine whether HIV infection and ART are associated with cardiovascular risk markers and changes in vascular structure and function over 18 months in adults from different provinces of South Africa. This paper describes the rationale, methodology and baseline cohort profile of the EndoAfrica study conducted in the North West Province, South Africa.

Methods

In this case-control study, conducted between August 2017 and June 2018, 382 volunteers of African descent (276 women; 106 men), comprising of 278 HIV infected and 104 HIV free individuals were included. We measured health behaviours, a detailed cardiovascular profile, and performed biomarker analyses. We compared baseline characteristics, blood pressure, vascular function and biochemical markers between those infected and HIV free.

Results

At baseline, the HIV infected participants were older (43 vs 39 years), less were employed (21% vs 40%), less had a tertiary education (7% vs 16%) and their body mass index was lower (26 vs 29 kg/m2) than that of the HIV free participants. While the cardiovascular profile, flow-mediated dilation and pulse wave velocity did not differ, glycated haemoglobin was lower (p = 0.017) and total cholesterol, high density lipoprotein cholesterol, triglycerides, gamma-glutamyltransferase and tobacco use were higher (all p < 0.047) in PLHIV.

Conclusion

Despite PLHIV being older, preliminary cross-sectional analysis suggests that PLHIV being treated with ART do not have poorer endothelial or vascular function compared to the HIV free participants. More detailed analyses on the baseline and follow-up data will provide further clarity regarding the cardiovascular profile of South Africans living with HIV.
The immune-checkpoint HLA-G/ILT4 is involved in the regulation of VEGF expression in clear cell renal cell carcinoma
Authors: García Marcela , Palma Maria Belen , Verine Jerome , Miriuka Santiago , Inda Ana M. , Errecalde Ana L. , Desgrandchamps François , Carosella Edgardo D. , Tronik-Le Roux Diana
Published: July 2020

Background

Clear cell renal cell carcinoma (ccRCC), the most aggressive renal cancer, is characterized by early lymph node metastases and bad prognosis. Most therapies targeting advanced or metastatic ccRCC are based, as first-line treatment, on the administration of the vascular endothelial growth factor (VEGF) neutralizing antibody termed Bevacizumab. Despite proven benefits, the expected results were not obtained for the majority of patients. The possibility that an intricate interplay between angiogenesis and immune-checkpoints might exist lead us to evaluate tumor angiogenesis, by means of VEGF expression together with the immune checkpoint HLA-G/ILT4.

Methods

Tumor specimens were obtained from patients from two separate cohorts: One from “Evita Pueblo” Hospital from Berazategui, (Buenos Aires, Argentina) and the second includes patients surgically operated at the Urology Department of Saint-Louis Hospital (Paris, France) with a confirmed ccRCC diagnosis. Immunohistochemistry was performed with specific antibodies directed against HLA-G, VEGF-A, VEGF-C, D240, CD34, ILT4 and Ca-IX. In addition, gene expression levels were measured in a cell line derived from a ccRCC patient by semi-quantitative RT-PCR.

Results

Our results show that the highly vascularized tumors of ccRCC patients express high levels of VEGF and the immune-checkpoint HLA-G. In addition, ILT4, one of the HLA-G receptors, was detected on macrophages surrounding tumor cells, suggesting the generation of an immune-tolerant microenvironment that might favor tumorigenesis. Notably, RT-qPCR analysis provided the first evidence on the transcriptional relationship between HLA-G/ILT4 and the VEGF family. Namely, in the presence of HLA-G or ILT4, the levels of VEGF-A are diminished whereas those of VEGF-C are increased.

Conclusions

In an effort to find new therapeutic molecules and fight against metastasis dissemination associated with the poor survival rates of ccRCC patients, these findings provide the rationale for co-targeting angiogenesis and the immune checkpoint HLA-G.
A double-blind, randomized pilot study for comparison of Melissa officinalis L. and Lavandula angustifolia Mill. with Fluoxetine for the treatment of depression
Authors: Araj-Khodaei Mostafa , Noorbala Ahmad Ali , Yarani Reza , Emadi Fatemeh , Emaratkar Elham , Faghihzadeh Soghrat , Parsian Zahra , Alijaniha Fatemeh , Kamalinejad Mohammad , Naseri Mohsen
Published: July 2020

Background

Depression has rapidly progressed worldwide, and the need for an efficient treatment with low side effect has risen. Melissa officinalis L and Lavandula angustifolia Mill have been traditionally used in Asia for the treatment of depression. Many textbooks of traditional Persian medicine refer to these herbs for the treatment of depression while there are no adequate clinical trials to support this claim.

The present study aimed to evaluate the efficacy of M. officinalis and L. angustifolia compared to fluoxetine for the treatment of mild to moderate depression in an 8-week randomized, double-blind clinical trial.

Methods

Forty-five adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) for major depression, were randomly assigned to 3 groups to daily receive either M. officinalis (2 g) or L. angustifolia (2 g) or fluoxetine (20 mg) and were assessed in weeks 0, 2, 4 and 8 by the Hamilton Rating Scale for Depression (HAM-D) including 17 items.

Results

Our study showed that M. officinalis and L. angustifolia effect similar to fluoxetine in mild to moderate depression. (F = 0.131, df = 2,42, p = 0.877).

Conclusion

Due to some restrictions in this study including absence of placebo group, large-scale trials are needed to investigate the anti-depressant effect of these two herbs with more details.

Trial registration

IRCT2014061718126N1. Registration date: 2015-06-04-“Retrospectively registered”.
Epigenomics and genotype-phenotype association analyses reveal conserved genetic architecture of complex traits in cattle and human
Authors: Liu Shuli , Yu Ying , Zhang Shengli , Cole John B. , Tenesa Albert , Wang Ting , McDaneld Tara G. , Ma Li , Liu George E. , Fang Lingzhao
Published: July 2020

Background

Lack of comprehensive functional annotations across a wide range of tissues and cell types severely hinders the biological interpretations of phenotypic variation, adaptive evolution, and domestication in livestock. Here we used a combination of comparative epigenomics, genome-wide association study (GWAS), and selection signature analysis, to shed light on potential adaptive evolution in cattle.

Results

We cross-mapped 8 histone marks of 1300 samples from human to cattle, covering 178 unique tissues/cell types. By uniformly analyzing 723 RNA-seq and 40 whole genome bisulfite sequencing (WGBS) datasets in cattle, we validated that cross-mapped histone marks captured tissue-specific expression and methylation, reflecting tissue-relevant biology. Through integrating cross-mapped tissue-specific histone marks with large-scale GWAS and selection signature results, we for the first time detected relevant tissues and cell types for 45 economically important traits and artificial selection in cattle. For instance, immune tissues are significantly associated with health and reproduction traits, multiple tissues for milk production and body conformation traits (reflecting their highly polygenic architecture), and thyroid for the different selection between beef and dairy cattle. Similarly, we detected relevant tissues for 58 complex traits and diseases in humans and observed that immune and fertility traits in humans significantly correlated with those in cattle in terms of relevant tissues, which facilitated the identification of causal genes for such traits. For instance,PIK3CG, a gene highly specifically expressed in mononuclear cells, was significantly associated with both age-at-menopause in human and daughter-still-birth in cattle.ICAM, a T cell-specific gene, was significantly associated with both allergic diseases in human and metritis in cattle.

Conclusion

Collectively, our results highlighted that comparative epigenomics in conjunction with GWAS and selection signature analyses could provide biological insights into the phenotypic variation and adaptive evolution. Cattle may serve as a model for human complex traits, by providing additional information beyond laboratory model organisms, particularly when more novel phenotypes become available in the near future.
The roles of hybridization and habitat fragmentation in the evolution of Brazil’s enigmatic longwing butterflies, Heliconius nattereri and H. hermathena
Authors: Massardo Darli , VanKuren Nicholas W. , Nallu Sumitha , Ramos Renato R. , Ribeiro Pedro G. , Silva-Brandão Karina L. , Brandão Marcelo M. , Lion Marília B. , Freitas André V. L. , Cardoso Márcio Z. , Kronforst Marcus R.
Published: July 2020

Background

Heliconiusbutterflies are widely distributed across the Neotropics and have evolved a stunning array of wing color patterns that mediate Müllerian mimicry and mating behavior. Their rapid radiation has been strongly influenced by hybridization, which has created new species and allowed sharing of color patterning alleles between mimetic species pairs. While these processes have frequently been observed in widespread species with contiguous distributions, manyHeliconiusspecies inhabit patchy or rare habitats that may strongly influence the origin and spread of species and color patterns. Here, we assess the effects of historical population fragmentation and unique biology on the origins, genetic health, and color pattern evolution of two rare and sparsely distributed Brazilian butterflies,Heliconius hermathenaandHeliconius nattereri.

Results

We assembled genomes and re-sequenced whole genomes of eightH. nattereriand 71H. hermathenaindividuals. These species harbor little genetic diversity, skewed site frequency spectra, and high deleterious mutation loads consistent with recent population bottlenecks.Heliconius hermathenaconsists of discrete, strongly isolated populations that likely arose from a single population that dispersed after the last glacial maximum. Despite having a unique color pattern combination that suggested a hybrid origin, we found no genome-wide evidence thatH. hermathenais a hybrid species. However,H. hermathenamimicry evolved via introgression, from co-mimeticHeliconius erato, of a small genomic region upstream of the color patterning genecortex.

Conclusions

Heliconius hermathenaandH. nattereripopulation fragmentation, potentially driven by historical climate change and recent deforestation, has significantly reduced the genetic health of these rare species. Our results contribute to a growing body of evidence that introgression of color patterning alleles between co-mimetic species appears to be a general feature ofHeliconiusevolution.
Analysis of H3K4me3 and H3K27me3 bivalent promotors in HER2+ breast cancer cell lines reveals variations depending on estrogen receptor status and significantly correlates with gene expression
Authors: Kaukonen Damien , Kaukonen Riina , Polit Lélia , Hennessy Bryan T. , Lund Riikka , Madden Stephen F.
Published: July 2020

Background

The role of histone modifications is poorly characterized in breast cancer, especially within the major subtypes. While epigenetic modifications may enhance the adaptability of a cell to both therapy and the surrounding environment, the mechanisms by which this is accomplished remains unclear. In this study we focus on the HER2 subtype and investigate two histone trimethylations that occur on the histone 3; the trimethylation located at lysine 4 (H3K4me3) found in active promoters and the trimethylation located at lysine 27 (H3K27me3) that correlates with gene repression. A bivalency state is the result of the co-presence of these two marks at the same promoter.

Methods

In this study we investigated the relationship between these histone modifications in promoter regions and their proximal gene expression in HER2+ breast cancer cell lines. In addition, we assessed these patterns with respect to the presence or absence of the estrogen receptor (ER). To do this, we utilized ChIP-seq and matching RNA-seq from publicly available data for the AU565, SKBR3, MB361 and UACC812 cell lines. In order to visualize these relationships, we used KEGG pathway enrichment analysis, and Kaplan-Meyer plots.

Results

We found that the correlation between the three types of promoter trimethylation statuses (H3K4me3, H3K27me3 or both) and the expression of the proximal genes was highly significant overall, while roughly a third of all genes are regulated by this phenomenon. We also show that there are several pathways related to cancer progression and invasion that are associated with the bivalent status of the gene promoters, and that there are specific differences between ER+ and ER- HER2+ breast cancer cell lines. These specific differences that are differentially trimethylated are also shown to be differentially expressed in patient samples. One of these genes, HIF1AN, significantly correlates with patient outcome.

Conclusions

This study highlights the importance of looking at epigenetic markings at a subtype specific level by characterizing the relationship between the bivalent promoters and gene expression. This provides a deeper insight into a mechanism that could lead to future targets for treatment and prognosis, along with oncogenesis and response to therapy of HER2+ breast cancer patients.