bluuebunny/crossref_metadata_2025 huggingface dataset:
Innate lymphoid cells in isocyanate-induced asthma: role of microRNA-155
Authors: Blomme Evy E. , Provoost Sharen , Bazzan Erica , Van Eeckhoutte Hannelore P. , Roffel Mirjam P. , Pollaris Lore , Bontinck Annelies , Bonato Matteo , Vandenbroucke Louise , Verhamme Fien , Joos Guy F. , Cosio Manuel G. , Vanoirbeek Jeroen A. J. , Brusselle Guy G. , Saetta Marina , Maes Tania
Published: June 2020

Background

Occupational asthma, induced by workplace exposures to low molecular weight agents such as toluene 2,4-diisocyanate (TDI), causes a significant burden to patients and society. Little is known about innate lymphoid cells (ILCs) in TDI-induced asthma. A critical regulator of ILC function is microRNA-155, a microRNA associated with asthma.

Objective

To determine whether TDI exposure modifies the number of ILCs in the lung and whether microRNA-155 contributes to TDI-induced airway inflammation and hyperresponsiveness.

Methods

C57BL/6 wild-type and microRNA-155 knockout mice were sensitised and challenged with TDI or vehicle. Intracellular cytokine expression in ILCs and T-cells was evaluated in bronchoalveolar lavage (BAL) fluid using flow cytometry. Peribronchial eosinophilia and goblet cells were evaluated on lung tissue, and airway hyperresponsiveness was measured using the forced oscillation technique. Putative type 2 ILCs (ILC2) were identified in bronchial biopsies of subjects with TDI-induced occupational asthma using immunohistochemistry. Human bronchial epithelial cells were exposed to TDI or vehicle.

Results

TDI-exposed mice had higher numbers of airway goblet cells, BAL eosinophils, CD4+T-cells and ILCs, with a predominant type 2 response, and tended to have airway hyperresponsiveness. In TDI-exposed microRNA-155 knockout mice, inflammation and airway hyperresponsiveness were attenuated. TDI exposure induced IL-33 expression in human bronchial epithelial cells and in murine lungs, which was microRNA-155 dependent in mice. GATA3+CD3−cells, presumably ILC2, were present in bronchial biopsies.

Conclusion

TDI exposure is associated with increased numbers of ILCs. The proinflammatory microRNA-155 is crucial in a murine model of TDI asthma, suggesting its involvement in the pathogenesis of occupational asthma due to low molecular weight agents.
Minimal clinically important difference for asthma endpoints: an expert consensus report
Authors: Bonini Matteo , Di Paolo Marcello , Bagnasco Diego , Baiardini Ilaria , Braido Fulvio , Caminati Marco , Carpagnano Elisiana , Contoli Marco , Corsico Angelo , Del Giacco Stefano , Heffler Enrico , Lombardi Carlo , Menichini Ilaria , Milanese Manlio , Scichilone Nicola , Senna Gianenrico , Canonica Giorgio W.
Published: June 2020

Minimal clinically important difference (MCID) can be defined as the smallest change or difference in an outcome measure that is perceived as beneficial and would lead to a change in the patient's medical management.

The aim of the current expert consensus report is to provide a “state-of-the-art” review of the currently available literature evidence about MCID for end-points to monitor asthma control, in order to facilitate optimal disease management and identify unmet needs in the field to guide future research.

A series of MCID cut-offs are currently available in literature and validated among populations of asthmatic patients, with most of the evidence focusing on outcomes as patient reported outcomes, lung function and exercise tolerance. On the contrary, only scant and partial data are available for inflammatory biomarkers. These clearly represent the most interesting target for future development in diagnosis and clinical management of asthma, particularly in view of the several biologic drugs in the pipeline, for which regulatory agencies will soon require personalised proof of efficacy and treatment response predictors.
Towards an understanding of the burdens of medication management affecting older people: the MEMORABLE realist synthesis
Authors: Maidment Ian , Lawson Sally , Wong Geoff , Booth Andrew , Watson Anne , Zaman Hadar , Mullan Judy , McKeown Jane , Bailey Sylvia
Published: June 2020

Background

More older people are living in the community with multiple diagnoses and medications. Managing multiple medications produces issues of unrivalled complexity for those involved. Despite increasing literature on the subject, gaps remain in understanding how, why and for whom complex medication management works, and therefore how best to improve practice and outcomes. MEMORABLE, MEdication Management in Older people: Realist Approaches Based on Literature and Evaluation, aimed to address these gaps.

Methods

MEMORABLE used realism to understand causal paths within medication management. Informed by RAMESES (Realist And Meta-narrative Evidence Synthesis: and Evolving Standards) guidelines, MEMORABLE involved three overlapping work packages: 1) Realist Review of the literature (24 articles on medication management exploring causality); 2) Realist Evaluation (50 realist-informed interviews with older people, family carers and health and care practitioners, explaining their experiences); and 3) data synthesis and theorising from 1) and 2).

Results

Medication management was viewed from the perspective of ‘implementation’ and structured into five stages: identifying a problem (Stage 1), getting a diagnosis and/or medications (Stage 2), starting, changing or stopping medications (Stage 3), continuing to take medications (Stage 4), and reviewing/reconciling medications (Stage 5).

Three individual stages (1, 3 and 4) are conducted by the older person sometimes with family carer support when they balance routines, coping and risk. Stages 2 and 5 are interpersonal where the older person works with a practitioner-prescriber-reviewer, perhaps with carer involvement.

Applying Normalisation Process Theory, four steps were identified within each stage: 1) sense making: information, clarification; 2) action: shared-decision-making; 3) reflection/monitoring; and 4) enduring relationships, based on collaboration and mutual trust.

In a detailed analysis of Stage 5: Reviewing/reconciling medications, adopting the lens of ‘burden’, MEMORABLE identified five burdens amenable to mitigation: ambiguity, concealment, unfamiliarity, fragmentation and exclusion. Two initial improvement propositions were identified for further research: a risk screening tool and individualised information.

Conclusions

Older people and family carers often find medication management challenging and burdensome particularly for complex regimens. Practitioners need to be aware of this potential challenge, and work with older people and their carers to minimise the burden associated with medication management.

Trial registration

PROSPERO 2016:CRD42016043506.
Early diagnosis of miliary tuberculosis in a hemodialysis patient by combining two interferon-γ-release assays: a case report
Authors: Bonkain Florence , De Clerck Dieter , Dirix Violette , Singh Mahavir , Locht Camille , Mascart Françoise , Corbière Véronique
Published: June 2020

Background

Patients with end-stage renal disease undergoing chronic hemodialysis (HD) are at high risk to develop tuberculosis (TB) associated with a high mortality rate. TB diagnosis is often delayed due to non-specific symptoms, frequent extra-pulmonary manifestations, and rare microbiological confirmation. This case report illustrates the clear added value of combined interferon-γ -release assays (IGRA) in response to different mycobacterial antigens for an early diagnosis of TB in HD patients.

Case presentation

We report the case of an Egyptian patient under chronic HD treatment, who presented with recurrent episodes of fever and myalgia of unknown origin, associated with an important inflammatory syndrome. These episodes resolved partially or completely within less than 1 month without any treatment but recurred 10 times within 3 years. Chest Computed Tomography and 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18FDG PET-CT) demonstrated several active mediastinal lymphadenopathies. TB was the first suspected diagnosis but cultures and polymerase chain reaction (PCR) remained negative on a mediastinal lymph node aspiration. In contrast, the results from two different IGRA performed on blood were highly suggestive of TB disease. Several granulomas, some of them with central non-caseating necrosis, were demonstrated on a pulmonary nodule obtained by thoracoscopic resection, but PCR and culture remained negative for M. tuberculosis. Three years after the initial symptoms, a new PET-CT revealed a retro-clavicular lymphadenopathy in addition to the mediastinal lymphadenopathies, and the M. tuberculosis culture performed on the resected lymphadenopathy was positive. Antibiotic treatment for TB was started and resulted in a clear improvement of the patient’s clinical condition, allowing him to successfully receive a renal graft.

Conclusions

In view of the high frequency of TB in patients undergoing chronic HD and of the limitations of the classical diagnosis procedures, nephrologists have to diagnose TB mostly on clinical suspicion. We demonstrate here that the use of a combined IGRA to two different mycobacterial antigens may significantly raise the index of suspicion and help clinicians to decide starting anti-TB treatment in HD patients.
Posterior cerebral artery stroke by reverse flow embolism in thoracic outlet syndrome - a case report
Authors: Celier Adam , Chabay Simon , Maurizot Aurélien , Cochennec Frédéric , Stanciu Daniela , Pico Fernando
Published: June 2020

Background

Arterial thoracic outlet syndrome is a rare condition characterized by a subclavian artery pathology associated with a bone abnormality. It is rarely associated with thromboembolic stroke. The mechanism of cerebral embolism associated with thoracic outlet syndrome have rarely been demonstrated. We present here a fully studied case with a high probability of reverse flow embolism.

Case presentation

A 24-year-old man with a known arterial thoracic outlet syndrome presented with a right cerebral posterior artery brain infarction. An ultrasound examination depicted the compression of the right subclavian artery in the scalene defile with a post stenotic aneurysm and the presence of a floating thrombus in this aneurysm. There was a reverse flow during diastole in this aneurysm. Anticoagulation was carried out with the disappearance of the floating thrombus with no new clinical or brain MRI event. Corrective surgery of this thoracic outlet syndrome was performed one month after stroke.

Conclusion

Very few cases of stroke in arterial thoracic outlet syndrome have been described with thorough dynamic vascular imaging. To our knowledge, this is the fourth reported case that advocates for a reverse flow embolism mechanism in stroke associated with thoracic outlet syndrome, and the first to realize an extensive ultrasound and doppler workup.
Experiences and training needs of healthcare providers involved in the care of Ghanaian adolescents living with HIV: an interventional study
Authors: Hayfron-Benjamin Anna , Obiri-Yeboah Dorcas , Bockarie Yemah Mariama , Asiedua Ernestina , Baidoo Ibrahim , Akorsu Angela D. , Ayisi-Addo Stephen
Published: June 2020

Background

Caring for adolescents living with HIV/AIDS (ALHIV) can be overwhelming due to their unique needs. Ghana is currently among nine countries in West and Central Africa contributing to 90% of new paediatric infections in the sub-region with a growing population of ALHIV. Regardless, gaps in paediatric related care including healthcare providers (HCPs) capacity issues have been identified. This study sought to assess the competencies of adolescent-oriented healthcare providers before, and after interventionist training to inform recommendation that would guide the psychosocial care they give to ALHIV.

Methods

The study adopted a mixed methods approach with a non-randomized interventional study involving three-phase multi-methods. The sample consisted of 28 adolescent-oriented and multi-disciplinary healthcare providers at the Cape Coast Teaching Hospital (CCTH) in Ghana. Data were obtained in three phases, namely, a baseline survey, interventionist training, and post-training in-depth interviews. Quantitative data were analyzed using Stata version 13 for descriptive analysis while the qualitative data were analyzed thematically using NVivo version 11.

Results

Although the majority of the HCPs claim to be knowledgeable about adolescent health issues (n = 21, 75.0%), only about a third (n = 10, 35.7%) could correctly define who an adolescent is. The majority (n = 18, 64.3%) had not received any training on how to work with the adolescent client. The main areas identified for improvement in the ALHIV care in phase 1 included issues with psychosocial assessment, communication and treatment adherence strategies, creating an adolescent-friendly work environment, and availability of job aids/protocols. During the post-training interviews, participants reported an improved understanding of the characteristics of an adolescent-friendly site and basic principles for ALHIV care. They were also able to correctly describe the widely used adolescent health assessment tool; the HEEADSSS. Post intervention interviews also revealed HCPs perception on increased practice related confidence levels and readiness to implement new knowledge and skills gained.

Conclusion

This study has shown that targeted training on routine ALHIV care is effective in increasing HCPs knowledge, skills and confidence. Addressing the healthcare system/facility related gaps serves as an impetus for improved ALHIV care among HCPs.
Combination of gamma-glutamyl transferase and liver stiffness measurement for biliary atresia screening at different ages: a retrospective analysis of 282 infants
Authors: Shen Qiulong , Tan Sarah Siyin , Wang Zengmeng , Cai Siyu , Pang Wenbo , Peng Chunhui , Chen Yajun
Published: June 2020

Background

This study aims to explore the diagnostic accuracy of the combination of gamma-glutamyl transferase (GGT) and liver stiffness measurement (LSM) for biliary atresia (BA) screening at different ages.

Methods

Our retrospective study involved 282 infants under the age of 120 days with jaundice who were admitted into Beijing Children’s Hospital between January 2016 to December 2018. The GGT and LSM levels of infants were obtained. A parallel test was used, and ROC curve was created to obtain cutoff values of GGT and LSM for BA infants at different ages.

Results

Of the 282 infants, 135 were diagnosed with BA and 147 were non-BA infants. In all age groups (A: ≤60 days; B: 61–90 days; C: 91–120 days), the LSM and GGT levels of the BA group were significantly higher than that of the non-BA group, P < 0.05. The cutoff value of GGT and LSM to diagnosis BA was 191.2 U/L, 213.2 U/L, 281.5 U/L and 7.5 kPa, 10.0 kPa, 11.0 kPa in groups A, B and C, respectively. The parallel test was used to determine a sensitivity of 97.3, 98.1 and 100% in group A, B and C when either GGT or LSM levels were met in BA infants. The sensitivities of parallel testing for group A and B were higher than LSM or GGT used alone.

Conclusions

Cutoff values of GGT and LSM to screen BA increased with age. Parallel testing of GGT and LSM in infants who are younger than 90 days old can decrease the rate of BA misdiagnosis.
Food habits in overweight and obese adolescent girls with Polycystic ovary syndrome (PCOS): a qualitative study in Iran
Authors: Hajivandi Leila , Noroozi Mahnaz , Mostafavi Firoozeh , Ekramzadeh Maryam
Published: June 2020

Background

Polycystic ovary syndrome (PCOS) is a hormonal disorder in women of reproductive age. It seems that over the recent years, PCOS has augmented in adolescent girls due to unhealthy food habits and obesity. So, the present study was conducted to explore the food habits in overweight and obese adolescent girls with PCOS.

Methods

In the present qualitative study, 33 participants were selected using a purposive sampling method. Data were collected through individual in-depth interviews, focus group discussions (FGDs), and field notes. These data were analyzed through the use of conventional qualitative content analysis.

Results

Three main categories were extracted: First, the high consumption of unhealthy food had three sub-categories: “high consumption of fatty and salty foods”, “high consumption of unhealthy snacks”, and “high consumption of sugar-rich foods”. Second, low consumption of healthy food had three sub-categories: “low consumption of dairy products”, “low consumption of fiber-rich foods”, and “low consumption of meat, beans, fish and seafood” Third, inappropriate behavioral habits had three sub-categories: “lack of concentration and consumption of large meals”, “inappropriate dietary and physical activity patterns”, and “skipping the meals and going on arbitrary diets”.

Conclusion

This research through presenting an image of food habits in overweight and obese adolescent girls with PCOS is able to help for designing the necessary interventions to change the food habits, control the symptoms and complications of PCOS, and finally, improve the reproductive health of these girls.
Patient and service-related barriers and facitators to the acceptance and use of interventions to promote communication in health and social care: a realist review
Authors: Leavey Gerard , Curran Emma , Fullerton Deirdre , Todd Steven , McIlfatrick Sonja , Coates Vivien , Watson Max , Abbott Aine , Corry Dagmar
Published: June 2020

Background

More people living into old age with dementia. The complexity of treatment and care, particularly those with multiple health problems, can be experienced as disjointed. As part of an evaluation of a ‘healthcare passport’ for people living with dementia we undertook a realist review of communication tools within health and social care for people living with dementia.

Aims

To explore how a ‘healthcare passport’ might work in the ‘real world’ of people living with dementia through a better understanding of the theoretical issues related to, and the contextual issues that facilitate, successful communication.

Methods

A realist review was considered the most appropriate methodology to inform the further development and evaluation of the healthcare passport. We undertook a purposive literature search related to communication tools to identify (a) underlying programme theories; (b) published reports and papers on their use in various healthcare settings; (c) evidence on barriers and facliitators of their use.

Results

Communication tools were noted as a way of improving communication and outcomes through: (1) improvement of service user autonomy; (2) strengthening the therapeutic alliance; and (3) building integrated care. However, while intuitively perceived to of benefit, evidence on their use is limited and key barriers to their acceptance and use include: (1) difficulties in clearly defining purpose, content, ownership and usage; (2) understanding the role of family caregivers; and (3) preparation among healthcare professionsals.

Conclusion

Patient-held communication tools may be helpful to some people living with dementia but will require considerable preparation and engagement with key stakeholders.
U-shaped association between plasma sphingosine-1-phosphate levels and mortality in patients with chronic systolic heart failure: a prospective cohort study
Authors: Xue Yanbo , Jiang Wei , Ma Qiong , Wang Xiqiang , Jia Pu , Li Qiang , Chen Shuping , Song Bingxue , Wang Ya , Zhang Jingwen , Liu Jing , Yang Guodong , Lin Yuyao , Liu Jing , Wei Linyan , Dong Caijuan , Li Haiquan , Xie Zhonglei , Bai Ling , Ma Aiqun
Published: June 2020

Background

The endogenous lipid molecule sphingosine-1-phosphate (S1P) has received attention in the cardiovascular field due to its significant cardioprotective effects, as revealed in animal studies. The purpose of our study was to identify the distribution characteristics of S1P in systolic heart failure patients and the prognostic value of S1P for long-term prognosis.

Methods

We recruited 210 chronic systolic heart failure patients from June 2014 to December 2015. Meanwhile 54 healthy people in the same area were selected as controls. Plasma S1P was measured by liquid chromatography-tandem mass spectrometry. Patients were grouped according to the baseline S1P level quartiles, and restricted cubic spline plots described the association between S1P and all-cause death. Cox proportional hazard analysis was used to determine the relationship between category of S1P and all-cause death.

Results

Compared with the control group, the plasma S1P in chronic heart failure patients demonstrated a higher mean level (1.269 μmol/L vs 1.122 μmol/L, P = 0.006) and a larger standard deviation (0.441 vs 0.316, P = 0.022). Based on multivariable Cox regression with restricted cubic spline analysis, a non-linear and U-shaped association between S1P levels and the risk of all-cause death was observed. After a follow-up period of 31.7 ± 10.3 months, the second quartile (0.967–1.192 μml/L) with largely normal S1P levels had the lowest all-cause mortality and either an increase (adjusted HR = 2.368, 95%CI 1.006–5.572, P = 0.048) or a decrease (adjusted HR = 0.041, 95%CI 0.002–0.808, P = 0.036) predicted a worse prognosis. The survival curves showed that patients in the lowest quartile and highest quartile were at a higher risk of death.

Conclusions

Plasma S1P levels in systolic heart failure patients are related to the long-term all-cause mortality with a U-shaped correlation.

Trial registration

CHiCTR, ChiCTR-ONC-14004463. Registered 20 March 2014.
Analysis of particles from hamster lungs following pulmonary talc exposures: implications for pathogenicity
Authors: Sato Erika , McDonald Sandra A. , Fan Yuwei , Peterson Shaina , Brain Joseph D. , Godleski John J.
Published: June 2020

Background

Talc, a hydrous magnesium silicate, often used for genital hygiene purposes, is associated with ovarian carcinoma in case-control studies. Its potential to cause inflammation, injury, and functional changes in cells has been described. A complication of such studies is that talc preparations may be contaminated with other materials. A previous study by (Beck et al. Toxicol Appl Pharmacol 87:222-34, 1987) used a hamster model to study talc and granite dust exposure effects on various biochemical and cellular inflammatory markers. Our current study accessed key materials used in that 1987 study; we re-analyzed the original talc dust with contemporary scanning electron microscopy and energy dispersive x-ray analysis (SEM/EDX) for contaminants. We also examined the original bronchoalveolar lavage (BAL) cells with polarized light microscopy to quantify cell-associated birefringent particles to gain insight into the talc used.

Results

SEM/EDX analyses showed that asbestos fibers, quartz, and toxic metal particulates were below the limits of detection in the original talc powder. However, fibers with aspect ratios ≥3:1 accounted for 22% of instilled material, mostly as fibrous talc. Talc (based on Mg/Si atomic weight % ratio) was the most abundant chemical signature, and magnesium silicates with various other elements made up the remainder. BAL cell counts confirmed the presence of acute inflammation, which followed intratracheal instillation. Measurements of cell associated birefringent particles phagocytosis revealed significant differences among talc, granite, and control exposures with high initial uptake of talc compared to granite, but over the 14-day experiment, talc phagocytosis by lavaged cells was significantly less than that of granite. Phagocytosis of talc fibers by macrophages was observed, and birefringent particles were found in macrophages, neutrophils, and multinucleate giant cells in lavaged cells from talc-exposed animals.

Conclusion

Our data support the contention that talc, even without asbestos and other known toxic contaminants, may elicit inflammation and contribute to lung disease. Our findings support the conclusions of (Beck et al. Toxicol Appl Pharmacol 87:222-34, 1987) study. By analyzing particulate exposures with polarized light microscopy and SEM/EDX, fibrous talc was identified and a distinctive pattern of impaired particulate ingestion was demonstrated.
A chromosome 1q22 microdeletion including ASH1L is associated with intellectual disability in a Chinese family
Authors: Xi Hui , Peng Ying , Xie Wanqin , Pang Jialun , Ma Na , Yang Shuting , Peng Jinping , Wang Hua
Published: June 2020

Background

Copy number variants (CNVs) associated with developmental delay and intellectual disability (DD/ID) continue to be identified in patients. This article reports identification of a chromosome 1q22 microdeletion as the genetic cause in a Chinese family affected by ID.

Case presentation

The proband was a 19-year-old pregnant woman referred for genetic counseling and prenatal diagnosis at 18 weeks of gestation. She had severe ID with basically normal stature (height 154 cm [0 SD], weight 61 kg [− 0.2 SD], and head circumference 54 cm [− 1.12 SD]). Her distinctive facial features included a prominent forehead; flat face; flat nasal bridge and a short upturned nose; thin lips; and small ears. The proband’s father was reported to have low intelligence, whereas her mother was of normal intelligence but with scoliosis. Chromosome microarray analysis (CMA) reveals that the proband, her father and the fetus all carry a 1q22 microdeletion of 936.3 Kb (arr[GRCh37] 1q22 (155016052_155952375)×1), which was not observed in her mother and paternal grandparents and uncles, suggesting a de novo mutation in the proband’s father. The microdeletion involves 24 OMIM genes including ASH1L (also known as KMT2H and encoding a histone lysine methyltransferase). Of note, haploinsufficiency of ASH1L has been shown to be associated with neurodevelopmental disorders. Based on the inheritance of the detected CNV in the pedigree and similar CNVs associated with ID in public databases (Decipher, DGV and ClinVar) and literature, the detected CNV is considered as pathogenic. The family chose to terminate the pregnancy.

Conclusions

The identified 1q22 microdeletion including ASH1L is pathogenic and associated with ID. This case broadens the spectrum of ID-related CNVs and may be useful as a reference for clinicians.
Cluster randomised trials of prescribing policy: an ethical approach to generating drug safety evidence? A discussion of the ethical application of a new research method
Authors: Rogers Amy , Craig Gillian , Flynn Angela , Mackenzie Isla , MacDonald Thomas , Doney Alexander
Published: June 2020

For most chronic medical conditions, multiple medications are available and prescribers often have limited evidence about which therapy is likely to be the most effective and safe for an individual patient. As many patients are exposed every day to medicines that may be less effective than available alternatives, this is of public health importance. Cluster randomised trials of prescribing policy offer an opportunity to rapidly obtain evidence of comparative effectiveness and safety. These trials can pose a low risk to patients and cause minimal disruption to usual care. Despite the potential scientific value of this approach, there remain valid concerns about consent, medication switching and the use of routinely collected data in research. We discuss these concerns with reference to an ongoing pilot study (Evaluating Diuretics in Normal Care (EVIDENCE) - a cluster randomised evaluation of hypertension prescribing policy, ISRCTN 46635087, registered 11 August 2017).
Human laminin-111 and laminin-211 protein therapy prevents muscle disease progression in an immunodeficient mouse model of LAMA2-CMD
Authors: Barraza-Flores Pamela , Hermann Hailey J. , Bates Christina R. , Allen Tyler G. , Grunert Timothy T. , Burkin Dean J.
Published: June 2020

Background

Laminin-α2-related congenital muscular dystrophy (LAMA2-CMD) is a devastating genetic disease caused by mutations in the LAMA2 gene. These mutations result in progressive muscle wasting and inflammation leading to delayed milestones, and reduced lifespan in affected patients. There is currently no cure or treatment for LAMA2-CMD. Preclinical studies have demonstrated that mouse laminin-111 can serve as an effective protein replacement therapy in a mouse model of LAMA2-CMD.

Methods

In this study, we generated a novel immunocompromised dyWmouse model of LAMA2-CMD to study the role the immune system plays in muscle disease progression. We used this immune-deficient dyWmouse model to test the therapeutic benefits of recombinant human laminin-111 and laminin-211 protein therapy on laminin-α2-deficient muscle disease progression.

Results

We show that immunodeficient laminin-α2 null mice demonstrate subtle differences in muscle regeneration compared to immunocompetent animals during early disease stages but overall exhibit a comparable muscle disease progression. We found human laminin-111 and laminin-211 could serve as effective protein replacement strategies with mice showing improvements in muscle pathology and function. We observed that human laminin-111 and laminin-211 exhibit differences on satellite and myoblast cell populations and differentially affect muscle repair.

Conclusions

This study describes the generation of a novel immunodeficient mouse model that allows investigation of the role the immune system plays in LAMA2-CMD. This model can be used to assess the therapeutic potential of heterologous therapies that would elicit an immune response. Using this model, we show that recombinant human laminin-111 can serve as effective protein replacement therapy for the treatment of LAMA2-CMD.
Approximation analysis of ontology learning algorithm in linear combination setting
Authors: Gao Wei , Chen Yaojun
Published: June 2020

In the past ten years, researchers have always attached great importance to the application of ontology to its relevant specific fields. At the same time, applying learning algorithms to many ontology algorithms is also a hot topic. For example, ontology learning technology and knowledge are used in the field of semantic retrieval and machine translation. The field of discovery and information systems can also be integrated with ontology learning techniques. Among several ontology learning tricks, multi-dividing ontology learning is the most popular one which proved to be in high efficiency for the similarity calculation of tree structure ontology. In this work, we study the multi-dividing ontology learning algorithm from the mathematical point of view, and an approximation conclusion is presented under the linear representation assumption. The theoretical result obtained here has constructive meaning for the similarity calculation and concrete engineering applications of tree-shaped ontologies. Finally, linear combination multi-dividing ontology learning is applied to university ontologies and mathematical ontologies, and the experimental results imply that the higher efficiency of the proposed approach in actual applications.
Mechanistic insights into the attenuation of intestinal inflammation and modulation of the gut microbiome by krill oil using in vitro and in vivo models
Authors: Liu Fang , Smith Allen D. , Solano-Aguilar Gloria , Wang Thomas T. Y. , Pham Quynhchi , Beshah Ethiopia , Tang Qingjuan , Urban Joseph F. , Xue Changhu , Li Robert W.
Published: June 2020

Background

The anti-inflammatory property of ω-3 polyunsaturated fatty acids (PUFA) has been exploited in the management of inflammatory bowel disease (IBD) with promising results. However, it remains unclear if PUFA play a significant role in the resolution of inflammation and promotion of mucosal healing. Krill oil (KO) is a natural product rich in PUFA and the potent antioxidant, astaxanthin. In this study, we attempted to understand the mechanisms through which KO modulates the gut microbiome and metabolome using in vitro and in vivo colitis models and a multi-omics based approach.

Results

KO significantly decreased LPS-induced IL1β and TNFα expression in human macrophages in vitro in a dose-dependent manner by regulating a broad spectrum of signaling pathways, including NF-κB and NOD-like receptor signaling, and displayed a synergistic effect with COX2 and IKK2 inhibitors in attenuating inflammatory pathways. Moreover, KO was involved in the resolution of inflammation by promoting M2 polarization and enhancing macrophage-mediated intracellular bacterial killing. Parasite-dependent intestinal mucosal damage and microbial dysbiosis induced by Trichuris suis infection in pigs were partially restored by feeding KO. KO supplementation reduced the abundance of Rickettsiales and several species of Lactobacillus, which were among the important features identified by random forests analysis contributing to classification accuracy for KO supplementation. Several microbial signatures with strong predictive power for the status of both infection and supplementation were identified. The inhibitory effect of KO on histidine metabolism was identified using untargeted metabolomics. KO supplementation reduced several key metabolites related to histamine metabolism by suppressing the expression of a gene encoding l-histidine decarboxylase in the colon mucosa and reducing histamine biosynthesis of microbial origin. Moreover, the pro-resolving properties of KO were validated using a Citrobacter rodentium-induced Th1-dependent colitis murine model. Further, microbial signatures with high prediction accuracy for colitis-related pathophysiological traits were identified in mice.

Conclusion

The findings from this study provided a mechanistic basis for optimizing microbiome-inspired alternative therapeutics in the management of IBD. The microbial signatures identified, particularly those with strong predictive accuracy for colitis phenotypes, will facilitate the development of biomarkers associated with appropriate dietary intervention to manage intestinal inflammation.
Earth microbial co-occurrence network reveals interconnection pattern across microbiomes
Authors: Ma Bin , Wang Yiling , Ye Shudi , Liu Shan , Stirling Erinne , Gilbert Jack A. , Faust Karoline , Knight Rob , Jansson Janet K. , Cardona Cesar , Röttjers Lisa , Xu Jianming
Published: June 2020

Background

Microbial interactions shape the structure and function of microbial communities; microbial co-occurrence networks in specific environments have been widely developed to explore these complex systems, but their interconnection pattern across microbiomes in various environments at the global scale remains unexplored. Here, we have inferred an Earth microbial co-occurrence network from a communal catalog with 23,595 samples and 12,646 exact sequence variants from 14 environments in the Earth Microbiome Project dataset.

Results

This non-random scale-free Earth microbial co-occurrence network consisted of 8 taxonomy distinct modules linked with different environments, which featured environment specific microbial co-occurrence relationships. Different topological features of subnetworks inferred from datasets trimmed into uniform size indicate distinct co-occurrence patterns in the microbiomes of various environments. The high number of specialist edges highlights that environmental specific co-occurrence relationships are essential features across microbiomes. The microbiomes of various environments were clustered into two groups, which were mainly bridged by the microbiomes of plant and animal surface. Acidobacteria Gp2 and Nisaea were identified as hubs in most of subnetworks. Negative edges proportions ranged from 1.9% in the soil subnetwork to 48.9% the non-saline surface subnetwork, suggesting various environments experience distinct intensities of competition or niche differentiation.

Conclusion

This investigation highlights the interconnection patterns across microbiomes in various environments and emphasizes the importance of understanding co-occurrence feature of microbiomes from a network perspective.
Effect of aerosolized nicotine on human bronchial epithelial cells is amplified after co-administration with cannabidiol (CBD): a pilot in vitro study
Authors: Leigh Noel J. , Goniewicz Maciej L.
Published: June 2020

Background

Population-based studies suggest increasing rates of concurrent use of vaping products that contain either nicotine or cannabinoids. The aim of this pilot study was to test in vitro the acute inhalation toxicity of vaporized flavored and unflavored nicotine solutions co-administered with cannabidiol (CBD).

Methods

Bronchial epithelial cells (H292) were exposed directly to aerosol generated from electronic cigarettes refilled with propylene glycol only, unflavored nicotine solutions in propylene glycol with and without CBD, as well as to solutions containing only CBD. Cells were also exposed to a commercially available flavored solution containing nicotine and CBD. The in vitro toxicological effects were assessed after exposure using the following methods: 1) a trypan blue exclusion assay (cell viability), 2) neutral red uptake assay (metabolic activity) and 3) ELISA (concentrations of inflammatory mediators).

Results

Unflavored solution containing only CBD was significantly more cytotoxic than unflavored solution containing only nicotine. Unflavored solution containing both CBD and nicotine was significantly more cytotoxic than unflavored solutions with only nicotine. Levels of released cytokines were significantly higher when cells were co-exposed to nicotine and CBD as compared to cells exposed to only nicotine or only CBD. Overall, flavored products showed increased toxicity as compared to unflavored solutions.

Conclusions

This pilot in vitro study suggests independent and additive toxic effects of vaporized nicotine and CBD. Observed toxic effects are accentuated by flavorings. Future studies are needed to determine the potential long-term health consequences of concurrent use of vaporized nicotine and cannabis products.
Image-based metric heritage modeling in the near-infrared spectrum
Authors: Adamopoulos Efstathios , Bovero Alessandro , Rinaudo Fulvio
Published: June 2020

Digital photogrammetry and spectral imaging are widely used in heritage sciences towards the comprehensive recording, understanding, and protection of historical artifacts and artworks. The availability of consumer-grade modified cameras for spectral acquisition, as an alternative to expensive multispectral sensors and multi-sensor apparatuses, along with semi-automatic software implementations of Structure-from-Motion (SfM) and Multiple-View-Stereo (MVS) algorithms, has made more feasible than ever the combination of those techniques. In the research presented here, the authors assess image-based modeling from near-infrared (NIR) imagery acquired with modified consumer-grade cameras, with applications on tangible heritage. Three-dimensional (3D) meshes, textured with the non-visible data, are produced and evaluated. Specifically, metric evaluations are conducted through extensive comparisons with models produced with image-based modeling from visible (VIS) imagery and with structured light scanning, to check the accuracy of results. Furthermore, the authors observe and discuss, how the implemented NIR modeling approach, affects the surface of the reconstructed models, and may counteract specific problems which arise from lighting conditions during VIS acquisition. The radiometric properties of the produced results are evaluated, in comparison to the respective results in the visible spectrum, on the capacity to enhance observation towards the characterization of the surface and under-surface state of preservation, and consequently, to support conservation interventions.
Subtle sexual plumage color dimorphism and size dimorphism in a South American colonial breeder, the Monk Parakeet (Myiopsitta monachus)
Authors: Morales Macarena , Gigena Deysi J. , Benitez-Vieyra Santiago M. , Valdez Diego J.
Published: June 2020

Background

Parrots (Psittacidae Family) are one of the most colorful groups of birds in the world, their colors produced both structurally and via unusual pigments (psittacofulvins). Most species are considered to be monogamous, and many have been viewed historically as sexually monomorphic and monochromatic. However, studies using morphometric analysis and spectrophotometric techniques have revealed sexual size dimorphism and also sexual plumage color dimorphism among some species. The Monk Parakeet (Myiopsitta monachus), a native parrot of South America, is an interesting species for the study of plumage coloration and size since it is considered sexually monochromatic and monomorphic. Furthermore, recent studies show that the Monk Parakeet has extra-bond paternity behavior and even breeding trios, which suggests that sexual selection may play an important role in this species, and that it might have sexually dimorphic plumage (albeit imperceptible by humans) and be dimorphic in size.

Methods

For the determination of plumage color we used spectrophotometry in the range of avian vision (300‒700 nm) and performed a morphological analysis.

Results

Our spectrophotometric results indicate that the Monk Parakeet shows subtle sexual plumage color dimorphism in three (crown, nape and wing) out of twelve body regions. Similarly, our morphometric analysis showed that there are subtle sex differences in body size (bill and weight).

Conclusions

Although the Monk Parakeet shows extra-bond paternity and breeding trio behaviors which could increase sexual dimorphism, these behaviors occur among highly related individuals; perhaps the high rate of inbreeding is responsible for the attenuation of sexual plumage color dimorphism and sex differences in body size observed.
Hepatoprotective potentials of Acridocarpus orientalis in mice
Authors: Lotfy Mohamed , Al-Hammadi Rasheed , Palakkott Abdul Rasheed , Yasin Javed , Al-Hammadi Suleiman , Ksiksi Taoufik
Published: June 2020

Background

Overdose of paracetamol affects liver cells leading to cell death. This is done through hepatic necrosis, which is characterized by a rupture of the plasma membrane. A variety of investigations has been conducted using herbal extracts to assess liver toxicity induced by paracetamol. Here we examined herbal plant species, Acridocarpus orientalis (A. orientalis), ethanolic extract to study its potential to protect against hepatotoxicity in mice. Serum alanine transaminase (ALT), aspartate transaminase (AST) and reduced glutathione (GSH) enzymes were estimated for all mice groups. A phytochemical screening was also conducted.

Results

Phytochemical screening showed that A. orientalis contains flavonoids, tannins, carbohydrates and phenolics derivatives. A. orientalis pretreatment showed significant reduction of liver marker enzymes ALT and AST in almost all concentrations. Furthermore, serum GSH levels were significantly increased in A. orientalis pretreated mice groups. In addition, a reduction in liver weights in pretreated mice with A. orientalis showed significant weight loss at dose 250 mg/kg BW (P < 0.05). Moreover, the histological liver analysis showed near normal restoration of liver architecture in A. orientalis pretreated mice.

Conclusion

pretreatment with A. orientalis protects mice against heplatotoxic adverse effects of paracetamol as indicated by reduction of serum ALT and AST enzymes, with elevation of GSH antioxidant protective enzyme, which may have contributed to the main hepatoprotective action of A. orientalis.
Encoding candlesticks as images for pattern classification using convolutional neural networks
Authors: Chen Jun-Hao , Tsai Yun-Cheng
Published: June 2020

Candlestick charts display the high, low, opening, and closing prices in a specific period. Candlestick patterns emerge because human actions and reactions are patterned and continuously replicate. These patterns capture information on the candles. According to Thomas Bulkowski’s Encyclopedia of Candlestick Charts, there are 103 candlestick patterns. Traders use these patterns to determine when to enter and exit. Candlestick pattern classification approaches take the hard work out of visually identifying these patterns. To highlight its capabilities, we propose a two-steps approach to recognize candlestick patterns automatically. The first step uses the Gramian Angular Field (GAF) to encode the time series as different types of images. The second step uses the Convolutional Neural Network (CNN) with the GAF images to learn eight critical kinds of candlestick patterns. In this paper, we call the approach GAF-CNN. In the experiments, our approach can identify the eight types of candlestick patterns with 90.7% average accuracy automatically in real-world data, outperforming the LSTM model.
In vitro effects of febrifugine on Schistosoma mansoni adult worms
Authors: Mitsui Yoshinori , Miura Mitsumasa , Kato Kentaro
Published: June 2020

Background

Reports on the antischistosomal effect of several antimalarial drugs such as artesunate, mefloquine, and amodiaquine suggest that febrifugine, which exerts an antimalarial effect, can also be expected to possess antischistosomal potential. The present study investigates the antischistosomal effects of febrifugine.

Methods

In experiment 1, Schistosoma mansoni adult worm pairs were incubated in a medium alone as a control or supplemented with febrifugine at 0.05, 0.1, 0.2, and 0.5 μg/ml for 14 days. The morphology of the worms and the egg production of the female worms were observed simultaneously. In experiment 2, the incubation was conducted as in experiment 1, except that the febrifugine concentrations were reduced to 0.005, 0.01, and 0.02 μg/ml. In addition, S. mansoni adult worms were incubated with either 0.5 μg/ml febrifugine or none as a control for 5 days and stained with neutral red dye.

Results

Febrifugine significantly reduced the survival of S. mansoni male and female worms at concentrations of 0.02–0.5 μg/ml following incubation for 14 days and remarkably inhibited the daily egg output of the female worms. The non-treated male and female worms remained morphologically normal within the period of 14 days, whereas male and female worms treated with febrifugine at different concentrations gradually twisted and subsequently died. In addition, S. mansoni adult worms were incubated with either 0.5 μg/ml febrifugine or none as a control for 5 days and stained with neutral red dye. Non-treated male worms were morphologically normal and stained dark red with neutral red, while febrifugine-treated male worms appeared similar to those in the control group and were stained at a slightly lower level of dark red than the non-treated male worms. Non-treated female worms were morphologically normal, and their intestinal tract and vitellaria were stained deep red and dark red, respectively. In contrast, febrifugine-treated female worms were morphologically damaged, and their intestinal tract and vitellaria remained mostly unstained and stained dark red, respectively.

Conclusion

Febrifugine exerts potent antischistosomal effects and can be expected to contribute to the development of a novel antischistosomal drug.