bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioengineered airway epithelial grafts with mucociliary function based on collagen IV- and laminin-containing extracellular matrix scaffolds
Authors: Hamilton Nick J.I. , Lee Dani Do Hyang , Gowers Kate H.C. , Butler Colin R. , Maughan Elizabeth F. , Jevans Benjamin , Orr Jessica C. , McCann Conor J. , Burns Alan J. , MacNeil Sheila , Birchall Martin A. , O'Callaghan Christopher , Hynds Robert E. , Janes Sam M.
Published: May 2020

Current methods to replace damaged upper airway epithelium with exogenous cells are limited. Existing strategies use grafts that lack mucociliary function, leading to infection and the retention of secretions and keratin debris. Strategies that regenerate airway epithelium with mucociliary function are clearly desirable and would enable new treatments for complex airway disease.

Here, we investigated the influence of the extracellular matrix (ECM) on airway epithelial cell adherence, proliferation and mucociliary function in the context of bioengineered mucosal grafts.In vitro, primary human bronchial epithelial cells (HBECs) adhered most readily to collagen IV. Biological, biomimetic and synthetic scaffolds were compared in terms of their ECM protein content and airway epithelial cell adherence.

Collagen IV and laminin were preserved on the surface of decellularised dermis and epithelial cell attachment to decellularised dermis was greater than to the biomimetic or synthetic alternatives tested. Blocking epithelial integrin α2 led to decreased adherence to collagen IV and to decellularised dermis scaffolds. At air–liquid interface (ALI), bronchial epithelial cells cultured on decellularised dermis scaffolds formed a differentiated respiratory epithelium with mucociliary function. Usingin vivochick chorioallantoic membrane (CAM), rabbit airway and immunocompromised mouse models, we showed short-term preservation of the cell layer following transplantation.

Our results demonstrate the feasibility of generating HBEC grafts on clinically applicable decellularised dermis scaffolds and identify matrix proteins and integrins important for this process. The long-term survivability of pre-differentiated epithelia and the relative merits of this approach against transplanting basal cells should be assessed further in pre-clinical airway transplantation models.
Stress cardiomyopathy associated with area postrema syndrome as a presentation of neuromyelitis optica: case report
Authors: An Sungsik , Ma Hyeo-il , Song Jooyeon , Choi Hong-Mi , Kim Young Eun
Published: May 2020

Background

Stress cardiomyopathy (Takotsubo cardiomyopathy) is very rare in the central nervous system (CNS) demyelinating disorders. Although this dysfunction of the heart-brain axis has been reported in several case series related to multiple sclerosis (MS), stress cardiomyopathy by neuromyelitis optica (NMO), which is rarer CNS demyelinating disorder than MS, is extremely rare. Herein, we report a case of stress cardiomyopathy associated with a medullary lesion as a presentation of NMO.

Case presentation

A 30-year-old woman was treated by veno-arterial extracorporeal membrane oxygenation due to catastrophic cardiopulmonary dysfunction after prolonged and unexplained nausea, vomiting, and cough. Myoclonus on the limbs developed afterward. Taken with suspicion of area postrema syndrome (APS), the brain MRI showed a demyelinating lesion in the medulla oblongata. APS and severe heart failure by stress cardiomyopathy were completely resolved by ECMO and hydrocortisone therapy. However, the CNS demyelinating lesion recurred after 1 month. The patient was diagnosed with NMO evident by the presence of aquaporin-4 antibody; Steroid therapy improved her symptoms.

Conclusion

NMO should be considered as one of the differential diagnoses in patients with APS preceding severe cardiopulmonary distress.
A systematic review to assess the effectiveness of technology-based interventions to address obesity in children
Authors: McMullan Megan , Millar Rachel , Woodside Jayne V.
Published: May 2020

Background

Childhood obesity is associated with a multitude of co-morbidities, including hypertension, hyperlipidaemia, cardiovascular disease and type 2 diabetes. Childhood obesity can also affect a young person’s social, emotional and mental health if they encounter negative prejudice and social marginalisation. Given the prevalence of overweight and obese children globally, it is imperative that effective interventions are developed. Children are receptive to information conveyed via digital means, therefore, the use of technology may play a crucial role in interventions to reduce childhood obesity. This systematic review aimed to review and critically appraise the literature published to date in relation to the effectiveness of technology-based interventions, employed as secondary prevention, in addressing childhood obesity.

Methods

An electronic search strategy was undertaken in Medline and Embase, covering publications up to and including 12th July 2018. Randomised controlled trials assessing the effectiveness of technology-based interventions on weight-related outcomes in children, aged 8 to 18, published only in the English language, were included.

Results

From an initial search total of 1012 studies, 11 met the inclusion criteria. They were assessed for methodological quality using the Cochrane Risk of Bias Tool for Randomised Controlled Trials and were analysed using a narrative approach. The findings of this review showed a limited potential of technology-based interventions, employed as secondary prevention, to address childhood obesity. Of the eleven studies reviewed, three (27%) showed a positive relationship between technology-based interventions and weight-related outcomes in overweight or obese children.

Conclusions

This review suggests that technology-based interventions, primarily active video games, as well as internet or web-based interventions and mobile phone communications, may, with further research, have the potential to impact positively on weight-related outcomes. It is difficult to determine the degree of efficacy of these technology-based interventions, as only two databases were searched, selecting only English language articles. Moreover, the included studies demonstrated a lack of high-quality evidence. The lack and heterogeneity of studies with technology-based interventions is a further limitation.
Pulmonary hypertension in late-onset Methylmalonic Aciduria and Homocystinemia: a case report
Authors: Wen Ling-yi , Guo Ying-kun , Shi Xiao-qing
Published: May 2020

Background

Methylmalonic Aciduria and Homocystinemia, cobalamin C (cblC) is an inherited disease of vitamin B12 metabolism with a wide spectrum of clinical manifestations. cblC presenting with pulmonary hypertension (PH) as leading sympotom is rare and easily misdiagnosed because of limited awareness. Timely diagnosis is crucial by the relentless progression without appropriate treatment.

Case presentation

We reported a 12-year-old girl with a 3-year history of progressively reduced activity tolerance and a 3-month history of orthopnea. Metabolic testing revealed increased levels of plasma homocysteine and urine methylmalonic acid. cblC deficiency was subsequently confirmed by genetic testing. The patient was treated with hydroxocobalamin, betaine, folinic acid and levocarnitine for cblC disease. Sildenafil, bosentan, spironolactone and hydrochlorothiazide was administrated for PH and right heart failure. At 3-month follow-up, she had an apparent resolution of dyspnea and cyanosis. Metabolic abnormalities resolved the decrease of plasma homocysteine and urine methylmalonic acid. A right heart catheterization showed a reduced pulmonary pressure.

Conclusions

This case emphasizes the importance of an early diagnosis and initiation of treatment for cblC deficiency. Unexplained PH in children and young adults should prompt metabolic screening for the differential diagnosis.
Right ventricular function among South East Nigeria children with sickle cell anaemia
Authors: Chinawa Josephat M. , Chukwu Bartholomew F. , Chinawa Awoere T. , Ossai Edmund N. , Ikefuna Anthony N. , Aronu Ann E. , Obidike Egbuna O.
Published: May 2020

Background

Sickle cell anaemia (SCA) is characterized by attendant ischemia-reperfusion injury especially to the heart.

Methods

The aim of this work is to compare the right ventricular function of children with SCA in steady state (subjects) with those with haemoglobin AA genotype (controls), using echocardiography. It is a cross-sectional study, which echocardiographic measurements to assess right ventricular function among children with SCA and their controls.

Results

The mean trans annular plane systolic excursion (TAPSE) in subjects, 28.24 ± 5.23 (Z score: 0.258 ± 1.10) was higher than that in control, 25.82 ± 3.59 (Z score: - 0.263 ± 0.80), and the difference in mean was statistically significant, (t = 2.703,p = 0.008).

Significantly higher proportion of subjects with sickle cell anaemia had right ventricular dysfunction (Abnormal TAPSE), 25 (50.0%) when compared with those in control, 11 (22.0%), {χ2 = 8.5,p = 0.0035}.

A higher proportion of subjects with sickle cell anaemia (25.5%) had Pulmonary hypertension (RVP) when compared with control (2.0%) and the difference in proportions was found to be statistically significant, (χ2 = 11.668,p = 0.001). The prevalence of right ventricular diastolic dysfunction in subjects was 9.8% while control was 0%.

Conclusion

Children with sickle cell anaemia present with right ventricular dysfunction. Prevalence of right ventricular systolic and diastolic dysfunction were higher in subjects. More of the subjects in this study (25.5%) had pulmonary hypertension.
The evaluation of Suchana, a large-scale development program to prevent chronic undernutrition in north-eastern Bangladesh
Authors: Choudhury Nuzhat , Raihan Mohammad Jyoti , Ahmed S. M. Tanvir , Islam Kazi Eliza , Self Vanessa , Rahman Shahed , Schofield Lilly , Hall Andrew , Ahmed Tahmeed
Published: May 2020

Evidence of the impact of community-based nutrition programs is uncommon for two main reasons: the lack of untreated controls, and implementation does not account for the evaluation design. Suchana is a large-scale program to prevent malnutrition in children in Sylhet division, Bangladesh by improving the livelihoods and nutrition knowledge of poor and very poor households. Suchana is being implemented in 157 unions, the smallest administrative unit of government, in two districts of Sylhet. Suchana will deliver a package of interventions to poor people in about 40 randomly selected new unions annually over 4 years, until all are covered. All beneficiaries will receive the normal government nutrition services. For evaluation purposes the last 40 unions will act as a control for the first 40 intervention unions. The remaining unions will receive the program but will not take part in the evaluation. A baseline survey was conducted in both intervention and control unions; it will be repeated after 3 years to estimate the impact on the prevalence of stunted children and other indicators. This stepped wedge design has several advantages for both the implementation and evaluation of services, as well as some disadvantages. The units of delivery are randomized, which controls for other influences on outcomes; the program supports government service delivery systems, so it is replicable and scalable; and the program can be improved over time as lessons are learned. The main disadvantages are the difficulty of estimating the impact of each component of the program, and the geographical distribution of unions, which increases program delivery costs. Stepped implementation allows a cluster randomized trial to be achieved within a large-scale poverty alleviation program and phased-in and scaled-up over a period of time. This paper may encourage evaluators to consider how to estimate attributable impact by using stepped implementation, which allows the counterfactual group eventually to be treated.
Development and validation of a multivariable prediction model for infection-related complications in patients with common infections in UK primary care and the extent of risk-based prescribing of antibiotics
Authors: Mistry Chirag , Palin Victoria , Li Yan , Martin Glen P. , Jenkins David , Welfare William , Ashcroft Darren M. , van Staa Tjeerd
Published: May 2020

Background

Antimicrobial resistance is driven by the overuse of antibiotics. This study aimed to develop and validate clinical prediction models for the risk of infection-related hospital admission with upper respiratory infection (URTI), lower respiratory infection (LRTI) and urinary tract infection (UTI). These models were used to investigate whether there is an association between the risk of an infection-related complication and the probability of receiving an antibiotic prescription.

Methods

The study used electronic health record data from general practices contributing to the Clinical Practice Research Datalink (CPRD GOLD) and Welsh Secure Anonymised Information Linkage (SAIL), both linked to hospital records. Patients who visited their general practitioner with an incidental URTI, LRTI or UTI were included and followed for 30 days for hospitalisation due to infection-related complications. Predictors included age, gender, clinical and medication risk factors, ethnicity and socioeconomic status. Cox proportional hazards regression models were used with predicted risks independently validated in SAIL.

Results

The derivation and validation cohorts included 8.1 and 2.7 million patients in CPRD and SAIL, respectively. A total of 7125 (0.09%) hospital admissions occurred in CPRD and 7685 (0.28%) in SAIL. Important predictors included age and measures of comorbidity. Initial attempts at validating in SAIL (i.e. transporting the models with no adjustment) indicated the need to recalibrate the models for age and underlying incidence of infections; internal bootstrap validation of these updated models yielded C-statistics of 0.63 (LRTI), 0.69 (URTI) and 0.73 (UTI) indicating good calibration. For all three infection types, the rate of antibiotic prescribing was not associated with patients’ risk of infection-related hospital admissions.

Conclusion

The risk for infection-related hospital admissions varied substantially between patients, but prescribing of antibiotics in primary care was not associated with risk of hospitalisation due to infection-related complications. Our findings highlight the potential role of clinical prediction models to help inform decisions of prescribing of antibiotics in primary care.
Estimating New Zealand’s harvested wood products carbon stocks and stock changes
Authors: Wakelin Stephen J. , Searles Nigel , Lawrence Daniel , Paul Thomas S. H.
Published: May 2020

Background

Reducing net greenhouse gas emissions through conserving existing forest carbon stocks and encouraging additional uptake of carbon in existing and new forests have become important climate change mitigation tools. The contribution of harvested wood products (HWPs) to increasing carbon uptake has been recognised and approaches to quantifying this pool developed. In New Zealand, harvesting has more than doubled since 1990 while log exports have increased by a factor of 11 due to past afforestation and comparatively little expansion in domestic processing. This paper documents New Zealand’s application of the IPCC approaches for reporting contributions of the HWP pool to net emissions, in order to meet international greenhouse gas inventory reporting requirements. We examine the implications of the different approaches and assumptions used in calculating the HWP contribution and highlight model limitations.

Results

Choice of system boundary has a large impact for a country with a small domestic market and significant HWP exports. Under the Production approach used for New Zealand’s greenhouse gas inventory reporting, stock changes in planted forests and in HWPs both rank highly as key categories. The contribution from HWPs is even greater under the Atmospheric Flow approach, because emissions from exported HWPs are not included. Conversely the Stock Change approach minimises the contribution of HWPs because the domestic market is small. The use of country-specific data to backfill the time series from 1900 to 1960 has little impact but using country-specific parameters in place of IPCC defaults results in a smaller HWP sink for New Zealand. This is because of the dominance of plantation forestry based on a softwood mainly used in relatively short-lived products.

Conclusions

The NZ HWP Model currently meets international inventory reporting requirements. Further disaggregation of the semi-finished HWP end uses both within New Zealand and in export markets is required to improve accuracy. Product end-uses and lifespans need to be continually assessed to capture changes. More extensive analyses that include the benefits of avoided emissions through product substitution and life cycle emissions from the forestry sector are required to fully assess the contribution of forests and forest products to climate change mitigation and a low emissions future.
Risk of cervical lesions in high-risk HPV positive women with normal cytology: a retrospective single-center study in China
Authors: Wang Zhiling , Liu Ting , Wang Yunjian , Gu Ying , Wang Hui , Liu Jingkang , Cui Baoxia , Yang Xingsheng
Published: May 2020

Background

To investigate high-risk HPV (hr-HPV) genotype distributions and the association between hr-HPV infection with severity of the cervical lesions in women with normal cytology.

Methods

In this cross-sectional study, the result of the hr-HPV test and biopsy of colposcopy of women with normal cytology from January 2012 to January 2019 were analyzed. The detection rate of high-grade squamous intraepithelial lesion (HSIL) and cervical cancer were calculated among different hr-HPV genotypes, viral load group, and age groups.

Results

Five thousand eight hundred eighty women were enrolled in this study. Overall, 59.97% had normal histological results, 19.32% had HSIL, and 1.07% had cervical cancer. The detection rate of HSIL or worse (HSIL+) in women with single HPV16(34.00%), HPV31(27.50%), HPV33(25.58%), and HPV52(20.88%) infection were higher significantly than single HPV18 (15.59%) infection, respectively. The HSIL+ detection rate between HPV16 single infection and multiple infections (excluding HPV18) was no significant difference (34% vs 35.47%, P = 0.638), contrary to HPV18(12.59% vs 21.67%, P = 0.022). In women without HPV16/18 infections, HSIL+ detection rates for single, double, and triple or more hr-HPV infections were 12.28, 20.31, and 37.50%, the risk of detection of HSIL+ significantly increasing. With the hr-HPV DNA load increases, the risk of detection of HSIL+ (χ2 = 91.01, P < 0.0001) and invasive cervical cancer (χ2 = 5.757, P = 0.016) increase. In age < 30, 31–40, 41–50, 51–60, > 60 group, HSIL+ detection rate were 24.80%、22.10%、19.59%、14.29, and 12.61%, respectively.

Conclusion

Women who have normal cytology with HPV 16/18/31/33/52/58 infections, multiple HPV infections and high viral load, have a higher detection rate of HSIL+.
Neuroradiology training in EU: international survey of 31 countries within UEMS frame
Authors: Pizzini Francesca B. , Sasiadek Marek , Tanzi Francesco , Ricci Paolo
Published: May 2020

Objective

To assess the current framework of interventional and diagnostic neuroradiology in Europe

Methods

The UEMS (European Union of Medical Specialists) Section of Radiology and the subspecialty UEMS Division of Neuroradiology collected by e-mail a survey on the situation of diagnostic and Interventional Neuroradiology’ training and practice in Europe. The questionnaire was sent to the national delegates from 31 UEMS member countries, belonging to the European Union, the European Economic Area and the Council of Europe. In case of uncertain or discordant replies, the survey envisaged the involvement of neuroradiology scientific societies’ experts for providing a decisive answer.

Results

A formal post-residency training in diagnostic and interventional neuroradiology is provided respectively by 12/31 and 20/31 of the European countries. Currently, for becoming neuroradiologist in a country without fellowship program, a radiologist should (1) get subspecialty credits, (2) follow training inside national or international neuroradiology departments, or (3) perform the main reporting activity in neuroradiology.

In nearly 2/3 of the States included in the survey, the neurointerventional procedures are provided by radiologists (22/31) and in the most frequent scenario a specific training in neurovascular is required to all radiologist or non-radiologist candidates (18/31).

Conclusions

The European framework of neuroradiology’s training and practice that emerged through this survey is fragmented, but there is an increasing attention by European scientific societies and institutions to create a common path of training and practice that can guarantee high educational and patient care standards.
Subducted oceanic crust as the origin of seismically slow lower-mantle structures
Authors: Jones Timothy D. , Maguire Ross R. , van Keken Peter E. , Ritsema Jeroen , Koelemeijer Paula
Published: May 2020

Mantle tomography reveals the existence of two large low-shear-velocity provinces (LLSVPs) at the base of the mantle. We examine here the hypothesis that they are piles of oceanic crust that have steadily accumulated and warmed over billions of years. We use existing global geodynamic models in which dense oceanic crust forms at divergent plate boundaries and subducts at convergent ones. The model suite covers the predicted density range for oceanic crust over lower mantle conditions. To meaningfully compare our geodynamic models to tomographic structures, we convert them into models of seismic wavespeed and explicitly account for the limited resolving power of tomography. Our results demonstrate that long-term recycling of dense oceanic crust naturally leads to the formation of thermochemical piles with seismic characteristics similar to the LLSVPs. The extent to which oceanic crust contributes to the LLSVPs depends upon its density in the lower mantle for which accurate data is lacking. We find that the LLSVPs are not composed solely of oceanic crust. Rather, they are basalt rich at their base (bottom 100–200 km) and grade into peridotite toward their sides and top with the strength of their seismic signature arising from the dominant role of temperature. We conclude that recycling of oceanic crust, if sufficiently dense, has a strong influence on the thermal and chemical evolution of Earth’s mantle.
Sensitivity study for ICON tidal analysis
Authors: Cullens Chihoko Y. , Immel Thomas J. , Triplett Colin C. , Wu Yen-Jung , England Scott L. , Forbes Jeffrey M. , Liu Guiping
Published: May 2020

Retrieval of the properties of the middle and upper atmosphere can be performed using several different interferometric and photometric methods. The emission-shape and Doppler shift of both atomic and molecular emissions can be observed from the ground and space to provide temperature and bulk velocity. These instantaneous measurements can be combined over successive times/locations along an orbit track, or successive universal/local times from a ground station to quantify the motion and temperature of the atmosphere needed to identify atmospheric tides. In this report, we explore how different combinations of space-based wind and temperature measurements affect the retrieval of atmospheric tides, a ubiquitous property of planetary atmospheres. We explore several scenarios informed by the use of a tidally forced atmospheric circulation model, an empirically based emissions reference, and a low-earth orbit satellite observation geometry based on the ICON mission design. This capability provides a necessary tool for design of an optimal mission concept for retrieval of atmospheric tides from ICON remote-sensing observations. Here it is used to investigate scenarios of limited data availability and the effects of rapid changes in the total wave spectrum on the retrieval of the correct tidal spectrum. An approach such as that described here could be used in the design of future missions, such as the NASA DYNAMIC mission (National Research Council, Solar and space physics: a science for a technological society, 2013).
Toxicological evaluations of combined administration of ethanolic stem bark extract of Enantia chlorantha and lisinopril in experimental type 2 diabetes
Authors: Ajani Emmanuel Oladipo , Ibrahim Latifat Bolanle
Published: May 2020

Background

Enantia chlorantha is a local medicinal plant commonly use in Nigeria for the treatment of diabetes but without support of scientific data. Large percentage of people suffering from diabetes who uses the plant as antidiabetic agent also combine its administration with standard antihypertensive drugs.

Aim

In the present study, we have investigated the possible toxicological effects of combined administration of E. chlorantha bark extract and lisinopril in diabetic model of experimental rats.

Methods

E. chlorantha stem bark was extracted by cold maceration of the pulverised stem bark in 70% ethanol. The acute toxicity effect of the plant was then evaluated in rats following oral administration of single dose of the extract. Diabetes was induced by intraperitoneal administration of 40 mg/kg streptozotocin into fructose fed rat. Diabetic rats were then randomly assigned into 6 groups of 7 rats each. One group was kept as the diabetic model while separate treatments were administered to the other six groups. Seven non diabetic rats were kept as the control group and administered normal saline.

Results

The LD50 of E. chlorantha stem bark was above 5000 mg/kg. Combined administration of lisinopril and E. chlorantha showed synergistic effects in the restoration of renal biomarkers (serum creatinine, urea, Na+ and K+), cardiac function biomarkers (CK-MB and LDH) and hematological parameters (RBC, WBC, HGB and PCV), while antagonistic effects were however observed with some of the liver biomarkers (AST, ALT, ALP, GGT, total protein and total bilirubin). Rats co-administered lisinopril and E. chlorantha also showed fatty liver with cholestasis.

Conclusion

The study concluded that diabetes is associated with kidney and cardiac dysfunction. Combined administration of lisinopril and E. chlorantha though may not aggravate these dysfunctions however, it may antagonize the efficacy of the plant in ameliorating liver dysfunction in diabetics.
Portfolio optimization of credit risky bonds: a semi-Markov process approach
Authors: Pasricha Puneet , Selvamuthu Dharmaraja , D’Amico Guglielmo , Manca Raimondo
Published: May 2020

This article presents a semi-Markov process based approach to optimally select a portfolio consisting of credit risky bonds. The criteria to optimize the credit portfolio is based onl∞-norm risk measure and the proposed optimization model is formulated as a linear programming problem. The input parameters to the optimization model are rate of returns of bonds which are obtained using credit ratings assuming that credit ratings of bonds follow a semi-Markov process. Modeling credit ratings by semi-Markov processes has several advantages over Markov chain models, i.e., it addresses the ageing effect present in the credit rating dynamics. The transition probability matrices generated by semi-Markov process and initial credit ratings are used to generate rate of returns of bonds. The empirical performance of the proposed model is analyzed using the real data. Further, comparison of the proposed approach with the Markov chain approach is performed by obtaining the efficient frontiers for the two models.
Predictors of CD4 count changes over time among children who initiated highly active antiretroviral therapy in Ethiopia
Authors: Birhan Tilahun Yemanu , Gezie Lemma Derseh , Teshome Destaw Fetene , Sisay Malede Mequanent
Published: May 2020

Introduction

Human immunodeficiency virus (HIV) infection results in a gradual depletion of immune function, particularly CD4 cells. The CD4 assessment plays a significant role in assessing treatment responses and clinical decision-making for patients on combination antiretroviral therapy (ART) in resource-limited settings. However, new data on CD4 count changes are scarce; the volatility of CD4 counts after initiation of ART over time remains largely uncharacterized. This study aimed to identify the predictors of CD4 changes over time among HIV-infected children who began ART in Amhara, Ethiopia.

Methods

A retrospective follow-up study was performed. A total of 983 HIV-infected children who initiated ART in government hospitals in the Amhara region between 2010 and 2016 were included using a simple random sampling technique. Data were extracted using a structured checklist. An exploratory data analysis was carried out to explain individual and average profile plots. The linear mixed model was used to identify the CD4 change count predictors over time. Variables with p value < 0.05 were considered statistically significant in a multivariable linear mixed regression analysis.

Results

The mean CD4 count of the participants was 465.1 cells/mm3 with an average CD4 count increase of 30.06 cells/mm3 over 6 months from baseline CD4 count and ART initiation. Childhood age (β = − 0.015; 95% Cl − 0.021, − 0.009), opportunistic infection at ART initiation (β = − 0.044, 95% CI − 0.085, − 0.004), hemoglobin level (β = 0.013; 95% CI 0.004, 0.022), and baseline WHO clinical stage II (β = − 0.046, 95% CI − 0.091, − 0.0003) were significant predictors of CD4 changes over time.

Conclusions

The average CD4 count increase was sufficient in HIV patients who began combined antiretroviral therapy over time. The younger age of the infant, the higher baseline level of hemoglobin, the baseline WHO clinical stage II, and opportunistic infections led to changes in CD4 counts. As a result, timely diagnosis and treatment of opportunistic infections will reduce the risk of opportunistic infections.
Membrane lipid raft organization during cotton fiber development
Authors: XU Fan , SUO Xiaodong , LI Fang , BAO Chaoya , HE Shengyang , HUANG Li , LUO Ming
Published: May 2020

Background

Cotton fiber is a single-celled seed trichome that originates from the ovule epidermis. It is an excellent model for studying cell elongation. Along with the elongation of cotton fiber cell, the plasma membrane is also extremely expanded. Despite progress in understanding cotton fiber cell elongation, knowledge regarding the relationship of plasma membrane in cotton fiber cell development remains elusive.

Methods

The plasma membrane of cotton fiber cells was marked with a low toxic fluorescent dye, di-4-ANEPPDHQ, at different stages of development. Fluorescence images were obtained using a confocal laser scanning microscopy. Subsequently, we investigated the relationship between lipid raft activity and cotton fiber development by calculating generalized polarization (GP values) and dual-channel ratio imaging.

Results

We demonstrated that the optimum dyeing conditions were treatment with 3 μmol·L− 1 di-4-ANEPPDHQ for 5 min at room temperature, and the optimal fluorescence images were obtained with 488 nm excitation and 500–580 nm and 620–720 nm dual channel emission. First, we examined lipid raft organization in the course of fiber development. The GP values were high in the fiber elongation stage (5–10 DPA, days past anthesis) and relatively low in the initial (0 DPA), secondary cell wall synthesis (20 DPA), and stable synthesis (30 DPA) stages. The GP value peaked in the 10 DPA fiber, and the value in 30 DPA fiber was the lowest. Furthermore, we examined the differences in lipid raft activity in fiber cells between the short fiber cotton mutant, Li-1, and its wild-type. The GP values of the Li-1 mutant fiber were lower than those of the wild type fiber at the elongation stage, and the GP values of 10 DPA fibers were lower than those of 5 DPA fibers in the Li-1 mutant.

Conclusions

We established a system for examining membrane lipid raft activity in cotton fiber cells. We verified that lipid raft activity exhibited a low-high-low change regularity during the development of cotton fiber cell, and the pattern was disrupted in the short lint fiber Li-1 mutant, suggesting that membrane lipid order and lipid raft activity are closely linked to fiber cell development.
Progress and mechanism of breaking glycoconjugates by glycosidases in skin for promoting unhairing and fiber opening-up in leather manufacture. A review
Authors: Luo Fengxiang , Zhong Xiang , Gao Mengchu , Peng Biyu , Long Zhongzhen
Published: May 2020

The glycoconjugates, herein glyco-proteins, existing in animal skins are closely related to the effectiveness of unhairing and fiber opening-up. Glycosidases have been used in leather making processes to reduce pollutants and improve leather quality. But the selection of glycosidases is still blind because the related mechanisms are not well understood yet. Hence, the animal skin structures and glycoconjugates components, the advances in the methods and mechanisms of removing glycoconjugates related to unhairing and fiber opening-up in leather manufacture, the kinds, compositions, structures and functions of typical glycoconjugates in skin are summarized. Then the approaches to destroy them, possible glycosidases suitable for leather making and their acting sites are analyzed based on the recognition of glycoconjugates in skin and the specificities of glycosidases toward substrates. It is expected to provide useful information for the optimization of glycosidases and the development of new enzymes and the cleaner technologies of unhairing and opening up fiber bundles assisted by glycosidases.

Graphical abstract
Can social isolation caused by physical distance in people with psychosis be overcome through a Phone Pal?
Authors: Pinto da Costa Mariana
Published: May 2020

The current pandemic has forced many people into self-isolation and to practice social distancing. When people are physically isolated and distant from each other, technology may play a fundamental role by enabling social connection and reducing feelings of loneliness caused by this prolonged social isolation. In response to the COVID-19 pandemic, many mental health services worldwide have had to shift their routine face-to-face outpatient appointments to remote telepsychiatry encounters. The increased pressure on mental health services highlights the importance of community-led health-promotion interventions, which can contribute to preventing mental illness or their relapses, and to reduce the burden on health services. Patients with psychosis are particularly socially isolated, have sedentary lifestyles, and commonly face stigma and discrimination from the general population. At the same time, patients with psychosis value technology, are interested in, use and own smart-phones to digitally connect, and are satisfied with their use. Thus, among psychosocial interventions, a helpful resource may be “Phone Pal,” a complex intervention which facilitates remote communication between volunteers and socially isolated patients with psychosis through different smart-phone tools. While “Phone Pal” has been originally developed for people with psychosis, it may also be useful to the wider population, helping to overcome the social isolation caused by physical distancing, particularly in these times of widespread isolation. “Phone Pal” may be a potential public health resource for society, providing important support to those that may need it the most, and possibly benefit most from it.
Core Hippo pathway components act as a brake on Yap/Taz in the development and maintenance of the biliary network
Authors: Brandt Zachary J. , Echert Ashley E. , Bostrom Jonathan R. , North Paula N. , Link Brian A.
Published: May 2020

The development of the biliary system is a complex yet poorly understood process, with relevance to multiple diseases including biliary atresia, choledochal cysts, and gallbladder agenesis. We present here a crucial role for Hippo-Yap/Taz signaling in this context. Analysis of sav1 mutant zebrafish revealed dysplastic morphology and expansion of both intrahepatic and extrahepatic biliary cells, and ultimately larval lethality. Biliary dysgenesis, but not larval lethality, is driven primarily by Yap signaling. Re-expression of Sav1 protein in sav1−/− hepatocytes is able to overcome these initial deficits and allow sav1−/− fish to survive, suggesting cell non-autonomous signaling from hepatocytes. Examination of sav1−/− rescued adults reveals loss of gallbladder and formation of dysplastic cell masses expressing biliary markers suggesting roles for Hippo signaling in extrahepatic biliary carcinomas. Deletion of stk3 revealed the phenotypes observed in sav1 mutant fish function primarily through canonical Hippo signaling and supports a role for phosphatase PP2A, but also suggests Sav1 has functions in addition to facilitating Stk3 activity. Overall, this study defines a role for Hippo-Yap signaling in the maintenance of both intra- and extrahepatic biliary ducts.
Branching morphogenesis
Authors: Goodwin Katharine , Nelson Celeste M.
Published: May 2020

Over the past 5 years, several studies have begun to uncover the links between the classical signal transduction pathways and the physical mechanisms that are used to sculpt branched tissues. These advances have been made, in part, thanks to innovations in live imaging and reporter animals. With modern research tools, our conceptual models of branching morphogenesis are rapidly evolving, and the differences in branching mechanisms between each organ are becoming increasingly apparent. Here, we highlight four branched epithelia that develop at different spatial scales, within different surrounding tissues and via divergent physical mechanisms. Each of these organs has evolved to employ unique branching strategies to achieve a specialized final architecture.
MLL4 is required after implantation whereas MLL3 becomes essential during late gestation
Authors: Ashokkumar Deepthi , Zhang Qinyu , Much Christian , Bledau Anita S. , Naumann Ronald , Alexopoulou Dimitra , Dahl Andreas , Goveas Neha , Fu Jun , Anastassiadis Konstantinos , Stewart A. Francis , Kranz Andrea
Published: May 2020

Methylation of histone 3 lysine 4 (H3K4) is a major epigenetic system associated with gene expression. In mammals there are six H3K4 methyltransferases related to yeast Set1 and fly Trithorax, including two orthologs of fly Trithorax-related: MLL3 and MLL4. Exome sequencing has documented high frequencies of MLL3 and MLL4 mutations in many types of human cancer. Despite this emerging importance, the requirements of these paralogs in mammalian development have only been incompletely reported. Here we examined the null phenotypes to establish that MLL3 is first required for lung maturation whereas MLL4 is first required for migration of the anterior visceral endoderm (AVE) that initiates gastrulation. This collective cell migration is preceded by a columnar to squamous transition in visceral endoderm cells that depends on MLL4. Furthermore, Mll4 mutants display incompletely penetrant, sex distorted, embryonic haploinsufficiency and adult heterozygous mutants show aspects of Kabuki syndrome, indicating that MLL4 action, unlike MLL3, is dosage dependent. The highly specific and discordant functions of these paralogs in mouse development argues against their action as general enhancer factors.
Autophagy and endocytosis – interconnections and interdependencies
Authors: Birgisdottir Åsa B. , Johansen Terje
Published: May 2020

Autophagy and endocytosis are membrane-vesicle-based cellular pathways for degradation and recycling of intracellular and extracellular components, respectively. These pathways have a common endpoint at the lysosome, where their cargo is degraded. In addition, the two pathways intersect at different stages during vesicle formation, fusion and trafficking, and share parts of the molecular machinery. Accumulating evidence shows that autophagy is dependent upon endocytosis and vice versa. The emerging joint network of autophagy and endocytosis is of vital importance for cellular metabolism and signaling, and thus also highly relevant in disease settings. In this Review, we will discuss examples of how the autophagy machinery impacts on endocytosis and cell signaling, and highlight how endocytosis regulates the different steps in autophagy in mammalian cells. Finally, we will focus on the interplay of these pathways in the quality control of their common endpoint, the lysosome.
Cofilin is required for polarization of tension in stress fiber networks during migration
Authors: Lee Stacey , Kumar Sanjay
Published: May 2020

Cell migration is associated with the establishment of defined leading and trailing edges, which in turn requires polarization of contractile forces. While the actomyosin stress fiber (SF) network plays a critical role in enforcing this polarity, precisely how this asymmetry is established remains unclear. Here, we provide evidence for a model in which the actin-severing protein cofilin (specifically cofilin-1) participates in symmetry breakage by removing low-tension actomyosin filaments during transverse arc assembly. Cofilin knockdown (KD) produces a non-polarized SF architecture that cannot be rescued with chemokines or asymmetric matrix patterns. Whereas cofilin KD increases whole-cell prestress, it decreases prestress within single SFs, implying an accumulation of low-tension SFs. This notion is supported by time-lapse imaging, which reveals weakly contractile and incompletely fused transverse arcs. Confocal and super-resolution imaging further associate this failed fusion with the presence of crosslinker-rich, tropomyosin-devoid nodes at the junctions of multiple transverse arc fragments and dorsal SFs. These results support a model in which cofilin facilitates the formation of high-tension transverse arcs, thereby promoting mechanical asymmetry.
A subset of flavaglines inhibits KRAS nanoclustering and activation
Authors: Yurugi Hajime , Zhuang Yinyin , Siddiqui Farid A. , Liang Hong , Rosigkeit Sebastian , Zeng Yongpeng , Abou-Hamdan Hussein , Bockamp Ernesto , Zhou Yong , Abankwa Daniel , Zhao Wenting , Désaubry Laurent , Rajalingam Krishnaraj
Published: May 2020

The RAS oncogenes are frequently mutated in human cancers and among the three isoforms (KRAS, HRAS and NRAS), KRAS is the most frequently mutated oncogene. Here, we demonstrate that a subset of flavaglines, a class of natural anti-tumour drugs and chemical ligands of prohibitins, inhibit RAS GTP loading and oncogene activation in cells at nanomolar concentrations. Treatment with rocaglamide, the first discovered flavagline, inhibited the nanoclustering of KRAS, but not HRAS and NRAS, at specific phospholipid-enriched plasma membrane domains. We further demonstrate that plasma membrane-associated prohibitins directly interact with KRAS, phosphatidylserine and phosphatidic acid, and these interactions are disrupted by rocaglamide but not by the structurally related flavagline FL1. Depletion of prohibitin-1 phenocopied the rocaglamide-mediated effects on KRAS activation and stability. We also demonstrate that flavaglines inhibit the oncogenic growth of KRAS-mutated cells and that treatment with rocaglamide reduces non-small-cell lung carcinoma (NSCLC) tumour nodules in autochthonous KRAS-driven mouse models without severe side effects. Our data suggest that it will be promising to further develop flavagline derivatives as specific KRAS inhibitors for clinical applications.
Predição de casos e óbitos de COVID-19 em Mato Grosso e no Brasil
Authors: Espinosa Mariano Martinez , Oliveira Elaine Cristina de , Melo Juliano Silva , Damaceno Roney Dias , Terças-Trettel Ana Cláudia Pereira
Published: May 2020

Objetivos: prever a tendência epidemiológica de casos e óbitos do COVID-19 no Brasil e, especificamente, em Mato Grosso, por meio do modelo estatístico duplo exponencial. Métodos: para a realização deste trabalho, foram utilizados dados de casos e óbitos do COVID-19 fornecidos pelo Ministério da Saúde do Brasil e Secretaria de Estado de Saúde de Mato Grosso, e, para realizar as previsões com esses dados, foi utilizada a técnica estatística de séries temporais, considerando o modelo exponencial duplo, e para o processamento dos dados, foi utilizado o programa MINITAB V 17. Resultados: os resultados mostram que os valores ajustados pelo modelo exponencial duplo transformado dos casos e óbitos estão muito próximos dos valores observados de COVID-19 noBrasil e, principalmente, em Mato Grosso, no período considerado, indicando que esse modelo é adequado para os dados em estudo, o qual foi verificado, prevendo alguns valores com seus respectivos intervalos de confiança de 95%. Conclusões: a possibilidade de se estimar, pautado em análises estatísticas, o número de casos e óbitos de COVID-19 que ocorrerá no Brasil e no estado de Mato Grosso poderá instrumentalizar os gestores para o planejamento deações estratégicas de prevenção, monitoramento e controle da pandemia.
Recent advances in understanding the neonatal microbiome
Authors: Dalby Matthew J. , Hall Lindsay J.
Published: May 2020

The neonatal developmental window represents a key time for establishment of the gut microbiota. First contact with these microbes within the infant gastrointestinal tract signifies the start of a critical mutualistic relationship, which is central for short- and longer-term health. Recent research has provided insights into the origin of these microbial pioneers, how they are maintained within the gut environment, and how factors such as antibiotics or preterm birth may disrupt the succession of beneficial microbes.  The acquisition, colonisation, and maintenance of the early life microbiota, and subsequent interactions with the host is a rapidly developing research area. In this review we explore some of these key topics which have been illuminated by recent research, and we highlight some of the important unresolved questions which currently limit our overall understanding of the neonatal gut microbiome.
The Benefits and Risks of Iron interventionS in Children (BRISC) trial: Statistical analysis plan
Authors: Braat Sabine , Larson Leila , Simpson Julie A. , Hasan Mohammed Imrul , Hamadani Jena Derakhshani , Hossain Sheikh Jamal , Shiraji Shamima , Bhuiyan Mohammad Saiful Alam , Biggs Beverley-Ann , Pasricha Sant-Rayn
Published: May 2020

Background: The Benefits and Risks of Iron interventionS in Children (BRISC) trial will evaluate the impact of universal supplementation with iron supplements or iron-containing multiple micronutrient powders (MNPs) compared with placebo given for 3 months on child development, growth, morbidity, laboratory indices of anaemia, iron deficiency, and inflammation at end of intervention and after a further 9 months post intervention in children aged 8 months living in rural Bangladesh. This paper describes the statistical analysis plan.

Methods: BRISC is a multi-site, three-arm, double-dummy blinded, parallel group, randomised control superiority trial in 3300 children. The statistical analysis plan was developed by the trial statistician in consultation with the trial steering committee and trial management committee based on the protocol, data collection forms, and study outcomes available in the blinded study database.  

Conclusion: This detailed statistical analysis plan published prior to unblinding the allocated treatments will support the statistical analyses and reporting of the BRISC trial to be undertaken after unblinding. It allows for transparency as well as reproducibility of statistical analyses and reporting.

Registration: Australian New Zealand Clinical Trials Registry ACTRN12617000660381 (registered on 8 May 2017); World Health Organization Universal Trial Number U1111-1196-1125.