bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling of neutrophil dynamics in children receiving busulfan or treosulfan for haematopoietic stem cell transplant conditioning
Authors: Solans Belén P. , Chiesa Robert , Doncheva Bilyana , Prunty Helen , Veys Paul , Trocóniz Iñaki F. , Standing Joseph F. 
Published: February 2020

AimsBusulfan and treosulfan are cytotoxic agents used in the conditioning regime prior to paediatric haematopoietic stem cell transplantation (HSCT). These agents cause suppression of myeloid cells leaving patients severely immunocompromised in the early post‐HSCT period. The main objectives were: (i) to establish a mechanistic pharmacokinetic–pharmacodynamic (PKPD) model for the treatment and engraftment effects on neutrophil counts comparing busulfan and treosulfan‐based conditioning, and (ii) to explore current dosing schedules with respect to time to HSCT.MethodsData on 126 patients, 72 receiving busulfan (7 months–18 years, 5.1–47.0 kg) and 54 treosulfan (4 months–17 years, 3.8–35.8 kg), were collected. In total, 8935 neutrophil count observations were recorded during the study period in addition to drug concentrations to develop a mechanistic PKPD model. Absolute neutrophil count profiles were modelled semimechanistically, accounting for transplant effects and differing set points pre‐ and post‐transplant.ResultsPK were best described by 2‐compartment models for both drugs. The Friberg semimechanistic neutropenia model was applied with a linear model for busulfan and a maximum efficacy model for treosulfan describing drug effects at various stages of neutrophil maturation. System parameters were consistent across both drugs. The HSCT was represented by an amount of progenitor cells enhancing the neutrophils' proliferation and maturation compartments. Alemtuzumab was found to enhance the proliferative rate under which the absolute neutrophil count begin to grow after HSCT.ConclusionA semimechanistic PKPD model linking exposure to either busulfan or treosulfan to the neutrophil reconstitution dynamics was successfully built. Alemtuzumab coadministration enhanced the neutrophil proliferative rate after HSCT. Treosulfan administration was suggested to be delayed with respect to time to HSCT, leaving less time between the end of the administration and stem cell infusion.
Late bedtime and dental caries incidence in Kuwaiti children: A longitudinal multilevel analysis
Authors: Alqaderi Hend , Tavares Mary , Al‐Mulla Fahd , Al‐Ozairi Ebaa , Goodson Jo Max 
Published: February 2020

AbstractObjectiveInadequate sleep contributes to several adverse systemic health outcomes due to hormonal and metabolic disorders. The purpose of this study was to determine the effect of bedtime on the development of dental caries and the relationship with salivary ghrelin and leptin in a prospective cohort study of Kuwaiti children.MethodsData were collected from 5456 10‐year‐old children in 2012 and repeated in 2014. We selected children from 138 middle schools representing the six governorates of Kuwait. We derived data from oral examinations, self‐reported sleep interviews, body and weight measurements, and chemical analysis of whole saliva samples. Leptin and ghrelin were determined by salivary assay in a subset of 744. Two separate analyses were performed. a) Using the entire longitudinal data set (n = 5456), multilevel random intercept analysis was conducted to assess the relationship between reported bedtime and dental caries. b) Using data from a subset of the original sample (n = 744), multiple linear regression analysis was conducted to determine the relationship between dental caries and salivary ghrelin and leptin. The outcome variable was the development of dental caries in children. The independent explanatory variables and confounders were bedtime, sleep duration, salivary ghrelin and leptin; confounders assessed were gingivitis, sex, age and governorate (school location).ResultsWith every additional hour past 8 pm for bedtime, there was a 20% increase in dental caries incidence over two years (B = 0.2, P = .01), adjusting for age, gender, gingivitis and governorate. There was a significant difference in the magnitude of dental caries between the six governorates of Kuwait. Lower levels of salivary leptin and higher levels of salivary ghrelin were associated with increased dental caries, and sleep duration was an effect modifier that negatively affected the relationship between leptin and dental caries (B = −0.09, P < .05) and positively affects the relationship between ghrelin and dental caries (B = 0.07, P < .05). Additionally, there was a significant clustering effect within schools in this cohort.ConclusionIn a cohort study of Kuwaiti children, late bedtime was associated with increased dental caries incidence. Additionally, dental caries experience increased with higher levels of salivary ghrelin and lower levels of salivary leptin, and sleep duration mediates the relationship between these two biomarkers and dental caries.
Molecular approaches to allergen‐specific immunotherapy: Are we so far from clinical implementation?
Authors: Pechsrichuang Phornsiri , Jacquet Alain 
Published: February 2020

AbstractConventional allergen‐specific immunotherapy (AIT), based on administrations of allergen extracts, represents up to now the unique protocol for the desensitization of allergic patients. Whereas the effectiveness of AIT was evidenced for the treatment of allergic rhinitis and allergic asthma, such strategy remains experimental for food allergies up to now. However, important issues are commonly associated with AIT as the quality of natural allergen extracts, the long duration and adverse side‐effects which negatively affect successful desensitization together with the patient compliance. The rapid progression of molecular allergology made possible the quest of safer, shorter and more effective immunotherapeutic approaches. The aim of this review was to provide an update on these different innovative recombinant derivatives including their efficacy but also their limitations. Despite promising preclinical and early clinical studies, the absence of convincing data in large phase III trials precludes so far the translation of these immunotherapeutic candidates into the clinic.
Oxidative stress‐induced retinal damage is prevented by mild hypothermia in an ex vivo model of cultivated porcine retinas
Authors: Mueller‐Buehl Ana M. , Doepper Hannah , Grauthoff Sven , Kiebler Tobias , Peters Laura , Hurst José , Kuehn Sandra , Bartz‐Schmidt Karl U. , Dick H. Burkard , Joachim Stephanie C. , Schnichels Sven 
Published: February 2020

AbstractBackgroundHydrogen peroxide (H2O2) can be used in vitro to simulate oxidative stress. In retinal organ cultures, H2O2 induces strong neurodegeneration of the retina. It is known that oxidative stress plays a role in the development of several retinal diseases including glaucoma and ischemia. Thus, we investigated whether processes underlying oxidative stress can be prevented by hypothermia using an ex vivo organ culture model of porcine retinas.MethodsPorcine retinal explants were cultivated for 5 and 8 days. Oxidative stress was induced via 300 μM H2O2 on day 1 for 3 hours. Hypothermia treatment at 30°C was applied simultaneously with H2O2, for 3 hours. Retinal ganglion cells (RGCs), apoptosis, bipolar and cholinergic amacrine cells, microglia and macroglia were evaluated immunohistologically. Apoptosis rate was additionally analysed via western blot.ResultsReduced apoptosis rates through hypothermia led to a preservation of RGCs (P < .001). Amacrine cells were rescued after hypothermia treatment (P = .17), whereas bipolar cells were only protected partly. Additionally, at 8 days, microglial response due to oxidative stress was completely counteracted via hypothermia (P < .001).ConclusionsH2O2 induced strong degenerative processes in porcine retinas. The role of oxidative stress in the progression of retinal diseases makes this ex vivo organ culture model suitable to investigate new therapeutic approaches. In the present study, the damaging effect of H2O2 to several retinal cell types was counteracted or strongly alleviated through hypothermia treatment. Especially RGCs, which are affected in glaucoma disease, were protected due to a reduced apoptosis rate through hypothermia.
How to ask about the use of new psychoactive substances to increase the validity of results in self‐report prevalence surveys
Authors: Drapalova Eva , Belackova Vendula , Cadet‐Taïrou Agnès 
Published: February 2020

AbstractIntroduction and AimsNew psychoactive substances (NPS) represent hundreds of novel compounds. However, the general public might not be familiar with the overarching term NPS. This can result in both under‐ and over‐reporting of NPS use.Design and MethodsThe study analysed the last‐year prevalence of NPS use in an online survey conducted across I‐TREND project countries (the Czech Republic, the Netherlands and Poland). Self‐reported NPS use was assessed within two types of questions—a generic and a checklist question. We analysed prevalence for each question separately, incorporated the free‐text probe ‘other’ that followed them, and combined the two questions into a conservative and an inclusive estimate.ResultsIncluding free‐text responses to the ‘other’ categories increased prevalence of NPS use (from 51% to 56% for the checklist question and 25% to 32% for the generic question). Taking an inclusive approach to estimating prevalence (i.e. indicating NPS use in either a generic list or from the checklist) yielded a higher prevalence estimate (60%, 95% confidence interval 58–62%), compared to a more conservative approach in which NPS use had to be affirmed by both questions (27%, 95% confidence interval 26–29%).Discussion and ConclusionsGeneric questions might lead to notably lower estimates of self‐reported NPS use in comparison to checklists. However, creating relevant checklists is challenging and lengthy survey instruments have limitations. Further surveys might benefit from featuring a combination of the strategies used in this study—a single (generic) question involving a number of locally specific NPSs and a free‐text ‘other’ probe.
Combined total skin radiotherapy and immune checkpoint inhibitors: A promising potential treatment for mycosis fungoides and Sezary syndrome
Authors: Elsayad Khaled , Stadler Rudolf , Steinbrink Kerstin , Eich Hans Theodor 
Published: February 2020

SummaryRadiotherapy, particularly total skin electron beam therapy (TSEB), is one of the main pillars in the strategy for treatment of cutaneous T‐cell lymphoma (CTCL). Low‐dose TSEB has gained considerable attention since it has a minimal toxicity profile. Low‐dose TSEB has been shown to yield an overall response rate up to 95 %, although the response duration is usually short. Few studies have been published on treatment outcomes after combined treatment of CTCL with TSEB and systemic therapy. Remission rates of patients who received immune checkpoint inhibitors alone ranged from 15–38 % with a two‐year progression‐free survival of 69 %. Given that TSEB results in rapid reduction of the disease burden in almost all patients, we hypothesized that TSEB followed by immune checkpoint inhibitors might be a reasonable treatment with a sustained effect for treatment‐experienced patients with mycosis fungoides and Sezary syndrome.
Efficacy and tolerability of sodium‐glucose co‐transporter‐2 inhibitors and glucagon‐like peptide‐1 receptor agonists: A systematic review and network meta‐analysis
Authors: Hussein Humaira , Zaccardi Francesco , Khunti Kamlesh , Davies Melanie J. , Patsko Emily , Dhalwani Nafeesa N. , Kloecker David E. , Ioannidou Ekaterini , Gray Laura J. 
Published: February 2020

AbstractAimTo compare the efficacy and tolerability of sodium‐glucose co‐transporter 2 inhibitors (SGLT‐2is) and glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) in adults with type 2 diabetes.Materials and methodsElectronic databases were searched from inception to 24 April 2019 for randomized controlled trials reporting change in glycated haemoglobin (HbA1c) at approximately 24 and/or 52 weeks for SGLT‐2is and/or GLP‐1RAs (classified as short‐ and long‐acting). Bayesian network meta‐analyses were conducted to compare within and between SGLT‐2i and GLP‐1RA classes for cardiometabolic efficacy and adverse events (PROSPERO registration number: CRD42018091306).ResultsSixty‐four trials (53 trials of 24 weeks; seven trials of 52 weeks; four trials of both 24 and 52 weeks), comprising 31 384 participants were identified. Compared with placebo, all treatments improved HbA1c. Long‐acting GLP‐1RAs reduced HbA1c compared with short‐acting GLP‐1RAs and SGLT‐2is, with semaglutide showing greater reduction compared with placebo [24 weeks: −1.49% (95% credible interval: −1.76, −1.22); 52 weeks: −1.38% (−2.05, −0.71)] and all other treatments. Long‐acting GLP‐1RAs showed benefits in body weight and waist circumference reduction, while SGLT‐2is reduced blood pressure. SGLT‐2is showed increased risk of genital infection in comparison with long‐acting GLP‐1RAs [odds ratio (95% credible interval): 5.26 (1.45, 25.00)], while GLP‐1RAs showed increased risk of diarrhoea in comparison with SGLT‐2is [short‐acting GLP‐1RAs: 1.65 (1.09, 2.49); long‐acting GLP‐1RAs: 2.23 (1.51, 3.28)]. No other differences were found between SGLT‐2is and GLP‐1RAs in adverse events.ConclusionLong‐acting GLP‐1RAs showed superiority in reducing HbA1c levels, body weight and waist circumference. SGLT‐2is showed reductions in blood pressure levels. This review provides essential evidence to guide treatment recommendations in the management of type 2 diabetes.
Myocardial longitudinal strain, fitness, and heart failure risk factors in young adults
Authors: Arenas Ivan A. , Podesta Carlos A. , Issa Omar , Lin Jeffrey , Brenes Juan C. 
Published: February 2020

AbstractAimsTo investigate the relationship between fitness, heart failure (HF) risk factors (age, blood pressure, and obesity), and global/regional myocardial longitudinal strain in young adults undergoing stress testing.MethodsIndividuals 25–55 years old without any significant medical history, not taking medications, and with a normal maximal stress echocardiogram were eligible. Global and regional longitudinal strain (LS) was evaluated by 2D speckle tracking echocardiography.ResultsOne hundred and seventy patients were included, of which 60% were males. The mean age was 43 years old, 49% had optimal blood pressure, and 30% were obese. On average, patients achieved 10.5 (3) METS, and the global LS was −19.9 (3.1) %. Reduced fitness was associated with decreased global longitudinal strain (GLS). Those in the top GLS quartile walked on average 1 minute and 21 seconds longer compared with the lowest quartile (P < .001). The effect of fitness on LS was preferential to the mid and apex, such that there was an apex‐to‐base gradient. Obesity was also independently associated with reduced GLS. However, the reduction in LS in obese individuals was more prominent at the base and mid‐walls with relative sparing of the apex. Similar to fitness, aging was also associated with an increase in the apex‐to‐base gradient of LS. Furthermore, diastolic filling parameters correlated distinctively with regional LS.ConclusionsIn young adults without cardiovascular disease, low fitness and obesity are independently associated with reduced left ventricular longitudinal strain. There is a differential effect of HF risk factors on regional longitudinal function.
Unusual place… unusual number
Authors: Vieira Maria João , Craveiro Nuno , Alves Miguel , Pitta Luz 
Published: February 2020

AbstractCardiac papillary fibroelastoma is a rare, benign cardiac tumor. It often arises from the valvular endocardium and is usually solitary. Nonvalvular location is rare and even more rare is the presentation as multiple masses. A 71‐year‐old female patient was referred for echocardiographic evaluation due to progressive fatigue. The presence of multiple left atrial masses was observed on echocardiographic evaluation. The patient was treated surgically for the prevention of embolic complications, and the histologic diagnosis of multiple nonvalvular papillary fibroelastoma was made. This case highlights the need to consider this unusual location and presentation for this type of tumor.
A core curriculum in the biological and biomedical sciences for dentistry
Authors: Bennett Jon H. , Beeley Josie A. , Anderson Paul , Belfield Louise , Brand Henk S. , Didilescu Andreea C. , Dymock David , Guven Yegane , Hector Mark P. , Holbrook Peter , Jayasinghe Jaya A. P. , O'Sullivan Jeff , Riggio Marcello , Roger‐Leroi Valerie , Scheven Ben , Sloan Alastair J. , Vandamme Katleen , Manzanares Maria‐Cristina 
Published: February 2020

AbstractIntroductionThe biomedical sciences (BMS) are a central part of the dental curriculum that underpins teaching and clinical practice in all areas of dentistry. Although some specialist groups have proposed curricula in their particular topic areas, there is currently no overarching view of what should be included in a BMS curriculum for undergraduate dental programmes. To address this, the Association for Dental Education in Europe (ADEE) convened a Special Interest Group (SIG) with representatives from across Europe to develop a consensus BMS curriculum for dental programmes.CurriculumThis paper summarises the outcome of the deliberations of this SIG and details a consensus view from the SIG of what a BMS curriculum should include.ConclusionsGiven the broad nature of BMS applied to dentistry, this curriculum framework is advisory and seeks to provide programme planners with an indicative list of topics which can be mapped to specific learning objectives within their own curricula. As dentistry becomes increasingly specialised, these will change, or some elements of the undergraduate curriculum may move to the post‐graduate setting. So, this document should be seen as a beginning and it will need regular review as BMS curricula in dentistry evolve.
Non‐memory cognitive symptom development in Alzheimer's disease
Authors: Blenkinsop A. , van der Flier W. M. , Wolk D. , Lehmann M. , Howard R. , Frost C. , Barnes J. 
Published: February 2020

Background and purposeMemory is known to be the most common first symptom in Alzheimer’s disease (AD). Assessing non‐memory cognitive symptom development in AD is important for understanding disease progression and the potential identification of treatment‐responsive subtypes.MethodsData from the National Alzheimer’s Coordinating Center were examined. Logistic regression models were fitted evaluating the development of judgement, language, visuospatial and attention symptoms at first and second visits to Alzheimer’s Disease Centers. Predictors were age and prior symptoms, adjusting for symptom length and sex. The models were then refitted assessing apolipoprotein E ε4 (APOE‐ε4) effects.ResultsEach decade reduction in presentation age increased the odds of language, visuospatial and attention symptom development at both visits by 8%–18% (P < 0.05, all tests), and judgement symptoms at the second visit by 13% (P < 0.05). Prior symptoms were not equally predictive of symptom development. For example, having first predominant language symptoms carried the lowest risk of developing other first‐visit symptoms and having memory symptoms was a stronger predictor of developing judgement than other symptoms. The APOE‐ε4 gene showed little impact on symptom development when included as a predictor.ConclusionsOur findings provide support for the concept that younger‐onset AD is associated with the progressive development of more non‐memory symptoms beyond the first time point. Associations between symptoms were evident, which may reflect that pathology can remain isolated in a network for some time. APOE‐ε4 status had little influence on cognitive symptom development which may indicate that the effect it has occurs very early in the disease course.
Pro‐islet amyloid polypeptide in micelles contains a helical prohormone segment
Authors: DeLisle Charles F. , Malooley Alexander L. , Banerjee Indrani , Lorieau Justin L. 
Published: February 2020

Pro‐islet amyloid polypeptide (proIAPP) is the prohormone precursor molecule to IAPP, also known as amylin. IAPP is a calcitonin family peptide hormone that is cosecreted with insulin, and largely responsible for hunger satiation and metabolic homeostasis. Amyloid plaques containing mixtures of mature IAPP and misprocessed proIAPP deposit on, and destroy pancreatic β‐cell membranes, and they are recognized as a clinical hallmark of type 2 diabetes mellitus. In order to better understand the interaction with cellular membranes, we solved the solution NMR structure of proIAPP bound to dodecylphosphocholine micelles at pH 4.5. We show that proIAPP is a dynamic molecule with four α‐helices. The first two helices are contained within the mature IAPP sequence, while the second two helices are part of the C‐terminal prohormone segment (Cpro). We mapped the membrane topology of the amphipathic helices by paramagnetic relaxation enhancement, and we used CD and diffusion‐ordered spectroscopy to identify environmental factors that impact proIAPP membrane affinity. We discuss how our structural results relate to prohormone processing based on the varied pH environments and lipid compositions of organelle membranes within the regulated secretory pathway, and the likelihood of Cpro survival for cosecretion with IAPP.DatabaseThe assigned resonances have been deposited in the Biological Magnetic Resonance Bank (BMRB) with accession numbers 50007 and 50019 for proIAPP and Cpro, respectively. The lowest energy structures have been deposited in the Protein Data Bank (PDB) with access codes 6UCJ and 6UCK.
Assessing the influence of wildfire on leaf decomposition and macroinvertebrate communities in boreal streams using mixed‐species leaf packs
Authors: Musetta‐Lambert Jordan L. , Kreutzweiser David P. , Sibley Paul K. 
Published: February 2020

Abstract

We investigated how compositional differences in riparian leaf litter derived from burned and undisturbed forests influenced leaf breakdown and macroinvertebrate communities using experimental mixed‐species leaf packs in boreal headwater streams. Leaf pack mixtures simulating leaf litter from dominant riparian woody‐stem species in burned and undisturbed riparian zones were incubated in two references and two fire‐disturbed streams for 5 weeks prior to measuring temperature‐corrected breakdown rates and macroinvertebrate community composition, richness, and functional metrics associated with decomposers such as shredder abundance and % shredders.

Leaf litter breakdown rates were higher and had greater variability in streams bordered by reference riparian forests than in streams where riparian forests had been burned during a wildfire. Streams bordered by fire disturbance showed significant effects of litter mixture on decomposition rates, observed as significantly higher decomposition rates of a fire‐simulated leaf mixture compared to all other mixtures.

Variation among sites was higher than variation among litter mixtures, especially for macroinvertebrate community composition. In general, fire‐simulated leaf mixtures had greater shredder abundances and proportions, but lower overall macroinvertebrate abundance; however, the shredder abundance trend was not consistent across all leaf mixtures at each stream.

These results show that disturbance‐driven riparian forest condition and resulting composition of leaf subsidies to streams can influence aquatic invertebrate community composition and their function as decomposers. Therefore, if one of the primary goals of modern forest management is to emulate natural disturbance patterns, boreal forest managers should adapt silvicultural practices to promote leaf litter input that would arise post‐fire, thereby supporting stream invertebrate communities and their function.