bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential for pharmacokinetic interactions between Schisandra sphenanthera and bosutinib, but not imatinib: in vitro metabolism study combined with a physiologically‐based pharmacokinetic modelling approach
Authors: Adiwidjaja Jeffry , Boddy Alan V. , McLachlan Andrew J. 
Published: April 2020

AimsThis study aimed to investigate the potential interaction between Schisandra sphenanthera, imatinib and bosutinib combining in vitro and in silico methods.MethodsIn vitro metabolism of imatinib and bosutinib using recombinant enzymes and human liver microsomes were investigated in the presence and absence of Schisandra lignans. Physiologically‐based pharmacokinetic (PBPK) models for the lignans accounting for reversible and mechanism‐based inhibitions and induction of CYP3A enzymes were built in the Simcyp Simulator (version 17) and evaluated for their capability to predict interactions with midazolam and tacrolimus. Their potential effect on systemic exposures of imatinib and bosutinib were predicted using PBPK in silico simulations.ResultsSchisantherin A and schisandrol B, but not schisandrin A, potently inhibited CYP3A4‐mediated metabolism of imatinib and bosutinib. All three compounds showed a strong reversible inhibition on CYP2C8 enzyme with ki of less than 0.5 μmol L−1. The verified PBPK models were able to describe the increase in systemic exposure of midazolam and tacrolimus due to co‐administration of S. sphenanthera, consistent with the reported changes in the corresponding clinical interaction study (AUC ratio of 2.0 vs 2.1 and 2.4 vs 2.1, respectively). The PBPK simulation predicted that at recommended dosing regimens of S. sphenanthera, co‐administration would result in an increase in bosutinib exposure (AUC ratio 3.0) but not in imatinib exposure.ConclusionPBPK models for Schisandra lignans were successfully developed. Interaction between imatinib and Schisandra lignans was unlikely to be of clinical importance. Conversely, S. sphenanthera at a clinically‐relevant dose results in a predicted three‐fold increase in bosutinib systemic exposure.
Effect of liraglutide on food consumption, appetite sensations and eating behaviours in overweight people with type 1 diabetes
Authors: Dubé Marie‐Christine , D'Amours Martin , Weisnagel S. John 
Published: April 2020

AbstractAimsTo investigate the effects of 24 weeks of treatment with liraglutide added to basal/bolus insulin on energy intake, appetite sensations and eating behaviours in overweight/obese participants with type 1 diabetes (T1D).MethodsIn a double‐blinded crossover fashion, 15 participants were randomly assigned (1:1) to receive placebo or liraglutide for 24 weeks including a 1‐month titration period from 0.6 to 1.2 to 1.8 mg, in addition to their insulin. The treatment was followed by a 1‐month wash‐out period. Participants were then assigned to the other treatment for another 24 weeks. Food intake was measured, visual analogue scales and Three‐Factor Eating Questionnaires were completed. Paired rank tests were used to compare the variables.ResultsWhen treated with liraglutide, participants modified their ad libitum food consumption with decreased total intake and % fat and increased carbohydrates. Their appetite sensations were modified: fasting desire to eat, hunger and prospective food consumption were significantly reduced. The sensation of fullness was prolonged for a few hours after a standardized breakfast. Restraint and disinhibition were significantly reduced by liraglutide.ConclusionsIn this randomized clinical trial, the addition of liraglutide to basal/bolus insulin therapy for 24 weeks in overweight/obese individuals with T1D significantly improved their food consumption, appetite sensations and eating behaviours.
Beyond antioxidant actions: Insights into the antioxidant activities of tyr‐containing dipeptides in aqueous solution systems and liposomal systems
Authors: Chen Chong , Sun‐Waterhouse Dongxiao , Zhao Mouming , Sun Weizheng 
Published: April 2020

SummaryTyr‐containing dipeptides deserve close attention because of their interesting bioactivities. This study aimed to make a contribution to the antioxidant activity evaluation of these dipeptides, through examining the chemical reactions underlying the results obtained in ABTS, ORAC assays and liposomal systems. Among Tyr‐Tyr, Tyr‐Phe, Phe‐Tyr, Tyr‐Ala and Tyr‐Ser, Tyr‐Tyr displayed the highest activity in all methods. Compared with Tyr‐Phe, Phe‐Tyr exhibited a higher activity in ORAC assay but a lower activity in ABTS assay. In liposomal systems, significant differences were found among the dipeptides in antioxidant actions against lipid peroxidation initiated by water or lipid‐soluble radicals. Electron and/or hydrogen transfer were involved in the detected antioxidant actions, with the location of Tyr at the C‐/N‐terminus being a crucial factor. Besides the structural features of peptides, the characteristics of liposomes, location of lipid oxidation initiation and peptide distribution in/on liposomal membranes all influenced the outcome of antioxidant actions.
I am the person who knows myself best: Perception on shared decision‐making among hospitalized people diagnosed with schizophrenia in China
Authors: Huang Chongmei , Plummer Virginia , Wang Yun , Lam Louisa , Cross Wendy 
Published: April 2020

AbstractShared decision‐making is related to better health outcomes in serious mental illness. It is not well addressed in non‐Western cultures, for example Chinese culture. Chinese could be influenced by both paternalism and familism when making treatment decisions. However, this is unexplored. The study purpose is to explore shared decision‐making from perspectives of inpatients diagnosed with schizophrenia in China. This study adopted qualitative descriptive approach. Through semi‐structured interviews, twelve participants from the psychiatry department of a tertiary hospital shared their perceptions of shared decision‐making. An inductive thematic approach was used to analyse the transcripts. Primary results included three main themes with nine subthemes: (1) Having a positive attitude: i) wanting my voice to be heard, ii) needing my family to be involved, and iii) preferring the psychiatrist to decide; (2) Feeling excluded: i) having limited financial capacity, ii) lacking interactive communication, iii) too few psychiatrists, and iv) being unsatisfied with informed consent process; and (3) Self‐motivation in decision‐making by: i) easing the burden on the family and ii) actively collecting health information. In this context, patients have fewer treatment options and a limited role in SDM. Yet, they have preference for SDM, actively seeking health information from mental health professionals particularly nurses.
Periodontal regeneration versus extraction and dental implant or prosthetic replacement of teeth severely compromised by attachment loss to the apex: A randomized controlled clinical trial reporting 10‐year outcomes, survival analysis and mean cumulative cost of recurrence
Authors: Cortellini Pierpaolo , Stalpers Gabrielle , Mollo Aniello , Tonetti Maurizio S. 
Published: April 2020

AbstractBackgroundPeriodontal regeneration can change tooth prognosis and represents an alternative to extraction in teeth compromised by severe intra‐bony defects. The aim of this study was to compare periodontal regeneration (PR) with tooth extraction and replacement (TER) in a population with attachment loss to or beyond the apex of the root in terms of professional, patient‐reported and economic outcomes.MethodsThis was a 10‐year randomized controlled clinical trial. 50 stage III or stage IV periodontitis subjects with a severely compromised tooth with attachment loss to or beyond the apex were randomized to PR or TER with either an implant‐ or a tooth‐supported fixed partial denture. Subjects were kept on a strict periodontal supportive care regimen every 3 months and examined yearly. Survival and recurrence analysis were performed.Results88% and 100% survival rates were observed in the PR and TER groups. Complication‐free survival was not significantly different: 6.7–9.1 years for PR and 7.3–9.1 years for TER (p = .788). In PR, the observed 10‐year attachment gain was 7.3 ± 2.3 mm and the residual probing depths were 3.4 ± 0.8 mm. Recurrence analysis showed that the 95% confidence interval of the costs was significantly lower for PR compared with TER throughout the whole 10‐year period. Patient‐reported outcomes and oral health‐related quality‐of‐life measurements improved in both groups.ConclusionsPeriodontal regeneration can change the prognosis of hopeless teeth and is a less costly alternative to tooth extraction and replacement. The complexity of the treatment limits widespread application to the most complex cases but provides powerful proof of principle for the benefits of PR in deep intra‐bony defect.
Perisynaptic Schwann cells phagocytose nerve terminal debris in a mouse model of Guillain‐Barré syndrome
Authors: Cunningham Madeleine E. , Meehan Gavin R. , Robinson Sophie , Yao Denggao , McGonigal Rhona , Willison Hugh J. 
Published: April 2020

AbstractIn mouse models of acute motor axonal neuropathy, anti‐ganglioside antibodies (AGAbs) bind to motor axons, notably the distal nerve, and activate the complement cascade. While complement activation is well studied in this model, the role of inflammatory cells is unknown. Herein we aimed to investigate the contribution of phagocytic cells including macrophages, neutrophils and perisynaptic Schwann cells (pSCs) to distal nerve pathology. To observe this, we first created a subacute injury model of sufficient duration to allow inflammatory cell recruitment. Mice were injected intraperitoneally with an anti‐GD1b monoclonal antibody that binds strongly to mouse motor nerve axons. Subsequently, mice received normal human serum as a source of complement. Dosing was titrated to allow humane survival of mice over a period of 3 days, yet still induce the characteristic neurological impairment. Behaviour and pathology were assessed in vivo using whole‐body plethysmography and post‐sacrifice by immunofluorescence and flow cytometry. ex vivo nerve‐muscle preparations were used to investigate the acute phagocytic role of pSCs following distal nerve injury. Following complement activation at distal intramuscular nerve sites in the diaphragm macrophage localisation or numbers are not altered, nor do they shift to a pro‐ or anti‐inflammatory phenotype. Similarly, neutrophils are not significantly recruited. Instead, ex vivo nerve‐muscle preparations exposed to AGAb plus complement reveal that pSCs rapidly become phagocytic and engulf axonal debris. These data suggest that pSCs, rather than inflammatory cells, are the major cellular vehicle for axonal debris clearance following distal nerve injury, in contrast to larger nerve bundles where macrophage‐mediated clearance predominates.
1,8‐cineole and castor oil in sodium lauryl ether sulphate disrupt reproduction and ovarian tissue of Rhipicephalus (Boophilus) microplus
Authors: de Queiroz V. T. , Campos N. C. , Nunes E. T. , Costa A. V. , Coelho J. D. , Trivilin L. O. , de Melo D. C. A. , Morais P. A. B. , Martins I. V. F. 
Published: April 2020

AbstractEssential and fixed oils have been researched as alternatives to chemical acaricides. The activity of volatile compounds from essential oils (1,8‐cineole, citral and eugenol) at 1.0% (w/v) and fixed oil (castor oil) at 0.3% (w/v) dissolved in 2.0% (v/v) dimethyl sulfoxide (DMSO) + 0.2% (w/v) Tween 80® was assessed against Rhipicephalus microplus using immersion tests. 1,8‐cineole (29.0%) and castor oil (30.2%) had the highest reproductive inhibition rate. A second experiment was performed to verify the effect of the 1,8‐cineole (10.0% w/v) and, or castor oil (0.3% w/v) on tick reproduction using different solubilizing agents. The highest reproductive inhibition was observed for the combination of 1,8‐cineole/castor oil (94.1%) and 1,8‐cineole in 2.0% (w/v) sodium lauryl ether sulphate (SLES) (92.8%). A third experiment showed morphological changes in R. microplus oocytes at different stages of development, as well as in pedicel cells. The most intense effects were observed when ticks were immersed in the formulation containing 1,8‐cineole (10.0% w/v) and castor oil (0.3% w/v) dissolved in 2% (w/v) SLES. These findings highlight the potential of this formulation as an alternative for managing cattle ticks as their cytotoxic effects can reduce R. microplus reproductive success.
Predictive value of control of COPD for risk of exacerbations: An international, prospective study
Authors: Miravitlles Marc , Sliwinski Pawel , Rhee Chin Kook , Costello Richard W. , Carter Victoria , Tan Jessica H.Y. , Lapperre Therese S. , Alcazar Bernardino , Gouder Caroline , Esquinas Cristina , García‐Rivero Juan Luis , Kemppinen Anu , Tee Augustine , Roman‐Rodríguez Miguel , Soler‐Cataluña Juan José , Price David B. ,   the Respiratory Effectiveness Group (REG)
Published: April 2020

ABSTRACTBackground and objectiveThe concept of clinical control in COPD has been developed to help in treatment decisions, but it requires validation in prospective studies.MethodsThis international, multicentre, prospective study aimed to validate the concept of control in COPD. Patients with COPD were classified as controlled/uncontrolled by clinical criteria or CAT scores at baseline and followed up for 18 months. The main outcome was the difference in rate of a composite endpoint of moderate and severe exacerbations or death over the 18‐month follow‐up period.ResultsA total of 307 patients were analysed (mean age = 68.6 years and mean FEV1% = 52.5%). Up to 65% and 37.9% of patients were classified as controlled by clinical criteria or CAT, respectively. Controlled patients had significantly less exacerbations during follow‐up (by clinical criteria: 1.1 vs 2.6, P < 0.001; by CAT: 1.1 vs 1.9, P = 0.014). Time to first exacerbation was significantly prolonged for patients controlled by clinical criteria only (median: 93 days, IQR: 63; 242 vs 274 days, IQR: 221; 497 days; P < 0.001). Control status by clinical criteria was a better predictor of exacerbations compared to CAT criteria (AUC: 0.67 vs 0.57).ConclusionControl status, defined by easy‐to‐obtain clinical criteria, is predictive of future exacerbation risk and time to the next exacerbation. The concept of control can be used in clinical practice at each clinical visit as a complement to the current recommendations of initial treatment proposed by guidelines.
Evaluation of sequencing strategies for whole-genome imputation with hybrid peeling
Authors: Ros-Freixedes Roger , Whalen Andrew , Gorjanc Gregor , Mileham Alan J. , Hickey John M. 
Published: April 2020

Abstract
Background
For assembling large whole-genome sequence datasets for routine use in research and breeding, the sequencing strategy should be adapted to the methods that will be used later for variant discovery and imputation. In this study, we used simulation to explore the impact that the sequencing strategy and level of sequencing investment have on the overall accuracy of imputation using hybrid peeling, a pedigree-based imputation method that is well suited for large livestock populations.

Methods
We simulated marker array and whole-genome sequence data for 15 populations with simulated or real pedigrees that had different structures. In these populations, we evaluated the effect on imputation accuracy of seven methods for selecting which individuals to sequence, the generation of the pedigree to which the sequenced individuals belonged, the use of variable or uniform coverage, and the trade-off between the number of sequenced individuals and their sequencing coverage. For each population, we considered four levels of investment in sequencing that were proportional to the size of the population.

Results
Imputation accuracy depended greatly on pedigree depth. The distribution of the sequenced individuals across the generations of the pedigree underlay the performance of the different methods used to select individuals to sequence and it was critical for achieving high imputation accuracy in both early and late generations. Imputation accuracy was highest with a uniform coverage across the sequenced individuals of 2× rather than variable coverage. An investment equivalent to the cost of sequencing 2% of the population at 2× provided high imputation accuracy. The gain in imputation accuracy from additional investment decreased with larger populations and higher levels of investment. However, to achieve the same imputation accuracy, a proportionally greater investment must be used in the smaller populations compared to the larger ones.

Conclusions
Suitable sequencing strategies for subsequent imputation with hybrid peeling involve sequencing ~2% of the population at a uniform coverage 2×, distributed preferably across all generations of the pedigree, except for the few earliest generations that lack genotyped ancestors. Such sequencing strategies are beneficial for generating whole-genome sequence data in populations with deep pedigrees of closely related individuals.
New genetic variant in the SERPINC1 gene: hereditary Antithrombin deficiency case report, familial thrombosis and considerations on genetic counseling
Authors: Polyak Margarita E. , Zaklyazminskaya Elena V. 
Published: April 2020

Abstract
Background
Inherited deficiency of the antithrombin (hereditary antithrombin deficiency, AT deficiency, OMIM #613118) is a relatively rare (1:2000–3000) autosomal-dominant disorder with high risk of venous thromboembolism. Mutations in the serpin family C member 1 gene (SERPINC1) can lead to Quantitative (type I) and Qualitative (type II) types of antithrombin deficiency. We describe a new genetic variant in the SERPINC1 gene and our approach to variant interpretation.

Case presentation
We observed a 29 y.o. female proband with the episode of venous thrombosis at the age of 18 and family history of thrombosis. The antithrombin level in our patient was low, 44–48% (AT deficiency type I). A new genetic variant c.662G > C (p.W221S) in the SERPINC1 gene was detected in proband and affected father but was absent in healthy sister. We used in silico tools to evaluate the possible impact of p.W221S variant on protein structure and function. In mutated SERPINC1 protein a new N-linked glycosylation site is formed, however, it is unclear if the glycosylation at 219–221 site is possible.

Conclusion
The proband was provided with appropriate genetic counseling and referred to a hematologist. Based on all the evidence we classify the p.W221S variant as variant of unknown clinical significance. In this paper we discuss some aspects of genetic counseling, variant interpretation and thromboembolic prophilaxis.
The urinary microbiome shows different bacterial genera in renal transplant recipients and non-transplant patients at time of acute kidney injury – a pilot study
Authors: Gerges-Knafl Daniela , Pichler Peter , Zimprich Alexander , Hotzy Christoph , Barousch Wolfgang , Lang Rita M. , Lobmeyr Elisabeth , Baumgartner-Parzer Sabina , Wagner Ludwig , Winnicki Wolfgang 
Published: April 2020

AbstractBackgroundIn the past urine was considered sterile. Through the introduction of next generation sequencing, it has become clear that a urinary microbiome exists. Acute kidney injury (AKI) represents a major threat to kidney transplant recipients. Remarkable changes in the urinary metabolome occur during AKI, which may influence the urinary microbiome. To our knowledge, this is the first study that examines the urinary microbiome in renal transplant recipients (RTX) and non-transplant recipients (nRTX) at time of AKI.MethodsIn this cross-sectional pilot-study the urinary microbiome of 21 RTX and 9 nRTX with AKI was examined. Clean catch morning urine samples were obtained from all patients on the first day of AKI diagnosis. AKI was defined according to KDIGO guidelines. Urinary microbiota and the urinary metabolome during AKI were assessed in one patient. 16S rRNA sequencing was performed. Sequences were processed using UPARSE-pipeline for operational taxonomic units (OTU) and taxon finding.ResultsWe successfully extracted and sequenced bacterial DNA from 100% of the urine samples. All 30 patients revealed at least 106,138 reads. 319 OTU and 211 different genera were identified. The microbiotic diversity richness in the RTX group was no different from the nRTX group. Eighteen genera were solely present in nRTX and 7 in RTX.ConclusionsThe urinary microbiome at time of AKI showed different bacterial genera in RTX compared to nRTX. The nRTX group exhibited no different diversity to the RTX group. Irrespective of the status of a previous renal transplantation, the urinary microbiome comprised > 210 different genera. An intraindividual change in microbiota diversity and richness was observed in one study patient during recovery from AKI.
Ammonia and coma – a case report of late onset hemizygous ornithine carbamyltransferase deficiency in 68-year-old female
Authors: Marquetand Justus , Freisinger Peter , Lindig Tobias , Euler Sebastian , Gasser Michael , Overkamp Dietrich 
Published: April 2020

Abstract
Background
Acute hyperammonemia without signs of common causes in the elderly might be challenging to identify. We report the oldest case known to date of a female patient with late onset ornithine carbamyltransferase deficiency (OTC), which was unmasked after a protein overload due to nutritional supplements. Our case illustrates how environmental factors (protein overload) in previously unknown OTC in the elderly leads to hyperammonemic encephalopathy and highlights that early treatment prevents persisting neurological deficits and should be considered in absence of common causes of hyperammonemic encephalopathy.

Case presentation
A 68-year-old woman presented with acute confusion, which progressed into a deep coma (Glasgow-Coma-Scale score 3) within a few hours.
The only remarkable finding was a plasma ammonia (NH3) concentration of 697 μmmol/l (range 12–47 μmmol/). Third party history revealed that the patient disliked meat for most of her life (meat = protein, which needs to be metabolized) and had taken nutritional supplements (since supplements often have a high protein-ratio) 2 days before the symptoms started. Protein catabolism results in NH3, which is metabolized via the urea cycle. Consequently, the acute hyperammonemia in our patient was thought to be related to an inherited metabolic disorder, which only unmasked itself as a result of an overload of the corresponding metabolite (in this case protein). Since ornithine carbamyltransferase deficiency (OTC) is the most common inherited urea cycle disorder, this diagnosis became likely and was confirmed later via genetic and metabolic testing (amino acids, orotic acid, etc.). After 2 weeks of treatment (dialysis, low-protein-diet, nitrogen-lowering medication) the patient was discharged in a healthy condition without any neurological deficits.

Conclusion
OTC is a x-chromosomal linked disorder, that usually manifests in newborn infants and children, but also rarely in adults and even rarer in the elderly (50- till 60-years-old), where it is probably underdiagnosed. In case of hyperammonemic encephalopathy – regardless of the underlying cause -, treatment should be started early to prevent persisting neurological deficits. OTC should be considered in absence of common causes of hyperammonemic encephalopathy.