bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the fitness consequences of mitonuclear interactions in natural populations
Authors: Hill Geoffrey E. , Havird Justin C. , Sloan Daniel B. , Burton Ronald S. , Greening Chris , Dowling Damian K. 
Published: December 2018

ABSTRACTMetazoans exist only with a continuous and rich supply of chemical energy from oxidative phosphorylation in mitochondria. The oxidative phosphorylation machinery that mediates energy conservation is encoded by both mitochondrial and nuclear genes, and hence the products of these two genomes must interact closely to achieve coordinated function of core respiratory processes. It follows that selection for efficient respiration will lead to selection for compatible combinations of mitochondrial and nuclear genotypes, and this should facilitate coadaptation between mitochondrial and nuclear genomes (mitonuclear coadaptation). Herein, we outline the modes by which mitochondrial and nuclear genomes may coevolve within natural populations, and we discuss the implications of mitonuclear coadaptation for diverse fields of study in the biological sciences. We identify five themes in the study of mitonuclear interactions that provide a roadmap for both ecological and biomedical studies seeking to measure the contribution of intergenomic coadaptation to the evolution of natural populations. We also explore the wider implications of the fitness consequences of mitonuclear interactions, focusing on central debates within the fields of ecology and biomedicine.
Phase I study of alpelisib (BYL719), an α‐specific PI3K inhibitor, in Japanese patients with advanced solid tumors
Authors: Ando Yuichi , Iwasa Satoru , Takahashi Shunji , Saka Hideo , Kakizume Tomoyuki , Natsume Kazuto , Suenaga Naoko , Quadt Cornelia , Yamada Yasuhide 
Published: December 2018

This phase I study aimed to determine tolerability and preliminary efficacy of single‐agent alpelisib (BYL719) in Japanese patients with advanced solid malignancies. The primary objective of the study was to estimate the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of oral alpelisib in patients with advanced solid tumors who had progressed despite standard therapy. The expansion part included patients with PIK3CA mutation/amplification; safety, preliminary efficacy, pharmacokinetic (PK)/pharmacodynamic profile, and food effect on the PK profile of alpelisib at the MTD/RP2D were determined. Oral alpelisib was given as a single agent on a continuous 28‐day treatment cycle once daily. Overall, 33 patients received alpelisib. Dose‐limiting toxicities were observed in 2 patients in the escalation part (at 400 mg/day) and 1 patient in the expansion part (at 350 mg/day). The RP2D of alpelisib was determined as 350 mg/day based on overall safety profile in the dose escalation part and previous data from a Western population; the MTD was not determined. The most common all‐grade treatment‐suspected adverse events were hyperglycemia and maculopapular rash (48.5% each) and diarrhea (45.5%). The PK of alpelisib in the Japanese population was similar to that reported in the Western population. The overall response rate, disease control rate, and median progression‐free survival at 350 mg/day were 3%, 57.6%, and 3.4 months, respectively. Alpelisib as single agent showed a favorable safety profile and encouraging preliminary efficacy in Japanese patients with advanced solid tumors.
Clinical Practice Guidance: Surveillance for phaeochromocytoma and paraganglioma in paediatric succinate dehydrogenase gene mutation carriers
Authors: Wong Mei Yin , Andrews Katrina A. , Challis Benjamin G. , Park Soo‐Mi , Acerini Carlo L. , Maher Eamonn R. , Casey Ruth T. 
Published: December 2018

SummaryThe succinate dehydrogenase (SDH) enzyme complex functions as a key enzyme coupling the oxidation of succinate to fumarate in the citric acid cycle. Inactivation of this enzyme complex results in the cellular accumulation of the oncometabolite succinate, which is postulated to be a key driver in tumorigenesis. Succinate accumulation inhibits 2‐oxoglutarate‐dependent dioxygenases, including DNA and histone demethylase enzymes and hypoxic gene response regulators. Biallelic inactivation (typically resulting from one inherited and one somatic event) at one of the four genes encoding the SDH complex (SDHA/B/C/D) is the most common cause for SDH deficient (dSDH) tumours. Germline mutations in the SDHx genes predispose to a spectrum of tumours including phaeochromocytoma and paraganglioma (PPGL), wild type gastrointestinal stromal tumours (wtGIST) and, less commonly, renal cell carcinoma and pituitary tumours. Furthermore, mutations in the SDHx genes, particularly SDHB, predispose to a higher risk of malignant PPGL, which is associated with a 5‐year mortality of 50%. There is general agreement that biochemical and imaging surveillance should be offered to asymptomatic carriers of SDHx gene mutations in the expectation that this will reduce the morbidity and mortality associated with dSDH tumours. However, there is no consensus on when and how surveillance should be performed in children and young adults. Here, we address the question: “What age should clinical, biochemical and radiological surveillance for PPGL be initiated in paediatric SDHx mutation carriers?”.
Clinical application of autogenous demineralized dentin matrix loaded with recombinant human bone morphogenetic‐2 for socket preservation: A case series
Authors: Um In‐Woong , Kim Young‐Kyun , Park Joo‐Cheol , Lee Jong‐Ho 
Published: December 2018

AbstractBackgroundDemineralized dentin matrix (DDM) has potential application as a carrier for recombinant human bone morphogenetic protein‐2 (rhBMP‐2) in bone regeneration.PurposeTo evaluate the efficacy of DDM loaded with rhBMP‐2 for socket preservation.Materials and MethodsDDM loaded with rhBMP‐2 (DDM/rhBMP‐2) was applied to 10 experimental sites and DDM alone to 6 control sites. The changes in height and width of the extraction socket after preservation were measured by cone beam computed tomography. Trephine cores were harvested for histomorphometric evaluation before placement of the implant.ResultsThe reductions in height and width of the socket were more significant in the group treated with DDM than in the group treated with DDM/rhBMP‐2. The amount of new bone formation was 34.39% with DDM/rhBMP‐2 and 29.75% with DDM; the respective amounts of residual dentin were 8.35% and 16.15%. Although the differences were not statistically significant, the dimensional changes, amount of bone formation, and replacement of DDM in DDM/rhBMP‐2 with bone were superior to those of DDM alone.ConclusionsWithin the limitations of this study, we suggest that DDM may be a potential carrier for rhBMP‐2 and that it may be possible to reduce the rhBMP‐2 concentration to 0.2 mg/mL.
Plasma sMer, sAxl and GAS6 levels correlate with disease activity and severity in lupus nephritis
Authors: Gong Siwen , Xu Zhaozhen , Liu Yang , Xing Li , Ma Jing , Yu Chengyuan , Liu Xiaogang , Jia Xibei , Xie Rujuan , Sui Manshu 
Published: December 2018

AbstractObjectiveThe purpose of this study is to determine whether TAM receptors and ligands associated with the activity and severity of lupus nephritis.MethodsClinical data were statistically analysed and studied in 122 SLE patients, diagnosed from 2013 to 2016 in First Hospital Affiliated to Harbin Medical University. Levels of TAM receptors and ligands in the plasma of 122 SLE patients were measured by ELISA. Renal biopsies were performed to confirm lupus nephritis (LN) by histopathology in 68 patients. The associations of TAM receptors and ligands with clinical and serological parameters were analysed in 68 LN patients.ResultsAmongst patients with SLE, those with LN had significantly higher plasma sMer, sAxl and GAS6 levels than those without renal involvement (P < 0.01 for all comparisons). Additional comparisons on the renal function‐associated clinical parameters confirmed an indicative role of the sMer, sAXL and GAS6 levels in the cohort of patients with more severe nephritis. Patients with higher sMer, sAXL and GAS6 levels of LN patients tended to suffer from proliferative glomerulonephritis. The sAXL and GAS6 levels had a strong positive correlation with activity index (AI) in LN patients. Furthermore, there was a significant drop of the sMer, sAXL and GAS6 concentrations from the time of the biopsy to month t6, but no further decrease from months t6 to t12.ConclusionsThese results suggest that plasma sMer, sAxl and GAS6 can be an additional clinical marker related to the disease activity and severity in LN.
Bi‐directional modulation of food habit expression by the endocannabinoid system
Authors: Gianessi Carol A. , Groman Stephanie M. , Taylor Jane R. 
Published: December 2018

AbstractThe compulsive, habitual behaviors that have been observed in individuals diagnosed with substance use disorders may be due to disruptions in the neural circuits that mediate goal‐directed actions. The endocannabinoid system has been shown to play a critical role in habit learning, but the role of this neuromodulatory system in habit expression is unclear. Here, we investigated the role of the endocannabinoid system in established habitual actions using contingency degradation in male C57BL/6 mice. We found that administration of the endocannabinoid transport inhibitor AM404 reduced habitual responding for food and that antagonism of cannabinoid receptor type 1 (CB1), but not transient receptor potential cation subfamily V (TRPV1), receptors produced a similar reduction in habitual responding. Moreover, pharmacological stimulation of CB1 receptors increased habitual responding for food. Co‐administration of an enzyme inhibitor that selectively increases the endocannabinoid 2‐arachidonoyl glycerol (2‐AG) with AM404 partially restored habitual responding for food. Together, these findings demonstrate an important role for the endocannabinoid system in the expression of habits and provide novel insights into potential pharmacological strategies for reducing habitual behaviors in mental disorders.
A Cost–Benefit Analysis of Automatic Item Generation
Authors: Kosh Audra E. , Simpson Mary Ann , Bickel Lisa , Kellogg Mark , Sanford‐Moore Ellie 
Published: December 2018

AbstractAutomatic item generation (AIG)—a means of leveraging technology to create large quantities of items—requires a minimum number of items to offset the sizable upfront investment (i.e., model development and technology deployment) in order to achieve cost savings. In this cost–benefit analysis, we estimated the cost of each step of AIG and manual item writing and applied cost—benefit formulas to calculate the number of items that would have to be produced before the upfront costs of AIG outweigh manual item writing costs in the context of K‐12 mathematics items. Results indicated that AIG is more cost‐effective than manual item writing when developing, at a minimum, 173 to 247 items within one fine‐grained content area (e.g., fourth‐ through seventh‐grade area of figures). The article concludes with a discussion of implications for test developers and the nonmonetary tradeoffs involved in AIG.
Motoric cognitive risk syndrome and mortality: results from the EPIDOS cohort
Authors: Beauchet O. , Sekhon H. , Launay C. P. , Chabot J. , Rolland Y. , Schott A.‐M. , Allali G. 
Published: December 2018

Background and purposeCognitive impairment, slow walking speed and motoric cognitive risk syndrome (MCR) have separately been associated with an increased risk for mortality in the short term. The aim of the study was to examine the association of MCR and its components [i.e. subjective cognitive complaint (SCC) and slow walking speed] with short‐, medium‐ and long‐term mortality in older community‐dwellers.MethodsIn all, 3778 participants from the Epidémiologie de l'Ostéoporose (EPIDOS) study were selected. MCR was defined as the combination of slow walking speed and SCC in participants without major neurocognitive disorders. Deaths were prospectively recorded using mail, phone calls, questionnaires and/or the French national death registry at 5, 10, 15 and 19 (end of follow‐up period) years.ResultsOver the follow‐up of 19 years, 80.5% (n = 3043) participants died. Slow walking speed and MCR were associated with mortality [hazard ratio (HR) 1.20 with P = 0.004 for slow walking speed and HR = 1.26 with P = 0.002 for MCR at 10 years; HR = 1.27 with P ≤ 0.001 for slow walking speed and HR = 1.22 with P = 0.001 for MCR at 15 years; HR = 1.41 with P ≤ 0.001 at 19 years for slow walking speed and MCR]. There was no association between SCC and mortality. Kaplan–Meier distributions of mortality showed that participants with MCR and slow walking speed died earlier compared to healthy participants and those with SCC (P < 0.001).ConclusionsSlow walking speed and MCR were associated with an increased risk for mortality at the medium and long term, whereas no association was found with SCC.
Localization yield and seizure outcome in patients undergoing bilateral SEEG exploration
Authors: Steriade Claude , Martins William , Bulacio Juan , Morita‐Sherman Marcia E. , Nair Dileep , Gupta Ajay , Bingaman William , Gonzalez‐Martinez Jorge , Najm Imad , Jehi Lara 
Published: December 2018

SummaryObjectiveWe aimed to determine the rates and predictors of resection and seizure freedom after bilateral stereo‐electroencephalography (SEEG) implantation.MethodsWe reviewed 184 patients who underwent bilateral SEEG implantation (2009‐2015). Noninvasive and invasive evaluation findings were collected. Outcomes of interest included subsequent resection and seizure freedom. Statistical analyses employed multivariable logistic regression and proportional hazard modeling. Preoperative and postoperative seizure frequency, severity, and quality of life scales were also compared.ResultsFollowing bilateral SEEG implantation, 106 of 184 patients (58%) underwent resection. Single seizure type (P = 0.007), a family history of epilepsy (P = 0.003), 10 or more seizures per month (P = 0.004), lower number of electrodes (P = 0.02), or sentinel electrode placement (P = 0.04) was predictive of undergoing a resection, as were lack of nonlocalized (P < 0.0001) or bilateral (P < 0.0001) ictal‐onset zones on SEEG. Twenty‐six of 81 patients (32% with follow‐up greater than 1 year) remained seizure‐free. Predictors of seizure freedom were single seizure type (P = 0.01), short epilepsy duration (P = 0.008), use of 2 or fewer antiepileptic drugs (AEDs) at the time of surgery (P = 0.0006), primary localization hypothesis involving the frontal lobe (P = 0.002), sentinel electrode placement only (P = 0.02), and lack of overlap between ictal‐onset zone and eloquent cortex (P = 0.04), along with epilepsy substrate histopathology (P = 0.007). Complete resection of a suspected focal cortical dysplasia showed a trend to increased likelihood of seizure freedom (P = 0.09). The 44 of 55 patients (80%) who underwent resection and experienced seizure recurrence had >50% seizure reduction, as opposed to 26 of 45 patients (58%) who continued medical therapy alone (P = 0.003). Seventy‐two percent of patients had a clinically meaningful quality of life improvement (>10% decrease in the Quality of Life in Epilepsy [QOLIE‐10] score) at 1 year.SignificanceA strong preimplantation hypothesis of a suspected unifocal epilepsy increases the odds of resection and seizure freedom. We discuss a tailored approach, taking into account localization hypothesis and suspected epilepsy etiology in guiding implantation and subsequent surgical strategy.
Ferrisia virgata Cockerell (Hemiptera: Pseudococcidae): first record in Tunisia
Authors: Kamel Ben Halima M. , Mdellel L. , Zouari S. , Germain J. F. 
Published: December 2018

In September 2016 and 2017, Ferrisia virgata Cockerell (Hemiptera: Pseudococcidae), the striped mealybug, was collected on Lantana camara (Verbenaceae) in Khezama City (Governorate Sousse, Tunisia). The mealybug was observed on leaves and shoots and also on the flowers. This is the first record of F. virgata in Tunisia and in North Africa. Brief information about its worldwide distribution and biology is presented.
Synovial sepsis is rare following intrasynovial medication in equine ambulatory practice
Authors: Smith L. C. R. , Wylie C. E. , Palmer L. , Ramzan P. H. L. 
Published: December 2018

SummaryBackgroundThere are few observational studies regarding the potentially serious complication of synovial sepsis following intrasynovial medication in general equine practice. Quantification of risk is fundamental to fully inform decision‐making and owner consent prior to undertaking procedures.ObjectivesTo describe the occurrence of synovial sepsis following intrasynovial injections in a large ambulatory equine practice between 2006–2011.Study designRetrospective cohort study.MethodsMedication records were cross‐referenced against synovial cytology submissions and hospital admissions for synovial sepsis. The occurrence of synovial sepsis within strata of interest, including horse age, sex and product used were described as proportions with corresponding 95% confidence intervals, and measures of attributable risks.ResultsIn the study period, 9456 intrasynovial medications were performed in 4331 sessions. The most frequently used medications were: corticosteroids (3869/4331, 89.3% [95% CI 88.4, 90.3%]), hyaluronate (3617/4331, 83.5% [95% CI 82.4, 84.6%]) and amikacin sulphate (4044/4331, 93.4% [95% CI 92.6, 94.1%]). Overall four horses developed post medication synovial sepsis (0.04% [95% CI 0.0, 0.08%] of all medications), two of these cases were given polysulphated glycosaminoglycans and hyaluronate (2/14, 14.3% [95% CI 0.0, 32.6%]), two were given triamcinolone acetonide (2/3592, 0.1% [95% CI 0.0, 0.1%]), and hyaluronate (2/3617, 0.06% [95% CI 0.0, 0.1%]). One of these cases had received concurrent medication with amikacin sulphate (1/4044, 0.02% [95% CI 0.0, 0.1%]). All four cases returned to racing following joint lavage.Main limitationsDue to the low frequency of cases multivariable statistical analysis was not performed. Although the study was conducted in an ambulatory setting, the population included a high number of racehorses, limiting application to the general horse population.ConclusionsThe frequency of synovial sepsis in this population of horses was 0.04%. These data may be helpful in informing clients regarding the potential risks of adverse complications resulting from intrasynovial medication.
Structural, thermodynamic and catalytic characterization of an ancestral triosephosphate isomerase reveal early evolutionary coupling between monomer association and function
Authors: Schulte‐Sasse Mariana , Pardo‐Ávila Fátima , Pulido‐Mayoral Nancy O. , Vázquez‐Lobo Alejandra , Costas Miguel , García‐Hernández Enrique , Rodríguez‐Romero Adela , Fernández‐Velasco Daniel Alejandro 
Published: December 2018

Function, structure, and stability are strongly coupled in obligated oligomers, such as triosephosphate isomerase (TIM). However, little is known about how this coupling evolved. To address this question, five ancestral TIMs (ancTIMs) in the opisthokont lineage were inferred. The encoded proteins were purified and characterized, and spectroscopic and hydrodynamic analysis indicated that all are folded dimers. The catalytic efficiency of ancTIMs is very high and all dissociate into inactive and partially unfolded monomers. The placement of catalytic residues in the three‐dimensional structure, as well as the enthalpy‐driven binding signature of the oldest ancestor (TIM63) resemble extant TIMs. Although TIM63 dimers dissociate more readily than do extant TIMs, calorimetric data show that the free ancestral subunits are folded to a greater extent than their extant counterparts are, suggesting that full catalytic proficiency was established in the dimer before the stability of the isolated monomer eroded. Notably, the low association energy in ancTIMs is compensated for by a high activation barrier, and by a significant shift in the dimer‐monomer equilibrium induced by ligand binding. Our results indicate that before the animal and fungi lineages diverged, TIM was an obligated oligomer with substrate binding properties and catalytic efficiency that resemble that of extant TIMs. Therefore, TIM function and association have been strongly coupled at least for the last third of biological evolution on earth.DatabasesPDB Entry: 6NEE.EnzymesTriosephosphate isomerase 5.3.1.1, Glycerol‐3‐phosphate dehydrogenase 1.1.1.8.
The physics and ecology of mining carbon dioxide from the atmosphere by ecosystems
Authors: Baldocchi Dennis , Penuelas Josep 
Published: December 2018

AbstractReforesting and managing ecosystems have been proposed as ways to mitigate global warming and offset anthropogenic carbon emissions. The intent of our opinion piece is to provide a perspective on how well plants and ecosystems sequester carbon. The ability of individual plants and ecosystems to mine carbon dioxide from the atmosphere, as defined by rates and cumulative amounts, is limited by laws of physics and ecological principles. Consequently, the rates and amount of net carbon uptake are slow and low compared to the rates and amounts of carbon dioxide we release by fossil fuels combustion. Managing ecosystems to sequester carbon can also cause unintended consequences to arise. In this paper, we articulate a series of key take‐home points. First, the potential amount of carbon an ecosystem can assimilate on an annual basis scales with absorbed sunlight, which varies with latitude, leaf area index and available water. Second, efforts to improve photosynthesis will come with the cost of more respiration. Third, the rates and amount of net carbon uptake are relatively slow and low, compared to the rates and amounts and rates of carbon dioxide we release by fossil fuels combustion. Fourth, huge amounts of land area for ecosystems will be needed to be an effective carbon sink to mitigate anthropogenic carbon emissions. Fifth, the effectiveness of using this land as a carbon sink will depend on its ability to remain as a permanent carbon sink. Sixth, converting land to forests or wetlands may have unintended costs that warm the local climate, such as changing albedo, increasing surface roughness or releasing other greenhouse gases. We based our analysis on 1,163 site‐years of direct eddy covariance measurements of gross and net carbon fluxes from 155 sites across the globe.
ALK and EGFR expression by immunohistochemistry are associated with Merkel cell polyomavirus status in Merkel cell carcinoma
Authors: Veija Tuukka , Kero Mia , Koljonen Virve , Böhling Tom 
Published: December 2018

AimsMerkel cell carcinoma, a rare cutaneous neuroendocrine tumour of the skin, can be categorised into two groups according to Merkel cell polyomavirus (MCV) presence. MCV‐negative tumours are more aggressive and frequently associated with gene mutations. Some of the genes are potential therapeutic targets. We have previously reported EGFR mutations in six of 27 MCC tumours and overexpression of ALK and EZH2 at mRNA level in MCC tumours. In this study, we sought to determine expression of ALK, EGFR and EZH2 in MCC samples and assess their correlation to MCV status and clinical parameters.Methods and resultsTissue microarrays were utilised and stained with primary antibodies. Staining data were statistically compared to patient sex, tumour location and development of metastasis and MCC‐specific death; 112 tumours and their corresponding patient data were included. We found strong expression of ALK in 51% and strong expression of EZH2 in 76% of the tumours. There was evident correlation of ALK expression with MCV‐positivity. Expression of EGFR was infrequent, presenting only in seven MCV‐negative tumours. None of the proteins associated with development of metastasis or MCC specific death.ConclusionsALK and EZH2 expression are frequent in MCC and ALK expression correlates to MCV positivity. EGFR positive tumours might respond to EGFR inhibiting treatment.