bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacophoric features for a very potent 5‐spirofluorenehydantoin inhibitor of cancer efflux pump ABCB1, based on X‐ray analysis
Authors: Żesławska Ewa , Kincses Annamária , Spengler Gabriella , Nitek Wojciech , Tejchman Waldemar , Handzlik Jadwiga 
Published: December 2018

AbstractIn order to extend knowledge about pharmacophoric features responsible for ABCB1 inhibitory properties of imidazolidin‐2,4‐dione derivatives, 1′‐[4‐(4‐(o‐methoxyphenyl)‐piperazin‐1‐yl)butyl]‐3′‐methyl‐spiro(fluoren‐9,5′‐imidazolidine)‐2′,4′‐dione (3) and its salt (4) with rhodanine‐3‐acetic acid (RA) were prepared and investigated by X‐ray diffraction method, as well as their efflux modulating effects in cancer cells (mouse T‐lymphoma), cytotoxic and antiproliferative activities were evaluated in vitro. The molecular geometry, intermolecular interactions, and crystal packing of base and acid forms of 3 were analyzed to see, if conformational changes influence the biological activities. The geometry of 2‐methoxyphenylpiperazine and 5‐spirofluorenehydantoin moieties was compared with other crystal structures containing these fragments. Our results indicated a very potent inhibitory action on ABCB1 pump, and significant cytotoxic and antiproliferative properties of 3 in T‐lymphoma, even more potent in the case of multidrug resistance cells. Furthermore, the compound 3 converted into the salt 4 of inactive acid (RA) has maintained both, the efflux pump inhibitory and antiproliferative activities, showing strong synergism with doxorubicin. A comparison of geometry of 3 in both crystal structures (3 and 4) shows a significant difference in the arrangement of piperazine ring with respect to the aliphatic linker.
Developmental Consequences of Child Abuse and Neglect: Implications for Intervention
Authors: Toth Sheree L. , Manly Jody T. 
Published: December 2018

AbstractChild maltreatment is a heterogeneous phenomenon that frequently results in negative developmental trajectories across many domains of child functioning. In this article, we selectively review the literature on child maltreatment from the perspective of developmental psychopathology, emphasizing the central role of attachment in setting the path for developmental risks and providing opportunities for prevention and early intervention. Intervention research has highlighted the role of relational interventions in potentially promoting resilient functioning by supporting the development of more positive parent–child interactions. We describe an intervention called child–parent psychotherapy to illustrate the positive impact of a treatment for trauma that is informed by attachment theory and based on evidence, and we suggest how it can ameliorate outcomes for maltreated children.
Family Stress Processes and Children's Self‐Regulation
Authors: Duran Chelsea A.K. , Cottone Elizabeth , Ruzek Erik A. , Mashburn Andrew J. , Grissmer David W. 
Published: December 2018

Economic hardship can affect children's development through child–caregiver interactions, which may mediate cascading effects of other family stress processes. This study examined, simultaneously, the relations of financial strain, caregiver general stress, and child–caregiver conflict—each measured at two time points—with child self‐regulatory outcomes in a high‐poverty sample (age 5–7 years; n = 343). Increase in child–caregiver conflict mediated negative relations between other processes and development of executive function. In contrast, only increase in financial strain had direct, negative association with development of delay of gratification and did not significantly mediate relations between any other process and children's outcomes. Results have implications for understanding effects of family stress on self‐regulatory outcomes and for interventions with low‐income families.
Comparison of recovery and outcome after left and right colectomy
Authors: Grass F. , Lovely J. K. , Crippa J. , Ansell J. , Hübner M. , Mathis K. L. , Larson D. W. 
Published: December 2018

AbstractAimThe present study aimed to compare functional recovery and surgical outcomes after left and right colectomies.MethodConsecutive elective left and right colon resections for benign and malignant indications, performed between 2011 and 2016 and recorded in a prospectively maintained enhanced recovery database, were analysed. Demographic and surgical items, as well as functional recovery and 30‐day complications, were compared between left‐sided and right‐sided colectomies. Multivariable analysis was performed to identify risk factors for postoperative ileus (POI).ResultsIn total, 1001 left and 1041 right colectomies were comparable regarding demographic factors; only body mass index (BMI) was higher in patients undergoing left‐sided resections (> 30 kg/m2: 33% vs 27%, P = 0.004). Malignancy (29% vs 67%, P < 0.001) and Crohn's disease (1% vs 31%, P < 0.001) were preponderant in right colectomies, whereas diverticular disease (68% vs 1%, P < 0.001) was the most common indication for left colectomy. Compliance with the enhanced recovery pathway (ERP) was comparable. While the minimally invasive approach was the preferred approach for both sides (61% vs 64%, P = 0.158), left colectomies took longer (180 ± 80 min vs 150 ± 70 min, P < 0.001), needed more perioperative fluids (3.1 ± 1.4 l vs 2.7 ± 1.5 l, P < 0.001) and resulted in greater postoperative weight gain (3.9 ± 6.5 kg vs 2.6 ± 6 kg, P = 0.025). Crohn's disease (OR = 2.64, 95% CI: 1.27–5.46) and fluid overload (OR = 2.02, 95% CI: 1.06–3.82) were independent risk factors for POI.ConclusionDespite equal ERP compliance, postoperative ileus was higher after right‐sided colectomies. This finding was associated with Crohn's disease and fluid overload.
A propensity‐score‐matched analysis of laparoscopic vs open surgery for rectal cancer in a population‐based study
Authors: Manchon‐Walsh P. , Aliste L. , Biondo S. , Espin E. , Pera M. , Targarona E. , Pallarès N. , Vernet R. , Espinàs J. A. , Guarga A. , Borràs J. M. 
Published: December 2018

AbstractAimThe oncological risk/benefit trade‐off for laparoscopy in rectal cancer is controversial. Our aim was to compare laparoscopic vs open surgery for resection of rectal cancer, using unselected data from the public healthcare system of Catalonia (Spain).MethodsThis was a multicentre retrospective cohort study of all patients who had surgery with curative intent for primary rectal cancer at Catalonian public hospitals from 2011 to 2012. We obtained follow‐up data for up to 5 years. To minimize the differences between the two groups, we performed propensity score matching on baseline patient characteristics. We used multivariate Cox proportional hazards regression analyses to assess locoregional relapse at 2 years and death at 2 and 5 years.ResultsOf 1513 patients with Stage I–III rectal cancer, 933 (61.7%) had laparoscopy (conversion rate 13.2%). After applying our propensity score matching strategy (2:1), 842 laparoscopy patients were matched to 517 open surgery patients. Multivariate Cox analysis of death at 2 years [hazard ratio (HR) 0.65, 95% CI 0.48, 0.87; P = 0.004] and 5 years (HR 0.61, 95% CI 0.5, 0.75; P < 0.001) and of local relapse at 2 years (HR 0.44, 95% CI 0.27, 0.72; P = 0.001) showed laparoscopy to be an independent protective factor compared with open surgery.ConclusionsLaparoscopy results in lower locoregional relapse and long‐term mortality in rectal cancer in unselected patients with all‐risk groups included. Studies using long‐term follow‐up of cohorts and unselected data can provide information on clinically relevant outcomes to supplement randomized controlled trials.
Radiotherapy after local excision of rectal cancer may offer reduced local recurrence rates
Authors: Jones H. J. S. , Goodbrand S. , Hompes R. , Mortensen N. , Cunningham C. 
Published: December 2018

AbstractAimEarly rectal cancer can be managed effectively with local excision, which is now the standard of care for many T1 lesions. However, the presence of unexpected adverse histopathological factors may indicate an increased risk of local recurrence, prompting consideration of completion radical surgery. Many patients are unfit or prefer to avoid radical surgery, relying instead on surveillance and early detection of recurrent disease. Recently, radiotherapy has shown promise as an adjuvant therapy in this group. This study assesses local recurrence rates after local excision with adjuvant radiotherapy at a single centre.MethodThis was a retrospective review of a prospective database of all patients undergoing transanal endoscopic microsurgery (TEM) in a single institution. Data covering a 10‐year period were analysed.ResultsOf 197 patients undergoing TEM for rectal cancer, 33 (17%) had adjuvant radiotherapy because of adverse histopathological features. At 3.2 years’ median follow‐up, there were three instances of local recurrence (9.1%). Estimated local recurrence at 1 and 3 years was 0% and 6.9%, compared to 16.8% and 21.2% in a propensity‐score‐matched group who were followed by surveillance alone. Local recurrence was diagnosed at a median of 23 months post‐TEM in the radiotherapy group, compared to 8 months in the matched group.ConclusionRadiotherapy after TEM is associated with a trend towards a reduced rate of local recurrence, even for high‐risk disease. Radiotherapy would appear to offer a viable alternative to radical completion surgery in the presence of unforeseen adverse histopathological features, as long as a meticulous surveillance programme is in place.
Small cell lung cancer in the young: Characteristics, diagnosis and outcome data
Authors: Jiang Shiyu , Hao Xuezhi , Li Junling , Hu Xingsheng , Xiao Zefen , Wang Hongyu , Wang Yan , Sun Yan , Shi Yuankai 
Published: December 2018

AbstractBackgroundPatients with small cell lung cancer (SCLC) younger than 40 years are limited in number. Our research aimed to assess the characteristics, diagnosis and outcomes of this patient population.MethodsRecords of patients under the age of 40 with SCLC at the Chinese Academy of Medical Sciences between January 2006 and December 2015 were reviewed and evaluated.ResultsOne hundred and three patients (67.0% limited stage, 33.0% extensive stage) were included, along with 54 (52.4%) never‐smokers. The median diagnostic interval and the median survival time (MST) were 51.0 days and 24.0 months, respectively. A total of 41 (39.8%) patients claimed to have undergone antibiotic treatment before diagnosis, with a median duration of 2 weeks. In univariate analysis, survival was better for the limited stage group than the extensive stage group (MST, 28.0 vs. 13.0 months, P < 0.0001). Also, patients who received concurrent radiochemotherapy had better survival than those who received chemotherapy alone (MST, 29.0 vs. 18.0 months, P = 0.001). Patients with antibiotic treatment before SCLC diagnosis have worse prognosis than those without (MST, 21.0 vs. 27.0 months, P = 0.008). Moreover, a timely diagnosis (≤1 month) exerted a positive impact on the overall survival in limited stage patients (48.0 vs. 26.0 months, P = 0.047) and on progression‐free survival in extensive stage patients (6.0 vs. 3.0 months, P = 0.030). Multivariate analysis suggested that disease stage, history of antibiotic treatment before SCLC diagnosis and performance status independently correlated with survival.ConclusionOur study identified distinct characteristics and prognostic factors of SCLC patients under 40 years. More timely care may improve patient prognosis.
Longitudinal immunosuppression data can minimize misclassification bias in solid organ transplantation cohorts
Authors: Laaksonen Maarit A. , Webster Angela C. , McCaughan Geoff W. , Keogh Anne M. , Grulich Andrew E. , Vajdic Claire M. 
Published: December 2018

AbstractBackgroundMost cohort studies investigating the effect of immunosuppression on transplant outcomes use drugs at first hospital discharge. We evaluated the extent of drug exposure misclassification and its impact on outcome prediction.MethodsWe retrospectively collected longitudinal immunosuppression data, at discharge and at 1, 5, 10, and 15 years after transplantation, and outcomes for solid organ transplant recipients 1984‐2006 (n = 3133). We compared the risk of death from exposure to individual immunosuppressive drugs (cyclosporine, tacrolimus, azathioprine, and mycophenolate) and dual therapies, as defined by discharge only vs longitudinal immunosuppression data, using adjusted Cox proportional hazards models.ResultsDuring a median follow‐up of 5.2 years, immunosuppressive drugs were altered for 947 (30%) recipients and 955 recipients died. Longitudinal receipt of cyclosporine and azathioprine were associated with an increased risk (HR 1.41, 95% CI 1.07‐1.89, and HR 1.34, 95% CI 1.00‐1.80), and mycophenolate with a reduced risk (HR 0.35, 0.16‐0.78), of death. Recipients on mycophenolate and tacrolimus dual therapy had a lower risk of death compared to those on azathioprine and cyclosporine dual therapy (HR 0.30, 0.10‐0.93). The increased risk of death associated with the receipt of cyclosporine or azathioprine was not shown in the analyses based on drugs allocated at discharge, and all of the associations between immunosuppressive regimens and death were strengthened in the analyses based on longitudinal immunosuppression data.ConclusionsCohort findings based on immunosuppressive drugs allocated at discharge should be interpreted with caution due to potential exposure misclassification. The use of granular, longitudinal data on immunosuppressive regimens could improve prediction.
Revision of the Capsaspora genome using read mating information adjusts the view on premetazoan genome
Authors: Denbo Seitaro , Aono Katsutoshi , Kai Takaaki , Yagasaki Rei , Ruiz‐Trillo Iñaki , Suga Hiroshi 
Published: December 2018

AbstractThe genome sequences of unicellular holozoans, the closest relatives to animals, are shedding light on the evolution of animal multicellularity, shaping the genetic contents of the putative premetazoans. However, the assembly quality of the genomes remains poor compared to the major model organisms such as human and fly. Improving the assembly is critical for precise comparative genomics studies and further molecular biological studies requiring accurate sequence information such as enhancer analysis and genome editing. In this report, we present a new strategy to improve the assembly by fully exploiting the information of Illumina mate‐pair reads. By visualizing the distance and orientation of the mapped read pairs, we could highlight the regions where possible assembly errors exist in the genome sequence of Capsaspora, a lineage of unicellular holozoans. Manual modification of these errors repaired 590 assembly problems in total and reassembled 84 supercontigs into 55. Our telomere prediction analysis using the read pairs containing the pan‐eukaryotic telomere‐like sequence identified at least 13 chromosomes. The resulting new assembly posed us a re‐annotation of 112 genes, including 15 putative receptor protein tyrosine kinases. Our strategy thus provides a useful approach for improving assemblies of draft genomes, and the new Capsaspora genome offers us an opportunity to adjust the view on the genome of the unicellular animal ancestor.
Wall motion tracking in fetal echocardiography—Application of low and high frame rates for strain analysis
Authors: Enzensberger Christian , Rostock Laura , Graupner Oliver , Götte Malena , Wolter Aline , Vorisek Carina , Herrmann Johannes , Axt‐Fliedner Roland 
Published: December 2018

ObjectiveCompared to adults, fetal heart rates (HR) are elevated necessitating higher frame rates (FR) for strain analysis by speckle tracking echocardiography. The aim of this study was to investigate the influence of high FR compared to low FR on strain analysis in 2D speckle tracking.MethodsFetal echocardiography was prospectively performed and acquired from the apical or basal four‐chamber views of the heart. Images were optimized for clear delineation of myocardial walls and stored in either raw Digital Imaging and Communications in Medicine (DICOM) cine‐loop format for offline analysis with a low FR of 60 frames per second (fps) or in the original FR (acoustic FR = AFR). For each loop, right (RV) and left (LV) ventricular fetal longitudinal peak systolic strain (LPSS) values were assessed by 2D Wall Motion tracking.ResultsOne hundred and three healthy fetuses were included with a mean gestational age of 26.3 ± 5.5 weeks. Mean AFR was 127 ± 26 fps. A mean FR/HR ratio was assessed of 0.42 and 0.90 between the low FR and AFR group, respectively. Relating to LPSS values, there was a significant difference between low FR and AFR for both ventricles (LV: −16.5% ± 3.9% (low FR) vs −13.6% ± 3.5% (AFR); and RV: −15.1% ± 3.6% (low FR) vs −12.6% ± 3.7% (AFR), both P < 0.001).ConclusionsFetal LV and RV LPSS values derived with high AFR were significantly lower than corresponding LPSS values analyzed with low FR of 60 fps. Future studies are needed to clarify the clinical importance of this relationship.
Impact of seed abundance on seed processing and dispersal by the red ant Myrmica rubra
Authors: Detrain Claire , Bologna Audrey 
Published: December 2018

1. Myrmecochory sensu stricto is an ant–plant mutualism in which non‐granivorous ants disperse plant diaspores after feeding on their nutrient‐rich seed appendage, the elaiosome. Phenological traits associated with the diaspore can influence the behaviour of ants and thus their ultimate efficiency as seed dispersers.2. This study investigated how a contrasting availability of seeds (20 vs. 200 seeds) from the diplochorous Chelidonium majus (Papaveraceae, Linnaeus) plant species influences the behaviour of Myrmica rubra (Formicidae, Linnaeus) ants, from the retrieval of seeds until their dispersal outside the ant nest.3. Regardless of seed abundance, the ants collected the first diaspores at similar rates. Then, seed retrieval sped up over time for large seed sources until satiation took place with only one‐third of the tested colonies wholly depleting abundant seed sources.4. No active recruitment by trail‐laying ants was triggered, even to an abundant seed source5. In both conditions of seed abundance, the majority of the diaspores retrieved inside the nest were discarded with the elaiosome removed and were dispersed at similar distances from the nest.6. The paper concludes with a discussion of how the quantity of seeds released by a plant with a dual mode of dispersal can potentially influence the behaviour of ant dispersers and hence the dispersal efficiency derived from myrmecochory.
Are PARKIN patients ideal candidates for dopaminergic cell replacement therapies?
Authors: Kunath Tilo , Natalwala Ammar , Chan Claire , Chen Yixi , Stecher Benjamin , Taylor Martin , Khan Sadaquate , Muqit Miratul M. K. 
Published: December 2018

AbstractParkinson's is a heterogeneous, complex condition. Stratification of Parkinson's subtypes will be essential to identify those that will benefit most from a cell replacement therapy. Foetal mesencephalic grafts can alleviate motor symptoms in some Parkinson's patients. However, on‐going synucleinopathy results in the grafts eventually developing Lewy bodies, and they begin to fail. We propose that Parkinson's patients with PARKIN mutations may benefit most from a cell replacement therapy because (a) they often lack synucleinopathy, and (b) their neurodegeneration is often confined to the nigrostriatal pathway. While patients with PARKIN mutations exhibit clinical signs of Parkinson's, post‐mortem studies to date indicate the majority lack Lewy bodies suggesting the nigral dopaminergic neurons are lost in a cell autonomous manner independent of α‐synuclein mechanisms. Furthermore, these patients are usually younger, slow progressing and typically do not suffer from complex non‐nigral symptoms that are unlikely to be ameliorated by a cell replacement therapy. Transplantation of dopaminergic cells into the putamen of these patients will provide neurons with wild‐type PARKIN expression to re‐innervate the striatum. The focal nature of PARKIN‐mediated neurodegeneration and lack of active synucleinopathy in most young‐onset cases makes these patients ideal candidates for a dopaminergic cell replacement therapy. Strategies to improve the outcome of cell replacement therapies for sporadic Parkinson's include the use of adjunct therapeutics that target α‐synuclein spreading and the use of genetically engineered grafts that are resistant to synucleinopathy.
Prefrontal cortex development and emergence of self‐regulatory competence: the two cardinal features of adolescence disrupted in context of alcohol abuse
Authors: Jadhav Kshitij S. , Boutrel Benjamin 
Published: December 2018

AbstractAdolescence is a tumultuous period in the lifetime of an individual confronted to major changes in emotional, social and cognitive appraisal. During this period of questioning and doubt, while the executive functions are still maturing, the abstract reasoning remains vague and the response inhibition loose; ultimately the adolescent scarcely resists temptation. Consequently, adolescence is often associated with uninhibited risk‐taking, reckless behaviours, among which are alcohol and illicit drugs use. Here, we discuss how the development of the prefrontal cortex (which critically contributes to rational decision‐making and temporal processing of complex events) can be associated with the idiosyncratic adolescent behaviour, and potentially uncontrolled alcohol use. Most importantly, we present clinical and preclinical evidence supporting that ethanol exposure has deleterious effects on the adolescent developing brain. Ultimately, we discuss why a late maturing prefrontal cortex represents a ripe candidate to environmental influences that contribute to shape the adolescent brain but, potentially, can also trigger lifelong maladaptive responses, including increased vulnerability to develop substance use disorder later in life.
Convergent synaptic inputs to layer 1 cells of mouse cortex
Authors: Lam Ying‐Wan , Sherman S. Murray 
Published: December 2018

AbstractWe used whole cell recordings from slice preparations of mouse cortex to identify various inputs to neurons of layer 1. Two sensory cortical areas were targeted: a primary somatosensory area, namely, the barrel cortex of S1, and a higher order visual area, namely, V2M. Results were similar from both areas. By activating local inputs using photostimulation with caged glutamate, we also identified glutamatergic (and possibly GABAergic) inputs from all lower layers plus GABAergic inputs from nearby layer 1 neurons. However, the patterns of such inputs to layer 1 neurons showed great variation among cells. In separate experiments, we found that electrical stimulation of axons running parallel to the cortical surface in layer 1 also evoked a variety of convergent input types to layer 1 neurons, including glutamatergic “drivers” and “modulators” plus classic modulatory inputs, including serotonergic, nicotinic, α‐ and β‐adrenergic, from subcortical sites. Given that these layer 1 cells significantly affect the responses of other cortical neurons, especially via affecting the apical dendrites of pyramidal cells so important to cortical functioning, their role in cortical processing is significant. We believe that the data presented here lead to better understanding of the functioning of layer 1 neurons in their role of influencing cortical processing.