bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotypic severity in a family with MEND syndrome is directly associated with the accumulation of potentially functional variants of cholesterol homeostasis genes
Authors: Barboza‐Cerda María Carmen , Barboza‐Quintana Oralia , Martínez‐Aldape Gerardo , Garza‐Guajardo Raquel , Déctor Miguel Angel 
Published: August 2019

AbstractBackgroundMale EBP disorder with neurologic defects (MEND) syndrome is an X‐linked disease caused by hypomorphic mutations in the EBP (emopamil‐binding protein) gene. Modifier genes may explain the clinical variability among individuals who share a primary mutation.MethodsWe studied four males (Patient 1 to Patient 4) exhibiting a descending degree of phenotypic severity from a family with MEND syndrome. To identify candidate modifier genes that explain the phenotypic variability, variants of homeostasis cholesterol genes identified by whole‐exome sequencing (WES) were ranked according to the predicted magnitude of their effect through an in‐house scoring system.ResultsTwenty‐seven from 105 missense variants found in 45 genes of the four exomes were considered significant (−5 to −9 scores). We found a direct genotype–phenotype association based on the differential accumulation of potentially functional gene variants among males. Patient 1 exhibited 17 variants, both Patients 2 and 3 exhibited nine variants, and Patient 4 exhibited only five variants.ConclusionWe conclude that APOA5 (rs3135506), ABCA1 (rs9282541), and APOB (rs679899 and rs12714225) are the most relevant candidate modifier genes in this family. Relative accumulation of the deficiencies associated with variants of these genes along with other lesser deficiencies in other genes appears to explain the variable expressivity in MEND syndrome.
The effects of physics‐based data augmentation on the generalizability of deep neural networks: Demonstration on nodule false‐positive reduction
Authors: Omigbodun Akinyinka O. , Noo Frederic , McNitt‐Gray Michael , Hsu William , Hsieh Scott S. 
Published: August 2019

PurposeAn important challenge for deep learning models is generalizing to new datasets that may be acquired with acquisition protocols different from the training set. It is not always feasible to expand training data to the range encountered in clinical practice. We introduce a new technique, physics‐based data augmentation (PBDA), that can emulate new computed tomography (CT) data acquisition protocols. We demonstrate two forms of PBDA, emulating increases in slice thickness and reductions of dose, on the specific problem of false‐positive reduction in the automatic detection of lung nodules.MethodsWe worked with CT images from the lung image database consortium (LIDC) collection. We employed a hybrid ensemble convolutional neural network (CNN), which consists of multiple CNN modules (VGG, DenseNet, ResNet), for a classification task of determining whether an image patch was a suspicious nodule or a false positive. To emulate a reduction in tube current, we injected noise by simulating forward projection, noise addition, and backprojection corresponding to 1.5 mAs (a “chest x‐ray” dose). To simulate thick slice CT scans from thin slice CT scans, we grouped and averaged spatially contiguous CT within thin slice data. The neural network was trained with 10% of the LIDC dataset that was selected to have either the highest tube current or the thinnest slices. The network was tested on the remaining data. We compared PBDA to a baseline with standard geometric augmentations (such as shifts and rotations) and Gaussian noise addition.ResultsPBDA improved the performance of the networks when generalizing to the test dataset in a limited number of cases. We found that the best performance was obtained by applying augmentation at very low doses (1.5 mAs), about an order of magnitude less than most screening protocols. In the baseline augmentation, a comparable level of Gaussian noise was injected. For dose reduction PBDA, the average sensitivity of 0.931 for the hybrid ensemble network was not statistically different from the average sensitivity of 0.935 without PBDA. Similarly for slice thickness PBDA, the average sensitivity of 0.900 when augmenting with doubled simulated slice thicknesses was not statistically different from the average sensitivity of 0.895 without PBDA. While there were cases detailed in this paper in which we observed improvements, the overall picture was one that suggests PBDA may not be an effective data enrichment tool.ConclusionsPBDA is a newly proposed strategy for mitigating the performance loss of neural networks related to the variation of acquisition protocol between the training dataset and the data that is encountered in deployment or testing. We found that PBDA does not provide robust improvements with the four neural networks (three modules and the ensemble) tested and for the specific task of false‐positive reduction in nodule detection.
Functional MRI in patients with detrusor sphincter dyssynergia: Is the neural circuit affected?
Authors: Seseke Sandra , Leitsmann Conrad , Hijazi Sameh , Trojan Lutz , Dechent Peter 
Published: August 2019

AbstractAimsIn recent years, the human brain‐bladder control network has been visualized in different functional magnetic resonance imaging (fMRI) studies. The role of the brainstem and suprapontine regions has been elucidated. Especially the pontine region and the periaqueductal gray, as the central structures of the micturition circuit, were demonstrated. Detrusor sphincter dyssynergia (DSD) is a common problem in patients with neurological diseases. Residual urine and consecutive urinary tract infections with the risk of kidney damage remain a problem. In the present study, we used fMRI of the brain to compare the activation sites of patients with DSD with those of our previously published healthy controls with special emphasis on the brainstem region.MethodsfMRI was performed in 11 patients with DSD who had an urge to void due to a filled bladder. In a nonvoiding model, they were instructed to contract or to relax the pelvic floor muscles repetitively.ResultsIn patients with DSD, we could reproduce the activation sites found in healthy subjects, showing the regions in the brainstem as well as the other micturition‐related areas. The activation of the pontine region was more rostral/dorsal compared with the healthy volunteers.ConclusionInterestingly, we detected the well‐known activation in the pontine region in the patients in the dorsal/rostral part compared with the more ventral activation in the healthy volunteers, suggesting that the L‐region of the pontine micturition center is more prominent in cases of DSD.
Incontinence and headache in preschool children
Authors: von Gontard Alexander , Overs Cornelia , Moritz Anna‐Michaela , Thomé‐Granz Sigrid , Hussong Justine 
Published: August 2019

AbstractAimsHeadaches in preschool children are associated with behavioral and gastrointestinal symptoms. As the co‐occurrence with incontinence is not known in young children, the aim of the study was to examine associations of headache, psychological symptoms and nocturnal enuresis (NE), daytime urinary incontinence (DUI), and fecal incontinence (FI) in a population‐based sample of preschool children.MethodsAll preschool children of a defined geographical area were examined at school‐entry. Parents completed a 22‐item questionnaire, including 14 headache, 4 incontinence, and 25 items of the Strength and Difficulties Questionnaire (SDQ). Five hundred eighty‐five children (50.4% males) with a mean age of 5.8 years were included.ResultsIn total, 27.2% of all children had headaches. 15.7% had secondary and 11.3% primary headaches. Five children had migraine and five tension‐type headaches, while all others were unclassifiable. 9.4% of children had incontinence (7.7% NE; 2.4% DUI, 1.2% FI) and 4.0% constipation. The rates of incontinence did not differ between children with primary and those without headache for NE (12.9% vs 7.5%), DUI (3.1% vs 2.7%) or FI (3.0% vs 1.0%), but for constipation (12.1% vs 2.6%). Incontinent children had significantly more behavioral and externalizing symptoms, children with headache more internalizing problems. Primary headache was a significant predictor for internalizing, while constipation and FI were predictors for externalizing symptoms.ConclusionsThis population‐based study showed that headache is associated with constipation, but not with incontinence in preschool children. Headache and incontinence are common risk factors for specific psychological symptoms and should be assessed in clinical practice.
Assessment of left ventricle magnetic resonance temperature stability in patients in the presence of arrhythmias
Authors: Ozenne Valéry , Bour Pierre , de Senneville Baudouin Denis , Toupin Solenn , Vaussy Alexis , Lepetit‐Coiffé Matthieu , Jaïs Pierre , Cochet Hubert , Quesson Bruno 
Published: August 2019

AbstractBackgroundMagnetic resonance (MR) thermometry allows visualization of lesion formation in real‐time during cardiac radiofrequency (RF) ablation. The present study was performed to evaluate the precision of MR thermometry without RF heating in patients exhibiting cardiac arrhythmia in a clinical setting. The evaluation relied on quantification of changes in temperature measurements caused by noise and physiological motion.MethodsFourteen patients referred for cardiovascular magnetic resonance imaging underwent an extra sequence to test the temperature mapping stability during free‐breathing acquisition. Phase images were acquired using a multi‐slice, cardiac‐triggered, single‐shot echo planar imaging sequence. Temperature maps were calculated and displayed in real‐time while the electrocardiogram (ECG) was recorded. The precision of temperature measurement was assessed by measuring the temporal standard deviation and temporal mean of consecutive temperature maps over a period of three minutes. The cardiac cycle was analyzed from ECG recordings to quantify the impact of arrhythmia events on the precision of temperature measurement. Finally, two retrospective strategies were tested to remove acquisition dynamics related either to arrhythmia events or sudden breathing motion.ResultsECG synchronization allowed categorization of inter‐beat intervals (RR) into distinct beat morphologies. Five patients were in stable sinus rhythm, while nine patients showed irregular RR intervals due to ectopic beats. An average temporal standard deviation of temperature of 1.6°C was observed in patients under sinus rhythm with a frame rate corresponding to the heart rate of the patient. The temporal standard deviation rose to 2.5°C in patients with arrhythmia. The retrospective rejection strategies increased the temperature precision measurement while maintaining a sufficient frame rate.ConclusionsOur results indicated that real‐time cardiac MR thermometry shows good precision in patients under clinical conditions, even in the presence of arrhythmia. By providing real‐time visualization of temperature distribution within the myocardium during RF delivery, MR thermometry could prevent insufficient or excessive heating and thus improve safety and efficacy.
Making sense of Cbp/p300 loss of function mutations in skin tumorigenesis
Authors: Anastasi Sergio , Alemà Stefano , Segatto Oreste 
Published: August 2019

AbstractCBP and p300 are highly homologous lysine acetyltransferases involved in cell cycle regulation, DNA synthesis and DNA repair. Loss of function mutations of CBP and p300 are found in about one‐third of cutaneous squamous cell carcinoma (cSCC) and often co‐occur, yet their role in cSCC pathogenesis is unclear. Writing in The Journal of Pathology, Ichise and colleagues modeled combined heterozygous loss of Cbp/p300 in mouse keratinocytes expressing a transgenic HrasS35 allele that allows selective coupling of Hras to the Erk pathway. Epidermal thickening caused by expression of HrasS35 was exacerbated by reduced dosage of Cbp/p300 and eventually resulted in development of skin papillomas. This phenotype was associated with reduced expression of Mig6, an Egfr feedback inhibitor, and attendant enhancement of Egfr signaling to the Ras‐Erk pathway. This model provides a mechanistic framework for understanding how Cbp/p300 loss of function mutations impact on skin tumorigenesis and suggests potential therapeutic options in CBP/p300 mutated human cSCC. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Trifluralin and two of its photodegradation products: Crystal structures and phase solubility/UV studies with cyclodextrins
Authors: Lobatto Virginia L. , Argüello Gustavo A. , Caira Mino R. , Bujan Elba I. 
Published: August 2019

AbstractThe crystal structures of the herbicide trifluralin (1), and two of its photodegradation products, namely, N‐n‐propyl‐2,6‐dinitro‐4‐trifluoromethylaniline (2) and 2‐ethyl‐7‐nitro‐5‐trifluoromethyl‐1H‐benzimidazole 3‐oxide (3), were determined by single‐crystal X‐ray diffraction. The presence of the N‐hydroxy tautomer of 3 was detected in the solid state both by X‐ray diffraction and infrared spectroscopy (IR), while in dimethyl sulfoxide‐d6 ((CD3)2SO) solution, the N‐oxide tautomer was observed by hydrogen‐1 nuclear magnetic resonance (1H NMR).In order to determine whether 1, 2, and 3 form complexes with cyclodextrins in aqueous solutions as well as in the solid state, the interaction of 1 to 3 with β‐cyclodextrin in aqueous solutions containing 1% acetonitrile (ACN) and the interaction of 1 to 3 in the solid state with both native and derivatized cyclodextrins were investigated. In aqueous solutions containing 1% ACN, the association constants for the formation of 1:1 complexes were calculated for 1 and 2 as (25 ± 7) × 101M–1 and (18 ± 2) × 101M–1, respectively, whereas that for 3 could not be determined. Extensive trials aimed at obtaining solid complexes of 1 to 3 with both native and selected crystalline derivatized cyclodextrins using different methods failed to produce inclusion complexes.
Anxiety and depression in young adult German cancer patients: Time course and associated factors
Authors: Geue Kristina , Göbel Philipp , Leuteritz Katja , Nowe Erik , Sender Annekathrin , Stöbel‐Richter Yve , Friedrich Michael 
Published: August 2019

AbstractObjectiveCancer in young adulthood is a nonnormative and critical life event. The experience of having cancer can have a strong impact on the mental health of young adults. This study investigated anxiety and depression in young adult cancer patients, examining changes over time and determining associated factors.MethodsYoung cancer patients (18‐39 years at time of diagnosis, diagnosis less than 4 years) were examined. Anxiety and depression were measured at two time points (t2 = 12 months after t1) using the Hospital Anxiety and Depression Scale (HADS). Regression analyses were conducted to determine whether sociodemographic, medical, and/or psychosocial factors (social support, adjustment to the illness, unmet supportive care needs) were associated with patients' anxiety and depression.ResultsFive hundred fourteen young cancer patients (mean age 29.6 years, 75.1% women) completed both questionnaires. A higher proportion showed elevated levels of anxiety (t1: 42.2%; t2: 45.3%) than of depression (t1: 16.9%; t2: 17.7%), and no significant changes in anxiety and depression levels over time were observed. Psychosocial factors explained a major proportion of the variances for anxiety and depression levels at both time points (adjusted R2 between.50 and.59). Furthermore, significant associations were found for anxiety (t1) with gender (women↑); anxiety (t2) and depression (t2) with sick leave (sick leave yes↑); depression (t2) with time since diagnosis (longer time↑).ConclusionPsychological distress among adolescents and young adults (AYA) manifests particularly as anxiety. Strong associations between anxiety/depression and psychosocial factors, as well as the stability of psychological distress over time, clearly illustrate the need for psycho‐oncological care in this patient group.
Signal transduction in photoreceptor histidine kinases
Authors: Möglich Andreas 
Published: August 2019

AbstractTwo‐component systems (TCS) constitute the predominant means by which prokaryotes read out and adapt to their environment. Canonical TCSs comprise a sensor histidine kinase (SHK), usually a transmembrane receptor, and a response regulator (RR). In signal‐dependent manner, the SHK autophosphorylates and in turn transfers the phosphoryl group to the RR which then elicits downstream responses, often in form of altered gene expression. SHKs also catalyze the hydrolysis of the phospho‐RR, hence, tightly adjusting the overall degree of RR phosphorylation. Photoreceptor histidine kinases are a subset of mostly soluble, cytosolic SHKs that sense light in the near‐ultraviolet to near‐infrared spectral range. Owing to their experimental tractability, photoreceptor histidine kinases serve as paradigms and provide unusually detailed molecular insight into signal detection, decoding, and regulation of SHK activity. The synthesis of recent results on receptors with light‐oxygen‐voltage, bacteriophytochrome and microbial rhodopsin sensor units identifies recurring, joint signaling strategies. Light signals are initially absorbed by the sensor module and converted into subtle rearrangements of α helices, mostly through pivoting and rotation. These conformational transitions propagate through parallel coiled‐coil linkers to the effector unit as changes in left‐handed superhelical winding. Within the effector, subtle conformations are triggered that modulate the solvent accessibility of residues engaged in the kinase and phosphatase activities. Taken together, a consistent view of the entire trajectory from signal detection to regulation of output emerges. The underlying allosteric mechanisms could widely apply to TCS signaling in general.
Synthesis of new tetronamides displaying inhibitory activity against bloom‐forming cyanobacteria
Authors: Acosta Jaime AM , Karak Milandip , Barbosa Luiz CA , Boukouvalas John , Straforini Andrea , Forlani Giuseppe 
Published: August 2019

AbstractBACKGROUNDThe increasing frequency and intensity of cyanobacterial blooms pose a serious threat to aquatic ecosystems. These blooms produce potent toxins that can contaminate drinking water and endanger the life of wild and domestic animals as well as humans. Consequently, the development of effective methods for their control is a matter of high priority. We have previously shown that some γ‐benzylidenebutenolides, related to the rubrolide family of natural products, are capable of inhibiting the photosynthetic electron transport chain (Hill reaction), a target of commercial herbicides. Here we report the synthesis and biological properties of a new class of rubrolide‐inspired molecules featuring a tetronamide motif.RESULTSA total of 47 N‐aryl tetronamides, including 38 aldol adducts, were prepared bearing phenyl, biphenyl, naphthyl, aliphatic and heteroaromatic groups. Some of the aldol adducts were dehydrated to the corresponding γ‐benzylidenetetronamides, although satisfactory yields were obtained in only three cases (52–97%). None of the synthesized compounds were capable of blocking the Hill reaction. This notwithstanding, several aldol adducts equipped with a biphenyl substituent displayed excellent inhibitory activity againstSynechococcus elongatusand other cyanobacterial strains (IC50 = 1–5 μM). Further, these tetronamides were found to be essentially inactive against eukaryotic microorganisms.CONCLUSIONSeveral newly synthesized biphenyl‐containing tetronamides were shown to display potent and selective inhibitory activity against cyanobacteria. These compounds appear to exert their biological effects without interfering with the Hill reaction. As such, they represent novel leads in the search of environmentally benign agents for controlling cyanobacterial blooms. © 2019 Society of Chemical Industry
Reciprocal convex approach to output‐feedback control of uncertain LPV systems with fast‐varying input delay
Authors: Salavati Saeed , Grigoriadis Karolos , Franchek Matthew 
Published: August 2019

SummaryRobust control of parameter‐dependent input delay linear parameter‐varying (LPV) systems via gain‐scheduled dynamic output‐feedback control is considered in this paper. The controller is designed to provide disturbance rejection in the context of the induced
‐norm or the
norm of the closed‐loop system in the presence of uncertainty and disturbances. A reciprocally convex approach is employed to bound the Lyapunov‐Krasovskii functional derivative and extract sufficient conditions for the controller characterization in terms of linear matrix inequalities (LMIs). The approach does not require the rate of the delay to be bounded, hence encompasses a broader family of input‐delay LPV systems with fast‐varying delays. The method is then applied to the air‐fuel ratio (AFR) control in spark ignition (SI) engines where the delay and the plant parameters are functions of the engine speed and mass air flow. The objectives are to track the commanded AFR signal and to optimize the performance of the three‐way catalytic converter (TWC) through the precise AFR control and oxygen level regulation, resulting in improved fuel efficiency and reduced emissions. The designed AFR controller seeks to provide canister purge disturbance rejection over the full operating envelope of the SI engine in the presence of uncertainties. Closed‐loop simulation results are presented to validate the controller performance and robustness while meeting AFR tracking and disturbance rejection requirements.
Stable camera position control of unmanned aerial vehicle with three‐degree‐of‐freedom manipulator for visual test of bridge inspection
Authors: Ikeda Takahiro , Minamiyama Satoshi , Yasui Shogo , Ohara Kenichi , Ichikawa Akihiko , Ashizawa Satoshi , Okino Akihisa , Oomichi Takeo , Fukuda Toshio 
Published: August 2019

AbstractThis paper describes a camera position control with aerial manipulator for visual test of bridge inspection. Our developed unmanned aerial vehicle (UAV) has three‐degree‐of‐freedom (3‐DoF) manipulator on its top to execute visual or hammering test of the inspection. This paper focuses on the visual test. A camera was implemented at the end of the manipulator to acquire images of the narrow space of the bridge such as bearings, which the conventional UAV without the camera‐attached manipulators at its top cannot achieve the fine visual test. For the visual test, it is desirable that the camera is above the body with enough distance between the camera and the body. As obvious, the camera position in the inertial coordinate system is effected by the movement of the body. Therefore we implement the camera position control compensating the body movement into the UAV. As a result of an experiment, it is assessed that the proposed control reduces the position error of the camera comparing the one of the body. The mean position error of the camera is 0.039 m that is 51.4% of the one of the body. Our world‐first study enables to acquire the image of the bearing of the bridge by a camera mounted at the end effector of aerial manipulator fixed on UAV.