bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromosomal microarray and whole‐exome sequence analysis in Taiwanese patients with autism spectrum disorder
Authors: Chang Ya‐Sian , Lin Chien‐Yu , Huang Hsi‐Yuan , Chang Jan‐Gowth , Kuo Haung‐Tsung 
Published: October 2019

AbstractBackgroundAutism spectrum disorder (ASD) is defined as a group of genetically and clinically heterogeneous neurodevelopmental disorders. Interplay between de novo and inherited rare variants has been suspected in the development of ASD.MethodsHere, we applied 750K oligonucleotide microarray analysis and whole‐exome sequencing (WES) to five trios from Taiwanese families with ASD.ResultsThe chromosomal microarray analysis revealed three representative known diagnostic copy number variants that contributed to the clinical presentation: the chromosome locations 2q13, 1q21.1q21.2, and 9q33.1. WES detected 22 rare variants in all trios, including four that were newly discovered, one of which is a de novo variant. Sequencing variants of JMJD1C, TCF12, BIRC6, and NHS have not been previously reported. A novel de novo variant was identified in NHS (p.I7T). Additionally, seven pathogenic variants, including SMPD1, FUT2, BCHE, MYBPC3, DUOX2, EYS, and FLG, were detected in four probands. One of the involved genes, SMPD1, had previously been reported to be mutated in patients with Parkinson's disease.ConclusionsThese findings suggest that de novo or inherited rare variants and copy number variants may be double or multiple hits of the probands that lead to ASD. WES could be useful in identifying possible causative ASD variants.
Prekallikrein inhibits innate immune signaling in the lung and impairs host defense during pneumosepsis in mice
Authors: Ding Chao , Scicluna Brendon P , Stroo Ingrid , Yang Jack , Roelofs Joris JTH , de Boer Onno J , de Vos Alex F , Nürnberg Peter , Revenko Alexey S , Crosby Jeff , van't Veer Cornelis , van der Poll Tom 
Published: October 2019

AbstractPrekallikrein (PKK, also known as Fletcher factor and encoded by the gene KLKB1 in humans) is a component of the contact system. Activation of the contact system has been implicated in lethality in fulminant sepsis models. Pneumonia is the most frequent cause of sepsis. We sought to determine the role of PKK in host defense during pneumosepsis. To this end, mice were infected with the common human pathogen Klebsiella pneumoniae via the airways, causing an initially localized infection of the lungs with subsequent bacterial dissemination and sepsis. Mice were treated with a selective PKK‐directed antisense oligonucleotide (ASO) or a scrambled control ASO for 3 weeks prior to infection. Host response readouts were determined at 12 or 36 h post‐infection, including genome‐wide messenger RNA profiling of lungs, or mice were followed for survival. PKK ASO treatment inhibited constitutive hepatic Klkb1 mRNA expression by >80% and almost completely abolished plasma PKK activity. Klkb1 mRNA could not be detected in lungs. Pneumonia was associated with a progressive decline in PKK expression in mice treated with control ASO. PKK ASO administration was associated with a delayed mortality, reduced bacterial burdens, and diminished distant organ injury. While PKK depletion did not influence lung pathology or neutrophil recruitment, it was associated with an upregulation of multiple innate immune signaling pathways in the lungs already prior to infection. Activation of the contact system could not be detected, either during infection in vivo or at the surface of Klebsiella in vitro. These data suggest that circulating PKK confines pro‐inflammatory signaling in the lung by a mechanism that does not involve contact system activation, which in the case of respiratory tract infection may impede early protective innate immunity. © 2019 Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Helping parents prepare for their child's end of life: A retrospective survey of cancer‐bereaved parents
Authors: Wiener Lori , Tager Julia , Mack Jennifer , Battles Haven , Bedoya Sima Zadeh , Gerhardt Cynthia A. 
Published: October 2019

AbstractBackgroundMost parents vividly recall the weeks, days, and moments preceding their child's death for years to come. Dissatisfaction with communication about their child's condition and lack of guidance can contribute to stress prior to a child's death. Based on findings from a study assessing the degree of preparation bereaved parents received and our collective clinical experience, the authors provide suggestions on end‐of‐life communication and guidance for parents.MethodsCaregivers of a child who died from cancer were invited to complete a 46‐item survey through a closed social media (Facebook) group (“Parents who lost children to cancer”). In four months’ time, 131 bereaved caregivers completed the survey. Results were analyzed using descriptive statistics, chi‐square analyses, and a thematic content analysis framework. The mean age of the child at the time of death was 12.ResultsApproximately 40% of the parents in this study felt unprepared for both the medical problems their child faced and how to respond to their child's emotional needs; fewer than 10% felt very prepared for either. Parents were more likely to feel unprepared when perceived suffering was high, highlighting the critical importance of communication and support from the healthcare team as an adjunct to optimal symptom control.ConclusionsThrough quantitative and open‐ended responses, this study identified specific medical and emotional issues about which parents wanted greater preparation. Future research to evaluate guidance strategies to reduce parental suffering prior to the child's death is needed.
Neuropsychological function in children with hemophilia: A review of the Hemophilia Growth and Development Study and introduction of the current eTHINK study
Authors: Buranahirun Cathy , Walsh Karin S. , Mrakotsky Christine , Croteau Stacy E. , Rajpurkar Madhvi , Kearney Susan , Hannemann Cara , Wilkening Greta N. , Shapiro Kevin A. , Cooper David L. 
Published: October 2019

AbstractAlmost all of what is known about neurologic and cognitive development in hemophilia derives from the Hemophilia Growth and Development Study, conducted during an era when treatment regimens and comorbidities differed significantly from the current environment. Results suggested hemophilia and human immunodeficiency virus had independent effects, and hemophilia negatively impacts academic achievement, attention, and behavior. The introduction of prophylaxis treatment in hemophilia has created the need for re‐evaluation of the effects of hemophilia on neurodevelopment and cognition. We outline the Evolving Treatment of Hemophilia's Impact on Neurodevelopment, Intelligence, and Other Cognitive Functions (NCT03660774) study, which aims to meet this need.
A nationwide, population‐based study of school grades, delayed graduation, and qualification for school years 10‐12, in children with brain tumors in Sweden
Authors: Lönnerblad Malin , van't Hooft Ingrid , Blomgren Klas , Berglund Eva 
Published: October 2019

AbstractBackgroundAs many as 95.7% of children diagnosed with a brain tumor will experience persistent late effects as adults. These include difficulties with general executive functions, lower IQ, and mental fatigue, which may negatively affect school performance.MethodsThrough the Swedish Childhood Cancer Registry, we identified 475 children born between 1988 and 1996, diagnosed with a brain tumor before their 15th birthday. School grades in “Swedish,” “mathematics,” and “English,” if their graduation was delayed, and qualification for school years 10‐12 were compared with 2197 matched controls. Furthermore, we checked for interaction effects between sex and age at diagnosis, and possible effects of tumor grade (high or low) as well as parents’ education.ResultsChildren treated for a brain tumor performed worse in the subjects compared to controls and also had delayed graduation to a greater extent. Fewer children treated for a brain tumor than controls qualified for school years 10‐12. Children treated at a young age, especially females, and children whose parents have low education seem to be at particular risk. Unexpectedly, there were no differences in outcomes between survivors with high‐ and low‐grade tumors.ConclusionsIt is important that schools provide regular pedagogical assessment and individualized support to meet the different needs of children treated for a brain tumor. Children treated for low‐grade tumors do not perform better than children treated for high‐grade tumors, despite the lighter treatment, and hence require the same attention and support.
Targeted fusion analysis can aid in the classification and treatment of pediatric glioma, ependymoma, and glioneuronal tumors
Authors: Lake Jessica A. , Donson Andrew M. , Prince Eric , Davies Kurtis D. , Nellan Anandani , Green Adam L. , Mulcahy Levy Jean , Dorris Kathleen , Vibhakar Rajeev , Hankinson Todd C. , Foreman Nicholas K. , Ewalt Mark D. , Kleinschmidt‐DeMasters Bette K. , Hoffman Lindsey M. , Gilani Ahmed 
Published: October 2019

AbstractBackgroundThe use of next‐generation sequencing for fusion identification is being increasingly applied and aids our understanding of tumor biology. Some fusions are responsive to approved targeted agents, while others have future potential for therapeutic targeting. Although some pediatric central nervous system tumors may be cured with surgery alone, many require adjuvant therapy associated with acute and long‐term toxicities. Identification of targetable fusions can shift the treatment paradigm toward earlier integration of molecularly targeted agents.MethodsPatients diagnosed with glial, glioneuronal, and ependymal tumors between 2002 and 2019 were retrospectively reviewed for fusion testing. Testing was done primarily using the ArcherDx FusionPlex Solid Tumor panel, which assesses fusions in 53 genes. In contrast to many previously published series chronicling fusions in pediatric patients, we compared histological features and the tumor classification subtype with the specific fusion identified.ResultsWe report 24 cases of glial, glioneuronal, or ependymal tumors from pediatric patients with identified fusions. With the exception ofBRAF:KIAA1549and pilocytic/pilomyxoid astrocytoma morphology, and possiblyQKI‐MYBand angiocentric glioma, there was not a strong correlation between histological features/tumor subtype and the specific fusion. We report the unusual fusions ofPPP1CB‐ALK,CIC‐LEUTX, FGFR2‐KIAA159, andMN1‐CXXC5and detail their morphological features.ConclusionsFusion testing proved to be informative in a high percentage of cases. A large majority of fusion events in pediatric glial, glioneuronal, and ependymal tumors can be identified by relatively small gene panels.
Phase II study of temozolomide and topotecan (TOTEM) in children with relapsed or refractory extracranial and central nervous system tumors including medulloblastoma with post hoc Bayesian analysis: A European ITCC study
Authors: Le Teuff Gwénaël , Castaneda‐Heredia Alicia , Dufour Christelle , Jaspan Timothy , Calmon Raphael , Devos Annick , McHugh Kieran , Leblond Pierre , Frappaz Didier , Aerts Isabelle , Zwaan Christian M. , Ducassou Stéphane , Chastagner Pascal , Verschuur Arnauld , Corradini Nadège , Casanova Michela , Rubie Hervé , Riccardi Riccardo , Le Deley Marie‐Cecile , Vassal Gilles , Geoerger Birgit ,   European consortium Innovative Therapies for Children with Cancer (ITCC)
Published: October 2019

AbstractAimTo assess objective response after two cycles of temozolomide and topotecan (TOTEM) in children with refractory or relapsed miscellaneous extracranial solid and central nervous system (CNS) tumors, including medulloblastoma and primitive neuroectodermal tumors (PNET).ProcedureMulticenter, nonrandomized, phase 2 basket trial including children with solid tumors, completed by a one‐stage design confirmatory cohort for medulloblastoma, and an exploratory cohort for PNET. Main eligibility criteria were refractory/relapsed measurable disease and no more than two prior treatment lines. Temozolomide was administered orally at 150 mg/m2/day followed by topotecan at 0.75 mg/m2/day intravenously for five consecutive days every 28 days. Tumor response was assessed every two cycles according to WHO criteria and reviewed independently.ResultsThirty‐two patients were enrolled and treated in the miscellaneous solid tumor and 33 in the CNS strata; 20 patients with medulloblastoma and six with PNET were included in the expansion cohorts. The median age at inclusion was 10.0 years (range, 0.9‐20.9). In the basket cohorts, confirmed complete and partial responses were observed in one glioma, four medulloblastoma, and one PNET, leading to the extension. The overall objective response rate (ORR) in medulloblastoma was 28% (95% CI, 12.7‐47.2) with 1/29 complete and 7/29 partial responses, those for PNET 10% (95% CI, 0.3‐44.5). Post hoc Bayesian analysis estimates that the true ORR in medulloblastoma is probably between 20% and 30% and below 20% in PNET. The most common treatment‐related toxicities of the combination therapy were hematologic.ConclusionsTemozolomide‐topotecan results in significant ORR in children with recurrent and refractory medulloblastoma with a favorable toxicity profile.
Medication Use for Comorbidities in People with Alzheimer's Disease: An Australian Population‐Based Study
Authors: Eshetie Tesfahun C. , Nguyen Tuan A. , Gillam Marianne H. , Kalisch Ellett Lisa M. 
Published: October 2019

BackgroundPeople with Alzheimer's disease (AD) often have multimorbidity and take multiple medicines. Yet few studies have examined medicine utilization for comorbidities comparing people with and without AD.ObjectiveThe aim was to investigate the patterns of medication use for comorbidities in people with and without AD.MethodsAn Australian population‐based study was conducted using the Pharmaceutical Benefits Scheme 10% sample of pharmacy claims data. People with AD were defined as those dispensed medicines for dementia (cholinesterase inhibitors, memantine, or risperidone for behavioral and psychological symptoms of dementia) between January 1, 2005, and December 31, 2015, who were aged 65 years or older and alive at the end of 2016. An age‐ and gender‐matched comparison cohort (5:1) of people without AD were identified. Medication use for comorbidities was identified using the validated comorbidity index, Rx‐Risk‐V. A χ2 test was used to compare differences in the pattern of medicine use between the two groups.ResultsA total of 8280 people with AD and 41,400 comparisons without AD were included; 63.4% were female and the median age was 82 years. The median number of comorbidities was greater in people with AD {median [interquartile range (IQR)]: 5 [3–7]} than the comparison group (median [IQR]: 4 [3–6], p<0.0001). Medications for depression, pain (treated with opioid analgesics), anxiety, diabetes, hyperthyroidism, epilepsy, Parkinson’s disease, and antipsychotics were used significantly more commonly in people with AD than in those without dementia. Medications for cardiac conditions, pain (treated with anti‐inflammatory medications), chronic airways disease, gout, glaucoma, renal disease, benign prostatic hyperplasia, cancer, and steroid‐responsive conditions were used significantly less commonly among people with AD than the comparison group.ConclusionsThis study highlighted significant variations in medication use for comorbidities between people with and without AD. Future studies should evaluate the reasons for the disparity in medicine utilization for comorbidities in people with AD.
Advanced Ultrashort‐Pulse Laser Diagnostics
Authors: Ibek Mateusz , Neicke Thomas 
Published: October 2019

AbstractThe simplest and most common method for the characterization of the duration of an ultrashort pulse laser is to measure an autocorrelation function. However, especially with modern high‐power fiber lasers, there are cases where the sensitivity and dynamic range of standard autocorrelators is not sufficient and require more sophisticated measurement methods. With type II autocorrelators, a cost‐efficient high‐contrast technique is available that can provide more detailed insights into a pulse topography that are not visible with normal autocorrelators.
High Power Fiber Laser Welding with Filler Material
Authors: Naeem Mohammed 
Published: October 2019

AbstractIndustry today is continually challenged to improve quality, reliability, reduced cycle times, and improve the overall manufacturing efficiency. This is driving manufacturers across various market sectors to consider fiber laser welding and the possibility to automate their welding processes to improve consistency and part quality. Another driver is the changing workforce dynamics. It is hard to find or train skilled workers who can consistently and reliably weld aluminum, titanium, and high‐strength nickel alloys. This is particularly true when welding with filler material where the base materials are subject to porosity and cracking during the welding process.
Application and Properties of CL‐20/HMX Cocrystal in Composite Modified Double Base Propellants
Authors: Wu Zongkai , Liu Ning , Zheng Wei , Chen Junbo , Song Xiuduo , Wang Jiangning , Cui Chang , Zhang Dongxiang , Zhao Fengqi 
Published: October 2019

AbstractThe composite modified double base (CMDB) propellants containing 2,4,6,8,10,12‐hexanitro‐2,4,6,8,10,12‐hexaazatetracyclo[5.5.0.05,9.03,11] dodecane (CL‐20), 1,3,5,7‐tetranitro‐1,3,5,7‐tetrazocane (HMX) or CL‐20/HMX cocrystal were prepared by the solventless extrusion formation technique. The performances of CMDB propellants were evaluated by means of stability, sensitivity, combustion and mechanical experiments. Raman spectra analysis indicated the stability of CL‐20/HMX cocrystal is partially destroyed in the rolling process under 90 °C, 10 MPa. Methyl violet tests revealed that the colored time of CMDB propellants containing CL‐20/HMX cocrystal, CL‐20 or HMX are 77, 60, and 75 min, respectively. Burning rate tests shown that the burning rates of CMDB propellants containing CL‐20/HMX cocrystal, CL‐20 or HMX in the pressure range of 8 to 18 MPa, increased 1.82, 4.67, and 4.67 mm/s, with the pressure exponents 0.095, 0.306, and 0.346, respectively. Mechanical property tests revealed that the mechanical properties of CMDB propellant containing CL‐20/HMX cocrystal are inconsistent, but the tensile strength has improved compare with CMDB propellant containing CL‐20. These results suggest that CL‐20/HMX cocrystal is a potential material to solve the application problem of the safety performance and stability of the propellants containing CL‐20.
Toxicity of microbial insecticides toward the non‐target freshwater insect Chironomus xanthus
Authors: Silvestre Pereira Dornelas Aline , A Sarmento Renato , C Rezende Silva Laila , de Souza Saraiva Althiéris , J de Souza Danival , D Bordalo Maria , MVM Soares Amadeu , LT Pestana João 
Published: October 2019

AbstractBACKGROUNDCommercial formulations based on Bacillus thuringiensis subs. kurstaki (Btk) and Beauveria bassiana (Bb) are commonly used microbial insecticides in Brazil and other tropical regions. However, and despite being considered environmentally friendly, their use generates concerns regarding possible adverse ecological effects in freshwater ecosystems. Here, we evaluate the effects of these bioinsecticides on the tropical aquatic dipteran Chironomus xanthus under laboratory conditions.RESULTSAfter laboratory exposures to these compounds 48‐h median lethal concentration (LC50) values of 1534 μg a.i./L for Btk and of 6.35 μg a.i./L for Bb were estimated. Chronic assays revealed different sublethal effects: Btk‐based bioinsecticide exposure reduced C. xanthus growth [lowest observed effect concentration (LOEC) was 126 μg a.i./L for head width], decreased emergence rate (LOEC = 8 μg a.i./L) and increased immunological response (LOEC = 50 μg a.i./L) measured as total hemocyte count in larvae hemolymph. Exposure to low concentrations of Bb‐based insecticide also reduced C. xanthus growth (LOEC = 0.07 μg a.i./L for larvae body length measurements), and emergence rate (LOEC = 0.28 μg a.i./L), despite no clear effects on the total hemocyte counts.CONCLUSIONOur results suggest that low concentrations of Btk and Bb bioinsecticides are toxic to C. xanthus. Given their widespread use and occurrence in tropical freshwater systems, research is needed to evaluate the potential effects of these compounds concerning natural freshwater insect communities and ecosystem functioning. © 2019 Society of Chemical Industry
Disruption of the ovarian serine protease (Osp) gene causes female sterility in Bombyx mori and Spodoptera litura
Authors: Xu Xia , Bi Honglun , Wang Yaohui , Li Xiaowei , Xu Jun , Liu Zulian , He Lin , Li Kai , Huang Yongping 
Published: October 2019

AbstractBACKGROUNDPrecise regulation of oogenesis is crucial to female reproduction. Seventy percent of pests belong to lepidopteran species, so it would be interesting to explore the highly conserved genes involved in oogenesis that do not affect growth and development in the lepidopteran model, Bombyx mori. This can provide potential target genes for pest control and promote the development of insect sterility technology.RESULTSIn lepidopteran species, ovarian serine protease (Osp), which encodes a member of the serine protease family, is essential for oogenesis. In this study, we used transgenic CRISPR/Cas9 technology to obtain Osp mutants in the model lepidopteran insect Bombyx mori and in the lepidopteran agricultural pest Spodoptera litura. Sequence analysis of mutants revealed an array of deletions in Osp loci in both species. We found that the deletion of Osp resulted in female sterility, whereas male fertility was not affected. Although B. mori and S. litura mutant females mated normally, they laid fewer eggs than wild‐type females and eggs did not hatch.CONCLUSIONOsp is crucial for female reproductive success in two species of Lepidoptera. As the Osp gene is highly conserved in insect species, this gene is a potential molecular target for genetic‐based pest management. © 2019 Society of Chemical Industry
Swath pattern analysis from a multi‐rotor unmanned aerial vehicle configured for pesticide application
Authors: Richardson Brian , Rolando Carol A , Somchit Chanatda , Dunker Christina , Strand Tara M , Kimberley Mark O 
Published: October 2019

AbstractBACKGROUNDAlthough unmanned aerial vehicles (UAVs) are increasingly used to deliver small‐scale aerial pesticide applications, there remains uncertainty over their efficiency in terms of uniformity of spray deposition and their application efficiency. Consequently, a field study was designed to quantify factors influencing the uniformity of spray deposition from a multi‐rotor UAV that is operated commercially in New Zealand. Two sampling systems for measuring spray deposition, a continuous horizontal string and steel plates placed on the ground were compared.RESULTS
The spray deposit distribution characteristics and calculated lane separation values (distance between flight lines that produces a maximum coefficient of variation of 30% for spray deposits) were strongly influenced by wind speed, nozzle position, release height, ground speed and droplet size. Lane separation values ranged from 1 to > 5 m. Swath distribution parameters (spread and position of peak deposition) derived from plates were not significantly different from those derived from string. However, total deposition on strings relative to plates increased with small droplets. Reducing plate sampling intensity from 0.25 m intervals to 0.5 m and even 1.0 m had only a minor effect on estimates of swath parameter values.CONCLUSIONSThe potential for precision spraying from UAV platforms has yet to be achieved with improvements required in hardware and software. Further, mechanistic models are needed to quantify how complex interactions among multiple operating and meteorological variables influence spray deposition. © 2019 Society of Chemical Industry