bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selecting short length nucleic acids localized in exosomes improves plasma EGFR mutation detection in NSCLC patients
Authors: Kim Yoonjung , Shin Saeam , Kim Boyeon , Lee Kyung-A 
Published: October 2019

AbstractBackgroundExosomal nucleic acid (exoNA) is a feasible target to improve the sensitivity ofEGFRmutation testing in non-small cell lung cancer patients with limited cell-free DNA (cfDNA) mutant copies. However, the type and size of target exoNA related to the sensitivity ofEGFRmutation testing has not been explored extensively.MethodsThe type and size of target exoNA related to the sensitivity ofEGFRmutation testing was evaluated using ddPCR. A total of 47 plasma samples was tested using short-length exoTNA (exosomal DNA and RNA) and cfDNA.ResultsThe sensitivity of short-length exoTNA (76.5%) was higher than that of cfDNA (64.7%) for detectingEGFRmutations in NSCLC patients. InEGFR-mutant NSCLC patients with intrathoracic disease (M0/M1a) or cases with low-copy T790M, the positive rate was 63.6% (N = 7/11) and 45.5% (N = 5/11) for short-length exoTNA and cfDNA, respectively. On average, the number absolute mutant copies of short-length exoTNA were 1.5 times higher than that of cfDNA. The mutant allele copies (Ex19del and T790M) in short-length exoTNA were relatively well preserved at 4 weeks after storage. The difference (%) in absolute mutant allele copies (Ex19del) between 0 days and 4 weeks after storage was − 61.0% for cfDNA.ConclusionTarget nucleic acids and their size distribution may be critical considerations for selecting an extraction method and a detection assay. A short-length exoTNA (200 bp) contained more detectable tumor-derived nucleic acids than exoDNA (~ 200 bp length or a full-length) or cfDNA. Therefore, a short-length exoTNA as a sensitive biomarker might be useful to detectEGFRmutants for NSCLC patients with low copy number of the mutation target.
Evaluation of the impacts of a district-level mental health care plan on contact coverage, detection and individual outcomes in rural Uganda: a mixed methods approach
Authors: Nakku J. E. M. , Rathod S. D. , Garman E. C. , Ssebunnya J. , Kangere S. , De Silva M. , Patel V. , Lund C. , Kigozi F. N. 
Published: October 2019

Abstract

Background
The burden of mental disorders in low- and middle-income countries is large. Yet there is a major treatment gap for these disorders which can be reduced by integrating the care of mental disorders in primary care.

Aim
We aimed to evaluate the impact of a district mental health care plan (MHCP) on contact coverage for and detection of mental disorders, as well as impact on mental health symptom severity and individual functioning in rural Uganda.

Results
For adults who attended primary care facilities, there was an immediate positive effect of the MHCP on clinical detection at 3 months although this was not sustained at 12 months. Those who were treated in primary care experienced significant reductions in symptom severity and functional impairment over 12 months. There was negligible change in population-level contact coverage for depression and alcohol use disorder.

Conclusion
The study found that it is possible to integrate mental health care into primary care in rural Uganda. Treatment by trained primary care workers improves clinical and functioning outcomes for depression, psychosis and epilepsy. Challenges remain in accessing the men for care, sustaining the improvement in detection over time, and creating demand for services among those with presumed need.
Discovery, activity and characterisation of an AA10 lytic polysaccharide oxygenase from the shipworm symbiont Teredinibacter turnerae
Authors: Fowler Claire. A. , Sabbadin Federico , Ciano Luisa , Hemsworth Glyn R. , Elias Luisa , Bruce Neil , McQueen-Mason Simon , Davies Gideon J. , Walton Paul H. 
Published: October 2019

Abstract

Background
The quest for novel enzymes for cellulosic biomass-degradation has recently been focussed on lytic polysaccharide monooxygenases (LPMOs/PMOs), Cu-containing proteins that catalyse the oxidative degradation of otherwise recalcitrant polysaccharides using O2 or H2O2 as a co-substrate.

Results
Although classical saprotrophic fungi and bacteria have been a rich source of lytic polysaccharide monooxygenases (LPMOs), we were interested to see if LPMOs from less evident bio-environments could be discovered and assessed for their cellulolytic activity in a biofuel context. In this regard, the marine shipworm Lyrodus pedicellatus represents an interesting source of new enzymes, since it must digest wood particles ingested during its natural tunnel boring behaviour and plays host to a symbiotic bacterium, Teredinibacter turnerae, the genome of which has revealed a multitude of enzymes dedicated to biomass deconstruction. Here, we show that T. turnerae encodes a cellulose-active AA10 LPMO. The 3D structure, at 1.4 Å resolution, along with its EPR spectrum is distinct from other AA10 polysaccharide monooxygenases insofar as it displays a “histidine-brace” catalytic apparatus with changes to the surrounding coordination sphere of the copper. Furthermore, TtAA10A possesses a second, surface accessible, Cu site 14 Å from the classical catalytic centre. Activity measurements show that the LPMO oxidises cellulose and thereby significantly augments the rate of degradation of cellulosic biomass by classical glycoside hydrolases.

Conclusion
Shipworms are wood-boring marine molluscs that can live on a diet of lignocellulose. Bacterial symbionts of shipworms provide many of the enzymes needed for wood digestion. The shipworm symbiont T. turnerae produces one of the few LPMOs yet described from the marine environment, notably adding to the capability of shipworms to digest recalcitrant polysaccharides.
Genomic analysis of the tryptome reveals molecular mechanisms of gland cell evolution
Authors: Babonis Leslie S. , Ryan Joseph F. , Enjolras Camille , Martindale Mark Q. 
Published: October 2019

Abstract

Background
Understanding the drivers of morphological diversity is a persistent challenge in evolutionary biology. Here, we investigate functional diversification of secretory cells in the sea anemone Nematostella vectensis to understand the mechanisms promoting cellular specialization across animals.

Results
We demonstrate regionalized expression of gland cell subtypes in the internal ectoderm of N. vectensis and show that adult gland cell identity is acquired very early in development. A phylogenetic survey of trypsins across animals suggests that this gene family has undergone numerous expansions. We reveal unexpected diversity in trypsin protein structure and show that trypsin diversity arose through independent acquisitions of non-trypsin domains. Finally, we show that trypsin diversification in N. vectensis was effected through a combination of tandem duplication, exon shuffling, and retrotransposition.

Conclusions
Together, these results reveal the numerous evolutionary mechanisms that drove trypsin duplication and divergence during the morphological specialization of cell types and suggest that the secretory cell phenotype is highly adaptable as a vehicle for novel secretory products.
Ethics of artificial intelligence in radiology: summary of the joint European and North American multisociety statement
Authors: Geis J. Raymond , Brady Adrian , Wu Carol C. , Spencer Jack , Ranschaert Erik , Jaremko Jacob L. , Langer Steve G. , Kitts Andrea Borondy , Birch Judy , Shields William F. , van den Hoven van Genderen Robert , Kotter Elmar , Gichoya Judy Wawira , Cook Tessa S. , Morgan Matthew B. , Tang An , Safdar Nabile M. , Kohli Marc 
Published: October 2019

Abstract
This is a condensed summary of an international multisociety statement on ethics of artificial intelligence (AI) in radiology produced by the ACR, European Society of Radiology, RSNA, Society for Imaging Informatics in Medicine, European Society of Medical Imaging Informatics, Canadian Association of Radiologists, and American Association of Physicists in Medicine.
AI has great potential to increase efficiency and accuracy throughout radiology, but also carries inherent pitfalls and biases. Widespread use of AI-based intelligent and autonomous systems in radiology can increase the risk of systemic errors with high consequence, and highlights complex ethical and societal issues. Currently, there is little experience using AI for patient care in diverse clinical settings. Extensive research is needed to understand how to best deploy AI in clinical practice.
This statement highlights our consensus that ethical use of AI in radiology should promote well-being, minimize harm, and ensure that the benefits and harms are distributed among stakeholders in a just manner. We believe AI should respect human rights and freedoms, including dignity and privacy. It should be designed for maximum transparency and dependability. Ultimate responsibility and accountability for AI remains with its human designers and operators for the foreseeable future.
The radiology community should start now to develop codes of ethics and practice for AI which promote any use that helps patients and the common good and should block use of radiology data and algorithms for financial gain without those two attributes.
Identification and molecular characterization of a psychrophilic GH1 β-glucosidase from the subtropical soil microorganism Exiguobacterium sp. GXG2
Authors: Yin Bangqiao , Gu Hengsen , Mo Xueyan , Xu Yue , Yan Bing , Li Quanwen , Ou Qian , Wu Bo , Guo Chen , Jiang Chengjian 
Published: October 2019

AbstractThe products of bacterial β-glucosidases with favorable cold-adapted properties have industrial applications. A psychrophilic β-glucosidase gene namedbglGfrom subtropical soil microorganismExiguobacteriumsp. GXG2 was isolated and characterized by function-based screening strategy. Results of multiple alignments showed that the derived protein BglG shared 45.7% identities with reviewed β-glucosidases in the UniProtKB/Swiss-Prot database. Functional characterization of the β-glucosidase BglG indicated that BglG was a 468 aa protein with a molecular weight of 53.2 kDa. The BglG showed the highest activity in pH 7.0 at 35 °C and exhibited consistently high levels of activity within low temperatures ranging from 5 to 35 °C. The BglG appeared to be a psychrophilic enzyme. The values ofKm,Vmax,kcat, andkcat/Kmof recombinant BglG towardρNPG were 1.1 mM, 1.4 µg/mL/min, 12.7 s−1, and 11.5 mM/s, respectively. The specific enzyme activity of BglG was 12.14 U/mg. The metal ion of Ca2+and Fe3+could stimulate the activity of BglG, whereas Mn2+inhibited the activity. The cold-adapted β-glucosidase BglG displayed remarkable biochemical properties, making it a potential candidate for future industrial applications.
Multiple integration of the gene ganA into the Bacillus subtilis chromosome for enhanced β-galactosidase production using the CRISPR/Cas9 system
Authors: Watzlawick Hildegard , Altenbuchner Josef 
Published: October 2019

Abstract
The ganA gene from Bacillus subtilis encoding a β-galactosidase for degradation of the galactomannan was integrated in different loci of the B. subtilis chromosome employing the CRISPR/Cas9 system. Hereby a total of five copies of ganA cassettes in which the ganA gene was fused with the glucitol-promoter were inserted in the recipient chromosome wherein hypothetical, sporulation and protease genes were deleted. The strain with five copies of ganA expression cassette showed a β-galactosidase activity similar to the one with the same gene on a pUB110 derived multi-copy plasmid and under the same regulatory control of the glucitol promoter and GutR activator. The production of β-galactosidase in the strain with the multi-copy plasmid decreased rapidly when growth was performed under induced conditions and without antibiotic selection. In contrast, the strain with the five copies of ganA in the chromosome produced β-galactosidase for at least 40 generations. This demonstrates that the CRISPR/Cas9 system is a valuable and easy tool for constructing stable producer strains. The bigger efforts that are needed for the multiple target gene integration into the chromosome compared to cloning in expression vectors were justified by the higher stability of the target genes and the lack of antibiotic resistance genes.
Histamine H4 receptor regulates IL-6 and INF-γ secretion in native monocytes from healthy subjects and patients with allergic rhinitis
Authors: Peng Hua , Wang Jian , Ye Xiao Yan , Cheng Jie , Huang Cheng Zhi , Li Li Yue , Li Tian Ying , Li Chun Wei 
Published: October 2019

Abstract
Histamine H1 receptor (H1R) and histamine H4 receptor (H4R) are essential in allergic inflammation. The roles of H4R have been characterized in T cell subsets, whereas the functional properties of H4R in monocytes remain unclear. In the current study, the responses of H4R in peripheral monocytes from patients with allergic rhinitis (AR) were investigated. The results confirmed that H4R has the functional effects of mediating cytokine production (i.e., down-regulating IFN-γ and up-regulating IL-6) in cells from a monocyte cell line following challenge with histamine. We demonstrated that when monocytes from AR patients were stimulated with allergen extracts of house dust mite (HDM), IFN-γ secretion was dependent on H4R activity, but IL-6 secretion was based on H1R activity. Furthermore, a combination of H1R and H4R antagonists was more effective at blocking the inflammatory response in monocytes than treatment with either type of antagonist alone.
15 years journey of idiopathic pulmonary arterial hypertension with BMPR2 mutation
Authors: Ahn Kyung Jin , Jang Albert Youngwoo , Park Su Jung , Chung Wook-Jin 
Published: October 2019

Abstract
Pulmonary arterial hypertension (PAH) is known as one of diseases with the worst prognosis. Recently, targeted PAH drugs have been developed and approved for use; therefore, the treatment strategy and goals have changed, and the prognosis has improved over two decades. We reviewed the case of a female who showed the natural disease course of heritable PAH in treatment with the targeted PAH drugs under the Korean Health Insurance policy. At the age of 15, she visited the outpatient clinic for dyspnea on exertion that occurred 3 years ago. At that time, severe pulmonary hypertension was revealed by an echocardiography and there was no evidence of significant shunt lesion or embolism. After 4 years of loss to follow-up, her performance was WHO functional class III and she still suffered from dyspnea. The initial monotherapy using an endothelin receptor antagonist was started in 2008. After 2 years, BMPR 2 mutation was detected. Her clinical symptoms gradually worsened because of poor compliance. To escalate therapy, combination therapy was given, and finally, triple maximal therapy was maintained. The next step is to consider intravenous prostanoids. Various combinations of targeted therapy have been tried, and several trials have been confirmed that improve the prognosis. Initial upfront combination therapy and a more enthusiastic approach make good a better prognosis. In this area, active support of the government insurance policy is indispensable in Korea.
Polymorphism in natural alleles of the avirulence gene Avr1c is associated with the host adaptation of Phytophthora sojae
Authors: Yang Jin , Wang Xiaomen , Guo Baodian , Huang Jie , Ye Wenwu , Dong Suomeng , Wang Yan , Zheng Xiaobo , Wang Yuanchao 
Published: October 2019

Abstract
Phytophthora sojae is a destructive pathogen of soybean that is widely distributed in the world. The interaction between P. sojae and soybean follows the gene-for-gene model. The use of resistant soybean cultivars is the primary and most effective method to combat the disease. However, variation in the Avr genes of the pathogen enables it to evade host defenses. We collected 81 isolates from four major soybean-production areas in China to analyze the polymorphism of Avr genes in P. sojae field population. The virulence of these isolates towards 14 differential soybean lines indicated complex pathotypes in P. sojae field population in China. In this study we found that Rps1c, which is cognate with Avr1c, could be deployed in Heilongjiang, Shandong, and Jiangsu Provinces but not in Anhui Province. To determine the mechanism by which Avr1c escapes recognition by Rps1c, we analyzed the polymorphism of Avr1c gene in 50 isolates of a field population of P. sojae and found multiple novel genotypes related to virulence and avirulence. By performing infection assays and gene co-bombardment, we showed that the K105 amino-acid residue was under strong positive selection and was a determinant of the avirulence of Avr1c. Structural analysis showed that K105 was exposed on the surface of the protein, suggesting it to be a critical site for interacting with Rps genes or their associated proteins.
Automated breast ultrasound (ABUS) as a screening tool: initial experience
Authors: Mostafa Amera Abd Elsalam , Eltomey Mohamed Adel , Elaggan Ashraf Mohammed , Hashish Amel A. 
Published: October 2019

Abstract

Background
Breast cancer is a major health problem, being the most common cancer in women. Early detection of breast cancer aims to the reduction of mortality and morbidity rates. Conventional screening methods include mammography and ultrasonography; however, both modalities have their limitations. Automated breast ultrasound (ABUS) is a recent technological advancement in the field of breast imaging having the benefit of standardization of the scans and lack of operator dependence as in conventional handheld ultrasound scans. The aim of this work was to report our initial experience of the added value of ABUS as a breast screening tool. The study included 200 patients who had screening mammograms, ultrasound, and ABUS.

Results
A significant difference was found between the number of lesions detected by ABUS and conventional ultrasound. A significant difference was found between lesions detected by ABUS and mammography which was most evident in patients with dense breasts.

Conclusions
ABUS is a valuable tool in the screening of the breast with improved lesion detection, especially in patients with dense breasts.
Next-Generation Sequencing and the Clinical Oncology Workflow: Data Challenges, Proposed Solutions, and a Call to Action
Authors: Conway Jake R. , Warner Jeremy L. , Rubinstein Wendy S. , Miller Robert S. 
Published: October 2019

PURPOSE Next-generation sequencing (NGS) of tumor and germline DNA is foundational for precision oncology, with rapidly expanding diagnostic, prognostic, and therapeutic implications. Although few question the importance of NGS in modern oncology care, the process of gathering primary molecular data, integrating it into electronic health records, and optimally using it as part of a clinical workflow remains far from seamless. Numerous challenges persist around data standards and interoperability, and clinicians frequently face difficulties in managing the growing amount of genomic knowledge required to care for patients and keep up to date. METHODS This review provides a descriptive analysis of genomic data workflows for NGS data in clinical oncology and issues that arise from the inconsistent use of standards for sharing data across systems. Potential solutions are described. RESULTS NGS technology, especially for somatic genomics, is well established and widely used in routine patient care, quality measurement, and research. Available genomic knowledge bases play an evolving role in patient management but lack harmonization with one another. Questions about their provenance and timeliness of updating remain. Potentially useful standards for sharing genomic data, such as HL7 FHIR and mCODE, remain primarily in the research and/or development stage. Nonetheless, their impact will likely be seen as uptake increases across care settings and laboratories. The specific use case of ASCO CancerLinQ, as a clinicogenomic database, is discussed. CONCLUSION Because the electronic health records of today seem ill suited for managing genomic data, other solutions are required, including universal data standards and applications that use application programming interfaces, along with a commitment on the part of sequencing laboratories to consistently provide structured genomic data for clinical use.
Impeller Blower Performance in Conveying Broiler Litter
Authors: Way Thomas R. , Tewolde Haile , Watts Dexter B. 
Published: October 2019

Abstract. Broadcast application is the typical application method for poultry litter, which is a mixture of poultry manure and a bedding material. Applying poultry litter in subsurface bands reduces concentrations of nutrients from the litter in surface runoff water, reduce loss of ammonia to volatilization, and has been shown to increase cotton lint yield, relative to conventional broadcast application. An impeller blower was developed for conveying poultry litter a short distance horizontally and downward to the soil. When relatively dry pine shavings-based broiler litter with a moisture content of 27% w.b. was used, and the impeller speed was 930 r min-1 [14.9 m s-1 (48.9 ft s-1) circumferential speed], the blower performed well conveying litter at a rate of 1.2 kg s-1 (2.6 lb s-1) [0.88 kg dry matter s-1 (1.9 lb dry matter s-1)]. The blower performance was unsatisfactory, however, when relatively moist litter with a moisture content of 45% w.b. was used because the litter adhered to the interior of the blower outlet and clogged the outlet. The blower was mounted beneath a litter hopper, and safety of people in the vicinity of the blower is a concern if the litter contains rocks or other hard objects, and there is no shield to prevent these objects from being flung upward, out of the hopper, from the blower inlet. When the blower was run at 889 ± 14 r min-1 without any litter, so it was conveying only air, as the area of the circular blower inlet increased by a factor of 25 from 0.00051 to 0.0127 m2 (0.79 to 19.6 in.2), the mean outlet air velocity increased by a factor of 4.0 from 3.0 to 12.0 m s-1 (9.8 to 39.4 ft s-1). The blower conveyed dry litter successfully for a single-band implement [1.2 kg s-1 (2.6 lb s-1) mass flow rate at 930 r min-1 impeller speed], for subsurface band application of poultry litter. Mesh chain conveyors, however, perform better for litter moisture contents up to 40% w.b. The mass flow rate of litter, up to 40% w.b. moisture content, can be controlled quite well with mesh chain conveyors (litter mass flow rate coefficients of variation typically 5% or less), but is more difficult to control with this impeller blower. Keywords: Animal waste, Band application, Impeller blower, Manures, Manure application equipment, Pneumatic conveying, Poultry manure, Subsurface banding.