bluuebunny/crossref_metadata_2025_split huggingface dataset:
An integrated clinical program and crowdsourcing strategy for genomic sequencing and Mendelian disease gene discovery
Authors: Haghighi Alireza , Krier Joel B. , Toth-Petroczy Agnes , Cassa Christopher A. , Frank Natasha Y. , Carmichael Nikkola , Fieg Elizabeth , Bjonnes Andrew , Mohanty Anwoy , Briere Lauren C. , Lincoln Sharyn , Lucia Stephanie , Gupta Vandana A. , Söylemez Onuralp , Sutti Sheila , Kooshesh Kameron , Qiu Haiyan , Fay Christopher J. , Perroni Victoria , Valerius Jamie , Hanna Meredith , Frank Alexander , Ouahed Jodie , Snapper Scott B. , Pantazi Angeliki , Chopra Sameer S. , Leshchiner Ignaty , Stitziel Nathan O. , Feldweg Anna , Mannstadt Michael , Loscalzo Joseph , Sweetser David A. , Liao Eric , Stoler Joan M. , Nowak Catherine B. , Sanchez-Lara Pedro A. , Klein Ophir D. , Perry Hazel , Patsopoulos Nikolaos A. , Raychaudhuri Soumya , Goessling Wolfram , Green Robert C. , Seidman Christine E. , MacRae Calum A. , Sunyaev Shamil R. , Maas Richard L. , Vuzman Dana ,   Undiagnosed Diseases Network, Brigham and Women’s Hospital FaceBase Project, Brigham Genomic Medicine (BGM)
Published: August 2018

AbstractDespite major progress in defining the genetic basis of Mendelian disorders, the molecular etiology of many cases remains unknown. Patients with these undiagnosed disorders often have complex presentations and require treatment by multiple health care specialists. Here, we describe an integrated clinical diagnostic and research program using whole-exome and whole-genome sequencing (WES/WGS) for Mendelian disease gene discovery. This program employs specific case ascertainment parameters, a WES/WGS computational analysis pipeline that is optimized for Mendelian disease gene discovery with variant callers tuned to specific inheritance modes, an interdisciplinary crowdsourcing strategy for genomic sequence analysis, matchmaking for additional cases, and integration of the findings regarding gene causality with the clinical management plan. The interdisciplinary gene discovery team includes clinical, computational, and experimental biomedical specialists who interact to identify the genetic etiology of the disease, and when so warranted, to devise improved or novel treatments for affected patients. This program effectively integrates the clinical and research missions of an academic medical center and affords both diagnostic and therapeutic options for patients suffering from genetic disease. It may therefore be germane to other academic medical institutions engaged in implementing genomic medicine programs.
Comparative analysis of surface coating properties of five hydrophobins from Aspergillus nidulans and Trichoderma reseei
Authors: Winandy Lex , Hilpert Felix , Schlebusch Oleksandra , Fischer Reinhard 
Published: August 2018

AbstractFungal hydrophobins are small amphiphilic proteins that self-assemble into monolayers on hydrophobic:hydrophilic interfaces and can be used for surface coatings. Because e.g. Aspergillus nidulans contains six different hydrophobins, it is likely that they have different properties and are used for different “applications” in the fungus. We established a method for recombinant production of different class hydrophobins in Escherichia coli. We produced DewA, DewC, DewD, DewE from A. nidulans and HFBI from Trichoderma reesei and compared surface coating properties of these hydrophobins. All tested proteins formed coatings on glass, strongly increasing the hydrophobicity of the surface, and showed emulsion-stabilizing properties. But whereas the typical class I hydrophobin DewA formed the most stable coating on glass, the intermediate class hydrophobins DewE and DewD were more effective in stabilization of oil:water emulsions. This work gives insights into correlations between structural characteristics of hydrophobins and their behaviour as surface binding agents. It could help with the clarification of their biological functions and lead to novel biotechnological applications.
Early-onset liver cancer in South America associates with low hepatitis B virus DNA burden
Authors: Marchio Agnès , Cerapio Juan Pablo , Ruiz Eloy , Cano Luis , Casavilca Sandro , Terris Benoît , Deharo Eric , Dejean Anne , Bertani Stéphane , Pineau Pascal 
Published: August 2018

AbstractIn Peru, hepatocellular carcinoma (HCC) arises in young non-cirrhotic patients. Hepatitis B virus (HBV) is suspected to be the prominent etiological agent. We thus performed a comprehensive molecular study of HBV infection in 65 Peruvian HCC patients. Only 51% were considered as persistently infected at the onset. HBV DNA was found by PCR in the tumor and/or matched non-tumor liver tissues in more than 80% of cases (n = 53/65). HBV DNA was significantly more abundant in livers of younger patients than in those of the older ones. We consistently observed low viral DNA burden (0.1–6.5 copies for 100 cells), with viral genomes in younger patients displaying higher proportion of mutations at di-pyrimidines (TpT and CpC, P = 0.006). A drastic activation of multiple DNA repair pathways in tumors of younger patients was observed. Our observations clearly challenge the current vision that associates high HBV DNA load with earlier tumor development. We concluded that in Peru, and maybe in other populations with Americas’ indigenous ancestry, HBV-associated liver tumorigenesis might differ significantly from that generally observed in the rest of the world. Procedures used to screen for HCC development in subjects at risk should be adapted to the local situation.
Cooperativity in Plant Plasma Membrane Intrinsic Proteins (PIPs): Mechanism of Increased Water Transport in Maize PIP1 Channels in Hetero-tetramers
Authors: Vajpai Manu , Mukherjee Mishtu , Sankararamakrishnan Ramasubbu 
Published: August 2018

AbstractPlant aquaporins (AQPs) play vital roles in several physiological processes. Plasma membrane intrinsic proteins (PIPs) belong to the subfamily of plant AQPs. They are further subdivided into two closely related subgroups PIP1s and PIP2s. While PIP2 members are efficient water channels, PIP1s from some plant species have been shown to be functionally inactive. Aquaporins form tetramers under physiological conditions. PIP2s can enhance the water transport of PIP1s when they form hetero-tetramers. However, the role of monomer-monomer interface and the significance of specific residues in enhancing the water permeation of PIP1s have not been investigated at atomic level. We have performed all-atom molecular dynamics (MD) simulations of homo-tetramers and four different hetero-tetramers containing ZmPIP1;2 and ZmPIP2;5 from Zea mays. ZmPIP1;2 in a tetramer assembly will have two interfaces, one formed by transmembrane segments TM4 and TM5 and the other formed by TM1 and TM2. We have analyzed channel radius profiles, water transport and potential of mean force profiles of ZmPIP1;2 monomers. Results of MD simulations clearly revealed the influence of TM4-TM5 interface in modulating the water transport of ZmPIP1;2. MD simulations indicate the importance of I93 residue from the TM2 segment of ZmPIP2;5 for the increased water transport in ZmPIP1;2.
Patient stratification in clinical glaucoma trials using the individual tear proteome
Authors: Nättinen Janika , Jylhä Antti , Aapola Ulla , Parkkari Minna , Mikhailova Alexandra , Beuerman Roger W. , Uusitalo Hannu 
Published: August 2018

AbstractGlaucoma patients are prone to concomitant ocular surface diseases; however, switching from preserved to preservative-free medication can often alleviate these symptoms. The objective of this study was to examine how the adverse effects and tear proteome change for glaucoma patients (n = 28) during a 12-month drug switch from preserved latanoprost (Xalatan) to preservative-free tafluprost (Taflotan). We hypothesized that patient stratification could help identify novel recovery patterns in both tear proteomics and clinical data. In order to accomplish patient stratification, we implemented sequential window acquisition of all theoretical mass spectrometry (SWATH-MS) as a tool for quantitative analysis of individual tear protein profiles. During each visit (baseline and four follow-up visits), the patients’ tears were sampled and the state of their ocular surface was evaluated clinically. Altogether 785 proteins were quantified from each tear sample using SWATH strategy and as these protein expression levels were compared between baseline and 12-month follow-up, three distinct patient groups were identified. We evaluated how these patient groups differed in their protein expression levels at baseline and discovered that the patients with increased levels of pro-inflammatory proteins and decreased levels of protective proteins benefitted most from the medication switch.
Differential expression of miRNA199b-5p as a novel biomarker for sporadic and hereditary parathyroid tumors
Authors: Hwang Sena , Jeong Jong Ju , Kim Se Hoon , Chung Yoon Jung , Song Sun Yong , Lee Yang Jong , Rhee Yumie 
Published: August 2018

AbstractMicroRNAs (miRNAs) are dysregulated in many tumors; however, miRNA regulation in parathyroid tumors remains poorly understood. To identify differentially expressed miRNAs between sporadic and hereditary parathyroid tumors and to analyze their correlation with clinicopathological features, a microarray containing 887 miRNAs was performed; then, the differentially expressed miRNAs were validated by qRT-PCR using 25 sporadic and 12 hereditary parathyroid tumors and 24 normal parathyroid tissue samples. A receiver operating characteristic curve (ROC) analysis was applied to evaluate the utility of the miRNAs for distinguishing parathyroid tumor types. Compared to the miRNAs in the normal parathyroid tissues, 10 miRNAs were differentially expressed between the sporadic and hereditary parathyroid tumors. Seven of these miRNAs (let-7i, miR-365, miR-125a-3p, miR-125a-5p, miR-142-3p, miR-193b, and miR-199b-5p) were validated in the parathyroid tumor samples. Among these miRNAs, only miR-199b-5p was differentially expressed (P < 0.001); miR-199b-5p was significantly downregulated and negatively associated with PTH levels (γ = −0.579, P = 0.002) in the sporadic tumors but was upregulated in the hereditary tumors. This miRNA showed 67% sensitivity and 100% specificity for distinguishing sporadic and hereditary parathyroid tumors. These results reveal altered expression of a miRNA between sporadic and hereditary parathyroid tumors and the potential role of miR-199b-5p as a novel biomarker for distinguishing these two types of parathyroid tumors.
Electromagnetic wave absorption and structural properties of wide-band absorber made of graphene-printed glass-fibre composite
Authors: Marra F. , Lecini J. , Tamburrano A. , Pisu L. , Sarto M. S. 
Published: August 2018

AbstractLightweight composites combining electromagnetic wave absorption and excellent mechanical properties are required in spacecraft and aircraft. A one- dimensional metamaterial absorber consisting of a stack of glass fibre/epoxy layers and graphene nanoplatelets/epoxy films was proposed and fabricated through a facile air-spraying based printing technology and a liquid resin infusion method. The production process allows an optimum dispersion of graphene nanoplatelets, promoting adhesion and mechanical integration of the glass fibre/epoxy layers with the graphene nanoplatelets/epoxy films. According to experimental results, the proposed wide-band absorber provides a reflection coefficient lower than −10 dB in the range 8.5–16.7 GHz and an improvement of flexural modulus of more than 15%, with a total thickness of ∼1 mm. Outstanding electromagnetic wave absorption and mechanical performance make the proposed absorber more competitive in aeronautical and aerospace applications.
PLGA-encapsulated CpG ODN and Campylobacter jejuni lysate modulate cecal microbiota composition in broiler chickens experimentally challenged with C. jejuni
Authors: Taha-Abdelaziz Khaled , Yitbarek Alexander , Alkie Tamiru Negash , Hodgins Douglas C. , Read Leah R. , Weese J. Scott , Sharif Shayan 
Published: August 2018

AbstractCampylobacter jejuni is a leading bacterial cause of human gastroenteritis. Reducing Campylobacter numbers in the intestinal tract of chickens will minimize transmission to humans, thereby reducing the incidence of infection. We have previously shown that oral pre-treatment of chickens with C. jejuni lysate and Poly D, L-lactide-co-glycolide polymer nanoparticles (PLGA NPs) containing CpG oligodeoxynucleotide (ODN) can reduce the number of C. jejuni in infected chickens. In the current study, the effects of these pre-treatments on the composition and functional diversity of the cecal microbiota, in chickens experimentally infected with C. jejuni, were investigated using next-generation sequencing. The taxonomic composition analysis revealed a reduction in cecal microbial diversity and considerable changes in the taxonomic profiles of the microbial communities of C. jejuni-challenged chickens. On the other hand, irrespective of the dose, the microbiota of PLGA-encapsulated CpG ODN- and C. jejuni lysate-treated chickens exhibited higher microbial diversity associated with high abundance of members of Firmicutes and Bacteroidetes and lower numbers of Campylobacter than untreated-chickens. These findings suggest that oral administration of encapsulated CpG ODN and C. jejuni lysate can reduce colonization by C. jejuni by enhancing the proliferation of specific microbial groups. The mechanisms that mediate these changes remain, however, to be elucidated.
Effect of maternal pre-pregnancy underweight and average gestational weight gain on physical growth and intellectual development of early school-aged children
Authors: Li Chao , Zhu Ni , Zeng Lingxia , Dang Shaonong , Zhou Jing , Pei Leilei , Watson Victoria , Chen Tao , Wang Duolao , Yan Hong 
Published: August 2018

AbstractThe aim of this study was to assess the effect of low maternal weight at pre-pregnancy and the average gestational weight gain on undernourished children and their intellectual development. From October 2012 to September 2013, we followed 1744 offspring of women who participated in a trial conducted from 2002 to 2006. Pregnant women recruited in the original trial could receive three prenatal health checks for free, at which maternal weight and height were measured. WISC-IV was used to estimate the intellectual development of children. Weight and height of both pregnant women and children were measured by trained anthropometrists using standard procedures. Having low maternal weight at pre-pregnancy was associated with an increased risk of undernutrition amongst children (underweight: OR = 2.02, 95%CI: 1.14–3.56, thinness: OR = 2.79, 95%CI: 1.50–5.17) and a decrease in verbal comprehension index (−2.70 points, 95%CI: −4.95–0.44) of children. The effect of average gestational weight gain on occurrences of underweight children (OR = 0.08, 95%CI: 0.01–0.55) was also found. We identified the effect of maternal pre-pregnancy underweight on impairment of the separate intellectual domains (verbal comprehension index) and increasing occurrence of undernourished children. Average gestational weight gain was positively associated with a decreased prevalence of underweight children but not with the intellectual development of children in rural China.
Room temperature processed high mobility W-doped In2O3 electrodes coated via in-line arc plasma ion plating for flexible OLEDs and quantum dots LEDs
Authors: Kim Jae-Gyeong , Lee Ji-Eun , Jo Sung Min , Chin Byung Doo , Baek Ju-Yeoul , Ahn Kyung-Jun , Kang Seong Jun , Kim Han-Ki 
Published: August 2018

AbstractWe fabricated W-doped In2O3 (IWO) films at room temperature on a flexible PET substrate using an in-line arc plasma ion plating system for application as flexible transparent conducting electrodes (FTCEs) in flexible organic light emitting diodes (OLEDs) and quantum dots light emitting diodes (QDLEDs). Due to the high-energy flux of the sublimated ions generated from the plasma region, the IWO films showed a well-developed crystalline structure with a low sheet resistance of 36.39 Ohm/square and an optical transmittance of 94.6% even though they were prepared at room temperature. The low sheet resistance of the IWO film processed at room temperature is attributed to the high mobility (59 cm2/V-s) in the well-developed crystalline structure of the ion-plated IWO film and screening effect of W dopants. In addition, the better adhesion of the ion-plated IWO film on the PET substrate led to small critical outer and inner bending radii of 6 and 3 mm, respectively, against substrate bending. Due to the low sheet resistance, high optical transmittance, better crystallinity, better adhesion, and outstanding flexibility of the ion-plated IWO films, the flexible OLEDs and QDLEDs with the IWO electrodes showed better performances than flexible OLEDs and QDLEDs with sputtered flexible ITO anodes. This indicates that in-line arc plasma ion plating is a promising large area coating technique to realize room temperature processed high-quality FTCEs for flexible OLEDs and QDLEDs.
Clinical Manifestations and Ophthalmic Outcomes of Ocular Syphilis at a Time of Re-Emergence of the Systemic Infection
Authors: Furtado João M. , Arantes Tiago E. , Nascimento Heloisa , Vasconcelos-Santos Daniel V. , Nogueira Natalia , de Pinho Queiroz Rafael , Brandão Luana P. , Bastos Thaís , Martinelli Ricardo , Santana Rodrigo C. , Muccioli Cristina , Belfort Rubens , Smith Justine R. 
Published: August 2018

AbstractRecent reports from different world regions suggest ocular syphilis is re-emerging, in parallel with an increasing incidence of the systemic infection globally. We conducted a large observational study of 127 persons consecutively treated for ocular syphilis at public medical centers in Brazil over a 2.5-year period ending July 2015. Of 104 individuals serologically tested for human immunodeficiency virus (HIV), 34.6% were positive. Ophthalmological evaluations included measurement of Snellen visual acuity and intraocular pressure, and assessment of inflammation by slit lamp examination and dilated posterior eye examination. Involvements in 214 eyes were anterior (6.1%), intermediate (8.4%), posterior (76.2%) and pan- (8.4%) uveitis, and scleritis (0.9%). Multiple anterior and posterior eye complications were observed, including cataract in the anterior eye (incidence rate, 0.18/eye-year) and epiretinal membrane in the posterior eye (incidence rate, 0.09/eye-year); incidence rates of reduction in best-corrected visual acuity to ≤20/50 and ≤20/200 were 0.10 and 0.06/eye-year, respectively. Rates of complications and visual acuity loss did not differ significantly between HIV- positive and negative individuals. In an era of re-emergence, syphilis has ocular complications that may compromise vision, despite treatment with appropriate anti-microbial drugs.
Snake Venom Extracellular vesicles (SVEVs) reveal wide molecular and functional proteome diversity
Authors: Carregari Victor Corassolla , Rosa-Fernandes Livia , Baldasso Paulo , Bydlowski Sergio Paulo , Marangoni Sergio , Larsen Martin R. , Palmisano Giuseppe 
Published: August 2018

AbstractProteins constitute almost 95% of snake venom’s dry weight and are produced and released by venom glands in a solubilized form during a snake bite. These proteins are responsible for inducing several pharmacological effects aiming to immobilize and initiate the pre-digestion of the prey. This study shows that proteins can be secreted and confined in snake venom extracellular vesicles (SVEVs) presenting a size distribution between 50 nm and 500 nm. SVEVs isolated from lyophilized venoms collected from four different species of snakes (Agkistrodon contortrix contortrix, Crotalus atrox, Crotalus viridis and Crotalus cerberus oreganus) were analyzed by mass spectrometry-based proteomic, which allowed the identification of proteins belonging to eight main functional protein classes such as SVMPs, serine proteinases, PLA2, LAAO, 5′nucleotidase, C-type lectin, CRISP and Disintegrin. Biochemical assays indicated that SVEVs are functionally active, showing high metalloproteinase and fibrinogenolytic activity besides being cytotoxic against HUVEC cells. Overall, this study comprehensively depicts the protein composition of SVEVs for the first time. In addition, the molecular function of some of the described proteins suggests a central role for SVEVs in the cytotoxicity of the snake venom and sheds new light in the envenomation process.
Biomimetic Super Anti-Wetting Coatings from Natural Materials: Superamphiphobic Coatings Based on Nanoclays
Authors: Dong Jie , Zhang Junping 
Published: August 2018

AbstractSuperamphiphobic coatings (SAPCs) that resist wetting of water and low-surface-tension liquids have generated widespread attention in academia, but are very challenging to invent. Liquid adhesion, low stability, complicated and expensive preparation methods are the typical characteristics of SAPCs, which seriously hinder real-world applications of SAPCs. Here, we report a comprehensive study about preparation of SAPCs from abundant nanoclays with fibrous, plate-like and porous microstructures. The SAPCs are prepared simply by hydrolytic condensation of silanes in the presence of nanoclays, followed by spray-coating the as-formed suspensions onto substrates. The SAPCs feature high superamphiphobicity for various liquids down to a surface tension of 23.8 mN m−1 (n-decane), and high mechanical, chemical and thermal stability. The superamphiphobicity and stability depend on microscale and nanoscale surface morphology of the coatings, which are controllable by the microstructures of nanoclays and their acid activation. The fibrous nanoclays with moderate aspect ratio like palygorskite are the most suitable building blocks for the preparation of SAPCs by effectively forming the reentrant surface morphology. We believe that the findings will promote the progress of SAPCs, and pave the way for the development of clay-based super anti-wetting coatings.
Electronic and optical properties of heterostructures based on transition metal dichalcogenides and graphene-like zinc oxide
Authors: Wang Sake , Tian Hongyu , Ren Chongdan , Yu Jin , Sun Minglei 
Published: August 2018

AbstractThe structural, electronic, and optical properties of heterostructures formed by transition metal dichalcogenides MX2 (M = Mo, W; X = S, Se) and graphene-like zinc oxide (ZnO) were investigated using first-principles calculations. The interlayer interaction in all heterostructures was characterized by van der Waals forces. Type-II band alignment occurs at the MoS2/ZnO and WS2/ZnO interfaces, together with the large built-in electric field across the interface, suggesting effective photogenerated-charge separation. Meanwhile, type-I band alignment occurs at the MoSe2/ZnO and WSe2/ZnO interfaces. Moreover, all heterostructures exhibit excellent optical absorption in the visible and infrared regions, which is vital for optical applications.