bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-93 is related to poor prognosis in pancreatic cancer and promotes tumor progression by targeting microtubule dynamics
Authors: Vila-Navarro Elena , Fernandez-Castañer Elena , Rovira-Rigau Maria , Raimondi Giulia , Vila-Casadesus Maria , Lozano Juan Jose , Soubeyran Philippe , Iovanna Juan , Castells Antoni , Fillat Cristina , Gironella Meritxell 
Published: May 2020

AbstractBiomarkers and effective therapeutic agents to improve the dismal prognosis of pancreatic ductal adenocarcinoma (PDAC) are urgently required. We aimed to analyze the prognostic value and mechanistic action of miR-93 in PDAC. Correlation of miR-93 tumor levels from 83 PDAC patients and overall survival (OS) was analyzed by Kaplan–Meier. MiR-93 depletion in PANC-1 and MIA PaCa-2 cells was achieved by CRISPR/Cas9 and miR-93 overexpression in HPDE cells by retroviral transduction. Cell proliferation, migration and invasion, cell cycle analysis, and in vivo tumor xenografts in nude mice were assessed. Proteomic analysis by mass spectrometry and western-blot was also performed. Finally, miR-93 direct binding to candidate mRNA targets was evaluated by luciferase reporter assays. High miR-93 tumor levels are significantly correlated with a worst prognosis in PDAC patients. MiR-93 abolition altered pancreatic cancer cells phenotype inducing a significant increase in cell size and a significant decrease in cell invasion and proliferation accompanied by a G2/M arrest. In vivo, lack of miR-93 significantly impaired xenograft tumor growth. Conversely, miR-93 overexpression induced a pro-tumorigenic behavior by significantly increasing cell proliferation, migration, and invasion. Proteomic analysis unveiled a large group of deregulated proteins, mainly related to G2/M phase, microtubule dynamics, and cytoskeletal remodeling. CRMP2, MAPRE1, and YES1 were confirmed as direct targets of miR-93. MiR-93 exerts oncogenic functions by targeting multiple genes involved in microtubule dynamics at different levels, thus affecting the normal cell division rate. MiR-93 or its direct targets (CRMP2, MAPRE1, or YES1) are new potential therapeutic targets for PDAC.
A standardized patient-centered characterization of the phenotypic spectrum of PCDH19 girls clustering epilepsy
Authors: Kolc Kristy L. , Sadleir Lynette G. , Depienne Christel , Marini Carla , Scheffer Ingrid E. , Møller Rikke S. , Trivisano Marina , Specchio Nicola , Pham Duyen , Kumar Raman , Roberts Rachel , Gecz Jozef 
Published: May 2020

AbstractProtocadherin-19 (PCDH19) pathogenic variants cause an early-onset seizure disorder called girls clustering epilepsy (GCE). GCE is an X-chromosome disorder that affects heterozygous females and mosaic males, however hemizygous (“transmitting”) males are spared. We aimed to define the neuropsychiatric profile associated with PCDH19 pathogenic variants and determine if a clinical profile exists for transmitting males. We also examined genotype- and phenotype–phenotype associations. We developed an online PCDH19 survey comprising the following standardized assessments: The Behavior Rating Inventory of Executive Function; the Social Responsiveness Scale, 2nd edition; the Strengths and Difficulties Questionnaire; and the Dimensional Obsessive-Compulsive Scale. Genetic, seizure, and developmental information were also collected. The survey was completed by patients or by caregivers on behalf of patients. Of the 112 individuals represented (15 males), there were 70 unique variants. Thirty-five variants were novel and included a newly identified recurrent variant Ile781Asnfs*3. There were no significant differences in phenotypic outcomes between published and unpublished cases. Seizures occurred in clusters in 94% of individuals, with seizures resolving in 28% at an average age of 17.5 years. Developmental delay prior to seizure onset occurred in 18% of our cohort. Executive dysfunction and autism spectrum disorder (ASD) occurred in approximately 60% of individuals. The ASD profile included features of attention-deficit hyperactivity disorder. In addition, 21% of individuals met criteria for obsessive-compulsive disorder that appeared to be distinct from ASD. There were no phenotypic differences between heterozygous females and mosaic males. We describe a mosaic male and two hemizygous males with atypical clinical profiles. Earlier seizure onset age and increased number of seizures within a cluster were associated with more severe ASD symptoms (p = 0.001), with seizure onset also predictive of executive dysfunction (p = 4.69 × 10−4) and prosocial behavior (p = 0.040). No clinical profile was observed for transmitting males. This is the first patient-derived standardized assessment of the neuropsychiatric profile of GCE. These phenotypic insights will inform diagnosis, management, and prognostic and genetic counseling.
Prognostic factors, therapeutic approaches, and distinct immunobiologic features in patients with primary mediastinal large B-cell lymphoma on long-term follow-up
Authors: Zhou Hui , Xu-Monette Zijun Y. , Xiao Ling , Strati Paolo , Hagemeister Fredrick B. , He Yizi , Chen Huan , Li Yajun , Manyam Ganiraju C. , Li Yong , Montes-Moreno Santiago , Piris Miguel A. , Young Ken H. 
Published: May 2020

AbstractPrimary mediastinal large B-cell lymphoma (PMBCL) is a rare and distinct subtype of diffuse large B-cell lymphoma (DLBCL) without prognostic factors or a single standard of treatment clearly defined. In this study we performed retrospective analysis for clinical outcomes of 166 patients with PMBCL. In overall PMBCL, higher International Prognostic Index, stage, Ki-67 proliferation index, and positron emission tomography (PET) maximum standardized uptake values (SUVmax) at diagnosis were significantly associated with poorer survival, whereas MUM1 expression and higher peripheral blood lymphocyte/monocyte ratios were significantly associated with better survival. Patients who received R-HCVAD or R-EPOCH had better clinical outcome than did those who received the standard treatment R-CHOP. Treatment response and end-of-treatment PET SUVmax had remarkable correlations with survival outcome. In patients with refractory or relapsed PMBCL, stem cell transplant significantly improved overall survival. PMBCL had distinct gene expression signatures compared with overall DLBCL–NOS but not with DLBCL with PD-L1/PD-L2 amplification. PMBCL also showed higher PD-L2 expression in B-cells, lower PD-1 expression in T-cells, and higher CTLA-4 expression in T-cells and distinct miRNA signatures compared with DLBCL-NOS. The prognostic factors, effectiveness of treatment, transcriptional and epigenetic signatures, and immunologic features revealed by this study enrich our understanding of PMBCL biology and support future treatment strategy.
Characteristics and outcomes of patients with therapy-related acute myeloid leukemia with normal karyotype
Authors: Samra Bachar , Richard-Carpentier Guillaume , Kadia Tapan M. , Ravandi Farhad , Daver Naval , DiNardo Courtney D. , Issa Ghayas C. , Bose Prithviraj , Konopleva Marina Y. , Yilmaz Musa , Ohanian Maro , Borthakur Gautam , Garcia-Manero Guillermo , Pierce Sherry , Cortes Jorge E. , Kantarjian Hagop , Short Nicholas J. 
Published: May 2020

AbstractNormal karyotype in therapy-related acute myeloid leukemia (t-AML) is rare and the relative contribution of prior exposure to chemotherapy or radiotherapy to outcomes in these patients remains uncertain. We performed a retrospective study of 742 patients with newly diagnosed AML and normal karyotype (t-AML, n = 61, and non-t-AML, n = 681). Patients with t-AML were older but had a similar mutational profile compared to those with non-t-AML. Overall survival (OS) and relapse-free survival (RFS) were significantly worse for patients with t-AML (P < 0.01 and P = 0.02, respectively). Patients with t-AML had a higher cumulative incidence of death in remission (51% versus 16%, P < 0.01), but not higher cumulative incidence of relapse (42% versus 56%, respectively, P = 0.21). Both intensive induction and allogeneic hematopoietic stem cell transplantation in first remission were associated with improved OS and RFS in non-t-AML but not in t-AML. Overall, although disease biology appears similar between t-AML and non-t-AML with normal karyotype as indicated by similar risks of relapse, death in remission is the main driver of inferior outcome in t-AML. Careful therapeutic decisions are required to mitigate potential treatment-related toxicity in this rare subgroup of patients with t-AML and normal karyotype.
Evaluation of medical and surgical decompression in patients with dysthyroid optic neuropathy
Authors: Garip Kuebler Aylin , Wiecha Caroline , Reznicek Lukas , Klingenstein Annemarie , Halfter Kathrin , Priglinger Siegfried , Hintschich Christoph 
Published: May 2020

Abstract
Purpose
To evaluate the effectiveness of steroid-pulse therapy and three-wall orbital decompression in patients with dysthyroid optic neuropathy (DON).

Methods
Twenty-five patients (46 eyes) with a diagnosis of DON between 2008 and 2015 were included in the study. The first group (7 patients, 16 eyes) consisted of patients with a steroid-pulse treatment only and the second group (18 patients, 30 eyes) included patients with medical and surgical decompression.

Results
Twenty patients were female; five patients were male. After the diagnosis of DON, all patients were treated with steroid-pulse treatment (intravenous 500 mg prednisolon twice/week for 4 weeks, 250 mg twice/week for 2 weeks) as a first-line treatment (medical decompression). In 30 eyes (18 patients) out of 46 eyes, (25 patients) an orbital decompression was needed to preserve the optic nerve function. In those therapy-resistant cases (surgical decompression group), the orbital decompression led to statistically significant improvements in best-corrected visual acuity (BCVA), protan and tritan value of the color vision (p = 0.007, p < 0.0001, p = 0.019, respectively, comparison of first visit to last visit).

Conclusion
According to our data, the mild cases of DON with better initial visual acuity (in our case series mean: 0.3 logMAR) seem to respond well to steroid treatment. However, therapy-resistant cases with an impaired initial BCVA (in our case series, mean: 0.6 logMAR) seem to need the surgery to preserve the optic nerve function. In conclusion, this retrospective study confirms the effectiveness of surgical decompression in therapy-resistant cases of DON.
Nucleoplasmic signals promote directed transmembrane protein import simultaneously via multiple channels of nuclear pores
Authors: Mudumbi Krishna C. , Czapiewski Rafal , Ruba Andrew , Junod Samuel L. , Li Yichen , Luo Wangxi , Ngo Christina , Ospina Valentina , Schirmer Eric C. , Yang Weidong 
Published: May 2020

AbstractRoughly 10% of eukaryotic transmembrane proteins are found on the nuclear membrane, yet how such proteins target and translocate to the nucleus remains in dispute. Most models propose transport through the nuclear pore complexes, but a central outstanding question is whether transit occurs through their central or peripheral channels. Using live-cell high-speed super-resolution single-molecule microscopy we could distinguish protein translocation through the central and peripheral channels, finding that most inner nuclear membrane proteins use only the peripheral channels, but some apparently extend intrinsically disordered domains containing nuclear localization signals into the central channel for directed nuclear transport. These nucleoplasmic signals are critical for central channel transport as their mutation blocks use of the central channels; however, the mutated proteins can still complete their translocation using only the peripheral channels, albeit at a reduced rate. Such proteins can still translocate using only the peripheral channels when central channel is blocked, but blocking the peripheral channels blocks translocation through both channels. This suggests that peripheral channel transport is the default mechanism that was adapted in evolution to include aspects of receptor-mediated central channel transport for directed trafficking of certain membrane proteins.
Diversity in medullary thymic epithelial cells controls the activity and availability of iNKT cells
Authors: Lucas Beth , White Andrea J. , Cosway Emilie J. , Parnell Sonia M. , James Kieran D. , Jones Nick D. , Ohigashi Izumi , Takahama Yousuke , Jenkinson William E. , Anderson Graham 
Published: May 2020

AbstractThe thymus supports multiple αβ T cell lineages that are functionally distinct, but mechanisms that control this multifaceted development are poorly understood. Here we examine medullary thymic epithelial cell (mTEC) heterogeneity and its influence on CD1d-restricted iNKT cells. We find three distinct mTEClow subsets distinguished by surface, intracellular and secreted molecules, and identify LTβR as a cell-autonomous controller of their development. Importantly, this mTEC heterogeneity enables the thymus to differentially control iNKT sublineages possessing distinct effector properties. mTEC expression of LTβR is essential for the development thymic tuft cells which regulate NKT2 via IL-25, while LTβR controls CD104+CCL21+ mTEClow that are capable of IL-15-transpresentation for regulating NKT1 and NKT17. Finally, mTECs regulate both iNKT-mediated activation of thymic dendritic cells, and iNKT availability in extrathymic sites. In conclusion, mTEC specialization controls intrathymic iNKT cell development and function, and determines iNKT pool size in peripheral tissues.
Encoding quantized fluorescence states with fractal DNA frameworks
Authors: Li Jiang , Dai Jiangbing , Jiang Shuoxing , Xie Mo , Zhai Tingting , Guo Linjie , Cao Shuting , Xing Shu , Qu Zhibei , Zhao Yan , Wang Fei , Yang Yang , Liu Lei , Zuo Xiaolei , Wang Lihua , Yan Hao , Fan Chunhai 
Published: May 2020

AbstractSignal amplification in biological systems is achieved by cooperatively recruiting multiple copies of regulatory biomolecules. Nevertheless, the multiplexing capability of artificial fluorescent amplifiers is limited due to the size limit and lack of modularity. Here, we develop Cayley tree-like fractal DNA frameworks to topologically encode the fluorescence states for multiplexed detection of low-abundance targets. Taking advantage of the self-similar topology of Cayley tree, we use only 16 DNA strands to construct n-node (n = 53) structures of up to 5 megadalton. The high level of degeneracy allows encoding 36 colours with 7 nodes by site-specifically anchoring of distinct fluorophores onto a structure. The fractal topology minimises fluorescence crosstalk and allows quantitative decoding of quantized fluorescence states. We demonstrate a spectrum of rigid-yet-flexible super-multiplex structures for encoded fluorescence detection of single-molecule recognition events and multiplexed discrimination of living cells. Thus, the topological engineering approach enriches the toolbox for high-throughput cell imaging.
Nanopore sequencing and the Shasta toolkit enable efficient de novo assembly of eleven human genomes
Authors: Shafin Kishwar , Pesout Trevor , Lorig-Roach Ryan , Haukness Marina , Olsen Hugh E. , Bosworth Colleen , Armstrong Joel , Tigyi Kristof , Maurer Nicholas , Koren Sergey , Sedlazeck Fritz J. , Marschall Tobias , Mayes Simon , Costa Vania , Zook Justin M. , Liu Kelvin J. , Kilburn Duncan , Sorensen Melanie , Munson Katy M. , Vollger Mitchell R. , Monlong Jean , Garrison Erik , Eichler Evan E. , Salama Sofie , Haussler David , Green Richard E. , Akeson Mark , Phillippy Adam , Miga Karen H. , Carnevali Paolo , Jain Miten , Paten Benedict 
Published: May 2020

AbstractDe novo assembly of a human genome using nanopore long-read sequences has been reported, but it used more than 150,000 CPU hours and weeks of wall-clock time. To enable rapid human genome assembly, we present Shasta, a de novo long-read assembler, and polishing algorithms named MarginPolish and HELEN. Using a single PromethION nanopore sequencer and our toolkit, we assembled 11 highly contiguous human genomes de novo in 9 d. We achieved roughly 63× coverage, 42-kb read N50 values and 6.5× coverage in reads >100 kb using three flow cells per sample. Shasta produced a complete haploid human genome assembly in under 6 h on a single commercial compute node. MarginPolish and HELEN polished haploid assemblies to more than 99.9% identity (Phred quality score QV = 30) with nanopore reads alone. Addition of proximity-ligation sequencing enabled near chromosome-level scaffolds for all 11 genomes. We compare our assembly performance to existing methods for diploid, haploid and trio-binned human samples and report superior accuracy and speed.
Genome-wide association study of emotional empathy in children
Authors: Woodbury-Smith M. R. , Paterson A. D. , Szatmari P. , Scherer S. W. 
Published: May 2020

AbstractThe genetic contribution to different aspects of empathy is now established, although the exact loci are unknown. We undertook a genome-wide association study of emotional empathy (EE) as measured by emotion recognition skills in 4,780 8-year old children from the ALSPAC cohort who were genotyped and imputed to Phase 1 version 3 of the 1000 Genomes Project. We failed to find any genome-wide significant signal in either our unstratified analysis or analysis stratified according to sex. A gene-based association analysis similarly failed to find any significant loci. In contrast, our transcriptome-wide association study (TWAS) with a whole blood reference panel identified two significant loci in the unstratified analysis, residualised for the effects of age, sex and IQ. One signal was for CD93 on chromosome 20; this gene is not strongly expressed in the brain, however. The other signal was for AL118508, a non-protein coding pseudogene, which completely lies within CD93’s genomic coordinates, thereby explaining its signal. Neither are obvious candidates for involvement in the brain processes that underlie emotion recognition and its developmental pathways.
Predicting circulating biomarker response and its impact on the survival of advanced melanoma patients treated with adjuvant therapy
Authors: Irurzun-Arana Itziar , Asín-Prieto Eduardo , Martín-Algarra Salvador , Trocóniz Iñaki F. 
Published: May 2020

AbstractAdvanced melanoma remains a disease with poor prognosis. Several serologic markers have been investigated to help monitoring and prognostication, but to date only lactate dehydrogenase (LDH) has been validated as a standard prognostic factor biomarker for this disease by the American Joint Committee on Cancer. In this work, we built a semi-mechanistic model to explore the relationship between the time course of several circulating biomarkers and overall or progression free survival in advanced melanoma patients treated with adjuvant high-dose interferon-$${\boldsymbol{\alpha }}{\bf{2}}{\bf{b}}$$α2b. Additionally, due to the adverse interferon tolerability, a semi-mechanistic model describing the side effects of the treatment in the absolute neutrophil counts is proposed in order to simultaneously analyze the benefits and toxic effects of this treatment. The results of our analysis suggest that the relative change from baseline of LDH was the most significant predictor of the overall survival of the patients. Unfortunately, there was no significant difference in the proportion of patients with elevated serum biomarkers between the patients who recurred and those who remained free of disease. Still, we believe that the modelling framework presented in this work of circulating biomarkers and adverse effects could constitute an additional strategy for disease monitoring in advance melanoma patients.
Variability and change in the hydro-climate and water resources of Iran over a recent 30-year period
Authors: Moshir Panahi Davood , Kalantari Zahra , Ghajarnia Navid , Seifollahi-Aghmiuni Samaneh , Destouni Georgia 
Published: May 2020

AbstractComprehensive assessment of hydro-climatic variations and change trends is essential for understanding, mitigating, and adapting to key water resource changes in different parts of the world. We performed such an assessment on Iran, as representative of an arid/semi-arid and geopolitically important world region. We acquired and calculated data time series of surface temperature (T), precipitation (P), runoff (R), evapotranspiration (ET), and water storage change (DS), to determine their status and changes in and among the 30 main hydrological basins in Iran over the period 1986–2016. From 1986–2000 to 2001–2016, the country warmed, P mostly decreased and R even more so, while water storage was depleted (DS < 0) and ET increased in some basins. Overall, the extra water provided from primarily groundwater depletion has fed and kept ET at levels beyond those sustained by the annually renewable water input from P. This indicates unsustainable use of water for maintaining and expanding human activities, such as irrigated agriculture, in this part of the world.
Single- and double-walled boron nitride nanotubes: Controlled synthesis and application for water purification
Authors: Cho Hyunjin , Kim Jun Hee , Hwang Jae Hun , Kim Cheol Sang , Jang Se Gyu , Park Cheol , Lee Hunsu , Kim Myung Jong 
Published: May 2020

AbstractResearch interest in boron nitride nanotubes (BNNTs) has increased after the recent success of large-scale BNNT syntheses using high-temperature-pressure laser ablation or high-temperature plasma methods. Nonetheless, there are limits to the application and commercialization of these materials because of the difficulties associated with their fine structural control. Herein, the growth kinetics of BNNTs were systemically studied for this purpose. The growth pressure of the nitrogen feed gas was varied while the growth temperature remained constant, which was confirmed by black body radiation measurements and calculations based on a heat loss model. Changing from the diffusion-limited regime to the supply-limited regime of growth kinetics based on the optimized BNNT synthesis condition afforded the control of the number of BNNT walls. The total amount of BNNTs possessing single and double walls was over 70%, and the BNNT surface area increased to 278.2 m2/g corresponding to small wall numbers and diameters. Taking advantage of the large surface area and high-temperature durability of the material, BNNTs utilized as a recyclable adsorbent for water purification. The efficiency of the BNNTs for capturing methylene blue particles in water was approximately 94%, even after three repetition cycles, showing the potential of the material for application in the filter industry.