bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic contributions to alcohol use disorder treatment outcomes: a genome-wide pharmacogenomics study
Authors: Biernacka Joanna M. , Coombes Brandon J. , Batzler Anthony , Ho Ada Man-Choi , Geske Jennifer R. , Frank Josef , Hodgkinson Colin , Skime Michelle , Colby Colin , Zillich Lea , Pozsonyiova Sofia , Ho Ming-Fen , Kiefer Falk , Rietschel Marcella , Weinshilboum Richard , O’Malley Stephanie S. , Mann Karl , Anton Ray , Goldman David , Karpyak Victor M. 
Published: July 2021

AbstractNaltrexone can aid in reducing alcohol consumption, while acamprosate supports abstinence; however, not all patients with alcohol use disorder (AUD) benefit from these treatments. Here we present the first genome-wide association study of AUD treatment outcomes based on data from the COMBINE and PREDICT studies of acamprosate and naltrexone, and the Mayo Clinic CITA study of acamprosate. Primary analyses focused on treatment outcomes regardless of pharmacological intervention and were followed by drug-stratified analyses to identify treatment-specific pharmacogenomic predictors of acamprosate and naltrexone response. Treatment outcomes were defined as: (1) time until relapse to any drinking (TR) and (2) time until relapse to heavy drinking (THR; ≥ 5 drinks for men, ≥4 drinks for women in a day), during the first 3 months of treatment. Analyses were performed within each dataset, followed by meta-analysis across the studies (N = 1083 European ancestry participants). Single nucleotide polymorphisms (SNPs) in the BRE gene were associated with THR (min p = 1.6E−8) in the entire sample, while two intergenic SNPs were associated with medication-specific outcomes (naltrexone THR: rs12749274, p = 3.9E−8; acamprosate TR: rs77583603, p = 3.1E−9). The top association signal for TR (p = 7.7E−8) and second strongest signal in the THR (p = 6.1E−8) analysis of naltrexone-treated patients maps to PTPRD, a gene previously implicated in addiction phenotypes in human and animal studies. Leave-one-out polygenic risk score analyses showed significant associations with TR (p = 3.7E−4) and THR (p = 2.6E−4). This study provides the first evidence of a polygenic effect on AUD treatment response, and identifies genetic variants associated with potentially medication-specific effects on AUD treatment response.
Human cell transformation by combined lineage conversion and oncogene expression
Authors: Sahu Biswajyoti , Pihlajamaa Päivi , Zhang Kaiyang , Palin Kimmo , Ahonen Saija , Cervera Alejandra , Ristimäki Ari , Aaltonen Lauri A. , Hautaniemi Sampsa , Taipale Jussi 
Published: July 2021

AbstractCancer is the most complex genetic disease known, with mutations implicated in more than 250 genes. However, it is still elusive which specific mutations found in human patients lead to tumorigenesis. Here we show that a combination of oncogenes that is characteristic of liver cancer (CTNNB1, TERT, MYC) induces senescence in human fibroblasts and primary hepatocytes. However, reprogramming fibroblasts to a liver progenitor fate, induced hepatocytes (iHeps), makes them sensitive to transformation by the same oncogenes. The transformed iHeps are highly proliferative, tumorigenic in nude mice, and bear gene expression signatures of liver cancer. These results show that tumorigenesis is triggered by a combination of three elements: the set of driver mutations, the cellular lineage, and the state of differentiation of the cells along the lineage. Our results provide direct support for the role of cell identity as a key determinant in transformation and establish a paradigm for studying the dynamic role of oncogenic drivers in human tumorigenesis.
Platelet-derived lysophosphatidic acid mediated LPAR1 activation as a therapeutic target for osteosarcoma metastasis
Authors: Takagi Satoshi , Sasaki Yuki , Koike Sumie , Takemoto Ai , Seto Yosuke , Haraguchi Mizuki , Ukaji Takao , Kawaguchi Tokuichi , Sugawara Minoru , Saito Masanori , Funauchi Yuki , Ae Keisuke , Matsumoto Seiichi , Fujita Naoya , Katayama Ryohei 
Published: July 2021

AbstractOsteosarcoma is the most common primary malignant bone cancer, with high rates of pulmonary metastasis. Osteosarcoma patients with pulmonary metastasis have worse prognosis than those with localized disease, leading to dramatically reduced survival rates. Therefore, understanding the biological characteristics of metastatic osteosarcoma and the molecular mechanisms of invasion and metastasis of osteosarcoma cells will lead to the development of innovative therapeutic intervention for advanced osteosarcoma. Here, we identified that osteosarcoma cells commonly exhibit high platelet activation-inducing characteristics, and molecules released from activated platelets promote the invasiveness of osteosarcoma cells. Given that heat-denatured platelet releasate maintained the ability to promote osteosarcoma invasion, we focused on heat-tolerant molecules, such as lipid mediators in the platelet releasate. Osteosarcoma-induced platelet activation leads to abundant lysophosphatidic acid (LPA) release. Exposure to LPA or platelet releasate induced morphological changes and increased invasiveness of osteosarcoma cells. By analyzing publicly available transcriptome datasets and our in-house osteosarcoma patient-derived xenograft tumors, we found that LPA receptor 1 (LPAR1) is notably upregulated in osteosarcoma. LPAR1 gene KO in osteosarcoma cells abolished the platelet-mediated osteosarcoma invasion in vitro and the formation of early pulmonary metastatic foci in experimental pulmonary metastasis models. Of note, the pharmacological inhibition of LPAR1 by the orally available LPAR1 antagonist, ONO-7300243, prevented pulmonary metastasis of osteosarcoma in the mouse models. These results indicate that the LPA–LPAR1 axis is essential for the osteosarcoma invasion and metastasis, and targeting LPAR1 would be a promising therapeutic intervention for advanced osteosarcoma.
The therapeutic and prognostic implications of immunobiology in colorectal cancer: a review
Authors: Zaborowski Alexandra M. , Winter Des C. , Lynch Lydia 
Published: July 2021

AbstractColorectal cancer represents the second leading cause of cancer-related death worldwide. The therapeutic field of immuno-oncology has rapidly gained momentum, with strikingly promising results observed in clinical practice. Increasing emphasis has been placed on the role of the immune response in tumorigenesis, therapy and predicting prognosis. Enhanced understanding of the dynamic and complex tumour-immune microenvironment has enabled the development of molecularly directed, individualised treatment. Analysis of intra-tumoural lymphocyte infiltration and the dichotomisation of colorectal cancer into microsatellite stable and unstable disease has important therapeutic and prognostic implications, with potential to capitalise further on this data. This review discusses the latest evidence surrounding the tumour biology and immune landscape of colorectal cancer, novel immunotherapies and the interaction of the immune system with each apex of the tripartite of cancer management (oncotherapeutics, radiotherapy and surgery). By utilising the synergy of chemotherapeutic agents and immunotherapies, and identifying prognostic and predictive immunological biomarkers, we may enter an era of unprecedented disease control, survivorship and cure rates.
miR-4293 upregulates lncRNA WFDC21P by suppressing mRNA-decapping enzyme 2 to promote lung carcinoma proliferation
Authors: Zhang Qian , Yan Yun-Fei , Lv Qing , Li You-Jie , Wang Ran-Ran , Sun Guang-Bin , Pan Li , Hu Jin-Xia , Xie Ning , Zhang Can , Tian Bao-Cheng , Jiao Fei , Xu Sen , Wang Ping-Yu , Xie Shu-Yang 
Published: July 2021

AbstractNon-coding RNAs (ncRNAs) involve in diverse biological processes by post-transcriptional regulation of gene expression. Emerging evidence shows that miRNA-4293 plays a significant role in the development of non-small cell lung cancer. However, the oncogenic functions of miR-4293 have not been studied. Our results demonstrated that miR-4293 expression is markedly enhanced in lung carcinoma tissue and cells. Moreover, miR-4293 promotes tumor cell proliferation and metastasis but suppresses apoptosis. Mechanistic investigations identified mRNA-decapping enzyme 2 (DCP2) as a target of miR-4293 and its expression is suppressed by miR-4293. DCP2 can directly or indirectly bind to WFDC21P and downregulates its expression. Consequently, miR-4293 can further promote WFDC21P expression by regulating DCP2. With a positive correlation to miR-4293 expression, WFDC21P also plays an oncogenic role in lung carcinoma. Furthermore, knockdown of WFDC21P results in functional attenuation of miR-4293 on tumor promotion. In vivo xenograft growth is also promoted by both miR-4293 and WFDC21P. Overall, our results establish oncogenic roles for both miR-4293 and WFDC21P and demonstrate that interactions between miRNAs and lncRNAs through DCP2 are important in the regulation of carcinoma pathogenesis. These results provided a valuable theoretical basis for the discovery of lung carcinoma therapeutic targets and diagnostic markers based on miR-4293 and WFDC21P.
Strainberry: automated strain separation in low-complexity metagenomes using long reads
Authors: Vicedomini Riccardo , Quince Christopher , Darling Aaron E. , Chikhi Rayan 
Published: July 2021

AbstractHigh-throughput short-read metagenomics has enabled large-scale species-level analysis and functional characterization of microbial communities. Microbiomes often contain multiple strains of the same species, and different strains have been shown to have important differences in their functional roles. Recent advances on long-read based methods enabled accurate assembly of bacterial genomes from complex microbiomes and an as-yet-unrealized opportunity to resolve strains. Here we present Strainberry, a metagenome assembly pipeline that performs strain separation in single-sample low-complexity metagenomes and that relies uniquely on long-read data. We benchmarked Strainberry on mock communities for which it produces strain-resolved assemblies with near-complete reference coverage and 99.9% base accuracy. We also applied Strainberry on real datasets for which it improved assemblies generating 20-118% additional genomic material than conventional metagenome assemblies on individual strain genomes. We show that Strainberry is also able to refine microbial diversity in a complex microbiome, with complete separation of strain genomes. We anticipate this work to be a starting point for further methodological improvements on strain-resolved metagenome assembly in environments of higher complexities.
Rapid discovery of self-assembling peptides with one-bead one-compound peptide library
Authors: Yang Pei-Pei , Li Yi-Jing , Cao Yan , Zhang Lu , Wang Jia-Qi , Lai Ziwei , Zhang Kuo , Shorty Diedra , Xiao Wenwu , Cao Hui , Wang Lei , Wang Hao , Liu Ruiwu , Lam Kit S. 
Published: July 2021

AbstractSelf-assembling peptides have shown tremendous potential in the fields of material sciences, nanoscience, and medicine. Because of the vast combinatorial space of even short peptides, identification of self-assembling sequences remains a challenge. Herein, we develop an experimental method to rapidly screen a huge array of peptide sequences for self-assembling property, using the one-bead one-compound (OBOC) combinatorial library method. In this approach, peptides on beads are N-terminally capped with nitro-1,2,3-benzoxadiazole, a hydrophobicity-sensitive fluorescence molecule. Beads displaying self-assembling peptides would fluoresce under aqueous environment. Using this approach, we identify eight pentapeptides, all of which are able to self-assemble into nanoparticles or nanofibers. Some of them are able to interact with and are taken up efficiently by HeLa cells. Intracellular distribution varied among these non-toxic peptidic nanoparticles. This simple screening strategy has enabled rapid identification of self-assembling peptides suitable for the development of nanostructures for various biomedical and material applications.
Lineage-defined leiomyosarcoma subtypes emerge years before diagnosis and determine patient survival
Authors: Anderson Nathaniel D. , Babichev Yael , Fuligni Fabio , Comitani Federico , Layeghifard Mehdi , Venier Rosemarie E. , Dentro Stefan C. , Maheshwari Anant , Guram Sheena , Wunker Claire , Thompson J. Drew , Yuki Kyoko E. , Hou Huayun , Zatzman Matthew , Light Nicholas , Bernardini Marcus Q. , Wunder Jay S. , Andrulis Irene L. , Ferguson Peter , Razak Albiruni R. Abdul , Swallow Carol J. , Dowling James J. , Al-Awar Rima S. , Marcellus Richard , Rouzbahman Marjan , Gerstung Moritz , Durocher Daniel , Alexandrov Ludmil B. , Dickson Brendan C. , Gladdy Rebecca A. , Shlien Adam 
Published: July 2021

AbstractLeiomyosarcomas (LMS) are genetically heterogeneous tumors differentiating along smooth muscle lines. Currently, LMS treatment is not informed by molecular subtyping and is associated with highly variable survival. While disease site continues to dictate clinical management, the contribution of genetic factors to LMS subtype, origins, and timing are unknown. Here we analyze 70 genomes and 130 transcriptomes of LMS, including multiple tumor regions and paired metastases. Molecular profiling highlight the very early origins of LMS. We uncover three specific subtypes of LMS that likely develop from distinct lineages of smooth muscle cells. Of these, dedifferentiated LMS with high immune infiltration and tumors primarily of gynecological origin harbor genomic dystrophin deletions and/or loss of dystrophin expression, acquire the highest burden of genomic mutation, and are associated with worse survival. Homologous recombination defects lead to genome-wide mutational signatures, and a corresponding sensitivity to PARP trappers and other DNA damage response inhibitors, suggesting a promising therapeutic strategy for LMS. Finally, by phylogenetic reconstruction, we present evidence that clones seeding lethal metastases arise decades prior to LMS diagnosis.
ER – lysosome contacts at a pre-axonal region regulate axonal lysosome availability
Authors: Özkan Nazmiye , Koppers Max , van Soest Inge , van Harten Alexandra , Jurriens Daphne , Liv Nalan , Klumperman Judith , Kapitein Lukas C. , Hoogenraad Casper C. , Farías Ginny G. 
Published: July 2021

AbstractNeuronal function relies on careful coordination of organelle organization and transport. Kinesin-1 mediates transport of the endoplasmic reticulum (ER) and lysosomes into the axon and it is increasingly recognized that contacts between the ER and lysosomes influence organelle organization. However, it is unclear how organelle organization, inter-organelle communication and transport are linked and how this contributes to local organelle availability in neurons. Here, we show that somatic ER tubules are required for proper lysosome transport into the axon. Somatic ER tubule disruption causes accumulation of enlarged and less motile lysosomes at the soma. ER tubules regulate lysosome size and axonal translocation by promoting lysosome homo-fission. ER tubule – lysosome contacts often occur at a somatic pre-axonal region, where the kinesin-1-binding ER-protein P180 binds microtubules to promote kinesin-1-powered lysosome fission and subsequent axonal translocation. We propose that ER tubule – lysosome contacts at a pre-axonal region finely orchestrate axonal lysosome availability for proper neuronal function.
From basic properties to the Mott design of correlated delafossites
Authors: Lechermann Frank 
Published: July 2021

AbstractThe natural-heterostructure concept realized in delafossites highlights these layered oxides. While metallic, band- or Mott-insulating character may be associated with individual layers, inter-layer coupling still plays a decisive role. We review the correlated electronic structure of PdCoO2, PdCrO2, and AgCrO2, showing that layer-entangled electronic states can deviate from standard classifications of interacting systems. This finding opens up possibilities for materials design in a subtle Mott-critical regime. Manipulated Hidden-Mott physics, correlation-induced semimetallicity, or Dirac/flat-band dispersions in a Mott background are emerging features. Together with achievements in the experimental preparation, this inaugurates an exciting research field in the arena of correlated materials.
Dynamic regulation of small RNAs in anthocyanin accumulation during blueberry fruit maturation
Authors: Li Xiaobai , Hong Yan , Jackson Aaron , Guo Fangqi 
Published: July 2021

AbstractBlueberry is rich in anthocyanins which accumulate during fruit maturation. Previous studies mostly focus on their translational/transcriptional regulation, but usually underestimate their post-transcriptional regulation, e.g. small RNAs. This study aimed to identify sRNAs and their potential pathways associated with anthocyanin biosynthesis. During three typical phases of fruit maturation (green, pink, and blue), we investigated dynamic changes of sRNA by deep sequencing sRNA and examined the interaction of sRNAs with their target genes by degradome and RLM-PCR. During maturation, up-regulation of VcmiRNA156 and VcmiR393 resulted in down-regulation of VcSPLs and VcTIR1/AFBs, respectively. An important gene of anthocyanin biosynthesis, VcDFR, was substantially down-regulated at both the mRNA and protein levels, and potentially responded to regulation of VcSPLs and VcTIR1/AFBs. Additionally, indole acetic acid (IAA) and abscisic acid (ABA) were involved in the regulation of anthocyanin biosynthesis by interacting with VcmiR393-TIR1/AFBs and VcmiRNA319-VcMYBs respectively. This information provides another insight into blueberry anthocyanin biosynthesis.
Plasmonic mode coupling and thin film sensing in metal–insulator–metal structures
Authors: Andam N. , Refki S. , Hayashi S. , Sekkat Z. 
Published: July 2021

AbstractOptical sensors based on surface plasmon resonance (SPR) in the attenuated total reflection (ATR) configuration in layered media have attracted considerable attention over the past decades owing to their ability of label free sensing in biomolecular interaction analysis, and highly sensitive detection of changes in refractive index and thickness, i.e. the optical thickness, of thin film adsorbates (thin film sensing). Furthermore, SPR is highly sensitive to the refractive index of the medium adjacent to the bare metal, and it allows for bulk sensing as well. When deposited at the metal/air interface, an adsorbed layer disturbs the highly localized, i.e. bound, wave at this interface and changes the plasmon resonance to allow for sensing in angular or wavelength interrogation and intensity measurement modes. A high degree of sensitivity is required for precise and efficient sensing, especially for biomolecular interaction analysis for early stage diagnostics; and besides conventional SPR (CSPR), several other configurations have been developed in recent years targeting sensitivity, including long-range SPR (LRSPR) and waveguide-coupled SPR (WGSPR) observed in MIM structures, referred here to by MIM modes, resulting from the coupling of SPRs at I/M interfaces, and Fano-type resonances occurring from broad and sharp modes coupling in layered structures. In our previous research, we demonstrated that MIM is better than CSPR for bulk sensing, and in this paper, we show that CSPR is better than MIM for thin film sensing for thicknesses of the sensing layer (SL) larger than 10 nm. We discuss and compare the sensitivity of CSPR and MIM for thin film sensing by using both experiments and theoretical calculations based on rigorous electromagnetic (EM) theory. We discuss in detail MIM modes coupling and anti-crossing, and we show that when a thin film adsorbate, i.e. a SL), is deposited on top of the outermost-layer of an optimized MIM structure, it modifies the characteristics of the coupled modes of the structure, and it reduces the electric field, both inside the SL and at the SL/air interface, and as a result, it decreases the sensitivity of the MIM versus the CSPR sensor. Our work is of critical importance to plasmonic mode coupling using MIM configurations, as well as to optical bio- and chemical-sensing.
Classification of ECG signals using multi-cumulants based evolutionary hybrid classifier
Authors: Dalal Sahil , Vishwakarma Virendra P. 
Published: July 2021

AbstractEvery human being has a different electro-cardio-graphy (ECG) waveform that provides information about the well being of a human heart. Therefore, ECG waveform can be used as an effective identification measure in biometrics and many such applications of human identification. To achieve fast and accurate identification of human beings using ECG signals, a novel robust approach has been introduced here. The databases of ECG utilized during the experimentation are MLII, UCI repository arrhythmia and PTBDB databases. All these databases are imbalanced; hence, resampling techniques are helpful in making the databases balanced. Noise removal is performed with discrete wavelet transform (DWT) and features are obtained with multi-cumulants. This approach is mainly based on features extracted from the ECG data in terms of multi-cumulants. The multi-cumulants feature based ECG data is classified using kernel extreme learning machine (KELM). The parameters of multi-cumulants and KELM are optimized using genetic algorithm (GA). Excellent classification rate is achieved with 100% accuracy on MLII and UCI repository arrhythmia databases, and 99.57% on PTBDB database. Comparison with existing state-of-art approaches has also been performed to prove the efficacy of the proposed approach. Here, the process of classification in the proposed approach is named as evolutionary hybrid classifier.
Natural processes dominate the pollution levels during COVID-19 lockdown over India
Authors: Madineni Venkat Ratnam , Dasari Hari Prasad , Karumuri Ramakrishna , Viswanadhapalli Yesubabu , Perumal Prasad , Hoteit Ibrahim 
Published: July 2021

AbstractThe lockdown measures that were taken to combat the COVID-19 pandemic minimized anthropogenic activities and created natural laboratory conditions for studying air quality. Both observations and WRF-Chem simulations show a 20–50% reduction (compared to pre-lockdown and same period of previous year) in the concentrations of most aerosols and trace gases over Northwest India, the Indo Gangetic Plain (IGP), and the Northeast Indian regions. It is shown that this was mainly due to a 70–80% increase in the height of the boundary layer and the low emissions during lockdown. However, a 60–70% increase in the pollutants levels was observed over Central and South India including the Arabian sea and Bay of Bengal during this period, which is attributed to natural processes. Elevated (dust) aerosol layers are transported from the Middle East and Africa via long-range transport, and a decrease in the wind speed (20–40%) caused these aerosols to stagnate, enhancing the aerosol levels over Central and Southern India. A 40–60% increase in relative humidity further amplified aerosol concentrations. The results of this study suggest that besides emissions, natural processes including background meteorology and dynamics, play a crucial role in the pollution concentrations over the Indian sub-continent.