Miracle-dz/UniFAR-FTUs huggingface dataset:
A 360° view of circular RNAs: From biogenesis to functions

The first circular RNA (circRNA) was identified more than 40 years ago, but it was only recently appreciated that circRNAs are common outputs of many eukaryotic protein‐coding genes. Some circRNAs accumulate to higher levels than their associated linear mRNAs, especially in the nervous system, and have clear regulatory functions that result in organismal phenotypes. The pre‐mRNA splicing machinery generates circRNAs via backsplicing reactions, which are often facilitated by intronic repeat sequences that base pair to one another and bring the intervening splice sites into close proximity. When spliceosomal components are limiting, circRNAs can become the preferred gene output, and backsplicing reactions are further controlled by exon skipping events and the combinatorial action of RNA binding proteins. This allows circRNAs to be expressed in a tissue‐ and stage‐specific manner. Once generated, circRNAs are highly stable transcripts that often accumulate in the cytoplasm. The functions of most circRNAs remain unknown, but some can regulate the activities of microRNAs or be translated to produce proteins. Circular RNAs can further interface with the immune system as well as control gene expression events in the nucleus, including alternative splicing decisions. Circular RNAs thus represent a large class of RNA molecules that are tightly regulated, and it is becoming increasingly clear that they likely impact many biological processes.
Germline but not somatic de novo mutations are common in human congenital diaphragmatic hernia.

OBJECTIVES Congenital diaphragmatic hernia (CDH) is a developmental defect of the diaphragm that causes high newborn morbidity and mortality. CDH is considered to be a multifactorial disease, with strong evidence implicating genetic factors. Although recent studies suggest the biological role of deleterious germline de novo variants, the effect of gene variants specific to the diaphragm remains unclear, and few single genes have been definitively implicated in human disease. METHODS We performed genome sequencing on 16 individuals with CDH and their unaffected parents, including 10 diaphragmatic samples. RESULTS We did not detect damaging somatic mutations in diaphragms, but identified germline heterozygous de novo functional mutations of 14 genes in nine patients. Although the majority of these genes are not known to be associated with CDH, one patient with CDH and cardiac anomalies harbored a frameshift mutation in NR2F2 (aka COUP-TFII), generating a premature truncation of the protein. This patient also carried a missense variant predicted to be damaging in XIRP2 (aka Myomaxin), a transcriptional target of MEF2A. Both NR2F2 and MEF2A map to chromosome 15q26, where recurring de novo deletions and unbalanced translocations have been observed in CDH. CONCLUSIONS Somatic variants are not common in CDH. To our knowledge, this is the second case of a germline de novo frameshift mutation in NR2F2 in CDH. Since NR2F2 null mice exhibit a diaphragmatic defect, and XIRP2 is implicated in cardiac development, our data suggest the role of these two variants in the etiology of CDH, and possibly cardiac anomalies.
Development and evaluation of pH-responsive single-walled carbon nanotube-doxorubicin complexes in cancer cells

Single-walled carbon nanotubes (SWNTs) have been identified as an efficient drug carrier. Here a controlled drug-delivery system based on SWNTs coated with doxorubicin (DOX) through hydrazone bonds was developed, because the hydrazone bond is more sensitive to tumor microenvironments than other covalent linkers. The SWNTs were firstly stabilized with polyethylene glycol (H2N-PEG-NH2). Hydrazinobenzoic acid (HBA) was then covalently attached on SWNTs via carbodiimide-activated coupling reaction to form hydrazine-modified SWNTs. The anticancer drug DOX was conjugated to the HBA segments of SWNT using hydrazine as the linker. The resulting hydrazone bonds formed between the DOX molecules and the HBA segments of SWNTs are acid cleavable, thereby providing a strong pH-responsive drug release, which may facilitate effective DOX release near the acidic tumor microenvironment and thus reduce its overall systemic toxicity. The DOX-loaded SWNTs were efficiently taken up by HepG2 tumor cells, and DOX was released intracellularly, as revealed by MTT assay and confocal microscope observations. Compared with SWNT-DOX conjugate formed by supramolecular interaction, the SWNT-HBA-DOX featured high weight loading and prolonged release of DOX, and thus improved its cytotoxicity against cancer cells. This study suggests that while SWNTs have great potential as a drug carrier, the efficient formulation strategy requires further study.
Isotropic resolution diffusion tensor imaging of lumbosacral and sciatic nerves using a phase‐corrected diffusion‐prepared 3D turbo spin echo

To perform in vivo isotropic‐resolution diffusion tensor imaging (DTI) of lumbosacral and sciatic nerves with a phase‐navigated diffusion‐prepared (DP) 3D turbo spin echo (TSE) acquisition and modified reconstruction incorporating intershot phase‐error correction and to investigate the improvement on image quality and diffusion quantification with the proposed phase correction.
Prolonged survival after second autologous transplantation and lenalidomide maintenance for salvage treatment of myeloma patients at first relapse after prior autograft

Autologous stem cell transplantation (ASCT) as part of the primary therapy in multiple myeloma (MM) is standard practice. In contrast, the role of a second ASCT (ASCT2) and subsequent lenalidomide maintenance for relapsed disease remains unclear. In this study, we analysed 86 consecutive MM patients with a first relapse after prior ASCT receiving either a second ASCT or conventional chemotherapy. After a median follow‐up of 37.7 months since first relapse, 54 (62.8%) patients were still alive and 29 (33.7%) without progression. Sixty‐one (71.0%) patients received ASCT2 and had better progression‐free survival (PFS) (30.2 versus 13.0 mo; P = .0262) and overall survival (OS) rates (129.6 versus 33.5 mo; P = .0003) compared with 25 (29.0%) patients with conventional treatment. Patients relapsing later than 12 months after ASCT1 benefitted from a second ASCT with better PFS2 (P = .0179) and OS2 (P = .0009). Finally, lenalidomide maintenance after ASCT2 was associated with longer PFS (41.0 vs 21.6 mo; P = .0034) and better OS (not yet reached vs 129.6 mo; P = .0434) compared with patients without maintenance. Our data suggest that a second ASCT and lenalidomide maintenance given at first relapse in MM after prior ASCT are associated with better survival rates.
Vertically distinct microbial communities in the Mariana and Kermadec trenches

Hadal trenches, oceanic locations deeper than 6,000 m, are thought to have distinct microbial communities compared to those at shallower depths due to high hydrostatic pressures, topographical funneling of organic matter, and biogeographical isolation. Here we evaluate the hypothesis that hadal trenches contain unique microbial biodiversity through analyses of the communities present in the bottom waters of the Kermadec and Mariana trenches. Estimates of microbial protein production indicate active populations under in situ hydrostatic pressures and increasing adaptation to pressure with depth. Depth, trench of collection, and size fraction are important drivers of microbial community structure. Many putative hadal bathytypes, such as members related to the Marinimicrobia, Rhodobacteraceae, Rhodospirilliceae, and Aquibacter, are similar to members identified in other trenches. Most of the differences between the two trench microbiomes consists of taxa belonging to the Gammaproteobacteria whose distributions extend throughout the water column. Growth and survival estimates of representative isolates of these taxa under deep-sea conditions suggest that some members may descend from shallower depths and exist as a potentially inactive fraction of the hadal zone. We conclude that the distinct pelagic communities residing in these two trenches, and perhaps by extension other trenches, reflect both cosmopolitan hadal bathytypes and ubiquitous genera found throughout the water column.
Morphological disparity despite genetic similarity; new species of Lobosorchis Miller & Cribb, 2005 (Digenea: Cryptogonimidae) from the Great Barrier Reef and the Maldives

Examination of the humpback red snapper, Lutjanus gibbus (Perciformes: Lutjanidae), from Lizard Island off the Great Barrier Reef and Rasdhoo Atoll, Maldives revealed the presence of a new species of Lobosorchis (Digenea: Cryptogonimidae), L. polygongylus n. sp. Lobosorchis polygongylus n. sp. is distinguished from the type- and only other species, L. tibaldiae by the combination of body size, oral spine number (60–81 in L. polygongylus, 47–56 in L. tibaldiae) and number of testes (13–25 in L. polygongylus, 9 in L. tibaldiae). Bayesian inference analysis using data from the internal transcribed spacers 1 and 2 (ITS1 and ITS2), 5.8S and the large subunit (LSU) nuclear ribosomal DNA of L. polygongylus, L. tibaldiae and species of Beluesca, Caulanus, Chelediadema, Neometadena, Latuterus, Retrovarium and Siphoderina was performed to explore phylogenetic relationships of species of Lobosorchis with other cryptogonimid taxa. Despite the significant morphological differences between Lobosorchis polygongylus and L. tibaldiae, these two species differed consistently by only 5 base pairs (bp) over the entire ITS region (3 bp in ITS1, 0 bp in 5.8S and 2 bp in ITS2) and 1 bp in the LSU rDNA regions examined. The ITS2 rDNA region was sequenced from metacercariae obtained from the fins, flesh or body cavities of a number of fishes belonging to the Blenniidae, Pomacentridae and Tetraodontidae and analysed using minimum evolution analysis with L. polygongylus and L. tibaldiae. This revealed the presence of two additional genotypes (putative Lobosorchis sp. A and B), which consistently differed from L. polygongylus by 1 and 4 bp, L. tibaldiae by 1 and 4 bp and from each other by 3 bp over the ITS2 dataset. Although these genetic differences are relatively small, when evaluated in light of the differences observed between L. polygongylus and L. tibaldiae (which are morphologically quite distinct) and differences seen in other congeneric cryptogonimid taxa, the ITS2 rDNA data alone suggest that at least two more species of Lobosorchis are present at Lizard Island. These data also suggest that the ITS2 rDNA region alone is suitable for resolving operational taxonomic units (OTUs) at the species level within the Cryptogonimidae based on what was observed in this and other cryptogonimid systems. A morphological description of metacercariae of L. tibaldiae obtained from two species of Pomacentridae at Heron Island, off the Great Barrier Reef is also provided.
Access to Medical and Mental Health Services Across the HIV Care Continuum Among Young Transgender Women: A Qualitative Study

Abstract Purpose: (1) To describe psychosocial, medical, and mental health outcomes of young transgender women (YTW) living with or at risk for HIV infection and (2) to explore barriers and facilitators to medical and mental health services across the HIV care continuum. Methods: We conducted a cross-sectional observational study of YTW aged 16–24 years who were at risk for contracting or living with HIV. Participants were recruited from an adolescent HIV clinic and local community-based organizations that serve YTW. The single study visit included: a computer-assisted self-interview of demographics, medical and mental health measures, a qualitative semi-structured interview, optional rapid HIV testing for HIV-negative/status-unknown participants, and a chart review to determine rates of antiretroviral therapy (ART) prescription and viral suppression among HIV+ participants. Descriptive statistics were used for quantitative data, and a modified-grounded theory approach was used for qualitative analysis. Results: Participants (n=25) had a mean age of 21.2 years; the majority were non-white (76%), had less than a college education (76%), were unemployed (52%), and had an income <$12,000/year (80%). More than one-third were unstably housed (36%) and uninsured (36%), and 28% reported having transactional sex. A majority had taken gender-affirming hormones (72%), but 17% obtained them from a source other than their doctor. Among HIV+ participants (n=8), 50% were prescribed ART and all four participants achieved viral suppression. Qualitative themes included lack of respect for or misunderstanding of gender identity, mismatch of mental health needs with available provider skills, challenges in finding HIV prevention services during adolescence or when transitioning to adult care, and importance of workforce diversity, including representation of transgender women in care teams. Conclusion: This study identified significant unmet mental health needs and several barriers and facilitators to engaging in healthcare for YTW across the HIV care continuum. Our data suggest an urgent need for provider competency training in gender-affirming care and integration of appropriate mental health and gender-affirming treatment with HIV prevention and treatment services for this population.
Concomitant changes in radiation resistance and trehalose levels during life stages of Drosophila melanogaster suggest radio-protective function of trehalose

Abstract Purpose: During development, various life stages of Drosophila melanogaster (D. melanogaster) show different levels of resistance to gamma irradiation, with the early pupal stage being the most radiation sensitive. This provides us an opportunity to explore the biochemical basis of such variations. The present study was carried out to understand the mechanisms underlying radiation resistance during life stages of D. melanogaster. Materials and methods: Homogenates from all the life stages of D. melanogaster were prepared at stipulated age. These homogenates were used for the determination of (1) enzymatic antioxidants: superoxide dismutase (SOD), catalase, D. melanogaster glutathione peroxidase (DmGPx), and glutathione S-transferase (GST); (2) reducing non-enzymatic antioxidants: total antioxidant capacity (TAC), reduced glutathione (GSH) and non-reducing non-enzymatic antioxidant trehalose; and (3) levels of protein carbonyl (PC) content. Age-dependent changes in radiation resistance and associated biochemical changes were also studied in young (2 d) and old (20 and 30 d) flies. Results: TAC and GSH were found high in the early pupal stage, whereas catalase and DmGPx were found to increase in the early pupal stage. The non-feeding third instar (NFTI) larvae were found to have high levels of SOD and GST, besides NFTI larvae showed high levels of trehalose. A remarkable decrease was observed in radiation resistance and trehalose levels during the early pupal stage. The PC level was the highest during early pupal stage and was the lowest in NFTI larvae. Older flies showed high level of PC compared with young flies. Conclusion: In vitro increments in trehalose concentration correspond to reduced formation of PCs, suggesting a protective role of trehalose against free radicals. A strong correlation between levels of trehalose and PC formation suggests amelioration of proteome damage due to ionizing radiation (IR). Stages with high trehalose levels showed protected proteome and high radiation resistance, suggesting a significant role for this disaccharide in radiation resistance.
2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

Background and Purpose— The purpose of these guidelines is to provide an up-to-date comprehensive set of recommendations for clinicians caring for adult patients with acute arterial ischemic stroke in a single document. The intended audiences are prehospital care providers, physicians, allied health professionals, and hospital administrators. These guidelines supersede the 2013 guidelines and subsequent updates. Methods— Members of the writing group were appointed by the American Heart Association Stroke Council’s Scientific Statements Oversight Committee, representing various areas of medical expertise. Strict adherence to the American Heart Association conflict of interest policy was maintained. Members were not allowed to participate in discussions or to vote on topics relevant to their relations with industry. The members of the writing group unanimously approved all recommendations except when relations with industry precluded members voting. Prerelease review of the draft guideline was performed by 4 expert peer reviewers and by the members of the Stroke Council’s Scientific Statements Oversight Committee and Stroke Council Leadership Committee. These guidelines use the American College of Cardiology/American Heart Association 2015 Class of Recommendations and Levels of Evidence and the new American Heart Association guidelines format. Results— These guidelines detail prehospital care, urgent and emergency evaluation and treatment with intravenous and intra-arterial therapies, and in-hospital management, including secondary prevention measures that are appropriately instituted within the first 2 weeks. The guidelines support the overarching concept of stroke systems of care in both the prehospital and hospital settings. Conclusions— These guidelines are based on the best evidence currently available. In many instances, however, only limited data exist demonstrating the urgent need for continued research on treatment of acute ischemic stroke.
Production, Manufacturing and Logistics The value of early order commitment in a two-level supply chain

One approach to supply chain coordination is early order commitment, whereby a retailer commits to purchase a fixedorder quantity at a fixed delivery time before demand uncertainty is resolved. In this paper, we develop an analytical model to quantify the cost savings of an early order commitment in a two-level supply chain where demand is serially correlated. A decision rule is derived to determine whether early order commitment will benefit the supply chain, and accordingly to determine the optimal timing for early commitment. Our results indicate that the supply chain would experience greater savings from early order commitment when – (a) the inventory item receives less value-added activities at the retailer site; (b) the manufacturing lead time is short; (c) demand correlation over time is positive but weak; or (d) the delivery lead time is long (if a condition exists). We also propose a rebate scheme for the supply chain partners to share the gains of practicing early order commitment. � 2006 Elsevier B.V. All rights reserved.
Cytohesins Are Cytoplasmic ErbB Receptor Activators

Anke Bill,1,8 Anton Schmitz,1,8 Barbara Albertoni,1 Jin-Na Song,1 Lukas C. Heukamp,2 David Walrafen,3 Franziska Thorwirth,4 Peter J. Verveer,4 Sebastian Zimmer,2 Lisa Meffert,2 Arne Schreiber,3 Sampurna Chatterjee,5 Roman K. Thomas,5,6,7 Roland T. Ullrich,5 Thorsten Lang,3 and Michael Famulok1,* 1LIMES Institute, Program Unit Chemical Biology & Medicinal Chemistry, Laboratory of Chemical Biology, Rheinische Friedrich-Wilhelms-Universität Bonn, Gerhard-Domagk-Str. 1, 53121 Bonn, Germany 2Institute of Pathology, Universitätsklinikum, Rheinische Friedrich-Wilhelms-Universität Bonn, Sigmund-Freud Strasse 25, 53123 Bonn, Germany 3LIMES Institute, Program Unit Membrane Biology & Lipid Biochemistry, Laboratory of Membrane Biochemistry, Rheinische Friedrich-Wilhelms-Universität Bonn, Carl-Troll-Straße 31, 53115 Bonn, Germany 4Department of Systemic Cell Biology, Max-Planck Institute of Molecular Physiology, Otto-Hahn-Str. 11, 44227 Dortmund, Germany 5Max Planck Institute for Neurological Researchwith Klaus-Joachim-Zülch Laboratories of theMax Planck Society and theMedical Faculty of the University of Köln, Gleueler Str. 50, 50931 Köln, Germany 6Chemical Genomics Centre of the Max Planck Society, Otto-Hahn Str. 15, 44227 Dortmund, Germany 7Center of Integrated Oncology and Department I of Internal Medicine, University of Köln, Kerpener Straße 62, 50937 Köln, Germany 8These authors contributed equally to this work *Correspondence: m.famulok@uni-bonn.de DOI 10.1016/j.cell. 2010.09. 011
Measurement of Odor Threshold by Triangular Odor Bag Method

The detection thresholds of odor substances analyzed in field investigations were measured by the triangle odor bag method. The number of substances used for the experiment is 223. The experiment was carried out from 1976 to 1988. As the results of the experiments, the odor thresholds were distributed over the concentration of large range depending on the odor substances. Isoamyl mercaptane exhibited the lowest threshold (0.77ppt), and propane exhibited the highest threshold (1500ppm). The distribution of thresholds expresses the normal distribution. Sulfur compounds with the exception of sulfur dioxide and carbon disulfide have the comparatively low threshold. It is showed the tendency that threshold becomes low as the increase of molecular weight in a certain range of molecular weight. When the dispersion of odor thresholds for the same substance was shown at the ratio of the highest to the lowest odor threshold tested, the dispersion of odor thresholds was about 5 at the maximum. The thresholds of 223 substances measured by our laboratory were considered to be the average values with small bias comparatively.
Succession of transiently active tumor‐initiating cell clones in human pancreatic cancer xenografts

Although tumor‐initiating cell (TIC) self‐renewal has been postulated to be essential in progression and metastasis formation of human pancreatic adenocarcinoma (PDAC), clonal dynamics of TICs within PDAC tumors are yet unknown. Here, we show that long‐term progression of PDAC in serial xenotransplantation is driven by a succession of transiently active TICs producing tumor cells in temporally restricted bursts. Clonal tracking of individual, genetically marked TICs revealed that individual tumors are generated by distinct sets of TICs with very little overlap between subsequent xenograft generations. An unexpected functional and phenotypic plasticity of pancreatic TICs in vivo underlies the recruitment of inactive TIC clones in serial xenografts. The observed clonal succession of TIC activity in serial xenotransplantation is in stark contrast to the continuous activity of limited numbers of self‐renewing TICs within a fixed cellular hierarchy observed in other epithelial cancers and emphasizes the need to target TIC activation, rather than a fixed TIC population, in PDAC.
FPGA acceleration by asynchronous parallelization for simultaneous image reconstruction and segmentation based on the Mumford-Shah regularization

X-ray computed tomography (CT) is an important technique for noninvasive clinical diagnosis and nondestructive testing. In many applications a number of image processing steps are needed before the image features are available. One of these processing steps is image segmentation, which generates the edge and the structural features of the regions of interest. The conventional flow is to first reconstruct images and then apply image segmentation methods on reconstructed images. In contrast, an emerging technique obtains the tomographic image and segmentation simultaneously, which is especially useful in the case of limited data. An iterative method for simultaneous reconstruction and segmentation (SRS) with Mumford-Shah model has been proposed, which not only regularizes the ill-posed tomographic reconstruction problem, but also produces the image segmentation at the same time. The Mumford-Shah model is both mathematically and computationally challenging. In this paper, we propose an asynchronous ray-parallel algorithm of the SRS method and accelerate it using field-programmable gate array (FPGA) devices, which drastically improves the energy efficiency. Experimental results show that the FPGA implementation achieves a 1:2× speedup with an energy efficiency as great as 58×, over the GPU implementation.