bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of current genetic testing reports in German-speaking countries with regard to secondary use and future electronic implementation
Authors: Radke Teja Falk , Patton Simon J. , Pantazoglou Elisabeth , Sass Julian , Thun Sylvia 
Published: February 2020

AbstractModern diagnostic methods (next-generation sequencing) are one of the current hopes with regard to a personalised medicine. By applying detailed genetic analysis, it is possible to not only improve the prediction of potential risks (as, e.g., concerning hereditary breast cancer) but also the precision of therapy by targeting it to a specific genetic variant. However, there is no international standard for creating, structuring and/or transferring the results of a genetic test report. This type of test report often contains large amounts of complex information, and a standardised and consistent structure would offer potential benefits to all. These include reduced expenditure of time (due to the elimination of information-conversion steps), improved safety (due to a reduction in the occurrence of transmission errors, misunderstanding or misinterpretation of content) and improved clinical information gathering (by the respective linkage to scientific data and literature). Especially in regard to secondary use, a standardised (electronic) format would improve the suitability of these data in retrospective studies and basic research. In this study, we analysed the format and content of 96 genetic testing reports (germline and somatic) from Germany, Switzerland and Austria. Based on these results, we summarised and discussed potentially critical data that were demonstrated to be reported inconsistently, and propose a baseline structure for reporting that would also ease future electronic conversion.
Enhancing neuronal chloride extrusion rescues α2/α3 GABAA-mediated analgesia in neuropathic pain
Authors: Lorenzo Louis-Etienne , Godin Antoine G. , Ferrini Francesco , Bachand Karine , Plasencia-Fernandez Isabel , Labrecque Simon , Girard Alexandre A. , Boudreau Dominic , Kianicka Irenej , Gagnon Martin , Doyon Nicolas , Ribeiro-da-Silva Alfredo , De Koninck Yves 
Published: February 2020

AbstractSpinal disinhibition has been hypothesized to underlie pain hypersensitivity in neuropathic pain. Apparently contradictory mechanisms have been reported, raising questions on the best target to produce analgesia. Here, we show that nerve injury is associated with a reduction in the number of inhibitory synapses in the spinal dorsal horn. Paradoxically, this is accompanied by a BDNF-TrkB-mediated upregulation of synaptic GABAARs and by an α1-to-α2GABAAR subunit switch, providing a mechanistic rationale for the analgesic action of the α2,3GABAAR benzodiazepine-site ligand L838,417 after nerve injury. Yet, we demonstrate that impaired Cl- extrusion underlies the failure of L838,417 to induce analgesia at high doses due to a resulting collapse in Cl- gradient, dramatically limiting the benzodiazepine therapeutic window. In turn, enhancing KCC2 activity not only potentiated L838,417-induced analgesia, it rescued its analgesic potential at high doses, revealing a novel strategy for analgesia in pathological pain, by combined targeting of the appropriate GABAAR-subtypes and restoring Cl- homeostasis.
Benchmarking tomographic acquisition schemes for high-resolution structural biology
Authors: Turoňová Beata , Hagen Wim J. H. , Obr Martin , Mosalaganti Shyamal , Beugelink J. Wouter , Zimmerli Christian E. , Kräusslich Hans-Georg , Beck Martin 
Published: February 2020

AbstractCryo electron tomography with subsequent subtomogram averaging is a powerful technique to structurally analyze macromolecular complexes in their native context. Although close to atomic resolution in principle can be obtained, it is not clear how individual experimental parameters contribute to the attainable resolution. Here, we have used immature HIV-1 lattice as a benchmarking sample to optimize the attainable resolution for subtomogram averaging. We systematically tested various experimental parameters such as the order of projections, different angular increments and the use of the Volta phase plate. We find that although any of the prominently used acquisition schemes is sufficient to obtain subnanometer resolution, dose-symmetric acquisition provides considerably better outcome. We discuss our findings in order to provide guidance for data acquisition. Our data is publicly available and might be used to further develop processing routines.
Macrophages employ quorum licensing to regulate collective activation
Authors: Muldoon Joseph J. , Chuang Yishan , Bagheri Neda , Leonard Joshua N. 
Published: February 2020

AbstractMacrophage-initiated inflammation is tightly regulated to eliminate threats such as infections while suppressing harmful immune activation. However, individual cells’ signaling responses to pro-inflammatory cues are heterogeneous, with subpopulations emerging with high or low activation states. Here, we use single-cell tracking and dynamical modeling to develop and validate a revised model for lipopolysaccharide (LPS)-induced macrophage activation that invokes a mechanism we term quorum licensing. The results show that bimodal phenotypic partitioning of macrophages is primed during the resting state, dependent on cumulative history of cell density, predicted by extrinsic noise in transcription factor expression, and independent of canonical LPS-induced intercellular feedback in the tumor necrosis factor (TNF) response. Our analysis shows how this density-dependent coupling produces a nonlinear effect on collective TNF production. We speculate that by linking macrophage density to activation, this mechanism could amplify local responses to threats and prevent false alarms.
A case report of multiple primary prostate tumors with differential drug sensitivity
Authors: Wilkinson Scott , Harmon Stephanie A. , Terrigino Nicholas T. , Karzai Fatima , Pinto Peter A. , Madan Ravi A. , VanderWeele David J. , Lake Ross , Atway Rayann , Bright John R. , Carrabba Nicole V. , Trostel Shana Y. , Lis Rosina T. , Chun Guinevere , Gulley James L. , Merino Maria J. , Choyke Peter L. , Ye Huihui , Dahut William L. , Turkbey Baris , Sowalsky Adam G. 
Published: February 2020

AbstractLocalized prostate cancers are genetically variable and frequently multifocal, comprising spatially distinct regions with multiple independently-evolving clones. To date there is no understanding of whether this variability can influence management decisions for patients with prostate tumors. Here, we present a single case from a clinical trial of neoadjuvant intense androgen deprivation therapy. A patient was diagnosed with a large semi-contiguous tumor by imaging, histologically composed of a large Gleason score 9 tumor with an adjacent Gleason score 7 nodule. DNA sequencing demonstrates these are two independent tumors, as only the Gleason 9 tumor harbors single-copy losses ofPTENandTP53. ThePTEN/TP53-deficient tumor demonstrates treatment resistance, selecting for subclones with mutations to the remaining copies ofPTENandTP53, while the Gleason 7PTEN-intact tumor is almost entirely ablated. These findings indicate that spatiogenetic variability is a major confounder for personalized treatment of patients with prostate cancer.
Inference and effects of barcode multiplets in droplet-based single-cell assays
Authors: Lareau Caleb A. , Ma Sai , Duarte Fabiana M. , Buenrostro Jason D. 
Published: February 2020

AbstractA widespread assumption for single-cell analyses specifies that one cell’s nucleic acids are predominantly captured by one oligonucleotide barcode. Here, we show that ~13–21% of cell barcodes from the 10x Chromium scATAC-seq assay may have been derived from a droplet with more than one oligonucleotide sequence, which we call “barcode multiplets”. We demonstrate that barcode multiplets can be derived from at least two different sources. First, we confirm that approximately 4% of droplets from the 10x platform may contain multiple beads. Additionally, we find that approximately 5% of beads may contain detectable levels of multiple oligonucleotide barcodes. We show that this artifact can confound single-cell analyses, including the interpretation of clonal diversity and proliferation of intra-tumor lymphocytes. Overall, our work provides a conceptual and computational framework to identify and assess the impacts of barcode multiplets in single-cell data.
Cross-talks of glycosylphosphatidylinositol biosynthesis with glycosphingolipid biosynthesis and ER-associated degradation
Authors: Wang Yicheng , Maeda Yusuke , Liu Yi-Shi , Takada Yoko , Ninomiya Akinori , Hirata Tetsuya , Fujita Morihisa , Murakami Yoshiko , Kinoshita Taroh 
Published: February 2020

AbstractGlycosylphosphatidylinositol (GPI)-anchored proteins and glycosphingolipids interact with each other in the mammalian plasma membranes, forming dynamic microdomains. How their interaction starts in the cells has been unclear. Here, based on a genome-wide CRISPR-Cas9 genetic screen for genes required for GPI side-chain modification by galactose in the Golgi apparatus, we report that β1,3-galactosyltransferase 4 (B3GALT4), the previously characterized GM1 ganglioside synthase, additionally functions in transferring galactose to the N-acetylgalactosamine side-chain of GPI. Furthermore, B3GALT4 requires lactosylceramide for the efficient GPI side-chain galactosylation. Thus, our work demonstrates previously unexpected functional relationships between GPI-anchored proteins and glycosphingolipids in the Golgi. Through the same screening, we also show that GPI biosynthesis in the endoplasmic reticulum (ER) is severely suppressed by ER-associated degradation to prevent GPI accumulation when the transfer of synthesized GPI to proteins is defective. Our data demonstrates cross-talks of GPI biosynthesis with glycosphingolipid biosynthesis and the ER quality control system.
Optical inter-site spin transfer probed by energy and spin-resolved transient absorption spectroscopy
Authors: Willems Felix , von Korff Schmising Clemens , Strüber Christian , Schick Daniel , Engel Dieter W. , Dewhurst J. K. , Elliott Peter , Sharma Sangeeta , Eisebitt Stefan 
Published: February 2020

AbstractOptically driven spin transport is the fastest and most efficient process to manipulate macroscopic magnetization as it does not rely on secondary mechanisms to dissipate angular momentum. In the present work, we show that such an optical inter-site spin transfer (OISTR) from Pt to Co emerges as a dominant mechanism governing the ultrafast magnetization dynamics of a CoPt alloy. To demonstrate this, we perform a joint theoretical and experimental investigation to determine the transient changes of the helicity dependent absorption in the extreme ultraviolet spectral range. We show that the helicity dependent absorption is directly related to changes of the transient spin-split density of states, allowing us to link the origin of OISTR to the available minority states above the Fermi level. This makes OISTR a general phenomenon in optical manipulation of multi-component magnetic systems.
Benchmark performance of low-cost Sb2Se3 photocathodes for unassisted solar overall water splitting
Authors: Yang Wooseok , Kim Jin Hyun , Hutter Oliver S. , Phillips Laurie J. , Tan Jeiwan , Park Jaemin , Lee Hyungsoo , Major Jonathan D. , Lee Jae Sung , Moon Jooho 
Published: February 2020

AbstractDetermining cost-effective semiconductors exhibiting desirable properties for commercial photoelectrochemical water splitting remains a challenge. Herein, we report a Sb2Se3 semiconductor that satisfies most requirements for an ideal high-performance photoelectrode, including a small band gap and favourable cost, optoelectronic properties, processability, and photocorrosion stability. Strong anisotropy, a major issue for Sb2Se3, is resolved by suppressing growth kinetics via close space sublimation to obtain high-quality compact thin films with favourable crystallographic orientation. The Sb2Se3 photocathode exhibits a high photocurrent density of almost 30 mA cm−2 at 0 V against the reversible hydrogen electrode, the highest value so far. We demonstrate unassisted solar overall water splitting by combining the optimised Sb2Se3 photocathode with a BiVO4 photoanode, achieving a solar-to-hydrogen efficiency of 1.5% with stability over 10 h under simulated 1 sun conditions employing a broad range of solar fluxes. Low-cost Sb2Se3 can thus be an attractive breakthrough material for commercial solar fuel production.
Ultra-long carrier lifetime in neutral graphene-hBN van der Waals heterostructures under mid-infrared illumination
Authors: Huang P. , Riccardi E. , Messelot S. , Graef H. , Valmorra F. , Tignon J. , Taniguchi T. , Watanabe K. , Dhillon S. , Plaçais B. , Ferreira R. , Mangeney J. 
Published: February 2020

AbstractGraphene/hBN heterostructures are promising active materials for devices in the THz domain, such as emitters and photodetectors based on interband transitions. Their performance requires long carrier lifetimes. However, carrier recombination processes in graphene possess sub-picosecond characteristic times for large non-equilibrium carrier densities at high energy. An additional channel has been recently demonstrated in graphene/hBN heterostructures by emission of hBN hyperbolic phonon polaritons (HPhP) with picosecond decay time. Here, we report on carrier lifetimes in graphene/hBN Zener-Klein transistors of ~30 ps for photoexcited carriers at low density and energy, using mid-infrared photoconductivity measurements. We further demonstrate the switching of carrier lifetime from ~30 ps (attributed to interband Auger) down to a few picoseconds upon ignition of HPhP relaxation at finite bias and/or with infrared excitation power. Our study opens interesting perspectives to exploit graphene/hBN heterostructures for THz lasing and highly sensitive THz photodetection as well as for phonon polariton optics.
Topochemical synthesis of different polymorphs of polymers as a paradigm for tuning properties of polymers
Authors: Mohanrao Raja , Hema Kuntrapakam , Sureshan Kana M. 
Published: February 2020

AbstractDifferent packing is a mechanism through which nature can produce materials of different properties from the same basic units. There is great interest in constructing different forms of the same polymer by utilising different packing. Common solution-synthesized polymers are amorphous and their post-synthesis crystallization into different topologies is almost impossible. Here we show solid-state polymerization of different reactive polymorphs of a monomer pre-organized in different topologies. Trimorphs of a dipeptide monomer pack in a head-to-tail fashion, placing the azide and alkyne of adjacent monomers in proximity. On heating, these crystals undergo a topochemical azide-alkyne cycloaddition reaction yielding triazole-linked polymer in three different crystalline states; one with antiparallel arrangement of polymer chains, another with parallelly oriented chains, and a third form containing a 1:1 blend of two different conformers aligned in parallel. This approach of exploiting different polymorphs of a monomer for topochemical polymerization to yield polymorphs of polymers is promising for future research.
Measurement properties from the Brazilian Portuguese version of the QUIP-RS
Authors: Guerra Daniela Freitas , Lemos Silva Ana Elisa , Paz Thiago da Silva Rocha , Filho Leandro Nogueira S. , Vasconcellos Luiz Felipe , de Britto Vera Lucia Santos , Allodi Silvana , Weintraub Daniel , Swarowsky Alessandra , Correa Clynton Lourenço 
Published: February 2020

AbstractParkinson’s disease (PD) has numerous motor and non-motor symptoms. Among non-motor manifestations impulse control disorders (ICDs) stand out. ICDs include compulsions for gambling, shopping, eating, and sexual behavior, and “related disorders” such as hobbyism, simple motor activities, and dopamine dysregulation syndrome. There is no rating scale translated and adapted transculturally into Brazilian Portuguese language. Therefore, we cross-culturally adapted and investigated the measurement properties of the Brazilian version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease-Rating Scale (QUIP-RS). Fifty-three patients participated in the study. Inter-evaluator and test–retest (patient and health professional) reliabilities (intraclass correlation coefficient) were all excellent (0.93, 0.93, and 0.99). The internal consistency was high (α = 0.92). The Minimal detectable change (MDC) value was 5.8 (patient) and 2.3 (health professional) points. There was a floor, but no ceiling, effect. In summary, the Brazilian version of the QUIP-RS has high reliability and content validity.
Strong local moment antiferromagnetic spin fluctuations in V-doped LiFeAs
Authors: Xu Zhuang , Dai Guangyang , Li Yu , Yin Zhiping , Rong Yan , Tian Long , Liu Panpan , Wang Hui , Xing Lingyi , Wei Yuan , Kajimoto Ryoichi , Ikeuchi Kazuhiko , Abernathy D. L. , Wang Xiancheng , Jin Changqing , Lu Xingye , Tan Guotai , Dai Pengcheng 
Published: February 2020

AbstractWe use neutron scattering to study Vanadium (hole)-doped LiFe1−xVxAs. In the undoped state, LiFeAs exhibits superconductivity at Tc = 18 K and transverse incommensurate spin excitations similar to electron overdoped iron pnictides. Upon Vanadium doping to form LiFe0.955V0.045, the transverse incommensurate spin excitations in LiFeAs transform into longitudinally elongated ones in a similar fashion to that of potassium (hole)-doped Ba0.7K0.3Fe2As2 but with dramatically enhanced magnetic scattering and elimination of superconductivity. This is different from the suppression of the overall magnetic excitations in hole-doped BaFe2As2 and the enhancement of superconductivity near optimal hole doping. These results are consistent with density function theory plus dynamic mean field theory calculations, suggesting that Vanadium doping in LiFeAs may induce an enlarged effective magnetic moment Seff with a spin crossover ground state arising from the inter-orbital scattering of itinerant electrons.
Molecular dynamics trajectories for 630 coarse-grained drug-membrane permeations
Authors: Hoffmann Christian , Centi Alessia , Menichetti Roberto , Bereau Tristan 
Published: February 2020

AbstractThe permeation of small-molecule drugs across a phospholipid membrane bears much interest both in the pharmaceutical sciences and in physical chemistry. Connecting the chemistry of the drug and the lipids to the resulting thermodynamic properties remains of immediate importance. Here we report molecular dynamics (MD) simulation trajectories using the coarse-grained (CG) Martini force field. A wide, representative coverage of chemistry is provided: across solutes—exhaustively enumerating all 105 CG dimers—and across six phospholipids. For each combination, umbrella-sampling simulations provide detailed structural information of the solute at all depths from the bilayer midplane to bulk water, allowing a precise reconstruction of the potential of mean force. Overall, the present database contains trajectories from 15,120 MD simulations. This database may serve the further identification of structure-property relationships between compound chemistry and drug permeability.
Enhanced homologous recombination by the modulation of targeting vector ends
Authors: Hirotsune Shinji , Kiyonari Hiroshi , Jin Mingyue , Kumamoto Kanako , Yoshida Kayo , Shinohara Miki , Watanabe Hitomi , Wynshaw-Boris Anthony , Matsuzaki Fumio 
Published: February 2020

AbstractThe field of genome editing was founded on the establishment of methods, such as the clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR-associated protein (CRISPR/Cas) system, used to target DNA double-strand breaks (DSBs). However, the efficiency of genome editing also largely depends on the endogenous cellular repair machinery. Here, we report that the specific modulation of targeting vectors to provide 3′ overhangs at both ends increased the efficiency of homology-directed repair (HDR) in embryonic stem cells. We applied the modulated targeting vectors to produce homologous recombinant mice directly by pronuclear injection, but the frequency of HDR was low. Furthermore, we combined our method with the CRISPR/Cas9 system, resulting in a significant increase in HDR frequency. Thus, our HDR-based method, enhanced homologous recombination for genome targeting (eHOT), is a new and powerful method for genome engineering.
Risk factors and clinical correlates of neoplastic transformation in gastric hyperplastic polyps in Chinese patients
Authors: Hu Haiyi , Zhang Qian , Chen Guangyong , Pritchard D. Mark , Zhang Shutian 
Published: February 2020

AbstractGastric hyperplastic polyps (GHPs) have a potential risk of neoplastic transformation, but the responsible mechanisms have not yet been established. We conducted a study involving 55 patients (33 female) who had undergone endoscopic or surgical resection of GHPs. We compared 16 patients who had GHPs showing neoplastic transformation with 39 patients who had non-neoplastic GHPs. We analyzed differences in serology, gastroscopic manifestations and pathology between the two groups in order to establish risk factors that may be associated with neoplastic transformation. The mean age of the cohort was 61.73 ± 9.024 years. The prevalence of positive serum gastric parietal cell antibody (PCA) was 61.8%. 30 of the GHPs with neoplastic formation had a “strawberry-like” appearance with erosions of polyps (P = 0.000). A history of anaemia was a risk factor for GHPs which demonstrated neoplastic transformation (odds ratio [OR], 3.729; 95% confidence interval [CI], 1.099–12.649; P = 0.035). Although the differences were not significant, our data showed higher prevalences of positive serum PCA (P = 0.057), hypergastrinemia (P = 0.062) and female gender (P = 0.146) in the GHP patients who had neoplastic transformation. Multiple polyps in the corpus (P = 0.024) occurred more frequently in serum PCA positive patients. Hypergastrinemia occurred more frequently in Helicobacter pylori negative patients and of these 20/22 patients had a positive PCA (P = 0.007). GHPs are associated with autoimmune metaplastic atrophic gastritis (AMAG). AMAG is probably one of the risk factors for GHPs to undergo neoplastic transformation.
Budgerigars adopt robust, but idiosyncratic flight paths
Authors: Karmaker Debajyoti , Groening Julia , Wilson Michael , Schiffner Ingo , Srinivasan Mandyam V. 
Published: February 2020

AbstractWe have investigated the paths taken by Budgerigars while flying in a tunnel. The flight trajectories of nine Budgerigars (Melopsittacus undulatus) were reconstructed in 3D from high speed stereo videography of their flights in an obstacle-free tunnel. Individual birds displayed highly idiosyncratic flight trajectories that were consistent from flight to flight over the course of several months. We then investigated the robustness of each bird’s trajectory by interposing a disk-shaped obstacle in its preferred flight path. We found that each bird continued to fly along its preferred trajectory up to a point very close to the obstacle before veering over the obstacle rapidly, making a minimal deviation to avoid a collision, and subsequently returning to its original path. Thus, Budgerigars show a high propensity to stick to their individual, preferred flight paths even when confronted with a clearly visible obstacle, and do not adopt a substantially different, unobstructed route. The robust preference for idiosyncratic flight paths, and the tendency to pass obstacles by flying above them, provide new insights into the strategies that underpin obstacle avoidance in birds. We believe that this is the first carefully controlled study of the behaviour of birds in response to a newly introduced obstacle in their flight path. The insights from the study could also have implications for conservation efforts to mitigate collisions of birds with man-made obstacles.