bluuebunny/crossref_metadata_2025_split huggingface dataset:
A mode-balanced reconfigurable logic gate built in a van der Waals strata
Authors: Cao Wei , Chu Jae Hwan , Parto Kamyar , Banerjee Kaustav 
Published: February 2021

AbstractTwo-dimensional (2D) semiconducting materials, in particular transition-metal dichalcogenides, have emerged as the preferred channel materials for sub-5 nm field-effect transistors (FETs). However, the lack of practical doping techniques for these materials poses a significant challenge to designing complementary logic gates containing both n- and p-type FETs. Although electrical tuning of the polarity of 2D-FETs can potentially circumvent this problem, such devices suffer from the lack of balanced n- and p-mode transistor performance, forming one of the most enigmatic challenges of the reconfigurable 2D-FET technology. Here we provide a solution to this dilemma by judicious use of van der Waals (vdW) materials consisting of conductors, dielectrics and semiconductors forming a 50 nm thin quantum engineered strata that can guarantee a purely vdW-type interlayer interaction, which faithfully preserves the mid-gap contact design and thereby achieves an intrinsically mode-balanced and fully reconfigurable all-2D logic gate. The intrinsically mode-balanced gate eliminates the need for transistor sizing and allows post-fabrication reconfigurability to the transistor operation mode, simultaneously allowing an ultra-compact footprint and increased circuit functionality, which can be potentially exploited to build more area-efficient and low-cost integrated electronics for the internet of things (IoT) paradigm.
Randomized controlled study using text messages to help connect new medicaid beneficiaries to primary care
Authors: Levine David M. , Kakani Pragya , Mehrotra Ateev 
Published: February 2021

AbstractAccessing primary care is often difficult for newly insured Medicaid beneficiaries. Tailored text messages may help patients navigate the health system and initiate care with a primary care physician. We conducted a randomized controlled trial of tailored text messages with newly enrolled Medicaid managed care beneficiaries. Text messages included education about the importance of primary care, reminders to obtain an appointment, and resources to help schedule an appointment. Within 120 days of enrollment, we examined completion of at least one primary care visit and use of the emergency department. Within 1 year of enrollment, we examined diagnosis of a chronic disease, receipt of preventive care, and use of the emergency department. 8432 beneficiaries (4201 texting group; 4231 control group) were randomized; mean age was 37 years and 24% were White. In the texting group, 31% engaged with text messages. In the texting vs control group after 120 days, there were no differences in having one or more primary care visits (44.9% vs. 45.2%; difference, −0.27%; p = 0.802) or emergency department use (16.2% vs. 16.0%; difference, 0.23%; p = 0.771). After 1 year, there were no differences in diagnosis of a chronic disease (29.0% vs. 27.8%; difference, 1.2%; p = 0.213) or appropriate preventive care (for example, diabetes screening: 14.1% vs. 13.4%; difference, 0.69%; p = 0.357), but emergency department use (32.7% vs. 30.2%; difference, 2.5%; p = 0.014) was greater in the texting group. Tailored text messages were ineffective in helping new Medicaid beneficiaries visit primary care within 120 days.
Recalibration of deep learning models for abnormality detection in smartphone-captured chest radiograph
Authors: Kuo Po-Chih , Tsai Cheng Che , López Diego M. , Karargyris Alexandros , Pollard Tom J. , Johnson Alistair E. W. , Celi Leo Anthony 
Published: February 2021

AbstractImage-based teleconsultation using smartphones has become increasingly popular. In parallel, deep learning algorithms have been developed to detect radiological findings in chest X-rays (CXRs). However, the feasibility of using smartphones to automate this process has yet to be evaluated. This study developed a recalibration method to build deep learning models to detect radiological findings on CXR photographs. Two publicly available databases (MIMIC-CXR and CheXpert) were used to build the models, and four derivative datasets containing 6453 CXR photographs were collected to evaluate model performance. After recalibration, the model achieved areas under the receiver operating characteristic curve of 0.80 (95% confidence interval: 0.78–0.82), 0.88 (0.86–0.90), 0.81 (0.79–0.84), 0.79 (0.77–0.81), 0.84 (0.80–0.88), and 0.90 (0.88–0.92), respectively, for detecting cardiomegaly, edema, consolidation, atelectasis, pneumothorax, and pleural effusion. The recalibration strategy, respectively, recovered 84.9%, 83.5%, 53.2%, 57.8%, 69.9%, and 83.0% of performance losses of the uncalibrated model. We conclude that the recalibration method can transfer models from digital CXRs to CXR photographs, which is expected to help physicians’ clinical works.
Intertissue small RNA communication mediates the acquisition and inheritance of hormesis in Caenorhabditis elegans
Authors: Okabe Emiko , Uno Masaharu , Kishimoto Saya , Nishida Eisuke 
Published: February 2021

AbstractEnvironmental conditions can cause phenotypic changes, part of which can be inherited by subsequent generations via soma-to-germline communication. However, the signaling molecules or pathways that mediate intertissue communication remain unclear. Here, we show that intertissue small RNA communication systems play a key role in the acquisition and inheritance of hormesis effects – stress-induced stress resistance – in Caenorhabditis elegans. The miRNA-processing enzyme DRSH-1 is involved in both the acquisition and the inheritance of hormesis, whereas worm-specific Argonaute (WAGO) proteins, which function with endo-siRNAs, are involved only in its inheritance. Further analyses demonstrate that the miRNA production system in the neuron and the small RNA transport machinery in the intestine are both essential for its acquisition and that both the transport of small RNAs in the germline and the germline Argonaute HRDE-1 complex are required for its inheritance. Our results thus demonstrate that overlapping and distinct roles of small RNA systems in the acquisition and inheritance of hormesis effects.
Biocompatible nucleus-targeted graphene quantum dots for selective killing of cancer cells via DNA damage
Authors: Qi Lei , Pan Tonghe , Ou Liling , Ye Zhiqiang , Yu Chunlei , Bao Bijun , Wu Zixia , Cao Dayong , Dai Liming 
Published: February 2021

AbstractGraphene quantum dots (GQDs) are nano-sized graphene slices. With their small size, lamellar and aromatic-ring structure, GQDs tend to enter into the cell nucleus and interfere with DNA activity. Thus, GQD alone is expected to be an anticancer reagent. Herein, we developed GQDs that suppress the growth of tumor by selectively damaging the DNA of cancer cells. The amine-functionalized GQDs were modified with nucleus targeting TAT peptides (TAT-NGs) and further grafted with cancer-cell-targeting folic acid (FA) modified PEG via disulfide linkage (FAPEG-TNGs). The resulting FAPEG-TNGs exhibited good biocompatibility, nucleus uptake, and cancer cell targeting. They adsorb on DNA via the π–π and electrostatic interactions, which induce the DNA damage, the upregulation of the cell apoptosis related proteins, and the suppression of cancer cell growth, ultimately. This work presents a rational design of GQDs that induce the DNA damage to realize high therapeutic performance, leading to a distinct chemotherapy strategy for targeted tumor therapy.
CASSPER is a semantic segmentation-based particle picking algorithm for single-particle cryo-electron microscopy
Authors: George Blesson , Assaiya Anshul , Roy Robin J. , Kembhavi Ajit , Chauhan Radha , Paul Geetha , Kumar Janesh , Philip Ninan S. 
Published: February 2021

AbstractParticle identification and selection, which is a prerequisite for high-resolution structure determination of biological macromolecules via single-particle cryo-electron microscopy poses a major bottleneck for automating the steps of structure determination. Here, we present a generalized deep learning tool, CASSPER, for the automated detection and isolation of protein particles in transmission microscope images. This deep learning tool uses Semantic Segmentation and a collection of visually prepared training samples to capture the differences in the transmission intensities of protein, ice, carbon, and other impurities found in the micrograph. CASSPER is a semantic segmentation based method that does pixel-level classification and completely eliminates the need for manual particle picking. Integration of Contrast Limited Adaptive Histogram Equalization (CLAHE) in CASSPER enables high-fidelity particle detection in micrographs with variable ice thickness and contrast. A generalized CASSPER model works with high efficiency on unseen datasets and can potentially pick particles on-the-fly, enabling data processing automation.
A high-throughput Galectin-9 imaging assay for quantifying nanoparticle uptake, endosomal escape and functional RNA delivery
Authors: Munson Michael J. , O’Driscoll Gwen , Silva Andreia M. , Lázaro-Ibáñez Elisa , Gallud Audrey , Wilson John T. , Collén Anna , Esbjörner Elin K. , Sabirsh Alan 
Published: February 2021

AbstractRNA-based therapies have great potential to treat many undruggable human diseases. However, their efficacy, in particular for mRNA, remains hampered by poor cellular delivery and limited endosomal escape. Development and optimisation of delivery vectors, such as lipid nanoparticles (LNPs), are impeded by limited screening methods to probe the intracellular processing of LNPs in sufficient detail. We have developed a high-throughput imaging-based endosomal escape assay utilising a Galectin-9 reporter and fluorescently labelled mRNA to probe correlations between nanoparticle-mediated uptake, endosomal escape frequency, and mRNA translation. Furthermore, this assay has been integrated within a screening platform for optimisation of lipid nanoparticle formulations. We show that Galectin-9 recruitment is a robust, quantitative reporter of endosomal escape events induced by different mRNA delivery nanoparticles and small molecules. We identify nanoparticles with superior escape properties and demonstrate cell line variances in endosomal escape response, highlighting the need for fine-tuning of delivery formulations for specific applications.
High-throughput behavioral screen in C. elegans reveals Parkinson’s disease drug candidates
Authors: Sohrabi Salman , Mor Danielle E. , Kaletsky Rachel , Keyes William , Murphy Coleen T. 
Published: February 2021

AbstractWe recently linked branched-chain amino acid transferase 1 (BCAT1) dysfunction with the movement disorder Parkinson’s disease (PD), and found that RNAi-mediated knockdown of neuronal bcat-1 in C. elegans causes abnormal spasm-like ‘curling’ behavior with age. Here we report the development of a machine learning-based workflow and its application to the discovery of potentially new therapeutics for PD. In addition to simplifying quantification and maintaining a low data overhead, our simple segment-train-quantify platform enables fully automated scoring of image stills upon training of a convolutional neural network. We have trained a highly reliable neural network for the detection and classification of worm postures in order to carry out high-throughput curling analysis without the need for user intervention or post-inspection. In a proof-of-concept screen of 50 FDA-approved drugs, enasidenib, ethosuximide, metformin, and nitisinone were identified as candidates for potential late-in-life intervention in PD. These findings point to the utility of our high-throughput platform for automated scoring of worm postures and in particular, the discovery of potential candidate treatments for PD.
Zn2+-dependent DNAzymes that cleave all combinations of ribonucleotides
Authors: Inomata Rika , Zhao Jing , Miyagishi Makoto 
Published: February 2021

AbstractAlthough several DNAzymes are known, their utility is limited by a narrow range of substrate specificity. Here, we report the isolation of two zinc-dependent DNAzymes, ZincDz1 and ZincDz2, which exhibit compact catalytic core sequences with highly versatile hydrolysis activity. They were selected through in vitro selection followed by deep sequencing analysis. Despite their sequence similarity, each DNAzyme showed different Zn2+-concentration and pH-dependent reaction profiles, and cleaved the target RNA sequences at different sites. Using various substrate RNA sequences, we found that the cleavage sequence specificity of ZincDz2 and its highly active mutant ZincDz2-v2 to be 5′-rN↓rNrPu-3′. Furthermore, we demonstrated that the designed ZincDz2 could cut microRNA miR-155 at three different sites. These DNAzymes could be useful in a broad range of applications in the fields of medicine and biotechnology.
Structure–function studies of ultrahigh molecular weight isoprenes provide key insights into their biosynthesis
Authors: Kajiura Hiroyuki , Yoshizawa Takuya , Tokumoto Yuji , Suzuki Nobuaki , Takeno Shinya , Takeno Kanokwan Jumtee , Yamashita Takuya , Tanaka Shun-ichi , Kaneko Yoshinobu , Fujiyama Kazuhito , Matsumura Hiroyoshi , Nakazawa Yoshihisa 
Published: February 2021

AbstractSome plant trans-1,4-prenyltransferases (TPTs) produce ultrahigh molecular weight trans-1,4-polyisoprene (TPI) with a molecular weight of over 1.0 million. Although plant-derived TPI has been utilized in various industries, its biosynthesis and physiological function(s) are unclear. Here, we identified three novel Eucommia ulmoides TPT isoforms—EuTPT1, 3, and 5, which synthesized TPI in vitro without other components. Crystal structure analysis of EuTPT3 revealed a dimeric architecture with a central hydrophobic tunnel. Mutation of Cys94 and Ala95 on the central hydrophobic tunnel no longer synthesizd TPI, indicating that Cys94 and Ala95 were essential for forming the dimeric architecture of ultralong-chain TPTs and TPI biosynthesis. A spatiotemporal analysis of the physiological function of TPI in E. ulmoides suggested that it is involved in seed development and maturation. Thus, our analysis provides functional and mechanistic insights into TPI biosynthesis and uncovers biological roles of TPI in plants.
A hexokinase isoenzyme switch in human liver cancer cells promotes lipogenesis and enhances innate immunity
Authors: Perrin-Cocon Laure , Vidalain Pierre-Olivier , Jacquemin Clémence , Aublin-Gex Anne , Olmstead Keedrian , Panthu Baptiste , Rautureau Gilles Jeans Philippe , André Patrice , Nyczka Piotr , Hütt Marc-Thorsten , Amoedo Nivea , Rossignol Rodrigue , Filipp Fabian Volker , Lotteau Vincent , Diaz Olivier 
Published: February 2021

AbstractDuring the cancerous transformation of normal hepatocytes into hepatocellular carcinoma (HCC), the enzyme catalyzing the first rate-limiting step of glycolysis, namely the glucokinase (GCK), is replaced by the higher affinity isoenzyme, hexokinase 2 (HK2). Here, we show that in HCC tumors the highest expression level of HK2 is inversely correlated to GCK expression, and is associated to poor prognosis for patient survival. To further explore functional consequences of the GCK-to-HK2 isoenzyme switch occurring during carcinogenesis, HK2 was knocked-out in the HCC cell line Huh7 and replaced by GCK, to generate the Huh7-GCK+/HK2− cell line. HK2 knockdown and GCK expression rewired central carbon metabolism, stimulated mitochondrial respiration and restored essential metabolic functions of normal hepatocytes such as lipogenesis, VLDL secretion, glycogen storage. It also reactivated innate immune responses and sensitivity to natural killer cells, showing that consequences of the HK switch extend beyond metabolic reprogramming.
Gravitational wave detectors with broadband high frequency sensitivity
Authors: Page Michael A. , Goryachev Maxim , Miao Haixing , Chen Yanbei , Ma Yiqiu , Mason David , Rossi Massimiliano , Blair Carl D. , Ju Li , Blair David G. , Schliesser Albert , Tobar Michael E. , Zhao Chunnong 
Published: February 2021

AbstractGravitational waves from the neutron star coalescence GW170817 were observed from the inspiral, but not the high frequency postmerger nuclear matter motion. Optomechanical white light signal recycling has been proposed for achieving broadband sensitivity in gravitational wave detectors, but has been reliant on development of suitable ultra-low loss mechanical components. Here we show demonstrated optomechanical resonators that meet loss requirements for a white light signal recycling interferometer with strain sensitivity below 10−24 Hz−1/2 at a few kHz. Experimental data for two resonators are combined with analytic models of interferometers similar to LIGO to demonstrate enhancement across a broader band of frequencies versus dual-recycled Fabry-Perot Michelson detectors. Candidate resonators are a silicon nitride membrane acoustically isolated by a phononic crystal, and a single-crystal quartz acoustic cavity. Optical power requirements favour the membrane resonator, while thermal noise performance favours the quartz resonator. Both could be implemented as add-on components to existing detectors.
Quantum simulation of parity–time symmetry breaking with a superconducting quantum processor
Authors: Dogra Shruti , Melnikov Artem A. , Paraoanu Gheorghe Sorin 
Published: February 2021

Abstract
The observation of genuine quantum effects in systems governed by non-Hermitian Hamiltonians has been an outstanding challenge in the field. Here we simulate the evolution under such Hamiltonians in the quantum regime on a superconducting quantum processor by using a dilation procedure involving an ancillary qubit. We observe the parity–time ($${\mathcal{PT}}$$
PT
)-symmetry breaking phase transition at the exceptional points, obtain the critical exponent, and show that this transition is associated with a loss of state distinguishability. In a two-qubit setting, we show that the entanglement can be modified by local operations.
Hypertensive Erkrankungen in der Schwangerschaft
Authors: Schneider Johanna , Walz Gerd , Neumann-Haefelin Elke 
Published: February 2021

AbstractHypertensive disorders occur in up to 10 % of pregnancies and increase both maternal and fetal morbidity and mortality. The most important differential diagnoses comprise pre-existing chronic hypertension, pregnancy-associated hypertension, and preeclampsia with simultaneous proteinuria. Antihypertensive therapy during pregnancy should be initiated when blood pressure is 150–160/100–110 mmHg. With regard to an earlier initiation of therapy, the data situation is not clear. Pre-eclampsia is defined as new or pre-existing elevated blood pressure ≥ 140/90 mmHg in pregnancy with at least one new organ manifestation, usually proteinuria ≥ 300 mg/day or ≥ 30 mg/mmol in the protein-creatinine ratio. Thrombotic microangiopathies TTP and aHUS are altogether rare but potentially life-threatening diseases that should be clarified in case of severe or atypical courses.
Kalkaneusfrakturen – operative Taktik und Erfolgskontrolle
Authors: Marx Christine , Kamin Konrad , Rammelt Stefan 
Published: February 2021

ZusammenfassungKalkaneusfrakturen sind häufige Verletzungen des Fußes und stellen ein anspruchsvolles Krankheitsbild dar. Sie bedürfen einer sorgfältigen Diagnostik einschließlich multiplanarer CT-Bildgebung und einer individuellen Therapieplanung. Insbesondere der Weichteilbefund hat großen Einfluss auf die therapeutischen Optionen und das Therapieergebnis. Nicht dislozierte und extraartikuläre Frakturen ohne relevante Achsfehlstellung und Verbreiterung des Fersenbeins können i. d. R. konservativ behandelt werden. Intraartikuläre Frakturen mit Verwerfungen ab 2 mm und relevante Fehlstellungen des Fersenbeins bedürfen der operativen Therapie. Diese erfolgt klassischerweise über einen ausgedehnten lateralen Zugang mittels Plattenosteosynthese. Aufgrund der vergleichsweise hohen Rate an Wundheilungsstörungen haben sich weniger invasive Verfahren, wie die Reposition über einen Sinus-tarsi-Zugang mit perkutaner Schraubenosteosynthese, etabliert.
Das „Interdisciplinary Spine Fellowship” in England
Authors: Rothenfluh Dominique A , Reynolds Jeremy , Bojanic Stana 
Published: February 2021

ZusammenfassungDie Wirbelsäulenchirurgie hat sich zu einer Subspezialität von Orthopädie und Neurochirurgie entwickelt, obwohl offiziell zurzeit noch nicht als solche anerkannt. Speziell in England haben hohe Wartezeiten für Patienten und geografische Lücken in der Versorgung von Wirbelsäulenpatienten die Bildung von Wirbelsäulennetzwerken begünstigt. Damit in dieser Struktur die Qualität verbessert werden kann, muss die Variabilität von Entscheidungen und Behandlungskonzepten vermindert werden. Dies soll mit einer strukturierten Weiterbildung gelingen, welche die speziellen Aspekte von Orthopädie und Neurochirurgie beinhaltet. Es wird erwartet, dass ein Fellowship die Kompetenz der Chirurgen erhöht und so die Qualität und Behandlungsresultate verbessert. Das interdisziplinäre Fellowship der Spinal Training Interface Group (STIG) vereinigt Lerninhalte von Orthopädie und Neurochirurgie in einem definierten Weiterbildungscurriculum. Dieses hat die Lernziele zur praktischen Umsetzung als sog. „Skills” in 4 Module eingeteilt: Allgemeine Prinzipien, Kritische Erkrankungen, Pathologische Wirbelsäule und optional Fortgeschrittene Behandlungsmethoden. Um die Bedingungen zur Komplettierung des Fellowships zu erfüllen, muss die Absolvierung der einzelnen Skills dokumentiert sein. Das Fellowship dauert mindestens ein Jahr. Die strukturierte Weiterbildung im Rahmen des interdisziplinären Fellowships soll so eine flächendeckende qualitativ hochstehende Grundversorgung gewährleisten und sicherstellen, dass Spezialwissen und Fertigkeiten dort zur Verfügung stehen, wo sie benötigt werden.
Das AO Spine Ausbildungskonzept
Authors: Scholz M. 
Published: February 2021

ZusammenfassungAO Spine ist einer der weltweit führenden Aus- und Weiterbildungsanbieter im Wirbelsäulensektor. In 2019 wurden ca. 260 Bildungsveranstaltungen angeboten, an denen über 13.800 Wirbelsäulenchirurgen teilnahmen. Das „lebenslange Lernen“ ist dabei der Leitgedanke, um Wirbelsäulenchirurgen in jeder Stufe ihrer Ausbildung mit den passenden Bildungsangeboten zu unterstützen. Die AOSpine setzt dabei auf ein curriculäres Ausbildungskonzept, welches die Basis jeder Ausbildungsveranstaltung bildet. Angeboten werden unter anderem Kurse, Seminare und online Webinare sowie auch eine logistische und finanzielle Unterstützungen für internationale wirbelsäulenchirurgische Hospitationen. Im Jahr 2019 wurde erstmals ein „AO Spine Diploma Examen“ etabliert, womit AO Spine Mitglieder ihr erworbenes Wissen auf internationaler Ebene zertifizieren lassen können.
Zusatzweiterbildung „Spezielle Wirbelsäulenchirurgie“ – Das Konzept einer interdisziplinären Weiterbildung
Authors: Kothe Ralph 
Published: February 2021

ZusammenfassungDie Zusatzweiterbildung „Spezielle Wirbelsäulenchirurgie“ soll zukünftig eine strukturierte Ausbildung von Wirbelsäulenchirurgen ermöglichen. Zugangsberechtigt sind Fachärzte für Neurochirurgie sowie Fachärzte für Orthopädie und Unfallchirurgie. Die Ausbildungsdauer beträgt 24 Monate und orientiert sich in den Inhalten an dem Weiterbildungscurriculum der DWG zur persönlichen Zertifizierung. Es gibt 6 Themenblöcke, die sich neben den Grundlagen mit den unterschiedlichen Pathologiegruppen befassen (degenerativ, Deformitäten, Trauma, Tumor/Entzündungen und intradurale Pathologien) Ein siebter Block bezieht sich auf die operativen Techniken. Das Ausbildungscurriculum ermöglicht damit eine umfassende interdisziplinäre Ausbildung, die der klinischen Realität mit ihrer zunehmenden operativen Spezialisierung gerecht wird. Die konservative Behandlung von Wirbelsäulenerkrankungen ist im vorliegenden Curriculum nicht enthalten, da es sich ausschließlich um eine operative Spezialisierung handelt. Die Einführung einer Zusatzweiterbildung kann nur durch die Bundesärztekammer und den Bundesärztetag erfolgen. Hierzu befindet sich die DWG aktuell in Gesprächen mit den Muttergesellschaften und der Ständigen Konferenz „Ärztliche Weiterbildung“ der Bundesärztekammer.