bluuebunny/crossref_metadata_2025_split huggingface dataset:
Context specificity of the EMT transcriptional response
Authors: Cook David P. , Vanderhyden Barbara C. 
Published: May 2020

AbstractEpithelial–mesenchymal plasticity contributes to many biological processes, including tumor progression. Various epithelial–mesenchymal transition (EMT) responses have been reported and no common, EMT-defining gene expression program has been identified. Here, we have performed a comparative analysis of the EMT response, leveraging highly multiplexed single-cell RNA sequencing (scRNA-seq) to measure expression profiles of 103,999 cells from 960 samples, comprising 12 EMT time course experiments and independent kinase inhibitor screens for each. We demonstrate that the EMT is vastly context specific, with an average of only 22% of response genes being shared between any two conditions, and over half of all response genes were restricted to 1–2 time course experiments. Further, kinase inhibitor screens revealed signaling dependencies and modularity of these responses. These findings suggest that the EMT is not simply a single, linear process, but is highly variable and modular, warranting quantitative frameworks for understanding nuances of the transition.
Increased mitochondrial calcium levels associated with neuronal death in a mouse model of Alzheimer’s disease
Authors: Calvo-Rodriguez Maria , Hou Steven S. , Snyder Austin C. , Kharitonova Elizabeth K. , Russ Alyssa N. , Das Sudeshna , Fan Zhanyun , Muzikansky Alona , Garcia-Alloza Monica , Serrano-Pozo Alberto , Hudry Eloise , Bacskai Brian J. 
Published: May 2020

AbstractMitochondria contribute to shape intraneuronal Ca2+ signals. Excessive Ca2+ taken up by mitochondria could lead to cell death. Amyloid beta (Aβ) causes cytosolic Ca2+ overload, but the effects of Aβ on mitochondrial Ca2+ levels in Alzheimer’s disease (AD) remain unclear. Using a ratiometric Ca2+ indicator targeted to neuronal mitochondria and intravital multiphoton microscopy, we find increased mitochondrial Ca2+ levels associated with plaque deposition and neuronal death in a transgenic mouse model of cerebral β-amyloidosis. Naturally secreted soluble Aβ applied onto the healthy brain increases Ca2+ concentration in mitochondria, which is prevented by blockage of the mitochondrial calcium uniporter. RNA-sequencing from post-mortem AD human brains shows downregulation in the expression of mitochondrial influx Ca2+ transporter genes, but upregulation in the genes related to mitochondrial Ca2+ efflux pathways, suggesting a counteracting effect to avoid Ca2+ overload. We propose lowering neuronal mitochondrial Ca2+ by inhibiting the mitochondrial Ca2+ uniporter as a novel potential therapeutic target against AD.
Discovery of high-entropy ceramics via machine learning
Authors: Kaufmann Kevin , Maryanovsky Daniel , Mellor William M. , Zhu Chaoyi , Rosengarten Alexander S. , Harrington Tyler J. , Oses Corey , Toher Cormac , Curtarolo Stefano , Vecchio Kenneth S. 
Published: May 2020

AbstractAlthough high-entropy materials are attracting considerable interest due to a combination of useful properties and promising applications, predicting their formation remains a hindrance for rational discovery of new systems. Experimental approaches are based on physical intuition and/or expensive trial and error strategies. Most computational methods rely on the availability of sufficient experimental data and computational power. Machine learning (ML) applied to materials science can accelerate development and reduce costs. In this study, we propose an ML method, leveraging thermodynamic and compositional attributes of a given material for predicting the synthesizability (i.e., entropy-forming ability) of disordered metal carbides. The relative importance of the thermodynamic and compositional features for the predictions are then explored. The approach’s suitability is demonstrated by comparing values calculated with density functional theory to ML predictions. Finally, the model is employed to predict the entropy-forming ability of 70 new compositions; several predictions are validated by additional density functional theory calculations and experimental synthesis, corroborating the effectiveness in exploring vast compositional spaces in a high-throughput manner. Importantly, seven compositions are selected specifically, because they contain all three of the Group VI elements (Cr, Mo, and W), which do not form room temperature-stable rock-salt monocarbides. Incorporating the Group VI elements into the rock-salt structure provides further opportunity for tuning the electronic structure and potentially material performance.
How to optimize knowledge construction in the brain
Authors: van Kesteren Marlieke Tina Renée , Meeter Martijn 
Published: May 2020

AbstractWell-structured knowledge allows us to quickly understand the world around us and make informed decisions to adequately control behavior. Knowledge structures, or schemas, are presumed to aid memory encoding and consolidation of new experiences so we cannot only remember the past, but also guide behavior in the present and predict the future. However, very strong schemas can also lead to unwanted side effects such as false memories and misconceptions. To overcome this overreliance on a schema, we should aim to create robust schemas that are on the one hand strong enough to help to remember and predict, but also malleable enough to avoid such undesirable side effects. This raises the question as to whether there are ways to deliberately influence knowledge construction processes, with the goal to reach such optimally balanced schemas. Here, we will discuss how the mnemonic processes in our brains build long-term knowledge and, more specifically, how different phases of memory formation (encoding, consolidation, retrieval, and reconsolidation) contribute to this schema build-up. We finally provide ways how to best keep a balance between generalized semantic and detailed episodic memories, which can prove very useful in, e.g., educational settings.
DNA methylation of chronic lymphocytic leukemia with differential response to chemotherapy
Authors: Yosifov Deyan Yordanov , Bloehdorn Johannes , Döhner Hartmut , Lichter Peter , Stilgenbauer Stephan , Mertens Daniel 
Published: May 2020

AbstractAcquired resistance to chemotherapy is an important clinical problem and can also occur without detectable cytogenetic aberrations or gene mutations. Chronic lymphocytic leukemia (CLL) is molecularly well characterized and has been elemental for establishing central paradigms in oncology. This prompted us to check whether specific epigenetic changes at the level of DNA methylation might underlie development of treatment resistance. We used Illumina Infinium HumanMethylation450 BeadChips to obtain DNA methylation profiles of 71 CLL patients with differential responses. Thirty-six patients were categorized as relapsed/refractory after treatment with fludarabine or bendamustine and 21 of them had genetic aberrations of TP53. The other 35 patients were untreated at the time of sampling and 15 of them had genetic aberration of TP53. Although we could not correlate chemoresistance with epigenetic changes, the patients were comprehensively characterized regarding relevant prognostic and molecular markers (e.g. IGHV mutation status, chromosome aberrations, TP53 mutation status, clinical parameters), which makes our dataset a unique and valuable resource that can be used by researchers to test alternative hypotheses.
The ANI-1ccx and ANI-1x data sets, coupled-cluster and density functional theory properties for molecules
Authors: Smith Justin S. , Zubatyuk Roman , Nebgen Benjamin , Lubbers Nicholas , Barros Kipton , Roitberg Adrian E. , Isayev Olexandr , Tretiak Sergei 
Published: May 2020

AbstractMaximum diversification of data is a central theme in building generalized and accurate machine learning (ML) models. In chemistry, ML has been used to develop models for predicting molecular properties, for example quantum mechanics (QM) calculated potential energy surfaces and atomic charge models. The ANI-1x and ANI-1ccx ML-based general-purpose potentials for organic molecules were developed through active learning; an automated data diversification process. Here, we describe the ANI-1x and ANI-1ccx data sets. To demonstrate data diversity, we visualize it with a dimensionality reduction scheme, and contrast against existing data sets. The ANI-1x data set contains multiple QM properties from 5 M density functional theory calculations, while the ANI-1ccx data set contains 500 k data points obtained with an accurate CCSD(T)/CBS extrapolation. Approximately 14 million CPU core-hours were expended to generate this data. Multiple QM calculated properties for the chemical elements C, H, N, and O are provided: energies, atomic forces, multipole moments, atomic charges, etc. We provide this data to the community to aid research and development of ML models for chemistry.
Conformation-dependent degradation of thermally activated delayed fluorescence materials bearing cycloamino donors
Authors: Hwang Sanju , Moon Yu Kyung , Jang Ho Jin , Kim Sinheui , Jeong Hyein , Lee Jun Yeob , You Youngmin 
Published: May 2020

AbstractOrganic light-emitting devices (OLEDs) containing organic molecules that exhibit thermally activated delayed fluorescence (TADF) produce high efficiencies. One challenge to the commercialization of the TADF OLEDs that remains to be addressed is their operational stability. Here we investigate the molecular factors that govern the stability of various archetypal TADF molecules based on a cycloamino donor–acceptor platform. Our results reveal that the intrinsic stability depends sensitively on the identity of the cycloamino donors in the TADF compounds. The rates and photochemical quantum yields of the degradation are positively correlated with the operation lifetimes of the devices. Our research shows that the stability is governed by the conformeric heterogeneity between the pseudo-axial and pseudo-equatorial forms of the cycloamino donor. Spontaneous bond dissociation occurs in the former (i.e., the pseudo-axial form), but the cleavage is disfavored in the pseudo-equatorial form. These findings provide valuable insights into the design of stable TADF molecules.
18 band ANSI S1.11 filter bank based on interpolated finite impulse response technique for hearing aids
Authors: S.P. Deepu , Kini M. Ramesh , David S. Sumam 
Published: May 2020

A low complexity interpolated finite impulse response (IFIR) based 18 band ANSI S1.11 1/3 octave digital filter bank for hearing aid is proposed and implemented using 65 nm UMC technology in this study. ANSI S1.11 specifications for 1/3 octave Class‐2 filters are chosen as design criteria in the proposed method. The strict requirements at lower bands make the hardware implementation of ANSI S1.11 filter bank complex and difficult in a power critical application like hearing aid. In the proposed technique, the maximum margin available in the filter specifications is utilised in both upper and lower band edge specifications to reduce the filter order. IFIR technique was used to reduce the computations at lower bands which can be implemented in hardware efficiently without altering the sampling frequency of the input signal. Compared to other recent architectures, >50% reduction in total number of filter coefficients is achieved and the group delay is kept <10 ms. Hardware implementation of the algorithm was done using 65 nm standard cell libraries and tested the outputs with NAL‐NL2 gain prescriptions. The matching errors are within and the core power consumption was obtained as 0.37 mW.
Research on Decorative and Integrated Thermal Insulation Board for External Wall
Authors: Zhanhua Zhang , jie lI , Changyu Shi , Chao Zhang , An Wang , Shan Zhang 
Published: May 2020

With the acceleration of globalization, industrialization and informatization, the consumption of energy resources is increasing, and the building energy consumption accounts for about 30%, so the building energy conservation has become an important part of energy conservation and emission reduction. At the same time of economic development, we should reduce building energy consumption and do a good job in building energy conservation [1], and put forward the following ways: the improvement of building’s own heat preservation and insulation performance; the improvement of energy utilization system efficiency such as electricity and heating; the development and utilization of new energy; and the proper management of energy utilization equipment system. Among them, the most effective way is to improve the thermal insulation performance of the building itself. The thermal insulation of enclosure and the air tightness of doors and windows are two important parts of thermal insulation. According to the relevant data [2], the heat loss of enclosure structure accounts for 40-50% of the building energy consumption, and the heat loss of wall structure accounts for about 70%. Therefore, the improvement of the thermal insulation requirements of the wall structure plays a huge role in building energy conservation
In this paper, the experimental research on the exterior wall thermal insulation board of decoration and heat preservation integration is carried out. The influence of fly ash content, asbestos fiber content, composite active activator, waterproof agent and other additives on the physical properties of fiber-reinforced fly ash / cement board is discussed. The optimal content of various factors is determined and its mechanism is analyzed. The optimum proportion of fiber reinforced fly ash / cement board was determined by orthogonal test.
Le complexe terminase, une cible de choix dans le traitement de l’infection à cytomégalovirus humain
Authors: Ligat Gaëtan , Muller Clotilde , Alain Sophie , Hantz Sébastien 
Published: May 2020

Le cytomégalovirus humain (CMVH) est un pathogène opportuniste majeur en cas d’immunodépression et représente la principale cause d’infection congénitale d’origine virale. Bien qu’efficace, l’utilisation des molécules conventionnelles est limitée par leur toxicité et par l’émergence de résistance du virus, rendant nécessaire le développement de nouveaux traitements. Lors de la réplication du CMVH, l’encapsidation de l’ADN est réalisée par le complexe terminase qui clive l’ADN pour empaqueter le génome dans la capside. L’absence d’homologues dans les cellules des mammifères rend les protéines du complexe terminase des cibles idéales pour des antiviraux spécifiques. Une nouvelle molécule, le letermovir, cible une étape exclusivement virale en interagissant avec le complexe terminase. Son efficacité a été prouvée lors d’essais cliniques de phase III. Néanmoins, son mécanisme d’action n’est, à ce jour, pas élucidé et aucune activité n’est observée contre les autres herpèsvirus.
Neoadjuvante Daylight Photodynamische Therapie bei Spinozellulärem Karzinom an der Kopfhaut zum Debulking des Nachexzisionsareals
Authors: Steinert S. , Steinert M. , Steinert U. 
Published: May 2020

ZusammenfassungDas spinozelluläre Karzinom ist der zweithäufigste diagnostizierte Hauttumor in Deutschland und die Inzidenz nicht melanozytärer Hauttumoren ist weltweit steigend. Solange eine ambulante Behandlung möglich ist, wird dies sowohl vom Patienten häufig gewünscht und ist weiterhin ökonomisch sinnvoll. Im Rahmen der Therapie der aktinischen Keratosen gewinnt die Tageslicht-PDT (DL-PDT) zunehmend Bedeutung gegenüber der klassischen PDT.Dieser Fall beschreibt die neoadjuvante DL-PDT als Therapiemöglichkeit zur Demarkation eines gesicherten, aber klinisch nicht abgrenzbaren spinozellulären Tumors mit nachfolgender R0-Resektion. Die DL-PDT ersetzt hierbei nicht die mikrografisch kontrollierte chirurgische Exzision mit histologisch tumorfreien Rändern, ergänzt diese jedoch, um eine kleinere Exzision vornehmen zu können.
Potential Drug interactions with Drugs used for Bipolar Disorder: A Comparison of 6 Drug Interaction Database Programs
Authors: Monteith Scott , Glenn Tasha , Gitlin Michael , Bauer Michael 
Published: May 2020

AbstractBackground Patients with bipolar disorder frequently experience polypharmacy, putting them at risk for clinically significant drug-drug interactions (DDI). Online drug interaction database programs are used to alert physicians, but there are no internationally recognized standards to define DDI. This study compared the category of potential DDI returned by 6 commercial drug interaction database programs for drug interaction pairs involving drugs commonly prescribed for bipolar disorder.Methods The category of potential DDI provided by 6 drug interaction database programs (3 subscription, 3 open access) was obtained for 125 drug interaction pairs. The pairs involved 103 drugs (38 psychiatric, 65 nonpsychiatric); 88 pairs included a psychiatric and nonpsychiatric drug; 37 pairs included 2 psychiatric drugs. Every pair contained at least 1 mood stabilizer or antidepressant. The category provided by 6 drug interaction database programs was compared using percent agreement and Fleiss kappa statistic of interrater reliability.Results For the 125 drug pairs, the overall percent agreement among the 6 drug interaction database programs was 60%; the Fleiss kappa agreement was slight. For drug interaction pairs with any category rating of severe (contraindicated), the kappa agreement was moderate. For drug interaction pairs with any category rating of major, the kappa agreement was slight.Conclusion There is poor agreement among drug interaction database programs for the category of potential DDI involving psychiatric drugs. Drug interaction database programs provide valuable information, but the lack of consistency should be recognized as a limitation. When assistance is needed, physicians should check more than 1 drug interaction database program.
Routine Histopathological Analysis of the Synovium in Patients with Primary Total Knee Arthroplasty
Authors: Utkan Ali , Caliskan Emrah , Gencer Batuhan , Ozkurt Bulent 
Published: May 2020

AbstractAlthough there are numerous studies about routine histopathological analysis during arthroplasty surgeries, most of them showed that new diagnoses have rarely been obtained as a result. The aim of this study was to evaluate the efficacy of routine pathological analyses of synovia resected during primary total knee arthroplasty in patients with osteoarthritis and its relevance in the treatment process. Of the 47 included patients who were followed up prospectively, 26 patients had clinical and histopathological concordant diagnoses and 21 patients had discrepant diagnoses. Oxford knee score and visual analogue score were performed for all the patients. Kallgren-Lawrence score was used for radiological analyses. The Mann-Whitney U test was used to examine the differences between the abnormally distributed variables. Mean age was 65.9 ± 4.3 years (range, 50–89 years) and mean follow-up time was 19 ± 7.8 months (range, 6–39 months). Grade IV gonarthrosis was found to be statistically lower in the discrepant group (p = 0.046). The mean preoperative Oxford knee score was 16.8 ± 2.3 (range, 2–23) and the mean postoperative Oxford knee score was 44.6 ± 1.8 (range, 27–48; p = 0.016). Postoperative Oxford knee scores and VAS were significantly increased in both the concordant and discrepant groups (p = 0.026 and p = 0.035, p = 0.019 and p = 0.039, respectively). Resection and histopathologic analyses of the hypertrophied and inflamed synovium encountered during primary arthroplasty procedure should be performed. This examination not only could provide crucial information that may influence the postoperative follow-up guidelines but also could help us to expand our knowledge and awareness of rare diseases that might yield osteoarthritis. The level of evidence for the study is level II.
Efficacy of Arthroscopic Arthrolysis in the Treatment of Arthrofibrosis: A Systematic Review
Authors: Cohen Jordan S. , Gu Alex , Kapani Nisha , Asadourian Paul A. , Stake Seth , Quan Theodore , Malahias Michael A. , Sculco Peter K. 
Published: May 2020

AbstractStiffness after total knee arthroplasty (TKA) remains a clinical challenge for health care professionals. Historically, arthroscopic arthrolysis is a treatment modality that has been reserved for patients that have failed other conservative modalities, including manipulation under anesthesia. However, a systematic review of the literature evaluating the clinical efficacy and complications of arthroscopic arthrolysis for stiffness after TKA has not been performed. A systematic review of medical databases (PubMed, EMBASE, Cochrane Library) was undertaken for articles published from January 1980 to October 2018. A descriptive and critical analysis of the results was performed. From 1,326 studies, 7 studies met the inclusion criteria for this study. A total of 160 patients who underwent arthroscopic arthrolysis for arthrofibrosis following TKA were included for analysis. The quality of the evidence for the included studies ranged between moderate and high. Overall, patients had significant increased range of motion and flexion by 32.5 and 26.7 degrees, respectively following arthroscopic arthrolysis. Functional outcome scores also significantly improved for patients who underwent arthroscopic arthrolysis after TKA. Arthroscopic arthrolysis is an efficacious modality for treatment of stiffness following TKA. The greatest benefit is seen among patients that present with significant loss of flexion. Arthroscopic arthrolysis should be reserved for patients that have previously failed more conservative modalities.
Single-Cut Single-Screw Capitate-Shortening Osteotomy for Kienbock's Disease
Authors: Bain Gregory I. , Krishna Sathya Vamsi , MacLean Simon Bruce Murdoch , Agrawal Parth 
Published: May 2020

Abstract
Background Kienbock's disease, in spite of an uncertain natural history, is known to cause lunate compromise, leading to central column collapse, carpal instability, and degenerative arthritis of the wrist. Joint leveling procedures are performed in the early stages of Kienbock's disease to “unload” the lunate. Capitate shortening is the preferred procedure in Kienbock's patients with positive ulnar variance.
Description of Technique We describe the rationale and a simplified technique of capitate shortening in early Kienbock's disease. This is a single-cut osteotomy with single-screw stabilization.
Patients and Methods We have performed this technique in three cases. We present a case of a 26-year-old male who presented with a 1-year history of pain in his right wrist. Radiology performed demonstrated lunate sclerosis. Diagnostic arthroscopy revealed healthy articular surfaces. Single osteotomy capitate shortening was performed with an oscillating saw and fixed with a single cannulated compression screw. A shortening of 1.5mm was obtained with this technique.
Results At 1- to 2-year follow-up, all three patients had considerable pain relief but did not have a complete resolution of pain. There was a significant improvement in function and grip strength. There have been no cases with infection, nonunion, avascular necrosis or a need for a salvage procedure.
Conclusion The simplified technique of capitate shortening is easy to perform, less traumatic to the capitate vascularity, and leads to good short-term functional results.