bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-dose steroids are associated with indeterminate QuantiFERON-TB Gold In-Tube assay results in immunocompetent children
Authors: Kim Kyu Ho , Kang Ji-Man , Ahn Jong Gyun 
Published: March 2021

AbstractImmunocompromised status can result in indeterminate QuantiFERON-TB Gold In-Tube (QFT-GIT) results, but the association of indeterminate results with immunocompetent status in children is unknown. Therefore, we aimed to identify factors associated with indeterminate QFT-GIT results for immunocompetent children. We conducted a retrospective chart review of children (aged ≤ 18 years) who underwent QFT-GIT between September 2006 and July 2017 at the Severance Hospital, Seoul, South Korea. Of the 2037 QFT-GIT assays included in the present study, 7.7% yielded indeterminate QFT-GIT results. Multivariable logistic regression analysis identified younger age (OR 0.88; 95% CI 0.836–0.927; P < 0.001), elevated white blood cell (WBC) count (OR 1.066; 95% CI 1.020–1.115; P = 0.005), decreased albumin levels (OR 0.505; 95% CI 0.316–0.807; P = 0.004), and low-dose steroid therapy (< 1 mg/kg per day of prednisone or equivalent for < 2 weeks) (OR 76.146; 95% CI 8.940–648.569; P < 0.001) as significant factors influencing indeterminate results. Younger age, high WBC count, low albumin levels, and low-dose steroid therapy were associated with indeterminate QFT-GIT results. Low-dose steroid therapy had the highest OR for the indeterminate results compared to other significant risk factors. Our study suggests that screening for steroid doses is important prior to performing interferon-gamma release assays for immunocompetent children.
Acetylation of ELF5 suppresses breast cancer progression by promoting its degradation and targeting CCND1
Authors: Li Xiahui , Li Shujing , Li Bowen , Li Yanan , Aman Sattout , Xia Kangkai , Yang Yuxi , Ahmad Bashir , Wu Huijian 
Published: March 2021

AbstractE74-like ETS transcription factor 5 (ELF5) is involved in a wide spectrum of biological processes, e.g., mammogenesis and tumor progression. We have identified a list of p300-interacting proteins in human breast cancer cells. Among these, ELF5 was found to interact with p300 via acetylation, and the potential acetylation sites were identified as K130, K134, K143, K197, K228, and K245. Furthermore, an ELF5-specific deacetylase, SIRT6, was also identified. Acetylation of ELF5 promoted its ubiquitination and degradation, but was also essential for its antiproliferative effect against breast cancer, as overexpression of wild-type ELF5 and sustained acetylation-mimicking ELF5 mutant could inhibit the expression of its target gene CCND1. Taken together, the results demonstrated a novel regulation of ELF5 as well as shedding light on its important role in modulation of breast cancer progression.
Precision medicine: preliminary results from the Initiative for Molecular Profiling and Advanced Cancer Therapy 2 (IMPACT2) study
Authors: Tsimberidou Apostolia Maria , Hong David S. , Fu Siqing , Karp Daniel D. , Piha-Paul Sarina , Kies Merrill S. , Ravi Vinod , Subbiah Vivek , Patel Sunil M. , Tu Shi-Ming , Janku Filip , Heymach John , Johnson Amber , Cartwright Carrie , Zhao Li , Zhang Jianhua , Berry Donald A. , Vining David J. , Futreal Andrew , Miller Vincent A. , Meric-Bernstam Funda 
Published: March 2021

AbstractPrecision medicine is associated with favorable outcomes in selected patients with cancer. Herein, we report an interim analysis of IMPACT2, an ongoing randomized study evaluating genomic profiling and targeted agents in metastatic cancer. Patients with metastatic cancer underwent tumor genomic profiling (ClinialTrials.gov: NCT02152254), and 69 patients met the criteria for randomization. Tumor board and multidisciplinary review of molecular alterations optimized treatment selection. From 5/2014 to 4/2017, 320 patients (median age, 63 years; men, 47%) had tumor molecular aberrations, and 213 (66.56%) received anticancer therapy. The most frequently mutated genes were TP53 (42%), KRAS (16%), PIK3CA (12%), and CDKN2A (11%). The median OS was 10.9 months (95% CI, 8.8–12.9). OS was shorter in patients with higher tumor mutational burden. Independent factors associated with shorter OS were age ≥60 years, liver metastases, low albumin levels, high LDH levels, and KRAS and TP53 mutations. Outcomes for randomized patients will be reported after completion of the study.
Circulating stromal cells in resectable pancreatic cancer correlates to pathological stage and predicts for poor clinical outcomes
Authors: Gardner Kirby P. , Aldakkak Mohammed , Tang Cha-Mei , Tsai Susan , Adams Daniel L. 
Published: March 2021

AbstractPancreatic cancer (PC) is notoriously difficult to diagnosis and properly stage resulting in incorrect primary treatment. Diagnostic and prognostic biomarkers are desperately needed to more accurately stage patients and select proper treatments. Recently, a newly discovered circulating stromal cell, i.e. cancer associated macrophage-like cell (CAML), was found to accurately identify solid cancers and predict for worse prognosis. In this pilot study, blood samples were procured from 63 PC patients prior to start of therapeutic intent. CAMLs were found in 95% of samples tested, with ≥12 CAMLs/7.5 mL and ≥50 µm CAMLs both predicting for advanced pathological stage and progression free survival. These data suggest that CAML assessment prior to treatment of PC predicts patients with under-staged disease and with more aggressive PC less likely to respond to standard of care treatment.
Immune microenvironment characterisation and dynamics during anti-HER2-based neoadjuvant treatment in HER2-positive breast cancer
Authors: Griguolo G. , Serna G. , Pascual T. , Fasani R. , Guardia X. , Chic N. , Paré L. , Pernas S. , Muñoz M. , Oliveira M. , Vidal M. , Llombart-Cussac A. , Cortés J. , Galván P. , Bermejo B. , Martínez N. , López R. , Morales S. , Garau I. , Manso L. , Alarcón J. , Martínez E. , Villagrasa P. , Prat A. , Nuciforo P. 
Published: March 2021

AbstractDespite their recognised role in HER2-positive (HER2+) breast cancer (BC), the composition, localisation and functional orientation of immune cells within tumour microenvironment, as well as its dynamics during anti-HER2 treatment, is largely unknown. We here investigate changes in tumour-immune contexture, as assessed by stromal tumour-infiltrating lymphocytes (sTILs) and by multiplexed spatial cellular phenotyping, during treatment with lapatinib-trastuzumab in HER2+ BC patients (PAMELA trial). Moreover, we evaluate the relationship of tumour-immune contexture with hormone receptor status, intrinsic subtype and immune-related gene expression. sTIL levels increase after 2 weeks of HER2 blockade in HR-negative disease and HER2-enriched subtype. This is linked to a concomitant increase in cell density of all four immune subpopulations (CD3+, CD4+, CD8+, Foxp3+). Moreover, immune contexture analysis showed that immune cells spatially interacting with tumour cells have the strongest association with response to anti-HER2 treatment. Subsequently, sTILs consistently decrease at the surgery in patients achieving pathologic complete response, whereas most residual tumours at surgery remain inflamed, possibly reflecting a progressive loss of function of T cells. Understanding the features of the resulting tumour immunosuppressive microenvironment has crucial implications for the design of new strategies to de-escalate or escalate systemic therapy in early-stage HER2+ BC.
Controllable potential barrier for multiple negative-differential-transconductance and its application to multi-valued logic computing
Authors: Seo Seunghwan , Koo Jiwan , Choi Jae-Woong , Heo Keun , Andreev Maksim , Lee Je-Jun , Lee Ju-Hee , Cho Jeong-Ick , Kim Hyeongjun , Yoo Gwangwe , Kang Dong-Ho , Shim Jaewoo , Park Jin-Hong 
Published: March 2021

AbstractVarious studies on multi-valued-logic (MVL) computing, which utilizes more than two logic states, have recently been resumed owing to the demand for greater power saving in the current logic technologies. In particular, unlike old-fashioned researches, extensive efforts have been focused on implementing single devices with multiple threshold voltages via a negative-differential current change phenomenon. In this work, we report a multiple negative-differential-transconductance (NDT) phenomenon, which is achieved through the control of partial gate potential and light power/wavelength in a van-der-Waals (vdW) multi-channel phototransistor. The partial gating formed a controllable potential barrier/well in the vdW channel, enabling control over the collection of carriers and eventually inducing the NDT phenomenon. Especially, the strategy shining lights with different powers/wavelengths facilitated the precise NDT control and the realization of the multiple NDT phenomenon. Finally, the usability of this multiple NDT device as a core device of MVL arithmetic circuits such as MVL inverters/NAND/NOR gates is demonstrated.
The potential of artificial intelligence to improve patient safety: a scoping review
Authors: Bates David W. , Levine David , Syrowatka Ania , Kuznetsova Masha , Craig Kelly Jean Thomas , Rui Angela , Jackson Gretchen Purcell , Rhee Kyu 
Published: March 2021

AbstractArtificial intelligence (AI) represents a valuable tool that could be used to improve the safety of care. Major adverse events in healthcare include: healthcare-associated infections, adverse drug events, venous thromboembolism, surgical complications, pressure ulcers, falls, decompensation, and diagnostic errors. The objective of this scoping review was to summarize the relevant literature and evaluate the potential of AI to improve patient safety in these eight harm domains. A structured search was used to query MEDLINE for relevant articles. The scoping review identified studies that described the application of AI for prediction, prevention, or early detection of adverse events in each of the harm domains. The AI literature was narratively synthesized for each domain, and findings were considered in the context of incidence, cost, and preventability to make projections about the likelihood of AI improving safety. Three-hundred and ninety-two studies were included in the scoping review. The literature provided numerous examples of how AI has been applied within each of the eight harm domains using various techniques. The most common novel data were collected using different types of sensing technologies: vital sign monitoring, wearables, pressure sensors, and computer vision. There are significant opportunities to leverage AI and novel data sources to reduce the frequency of harm across all domains. We expect AI to have the greatest impact in areas where current strategies are not effective, and integration and complex analysis of novel, unstructured data are necessary to make accurate predictions; this applies specifically to adverse drug events, decompensation, and diagnostic errors.
Lin28, a major translation reprogramming factor, gains access to YB-1-packaged mRNA through its cold-shock domain
Authors: Samsonova Anastasiia , El Hage Krystel , Desforges Bénédicte , Joshi Vandana , Clément Marie-Jeanne , Lambert Guillaume , Henrie Hélène , Babault Nicolas , Craveur Pierrick , Maroun Rachid C. , Steiner Emilie , Bouhss Ahmed , Maucuer Alexandre , Lyabin Dmitry N. , Ovchinnikov Lev P. , Hamon Loic , Pastré David 
Published: March 2021

AbstractThe RNA-binding protein Lin28 (Lin28a) is an important pluripotency factor that reprograms translation and promotes cancer progression. Although Lin28 blocks let-7 microRNA maturation, Lin28 also binds to a large set of cytoplasmic mRNAs directly. However, how Lin28 regulates the processing of many mRNAs to reprogram global translation remains unknown. We show here, using a structural and cellular approach, a mixing of Lin28 with YB-1 (YBX1) in the presence of mRNA owing to their cold-shock domain, a conserved β-barrel structure that binds to ssRNA cooperatively. In contrast, the other RNA binding-proteins without cold-shock domains tested, HuR, G3BP-1, FUS and LARP-6, did not mix with YB-1. Given that YB-1 is the core component of dormant mRNPs, a model in which Lin28 gains access to mRNPs through its co-association with YB-1 to mRNA may provide a means for Lin28 to reprogram translation. We anticipate that the translational plasticity provided by mRNPs may contribute to Lin28 functions in development and adaptation of cancer cells to an adverse environment.
Myopathy associated LDB3 mutation causes Z-disc disassembly and protein aggregation through PKCα and TSC2-mTOR downregulation
Authors: Pathak Pankaj , Blech-Hermoni Yotam , Subedi Kalpana , Mpamugo Jessica , Obeng-Nyarko Charissa , Ohman Rachel , Molloy Ilda , Kates Malcolm , Hale Jessica , Stauffer Stacey , Sharan Shyam K. , Mankodi Ami 
Published: March 2021

AbstractMechanical stress induced by contractions constantly threatens the integrity of muscle Z-disc, a crucial force-bearing structure in striated muscle. The PDZ-LIM proteins have been proposed to function as adaptors in transducing mechanical signals to preserve the Z-disc structure, however the underlying mechanisms remain poorly understood. Here, we show that LDB3, a well-characterized striated muscle PDZ-LIM protein, modulates mechanical stress signaling through interactions with the mechanosensing domain in filamin C, its chaperone HSPA8, and PKCα in the Z-disc of skeletal muscle. Studies of Ldb3Ala165Val/+ mice indicate that the myopathy-associated LDB3 p.Ala165Val mutation triggers early aggregation of filamin C and its chaperones at muscle Z-disc before aggregation of the mutant protein. The mutation causes protein aggregation and eventually Z-disc myofibrillar disruption by impairing PKCα and TSC2-mTOR, two important signaling pathways regulating protein stability and disposal of damaged cytoskeletal components at a major mechanosensor hub in the Z-disc of skeletal muscle.
Development of a functional salivary gland tissue chip with potential for high-content drug screening
Authors: Song Yuanhui , Uchida Hitoshi , Sharipol Azmeer , Piraino Lindsay , Mereness Jared A. , Ingalls Matthew H. , Rebhahn Jonathan , Newlands Shawn D. , DeLouise Lisa A. , Ovitt Catherine E. , Benoit Danielle S. W. 
Published: March 2021

AbstractRadiation therapy for head and neck cancers causes salivary gland dysfunction leading to permanent xerostomia. Limited progress in the discovery of new therapeutic strategies is attributed to the lack of in vitro models that mimic salivary gland function and allow high-throughput drug screening. We address this limitation by combining engineered extracellular matrices with microbubble (MB) array technology to develop functional tissue mimetics for mouse and human salivary glands. We demonstrate that mouse and human salivary tissues encapsulated within matrix metalloproteinase-degradable poly(ethylene glycol) hydrogels formed in MB arrays are viable, express key salivary gland markers, and exhibit polarized localization of functional proteins. The salivary gland mimetics (SGm) respond to calcium signaling agonists and secrete salivary proteins. SGm were then used to evaluate radiosensitivity and mitigation of radiation damage using a radioprotective compound. Altogether, SGm exhibit phenotypic and functional parameters of salivary glands, and provide an enabling technology for high-content/throughput drug testing.
Exploration of natural red-shifted rhodopsins using a machine learning-based Bayesian experimental design
Authors: Inoue Keiichi , Karasuyama Masayuki , Nakamura Ryoko , Konno Masae , Yamada Daichi , Mannen Kentaro , Nagata Takashi , Inatsu Yu , Yawo Hiromu , Yura Kei , Béjà Oded , Kandori Hideki , Takeuchi Ichiro 
Published: March 2021

AbstractMicrobial rhodopsins are photoreceptive membrane proteins, which are used as molecular tools in optogenetics. Here, a machine learning (ML)-based experimental design method is introduced for screening rhodopsins that are likely to be red-shifted from representative rhodopsins in the same subfamily. Among 3,022 ion-pumping rhodopsins that were suggested by a protein BLAST search in several protein databases, the ML-based method selected 65 candidate rhodopsins. The wavelengths of 39 of them were able to be experimentally determined by expressing proteins with theEscherichia colisystem, and 32 (82%,p = 7.025 × 10−5) actually showed red-shift gains. In addition, four showed red-shift gains >20 nm, and two were found to have desirable ion-transporting properties, indicating that they would be potentially useful in optogenetics. These findings suggest that data-driven ML-based approaches play effective roles in the experimental design of rhodopsin and other photobiological studies. (141/150 words).
Cancer genome datamining and functional genetic analysis implicate mechanisms of ATM/ATR dysfunction underpinning carcinogenesis
Authors: Waskiewicz Erik , Vasiliou Michalis , Corcoles-Saez Isaac , Cha Rita S. 
Published: March 2021

AbstractATM and ATR are conserved regulators of the DNA damage response linked to cancer. Comprehensive DNA sequencing efforts identified ~4,000 cancer-associated mutations in ATM/ATR; however, their cancer implications remain largely unknown. To gain insights, we identify functionally important conserved residues in ATM, ATR and budding yeast Mec1ATR via cancer genome datamining and a functional genetic analysis, respectively. Surprisingly, only a small fraction of the critical residues is in the active site of the respective enzyme complexes, implying that loss of the intrinsic kinase activity is infrequent in carcinogenesis. A number of residues are solvent accessible, suggestive of their involvement in interacting with a protein-partner(s). The majority, buried inside the respective enzyme complexes, might play a structural or regulatory role. Together, these findings identify evolutionarily conserved ATM, ATR, and Mec1ATR residues involved in diverse aspects of the enzyme function and provide fresh insights into the elusive genotype-phenotype relationships in ATM/ATR and their cancer-associated variants.
Wound-inducible ANAC071 and ANAC096 transcription factors promote cambial cell formation in incised Arabidopsis flowering stems
Authors: Matsuoka Keita , Sato Ryosuke , Matsukura Yuki , Kawajiri Yoshiki , Iino Hiromi , Nozawa Naoyuki , Shibata Kyomi , Kondo Yuki , Satoh Shinobu , Asahina Masashi 
Published: March 2021

AbstractANAC071 and its homolog ANAC096 are plant-specific transcription factors required for the initiation of cell division during wound healing in incised Arabidopsis flowering stems and Arabidopsis hypocotyl grafts; however, the mechanism remains mostly unknown. In this study, we showed that wound-induced cambium formation involved cell proliferation and the promoter activity of TDR/PXY (cambium-related gene) in the incised stem. Prior to the wound-induced cambium formation, both ANAC071 and ANAC096 were expressed at these sites. anac-multiple mutants significantly decreased wound-induced cambium formation in the incised stems and suppressed the conversion from mesophyll cells to cambial cells in an ectopic vascular cell induction culture system (VISUAL). Our results suggest that ANAC071 and ANAC096 are redundantly involved in the process of “cambialization”, the conversion from differentiated cells to cambial cells, and these cambium-like cells proliferate and provide cells in wound tissue during the tissue-reunion process.
Monopole matter from magnetoelastic coupling in the Ising pyrochlore
Authors: Slobinsky D. , Pili L. , Baglietto G. , Grigera S. A. , Borzi R. A. 
Published: March 2021

AbstractIsing models on a pyrochlore oxide lattice have become associated with spin ice materials and magnetic monopoles. Ever more often, effects connecting magnetic and elastic degrees of freedom are reported on these and other related frustrated materials. Here we extend a spin-ice Hamiltonian to include coupling between spins and the O−2 ions mediating superexchange; we call it the magnetoelastic spin ice model (MeSI). There has been a long search for a model in which monopoles would spontaneously become the building blocks of new ground-states: the MeSI Hamiltonian is such a model. In spite of its simplicity and classical approach, it describes the double-layered monopole crystal observed in Tb2Ti2O7. Additionally, the dipolar electric moment of single monopoles emerges as a probe for magnetism. As an example we show that some Coulomb phases could, in principle, be detected through pinch points associated with O−2-ion displacements.
Evolution of aseismic slip rate along plate boundary faults before and after megathrust earthquakes
Authors: Igarashi Toshihiro , Kato Aitaro 
Published: March 2021

AbstractSimilar earthquakes that occur in approximately the same location have the potential to reveal the spatio-temporal changes in aseismic slip along plate boundaries. Here we identify similar earthquakes with moderate magnitudes that occurred worldwide between 1989 and 2016 by using seismograms recorded by the Japanese dense seismic network. The slip rate along the plate boundaries estimated from similar earthquakes increased rapidly followingM > 8 megathrust ruptures and then gradually decayed over periods of ~10 years, which correlates with after-slip progressing around the source areas. More than 30 years after large megathrust earthquakes, the slip rate begins to show a gradual increase. This gradual increase in slip rate after the decay may be due to an increase in stress levels that accumulate during tectonic loading. The spatio-temporal characteristics of inter-plate aseismic slip can be used to provide a valuable framework for understanding the long-term evolution of slip-rate during megathrust earthquake cycles.
Past megadroughts in central Europe were longer, more severe and less warm than modern droughts
Authors: Ionita M. , Dima M. , Nagavciuc V. , Scholz P. , Lohmann G. 
Published: March 2021

AbstractMegadroughts are notable manifestations of the American Southwest, but not so much of the European climate. By using long-term hydrological and meteorological observations, as well as paleoclimate reconstructions, here we show that central Europe has experienced much longer and severe droughts during the Spörer Minimum (~AD 1400–1480) and Dalton Minimum (~AD 1770–1840), than the ones observed during the 21st century. These two megadroughts appear to be linked with a cold state of the North Atlantic Ocean and enhanced winter atmospheric blocking activity over the British Isles and western part of Europe, concurrent with reduced solar forcing and explosive volcanism. Moreover, we show that the recent drought events (e.g., 2003, 2015, and 2018), are within the range of natural variability and they are not unprecedented over the last millennium.
Temperature and salinity extremes from 2014-2019 in the California Current System and its source waters
Authors: Ren Alice S. , Rudnick Daniel L. 
Published: March 2021

AbstractThe California Current System in the eastern North Pacific Ocean has experienced record high temperatures since the marine heatwave of 2014-2016. Here we show, through a compilation of data from shipboard hydrography, ocean gliders, and the Argo floats, that a high-salinity anomaly affected the California Current System from 2017-2019 in addition to the anomalously high temperatures. The salinity anomaly formed in 2015 in the North Pacific Subtropical Gyre and was subsequently advected into the California Current System, in a generation mechanism different from the events leading to the marine heatwaves of 2013/2014 and 2019 in the North Pacific. The salinity anomaly was unique in at least 16 years with an annual mean deviation from the long-term average greater than 0.2 and anomalies greater than 0.7 observed offshore. Our results imply that different source waters were found in the California Current from 2017-2019, with the near-surface California Current salinity rivaling that of the California Undercurrent.