bluuebunny/crossref_metadata_2025_split huggingface dataset:
The evolution of RET inhibitor resistance in RET-driven lung and thyroid cancers
Authors: Rosen Ezra Y. , Won Helen H. , Zheng Youyun , Cocco Emiliano , Selcuklu Duygu , Gong Yixiao , Friedman Noah D. , de Bruijn Ino , Sumer Onur , Bielski Craig M. , Savin Casey , Bourque Caitlin , Falcon Christina , Clarke Nikeysha , Jing Xiaohong , Meng Fanli , Zimel Catherine , Shifman Sophie , Kittane Srushti , Wu Fan , Ladanyi Marc , Ebata Kevin , Kherani Jennifer , Brandhuber Barbara J. , Fagin James , Sherman Eric J. , Rekhtman Natasha , Berger Michael F. , Scaltriti Maurizio , Hyman David M. , Taylor Barry S. , Drilon Alexander 
Published: March 2022

AbstractThe efficacy of the highly selective RET inhibitor selpercatinib is now established in RET-driven cancers, and we sought to characterize the molecular determinants of response and resistance. We find that the pre-treatment genomic landscape does not shape the variability of treatment response except for rare instances of RAS-mediated primary resistance. By contrast, acquired selpercatinib resistance is driven by MAPK pathway reactivation by one of two distinct routes. In some patients, on- and off-target pathway reactivation via secondary RET solvent front mutations or MET amplifications are evident. In other patients, rare RET-wildtype tumor cell populations driven by an alternative mitogenic driver are selected for by treatment. Multiple distinct mechanisms are often observed in the same patient, suggesting polyclonal resistance may be common. Consequently, sequential RET-directed therapy may require combination treatment with inhibitors targeting alternative MAPK effectors, emphasizing the need for prospective characterization of selpercatinib-treated tumors at the time of monotherapy progression.
Characterization of protein unfolding by fast cross-linking mass spectrometry using di-ortho-phthalaldehyde cross-linkers
Authors: Wang Jian-Hua , Tang Yu-Liang , Gong Zhou , Jain Rohit , Xiao Fan , Zhou Yu , Tan Dan , Li Qiang , Huang Niu , Liu Shu-Qun , Ye Keqiong , Tang Chun , Dong Meng-Qiu , Lei Xiaoguang 
Published: March 2022

AbstractChemical cross-linking of proteins coupled with mass spectrometry is widely used in protein structural analysis. In this study we develop a class of non-hydrolyzable amine-selective di-ortho-phthalaldehyde (DOPA) cross-linkers, one of which is called DOPA2. Cross-linking of proteins with DOPA2 is 60–120 times faster than that with the N-hydroxysuccinimide ester cross-linker DSS. Compared with DSS cross-links, DOPA2 cross-links show better agreement with the crystal structures of tested proteins. More importantly, DOPA2 has unique advantages when working at low pH, low temperature, or in the presence of denaturants. Using staphylococcal nuclease, bovine serum albumin, and bovine pancreatic ribonuclease A, we demonstrate that DOPA2 cross-linking provides abundant spatial information about the conformations of progressively denatured forms of these proteins. Furthermore, DOPA2 cross-linking allows time-course analysis of protein conformational changes during denaturant-induced unfolding.
Hydrogen spillover assisted by oxygenate molecules over nonreducible oxides
Authors: Tan Mingwu , Yang Yanling , Yang Ying , Chen Jiali , Zhang Zhaoxia , Fu Gang , Lin Jingdong , Wan Shaolong , Wang Shuai , Wang Yong 
Published: March 2022

AbstractSpontaneous migration of atomic hydrogen species from metal particles to the surface of their support, known as hydrogen spillover, has been claimed to play a major role in catalytic processes involving hydrogen. While this phenomenon is well established on reducible oxide supports, its realization on much more commonly used non-reducible oxides is still challenged. Here we present a general strategy to enable effective hydrogen spillover over non-reducible SiO2 with aid of gaseous organic molecules containing a carbonyl group. By using hierarchically-porous-SiO2-supported bimetallic Pt-Fe catalysts with Pt nanoparticles exclusively deposited into the micropores, we demonstrate that activated hydrogen species generated on the Pt sites within the micropores can be readily transported by these oxygenate molecules to Fe sites located in macropores, leading to significantly accelerated hydrodeoxygenation rates on the latter sites. This finding provides a molecule-assisted approach to the rational design and optimization of multifunctional heterogeneous catalysts, reminiscent of the role of molecular coenzymes in bio-catalysis.
A point mutation in HIV-1 integrase redirects proviral integration into centromeric repeats
Authors: Winans Shelby , Yu Hyun Jae , de los Santos Kenia , Wang Gary Z. , KewalRamani Vineet N. , Goff Stephen P. 
Published: March 2022

AbstractRetroviruses utilize the viral integrase (IN) protein to integrate a DNA copy of their genome into host chromosomal DNA. HIV-1 integration sites are highly biased towards actively transcribed genes, likely mediated by binding of the IN protein to specific host factors, particularly LEDGF, located at these gene regions. We here report a substantial redirection of integration site distribution induced by a single point mutation in HIV-1 IN. Viruses carrying the K258R IN mutation exhibit a high frequency of integrations into centromeric alpha satellite repeat sequences, as assessed by deep sequencing, a more than 10-fold increase over wild-type. Quantitative PCR and in situ immunofluorescence assays confirm this bias of the K258R mutant virus for integration into centromeric DNA. Immunoprecipitation studies identify host factors binding to IN that may account for the observed bias for integration into centromeres. Centromeric integration events are known to be enriched in the latent reservoir of infected memory T cells, as well as in elite controllers who limit viral replication without intervention. The K258R point mutation in HIV-1 IN is also present in databases of latent proviruses found in patients, and may reflect an unappreciated aspect of the establishment of viral latency.
N7-methylguanosine tRNA modification promotes esophageal squamous cell carcinoma tumorigenesis via the RPTOR/ULK1/autophagy axis
Authors: Han Hui , Yang Chunlong , Ma Jieyi , Zhang Shuishen , Zheng Siyi , Ling Rongsong , Sun Kaiyu , Guo Siyao , Huang Boxuan , Liang Yu , Wang Lu , Chen Shuang , Wang Zhaoyu , Wei Wei , Huang Ying , Peng Hao , Jiang Yi-Zhou , Choe Junho , Lin Shuibin 
Published: March 2022

AbstractMis-regulated RNA modifications promote the processing and translation of oncogenic mRNAs to facilitate cancer progression, while the molecular mechanisms remain unclear. Here we reveal that tRNA m7G methyltransferase complex proteins METTL1 and WDR4 are significantly up-regulated in esophageal squamous cell carcinoma (ESCC) tissues and associated with poor ESCC prognosis. In addition, METTL1 and WDR4 promote ESCC progression via the tRNA m7G methyltransferase activity in vitro and in vivo. Mechanistically, METTL1 or WDR4 knockdown leads to decreased expression of m7G-modified tRNAs and reduces the translation of a subset of oncogenic transcripts enriched in RPTOR/ULK1/autophagy pathway. Furthermore, ESCC models using Mettl1 conditional knockout and knockin mice uncover the essential function of METTL1 in promoting ESCC tumorigenesis in vivo. Our study demonstrates the important oncogenic function of mis-regulated tRNA m7G modification in ESCC, and suggest that targeting METTL1 and its downstream signaling axis could be a promising therapeutic target for ESCC treatment.
S100A9-CXCL12 activation in BRCA1-mutant breast cancer promotes an immunosuppressive microenvironment associated with resistance to immunotherapy
Authors: Li Jianjie , Shu Xiaodong , Xu Jun , Su Sek Man , Chan Un In , Mo Lihua , Liu Jianlin , Zhang Xin , Adhav Ragini , Chen Qiang , Wang Yuqing , An Tingting , Zhang Xu , Lyu Xueying , Li Xiaoling , Lei Josh Haipeng , Miao Kai , Sun Heng , Xing Fuqiang , Zhang Aiping , Deng Chuxia , Xu Xiaoling 
Published: March 2022

AbstractImmune checkpoint blockade (ICB) is a powerful approach for cancer therapy although good responses are only observed in a fraction of cancer patients. Breast cancers caused by deficiency of breast cancer-associated gene 1 (BRCA1) do not have an improved response to the treatment. To investigate this, here we analyze BRCA1 mutant mammary tissues and tumors derived from both BRCA1 mutant mouse models and human xenograft models to identify intrinsic determinants governing tumor progression and ICB responses. We show that BRCA1 deficiency activates S100A9-CXCL12 signaling for cancer progression and triggers the expansion and accumulation of myeloid-derived suppressor cells (MDSCs), creating a tumor-permissive microenvironment and rendering cancers insensitive to ICB. These oncogenic actions can be effectively suppressed by the combinatory treatment of inhibitors for S100A9-CXCL12 signaling with αPD-1 antibody. This study provides a selective strategy for effective immunotherapy in patients with elevated S100A9 and/or CXCL12 protein levels.
CrysXPP: An explainable property predictor for crystalline materials
Authors: Das Kishalay , Samanta Bidisha , Goyal Pawan , Lee Seung-Cheol , Bhattacharjee Satadeep , Ganguly Niloy 
Published: March 2022

AbstractWe present a deep-learning framework, CrysXPP, to allow rapid and accurate prediction of electronic, magnetic, and elastic properties of a wide range of materials. CrysXPP lowers the need for large property tagged datasets by intelligently designing an autoencoder, CrysAE. The important structural and chemical properties captured by CrysAE from a large amount of available crystal graphs data helped in achieving low prediction errors. Moreover, we design a feature selector that helps to interpret the model’s prediction. Most notably, when given a small amount of experimental data, CrysXPP is consistently able to outperform conventional DFT. A detailed ablation study establishes the importance of different design steps. We release the large pre-trained model CrysAE. We believe by fine-tuning the model with a small amount of property-tagged data, researchers can achieve superior performance on various applications with a restricted data source.
Antioxidant high-conductivity copper paste for low-cost flexible printed electronics
Authors: Hong Shuqing , Liu Chimin , Hao Shuqiang , Fu Wenxing , Peng Jian , Wu Binghui , Zheng Nanfeng 
Published: March 2022

AbstractThe flexible printed electronics (e.g., wearable devices, roll-up displays, heating circuits, radio frequency identification (RFID) tags) calls for high-conductivity and low-cost materials, particularly for copper pastes. It is still a big challenge to develop reliable copper pastes for both antioxidant and high-conductivity flexible printed films and lines. In this work, an antioxidant copper paste was achieved using copper microflakes with surface passivation by formate ions and thiols, with high conductivity of 13400 S cm−1 (the same order of magnitude of silver pastes, 1.8–2.5 × 104 S cm−1). The universal applications of as-prepared copper paste in flexible printed electronics (e.g., electromagnetic interference (EMI) shielding films, anti-fog films, and RFID tags) via screen printing and curing at 170 °C under ambient atmosphere were demonstrated. The as-printed electronics showed high performance in flexibility, stability, and reliability. This work shows the great potential of anti-oxidation copper pastes in low-cost flexible printed electronics for commercial usage.
Molecular ferroelectric/semiconductor interfacial memristors for artificial synapses
Authors: Cai Yichen , Zhang Jialong , Yan Mengge , Jiang Yizhou , Jawad Husnain , Tian Bobo , Wang Wenchong , Zhan Yiqiang , Qin Yajie , Xiong Shisheng , Cong Chunxiao , Qiu Zhi-Jun , Duan Chungang , Liu Ran , Hu Laigui 
Published: March 2022

AbstractWith the burgeoning developments in artificial intelligence, hardware implementation of artificial neural network is also gaining pace. In this pursuit, ferroelectric devices (i.e., tunneling junctions and transistors) with voltage thresholds were recently proposed as suitable candidates. However, their development is hindered by the inherent integration issues of inorganic ferroelectrics, as well as poor properties of conventional organic ferroelectrics. In contrast to the conventional ferroelectric synapses, here we demonstrated a two-terminal ferroelectric synaptic device using a molecular ferroelectric (MF)/semiconductor interface. The interfacial resistance can be tuned via the polarization-controlled blocking effect of the semiconductor, owing to the high ferroelectricity and field amplification effect of the MF. Typical synaptic features including spike timing-dependent plasticity are substantiated. The introduction of the semiconductor also enables the attributes of optoelectronic synapse and in-sensor computing with high image recognition accuracies. Such interfaces may pave the way for the hardware implementation of multifunctional neuromorphic devices.
The emerging postural instability phenotype in idiopathic Parkinson disease
Authors: Skidmore Frank M. , Monroe William S. , Hurt Christopher P. , Nicholas Anthony P. , Gerstenecker Adam , Anthony Thomas , Jololian Leon , Cutter Gary , Bashir Adil , Denny Thomas , Standaert David , Disbrow Elizabeth A. 
Published: March 2022

AbstractIdentification of individuals at high risk for rapid progression of motor and cognitive signs in Parkinson disease (PD) is clinically significant. Postural instability and gait dysfunction (PIGD) are associated with greater motor and cognitive deterioration. We examined the relationship between baseline clinical factors and the development of postural instability using 5-year longitudinal de-novo idiopathic data (n = 301) from the Parkinson’s Progressive Markers Initiative (PPMI). Logistic regression analysis revealed baseline features associated with future postural instability, and we designated this cohort the emerging postural instability (ePI) phenotype. We evaluated the resulting ePI phenotype rating scale validity in two held-out populations which showed a significantly higher risk of postural instability. Emerging PI phenotype was identified before onset of postural instability in 289 of 301 paired comparisons, with a median progression time of 972 days. Baseline cognitive performance was similar but declined more rapidly in ePI phenotype. We provide an ePI phenotype rating scale (ePIRS) for evaluation of individual risk at baseline for progression to postural instability.
Amantadine delayed release/extended release capsules significantly reduce OFF time in Parkinson’s disease
Authors: Hauser Robert A. , Lytle Judy , Formella Andrea E. , Tanner Caroline M. 
Published: March 2022

AbstractMaintaining consistent levodopa benefits while simultaneously controlling dyskinesia can be difficult. Recently, an amantadine delayed release/extended release (DR/ER) formulation (Gocovri®) indicated for dyskinesia received additional FDA approval as an adjunct to levodopa for the treatment of OFF episodes. We evaluated OFF time reductions with amantadine-DR/ER in a pooled analysis of two phase III amantadine-DR/ER trials (NCT02136914, NCT02274766) followed by a 2-year open-label extension trial (NCT02202551). OFF outcomes were analyzed for the mITT population, as well as stratified by baseline OFF time of ≥2.5 h/day or <2.5 h/day. At Week 12, mean placebo-subtracted treatment difference in OFF time was −1.00 [−1.57, −0.44] h in the mITT population (n = 196), −1.2 [−2.08, −0.32] h in the ≥2.5 h subgroup (n = 102) and −0.77 [−1.49, −0.06] in the <2.5 h subgroup (n = 94). Amantadine-DR/ER-treated participants showed reduced MDS-UPDRS Part IV motor fluctuation subscores by week 2 that were maintained below baseline to Week 100.
Reconstructing social mixing patterns via weighted contact matrices from online and representative surveys
Authors: Koltai Júlia , Vásárhelyi Orsolya , Röst Gergely , Karsai Márton 
Published: March 2022

AbstractThe unprecedented behavioural responses of societies have been evidently shaping the COVID-19 pandemic, yet it is a significant challenge to accurately monitor the continuously changing social mixing patterns in real-time. Contact matrices, usually stratified by age, summarise interaction motifs efficiently, but their collection relies on conventional representative survey techniques, which are expensive and slow to obtain. Here we report a data collection effort involving over $$2.3\%$$

2.3
%

of the Hungarian population to simultaneously record contact matrices through a longitudinal online and sequence of representative phone surveys. To correct non-representative biases characterising the online data, by using census data and the representative samples we develop a reconstruction method to provide a scalable, cheap, and flexible way to dynamically obtain closer-to-representative contact matrices. Our results demonstrate that although some conventional socio-demographic characters correlate significantly with the change of contact numbers, the strongest predictors can be collected only via surveys techniques and combined with census data for the best reconstruction performance. We demonstrate the potential of combined online-offline data collections to understand the changing behavioural responses determining the future evolution of the outbreak, and to inform epidemic models with crucial data.
Identification of hub genes and transcription factors in patients with rheumatoid arthritis complicated with atherosclerosis
Authors: Xiao Lu , Yang Zhou , Lin Shudian 
Published: March 2022

AbstractThe aim of this study was to explore the overlapping key genes, pathway networks and transcription factors (TFs) related to the pathogenesis of rheumatoid arthritis (RA) and atherosclerosis. The gene expression profiles of RA and atherosclerosis were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between RA and atherosclerosis were identified. The biological roles of common DEGs were explored through enrichment analysis. Hub genes were identified using protein–protein interaction networks. TFs were predicted using Transcriptional Regulatory Relationships Unraveled by Sentence Based Text Mining (TRRUST) database. The hub genes and TFs were validated with other datasets. The networks between TFs and hub genes were constructed by CytoScape software. A total of 131 DEGs (all upregulated) were identified. Functional enrichment analyses indicated that DEGs were mostly enriched in leukocyte migration, neutrophil activation, and phagocytosis. CytoScape demonstrated 12 hub genes and one gene cluster module. Four of the 12 hub genes (CSF1R, CD86, PTPRC, and CD53) were validated by other datasets. TRRUST predicted two TFs, including Spi-1 proto-oncogene (SPI1) and RUNX family transcription factor 1(RUNX1). The expression of RUNX1 was validated with another dataset. Our study explored the common pathogenesis of RA and atherosclerosis. These results may guide future experimental research and clinical transformation.
Response of tomatoes primed by mycorrhizal colonization to virulent and avirulent bacterial pathogens
Authors: Fujita Moeka , Kusajima Miyuki , Fukagawa Masatomo , Okumura Yasuko , Nakajima Masami , Akiyama Kohki , Asami Tadao , Yoneyama Koichi , Kato Hisaharu , Nakashita Hideo 
Published: March 2022

AbstractMost plants interact with arbuscular mycorrhizal fungi, which enhance disease resistance in the host plant. Because the effects of resistance against bacterial pathogens are poorly understood, we investigated the effects of mycorrhizal colonization on virulent and avirulent pathogens using phytopathological and molecular biology techniques. Tomato plants colonized by Gigaspora margarita acquired resistance not only against the fungal pathogen, Botrytis cinerea, but also against a virulent bacterial pathogen, Pseudomonas syringae pv. tomato DC3000 (Pst). In G. margarita-colonized tomato, salicylic acid (SA)- and jasmonic acid (JA)-related defense genes were expressed more rapidly and strongly compared to those in the control plants when challenged by Pst, indicating that the plant immunity system was primed by mycorrhizal colonization. Gene expression analysis indicated that primed tomato plants responded to the avirulent pathogen, Pseudomonas syringae pv. oryzae, more rapidly and strongly compared to the control plant, where the effect on the JA-mediated signals was stronger than in the case with Pst. We found that the resistance induced by mycorrhizal colonization was effective against both fungal and bacterial pathogens including virulent and avirulent pathogens. Moreover, the activation of both SA- and JA-mediated signaling pathways can be enhanced in the primed plant by mycorrhizal colonization.
Emission from human skin in the sub THz frequency band
Authors: Betzalel Noa , Ben Ishai Paul , Puzenko Alexander , Feldman Yuri 
Published: March 2022

AbstractRecently published Radiometric measurements of human subjects in the frequency range 480–700 GHz, demonstrate the emission of blackbody radiation from the body core, rather than the skin surface. We present a detailed electromagnetic simulation of the dermis and epidermis, taking into account the presence of the sweat duct. This complex structure can be considered as an electromagnetic bio-metamaterial, whereby the layered structure, along with the topology of the sweat duct, reveals a complex interference pattern in the skin. The model is capable of accurately representing the skin greyness factor as a function of frequency and this is confirmed by radiometry of living human skin.
Residual characteristics and safety assessment of the insecticides spiromesifen and chromafenozide in lettuce and perilla
Authors: Sardar Syed Wasim , Byeon Geon Doo , Choi Jeong Yoon , Ham Hun Ju , Ishag Abd Elaziz Sulieman Ahmed , Hur Jang Hyun 
Published: March 2022

AbstractThis study was performed to investigate the residual characteristics, safety assessment, and pre-harvest interval (PHI) of spiromesifen and chromafenozide in lettuce (Latuca sativa L.) and perilla (Perilla frutescens (L.) Britton) leaves. Samples were harvested periodically, extracted using QuEChERS method, and analyzed by LC-MS/MS. Average recoveries of spiromesifen and its metabolite BSN2060-enol and chromafenozide were ranged from 80.6 to 107.9%, with relative standard deviation < 10%. Spiromesifen and cromafenozide initial residues in lettuce were dissipated to 81.45 and 95.52% after 7 days, with half-lives of 2.89 and 1.69 days respectively. Values in perilla leaves were 76.68 and 61.27% after the same period, with half-lives of 4.25 and 6.30 days, respectively. Risk assessment results showed that %ADI (acceptable daily intake) of spiromesifen and chromafenozide was 6.83 and 0.56, in lettuce and 4.60 and 0.25% in perilla leaves, respectively. Theoretical maximum daily intakes of spiromesifen and chromafenozide were 67.49 and 3.43%, respectively, indicating that residues of both compounds pose no considerable health risks to consumers. This study provides data for setting maximum residue limits and PHIs for the safe use of spiromesifen and chromafenozide in lettuce and perilla.