bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polymerase-guided base editing enables in vivo mutagenesis and rapid protein engineering
Authors: Cravens Aaron , Jamil Osman K. , Kong Deze , Sockolosky Jonathan T. , Smolke Christina D. 
Published: March 2021

AbstractRandom mutagenesis is a technique used to generate diversity and engineer biological systems. In vivo random mutagenesis generates diversity directly in a host organism, enabling applications such as lineage tracing, continuous evolution, and protein engineering. Here we describe TRIDENT (TaRgeted In vivo Diversification ENabled by T7 RNAP), a platform for targeted, continual, and inducible diversification at genes of interest at mutation rates one-million fold higher than natural genomic error rates. TRIDENT targets mutagenic enzymes to precise genetic loci by fusion to T7 RNA polymerase, resulting in mutation windows following a mutation targeting T7 promoter. Mutational diversity is tuned by DNA repair factors localized to sites of deaminase-driven mutation, enabling sustained mutation of all four DNA nucleotides at rates greater than 10−4 mutations per bp. We show TRIDENT can be applied to routine in vivo mutagenesis applications by evolving a red-shifted fluorescent protein and drug-resistant mutants of an essential enzyme.
N6-methyladenosine RNA modification suppresses antiviral innate sensing pathways via reshaping double-stranded RNA
Authors: Qiu Weinan , Zhang Qingyang , Zhang Rui , Lu Yangxu , Wang Xin , Tian Huabin , Yang Ying , Gu Zijuan , Gao Yanan , Yang Xin , Cui Guanshen , Sun Baofa , Peng Yanan , Deng Hongyu , Peng Hua , Yang Angang , Yang Yun-Gui , Yang Pengyuan 
Published: March 2021

AbstractDouble-stranded RNA (dsRNA) is a virus-encoded signature capable of triggering intracellular Rig-like receptors (RLR) to activate antiviral signaling, but whether intercellular dsRNA structural reshaping mediated by theN6-methyladenosine (m6A) modification modulates this process remains largely unknown. Here, we show that, in response to infection by the RNA virus Vesicular Stomatitis Virus (VSV), the m6A methyltransferase METTL3 translocates into the cytoplasm to increase m6A modification on virus-derived transcripts and decrease viral dsRNA formation, thereby reducing virus-sensing efficacy by RLRs such as RIG-I and MDA5 and dampening antiviral immune signaling. Meanwhile, the genetic ablation of METTL3 in monocyte or hepatocyte causes enhanced type I IFN expression and accelerates VSV clearance. Our findings thus implicate METTL3-mediated m6A RNA modification on viral RNAs as a negative regulator for innate sensing pathways of dsRNA, and also hint METTL3 as a potential therapeutic target for the modulation of anti-viral immunity.
Quantum spin liquid and cluster Mott insulator phases in the Mo3O8 magnets
Authors: Nikolaev S. A. , Solovyev I. V. , Streltsov S. V. 
Published: March 2021

AbstractWe unveil the microscopic origin of largely debated magnetism in the Mo3O8 quantum systems. Upon considering an extended Hubbard model at 1/6 filling on the anisotropic kagomé lattice formed by the Mo atoms, we argue that its ground state is determined by the competition between kinetic energy and intersite Coulomb interactions, which is controlled by the trimerisation of the kagomé lattice into the Mo3O13 clusters, and the sign of hopping parameters, specifying the electron localisation at such clusters. Based on first-principles calculations, we show that the strong interaction limit reveals a plaquette charge order with unpaired spins at the resonating hexagons that can be realised in LiZn2Mo3O8, and whose origin is solely related to the opposite signs of intracluster and intercluster hoppings, in contrast to all previous scenarios. On the other hand, both Li2InMo3O8 and Li2ScMo3O8 are demonstrated to fall into the weak interaction limit where the electrons are well localised at the Mo3O13 clusters. While the former is found to exhibit long-range antiferromagnetic order, the latter is more likely to reveal short-range order with quantum spin liquid-like excitations. Our results not only reproduce most of the experimentally observed features of the Mo3O8 systems, but will also help to describe various properties in other quantum cluster magnets.
Mutational landscape of multiple primary lung cancers and its correlation with non-intrinsic risk factors
Authors: Izumi Motohiro , Oyanagi Jun , Sawa Kenji , Fukui Mitsuru , Ogawa Koichi , Matsumoto Yoshiya , Tani Yoko , Suzumura Tomohiro , Watanabe Tetsuya , Kaneda Hiroyasu , Mitsuoka Shigeki , Asai Kazuhisa , Ohsawa Masahiko , Yamamoto Nobuyuki , Koh Yasuhiro , Kawaguchi Tomoya 
Published: March 2021

AbstractMultiple primary lung cancers (MPLCs) harbour various genetic profiles among the tumours, even from individuals with same non-intrinsic risk factors. Paired mutational analyses were performed to obtain a census of mutational events in MPLC and assess their relationship with non-intrinsic risk factors. Thirty-eight surgical specimens from 17 patients diagnosed as MPLC were used. Extracted DNAs were sequenced for somatic mutations in 409 cancer-associated genes from a comprehensive cancer panel. We statistically analysed the correlation between each driver mutation frequency and non-intrinsic risk factors using Fisher's exact test, and whether genetic mutations occurred concomitantly or randomly in MPLC using an exact test. Comprehensive genetic analyses suggested different mutation profiles in tumours within the same individuals, with some exceptions. EGFR, KRAS, TP53, or PARP1 mutations were concomitantly detected in some MPLC cases. EGFR mutations were significantly more frequent in never or light smokers and females. Concomitant EGFR or KRAS mutations in MPLCs were significantly more frequent than expected by chance (P = .0023 and .0049, respectively) suggesting a more prominent role of non-intrinsic risk factors in EGFR and KRAS mutations than other mutations, which occurred more randomly. Concomitant EGFR or KRAS mutations were particularly prominent in never or light smokers and males.
Abatacept enhances blood regulatory B cells of rheumatoid arthritis patients to a level that associates with disease remittance
Authors: Alenazy Maha Fahad , Saheb Sharif-Askari Fatemeh , Omair Mohammed A. , El-Wetidy Mohammad S. , Omair Maha A. , Mitwalli Hussam , Al-Muhsen Saleh , Al-Masri Abeer , Hamid Qutayba , Halwani Rabih 
Published: March 2021

AbstractAbatacept, an inhibitor of CD28 mediated T-cell activation, has been shown to be effective in controlling inflammation during rheumatoid arthritis (RA). However, its effects on immune regulatory B and T cells (Bregs and Tregs) has not been fully explored. Thirty-one RA patients treated with abatacept for ≥ 6 months along with 31 RA patients treated with other modalities as well as 30 healthy controls were recruited. Of these 62 RA patient, 49 (79%) were females with a mean age of 54 ± 12 years and disease duration of 10 ± 6 years. The blood levels of Tregs and Bregs and their production of immunosuppressive cytokines, were determined using FACS analysis and Luminex Multiplex assay. Treatment with abatacept significantly enhanced the blood level of IL-35+ IL-10+ Bregs (P = 0.0007). Their levels were higher in the blood of remitted patients (DAS28-CRP < 2.6) compared to the unremitted ones (P = 0.0173), 6 months following abatacept treatment initiation. Moreover, abatacept treatment significantly enhanced the blood levels of LAG3+ conventional and unconventional Tregs of RA patients. This increase in the blood levels of Bregs and Tregs was accompanied with an elevated serum level of IL-35 and IFN-β in abatacept-treated patients. Therefore, Abatacept efficiency to achieve remittance in RA could be attributed, in part, to its ability to enhance immune regulatory cells, especially IL-35+ IL-10+ Bregs.
New species and records of Trichoderma isolated as mycoparasites and endophytes from cultivated and wild coffee in Africa
Authors: del Carmen H. Rodríguez María , Evans Harry C. , de Abreu Lucas M. , de Macedo Davi M. , Ndacnou Miraine K. , Bekele Kifle B. , Barreto Robert W. 
Published: March 2021

AbstractA survey for species of the genus Trichoderma occurring as endophytes of Coffea, and as mycoparasites of coffee rusts (Hemileia), was undertaken in Africa; concentrating on Cameroon and Ethiopia. Ninety-four isolates of Trichoderma were obtained during this study: 76 as endophytes of healthy leaves, stems and berries and, 18 directly from colonized rust pustules. A phylogenetic analysis of all isolates used a combination of three genes: translation elongation factor-1α (tef1), rpb2 and cal for selected isolates. GCPSR criteria were used for the recognition of species; supported by morphological and cultural characters. The results reveal a previously unrecorded diversity of Trichoderma species endophytic in both wild and cultivated Coffea, and mycoparasitic on Hemileia rusts. Sixteen species were delimited, including four novel taxa which are described herein: T. botryosum, T. caeruloviride, T. lentissimum and T. pseudopyramidale. Two of these new species, T. botryosum and T. pseudopyramidale, constituted over 60% of the total isolations, predominantly from wild C. arabica in Ethiopian cloud forest. In sharp contrast, not a single isolate of Trichoderma was obtained using the same isolation protocol during a survey of coffee in four Brazilian states, suggesting the existence of a ‘Trichoderma void’ in the endophyte mycobiota of coffee outside of Africa. The potential use of these African Trichoderma isolates in classical biological control, either as endophytic bodyguards—to protect coffee plants from Hemileia vastatrix, the fungus causing coffee leaf rust (CLR)—or to reduce its impact through mycoparasitism, is discussed, with reference to the on-going CLR crisis in Central America.
Simulation of the Bell inequality violation based on quantum steering concept
Authors: Ruzbehani Mohsen 
Published: March 2021

AbstractViolation of Bell’s inequality in experiments shows that predictions of local realistic models disagree with those of quantum mechanics. However, despite the quantum mechanics formalism, there are debates on how does it happen in nature. In this paper by use of a model of polarizers that obeys the Malus’ law and quantum steering concept, i.e. superluminal influence of the states of entangled pairs to each other, simulation of phenomena is presented. The given model, as it is intended to be, is extremely simple without using mathematical formalism of quantum mechanics. However, the result completely agrees with prediction of quantum mechanics. Although it may seem trivial, this model can be applied to simulate the behavior of other not easy to analytically evaluate effects, such as deficiency of detectors and polarizers, different value of photons in each run and so on. For example, it is demonstrated, when detector efficiency is 83% the S factor of CHSH inequality will be 2, which completely agrees with famous detector efficiency limit calculated analytically. Also, it is shown in one-channel polarizers the polarization of absorbed photons, should change to the perpendicular of polarizer angle, at very end, to have perfect violation of the Bell inequality (2 $$\sqrt 2$$

2

) otherwise maximum violation will be limited to (1.5 $$\sqrt{2}$$

2

).
Synthesis and characterization of Cu(OH)2-NWs-PVA-AC Nano-composite and its use as an efficient adsorbent for removal of methylene blue
Authors: Lakkaboyana Sivarama Krishna , Soontarapa Khantong , Asmel Nabel Kalel , Kumar Vinay , Marella Ravi Kumar , Yuzir Ali , Wan Yaacob Wan Zuhairi 
Published: March 2021

AbstractThe present study focused on the synthesis of copper hydroxide nanowires decorated on activated carbon (Cu(OH)2-NWs-PVA-AC). The obtained Cu(OH)2-NWs-PVA-AC Nano-composite was distinguished by XRD, SEM, EDX, BET, FTIR and XPS respectively. Besides, different variables such as solution pH, and initial dye concentration, contact time, and temperature were performed on the adsorption efficiency of MB in a small batch reactor. Further, the experimental results are analyzed by various kinetic models via PFO, PSO, intra-particle diffusion and Elovich models, and the results revealed that among the kinetic models, PSO shows more suitability. In addition, different adsorption isotherms were applied to the obtained experimental data and found that Langmuir–Freundlich and Langmuir isotherm were best fits with the maximum adsorption capacity of 139.9 and 107.6 mg/g, respectively. The Nano-composite has outstanding MB removal efficiency of 94–98.5% with a span of 10 min. and decent adsorption of about 98.5% at a pH of 10. Thermodynamic constants like Gibbs free energy, entropy, and enthalpy were analyzed from the temperature reliance. The results reveal the adsorption processes are spontaneous and exothermic in nature. The high negative value of ΔG° (− 44.11 to − 48.86 kJ/mol) and a low negative value of ΔH° (− 28.96 kJ/mol) show the feasibility and exothermic nature of the adsorption process. The synthesized dye was found to be an efficient adsorbent for the potential removal of cationic dye (methylene blue) from wastewater within a short time.
Obstructive sleep apnea is associated with impaired renal function in patients with diabetic kidney disease
Authors: Zamarrón Ester , Jaureguizar Ana , García-Sánchez Aldara , Díaz-Cambriles Trinidad , Alonso-Fernández Alberto , Lores Vanesa , Mediano Olga , Rodríguez-Rodríguez Paula , Cabello-Pelegrín Sheila , Morales-Ruíz Enrique , Ramírez-Prieto María T. , Valiente-Díaz María Isabel , Gómez-García Teresa , García-Río Francisco ,   Spanish Sleep Network, Arias-Melgar Beatriz , Barceló-Bennasar Antonia , Barquiel Beatriz , Candel-Pizarro Ana , Casitas Raquel , Costero Olga , De-La-Peña-Bravo Mónica , Díaz-Rubio Ana María , Galera Raúl , Giménez-Carrero María Paloma , Lozano-Alcocer Héctor , Mangas Alberto , Martínez-Cerón Elizabet , Peña-Zarza José Antonio , Rodríguez-Pérez Rocío , Romero-Peralta Sofía , Silgado Laura , Troncoso-Acevedo Fernanda 
Published: March 2021

AbstractObstructive sleep apnea (OSA) is a recognized risk factor for the development of diabetic kidney disease (DKD). Our objectives were to compare the urinary albumin–creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) of patients with DKD according to OSA severity, and to evaluate the contribution of sleep parameters to their renal function. In a multicenter, observational, cross-sectional study, 214 patients with DKD were recruited. After a sleep study, UACR and eGFR were measured, as well as serum creatinine, fasting glucose, glycated hemoglobin, insulin resistance, lipid profile and C-reactive protein. UACR was higher in severe OSA patients (920 ± 1053 mg/g) than in moderate (195 ± 232 mg/g, p < 0.001) or mild OSA/non-OSA subjects (119 ± 186 mg/g, p < 0.001). At the same time, eGFR showed an OSA severity-dependent reduction (48 ± 23 vs. 59 ± 21 vs. 73 ± 19 ml/min per 1.73 m2, respectively; p < 0.001). Apnea–hypopnea index (AHI and desaturation index (ODI) were identified as independent predictors for UACR and eGFR, respectively. Therefore, in patients with DKD under optimized treatment, severe OSA is associated with a higher UACR and a lower eGFR, reflecting an additional contribution to the impairment of their renal function, although no causality can be inferred.
Four-decade trends in lymph node status of patients with vulvar squamous cell carcinoma in northern Italy
Authors: Preti Mario , Bucchi Lauro , Micheletti Leonardo , Privitera Silvana , Corazza Monica , Cosma Stefano , Gallio Niccolò , Borghi Alessandro , Bevilacqua Federica , Benedetto Chiara 
Published: March 2021

AbstractThe 4-decade (1980–2017) trends in lymph node status of patients with vulvar squamous cell carcinoma (VSCC) in a province of northern Italy were investigated. Information was collected on lymph node dissection, number of lymph nodes dissected, lymph node involvement, and number of positive lymph nodes from a series of 760 patients admitted to a tertiary referral centre for vulvar disease. The adjusted odds ratios (ORs) for lymph node involvement, for ≥ 2 positive nodes, and for a lymph node ratio ≥ 20% were estimated from multiple logistic regression models. The adjusted OR for lymph node dissection was greater in the 2000s and 2010s versus the 1980s. The adjusted OR for lymph node involvement was 1.36 (95% confidence interval (CI), 0.72–2.60) in the 1990s, 1.31 (95% CI, 0.72–2.38) in the 2000s and 1.32 (95% CI, 0.73–2.41) in the 2010s versus the 1980s. The adjusted OR for ≥ 2 positive nodes was 1.36 (95% CI, 0.68–2.72), 0.86 (95% CI, 0.44–1.65) and 0.67 (95% CI, 0.34–1.31), respectively. The adjusted OR for lymph node ratio ≥ 20% was 1.45 (95% CI, 0.62–3.43), 1.21 (95% CI, 0.54–2.72) and 0.81 (95% CI, 0.35–1.89), respectively. This stagnation indicates the need for a serious rethink of the local model for the care of VSCC.
The gut microbiota composition of Trichoplusia ni is altered by diet and may influence its polyphagous behavior
Authors: Leite-Mondin M. , DiLegge M. J. , Manter D. K. , Weir T. L. , Silva-Filho M. C. , Vivanco J. M. 
Published: March 2021

AbstractInsects are known plant pests, and some of them such as Trichoplusia ni feed on a variety of crops. In this study, Trichoplusia ni was fed distinct diets of leaves of Arabidopsis thaliana or Solanum lycopersicum as well as an artificial diet. After four generations, the microbial composition of the insect gut was evaluated to determine if the diet influenced the structure and function of the microbial communities. The population fed with A. thaliana had higher proportions of Shinella, Terribacillus and Propionibacterium, and these genera are known to have tolerance to glucosinolate activity, which is produced by A. thaliana to deter insects. The population fed with S. lycopersicum expressed increased relative abundances of the Agrobacterium and Rhizobium genera. These microbial members can degrade alkaloids, which are produced by S. lycopersicum. All five of these genera were also present in the respective leaves of either A. thaliana or S. lycopersicum, suggesting that these microbes are acquired by the insects from the diet itself. This study describes a potential mechanism used by generalist insects to become habituated to their available diet based on acquisition of phytochemical degrading gut bacteria.
NTRK fusion in Japanese colorectal adenocarcinomas
Authors: Yamashiro Yuya , Kurihara Taisei , Hayashi Takuo , Suehara Yoshiyuki , Yao Takashi , Kato Shunsuke , Saito Tsuyoshi 
Published: March 2021

AbstractNTRK fusion-positive tumors are known to be highly sensitive to TRK inhibitors, such as larotrectinib and entrectinib. Therefore, identification of patients who can potentially benefit from these inhibitors is important; however, the frequency of NTRK fusions in Japanese patients with colorectal cancer (CRC) is unknown. We performed pan-TRK staining using TMA-based immunohistochemistry (IHC) on samples from 971 consecutive Japanese CRC cases from a single institution. Positive cases were further analyzed using NanoString and subsequent targeted RNA sequencing. We found three positive cases using TRK-IHC. Furthermore, the Nanostring assay supported the presence of NTRK fusion in these cases. Subsequent targeted RNA-sequencing and RT-PCR revealed two cases with TPM3-NTRK1 and one with TPR-NTRK1. The TNM stages of these cases were stage I, stage IIA, and stage IIIB, and two showed microsatellite instability-high status. Next-generation sequencing analysis using Cancer hotspot panel revealed TP53 and SMAD4 mutations in separate cases. IHC of β-catenin did not show nuclear accumulation. We found three cases (0.31%) of CRC with NTRK1 fusion among 971 consecutive Japanese CRC cases. No potential driver alterations other than NTRK fusion were identified in these three patients.
Universal image segmentation for optical identification of 2D materials
Authors: Sterbentz Randy M. , Haley Kristine L. , Island Joshua O. 
Published: March 2021

AbstractMachine learning methods are changing the way data is analyzed. One of the most powerful and widespread applications of these techniques is in image segmentation wherein disparate objects of a digital image are partitioned and classified. Here we present an image segmentation program incorporating a series of unsupervised clustering algorithms for the automatic thickness identification of two-dimensional materials from digital optical microscopy images. The program identifies mono- and few-layer flakes of a variety of materials on both opaque and transparent substrates with a pixel accuracy of roughly 95%. Contrasting with previous attempts, application generality is achieved through preservation and analysis of all three digital color channels and Gaussian mixture model fits to arbitrarily shaped data clusters. Our results provide a facile implementation of data clustering for the universal, automatic identification of two-dimensional materials exfoliated onto any substrate.
Telocytes are major constituents of the angiogenic apparatus
Authors: Soliman Soha A. 
Published: March 2021

AbstractThe current study investigated role of telocytes (TCs) in angiogenesis during embryonic development of quail using immunohistochemistry (IHC), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The angiogenic apparatus consisted of TCs, endothelial cells, and macrophages. TCs were identified morphologically by their telopodes and podoms using TEM and SEM and immunohistochemically using CD34, and vascular endothelial growth factor (VEGF). TCs also expressed CD68. TCs formed a three-dimensional network and established direct contact with blood vessels, sprouting endothelial cells, and active macrophages, while exerting their effect through paracrine signaling. VEGF was also expressed by endothelial cells and macrophages. Matrix metalloproteinase–9 (MMP-9) was expressed by TCs, endothelial cells, and macrophages. In conclusion, the expression of VEGF by TCs, endothelial cells, and macrophages is required for the proliferation and migration of endothelial cells and vascular growth. The expression of MMP-9 by TCs, endothelial cells, and macrophages is essential for the degradation of extracellular matrix (ECM) components during neoangiogenesis. Macrophages may facilitate phagocytosis and elimination of the degraded ECM components.
A modified MRI protocol for the increased detection of sacrococcygeal fractures in patients with thoracolumbar junction fractures
Authors: Khil Eun Kyung , Choi Il , Choi Jung-Ah , Kim Young Woo 
Published: March 2021

AbstractThis study aimed to identify concurrent thoracolumbar junction (TLJ) and sacrococcygeal (SC) fractures using a modified MRI protocol and analyze the risk factors associated with tandem fractures. We retrospectively investigated patients with MRI-confirmed TLJ fractures from January 2017 to March 2020. Patients were divided into two study groups: study 1 with a modified MRI protocol and study 2 with a routine protocol. The modified protocol included an extended field of view of sagittal scans in L-spine MRI covering the full SC spine. In study 1, frequency of concurrent TLJ and SC fractures was investigated. And we analyzed risk factors and compared CT and MRI for detecting SC fractures. In study 2, co-occurrence of both fractures was investigated. A total of 176 and 399 patients with TLJ fractures were enrolled in study 1 and 2, then SC fractures were identified in 53 (30.14%) and 36 patients (9.02%), respectively. An axial loading trauma mechanism was a significant risk factor (Odds ratio 7.0, p < 0.001), and MRI was more sensitive than CT in detecting SC fractures (p < 0.002). Thus, a modified MRI protocol was useful to detect the high occurrence of SC fractures in TLJ fractures, which concurrent fractures increased by an axial loading mechanism.