bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pevonedistat, a Nedd8-activating enzyme inhibitor, in combination with ibrutinib in patients with relapsed/refractory B-cell non-Hodgkin lymphoma
Authors: Torka Pallawi , Thiruvengadam Swetha Kambhampati , Chen Lu , Wang Xiaoguang , Chen Canping , Vuong Dan , Qin Hanjun , Muir Alexandra , Orand Kirsten , Borja Ivana , Lynne Smith D. , Herrera Alex F. , Spurgeon Stephen E. F. , Park Byung , Lewis Lionel D. , Hernandez-Ilizaliturri Francisco , Xia Zheng , Danilov Alexey V. 
Published: January 2023

AbstractPevonedistat (TAK924) is a Nedd8-activating enzyme inhibitor with preclinical activity in non-Hodgkin lymphoma (NHL). This open-label, Phase I, multicenter, investigator-sponsored study enrolled patients with relapsed/refractory (R/R) NHL and chronic lymphocytic leukemia (CLL). The primary objective was safety. Pevonedistat was given intravenously on days 1, 3, 5 of a 21-day cycle for 8 cycles at five dose levels (15 to 50 mg/m2); ibrutinib was administered at 420 or 560 mg orally daily continuously. Eighteen patients with NHL were enrolled, including 8 patients with mantle cell lymphoma (MCL) and 4 patients with CLL. One dose-limiting toxicity (mediastinal hemorrhage) occurred at 50 mg/m2 of pevonedistat which is the estimated maximum tolerated dose. Bruising and diarrhea were the most common adverse events (56% and 44%). Atrial fibrillation occurred in 3 patients (17%). Grade ≥3 toxicities included arthralgia, atrial fibrillation, bone pain, diarrhea, hypertension, and mediastinal hemorrhage (one patient each). The overall response rate (ORR) was 65% (100% ORR in MCL). Pevonedistat disposition was not modified by ibrutinib. scRNA-Seq analysis showed that pevonedistat downregulated NFκB signaling in malignant B-cells in vivo. Thus, pevonedistat combined with ibrutinib demonstrated safety and promising early efficacy in NHL and CLL. NAE inhibition downregulated NFκB signaling in vivo.
SiO-induced thermal instability and interplay between graphite and SiO in graphite/SiO composite anode
Authors: Lee Ban Seok , Oh Sang-Hwan , Choi Yoon Jeong , Yi Min-Jeong , Kim So Hee , Kim Shin-Yeong , Sung Yung-Eun , Shin Sun Young , Lee Yongju , Yu Seung-Ho 
Published: January 2023

AbstractSilicon monoxide (SiO), which exhibits better cyclability compared to silicon while delivering higher capacity than that of graphite, is an adequate material for the development of lithium-ion batteries (LIBs) having higher energy densities. However, incorporating silicon-based materials including SiO into stable graphite anode inevitably degrades not only cycle life but also calendar life of LIBs, while little is known about their aging mechanisms. Here, SiO-induced thermal instability of the graphite/SiO composite anode is investigated. We reveal that under thermal exposure, SiO accelerates the loss of lithium inventory and concomitantly facilitates the lithium de-intercalation from graphite. This self-discharge phenomenon, which is weakly observed in the graphite anode without SiO, is the result of preferential parasitic reaction on the SiO interface and spontaneous electron and lithium-ion migration to equilibrate the electron energy imbalance between graphite and SiO. Understanding this underlying electron-level interplay between graphite and SiO in the composite anode will contribute toward improving shelf life of SiO-containing LIBs in actual operating conditions.
The SPOC domain is a phosphoserine binding module that bridges transcription machinery with co- and post-transcriptional regulators
Authors: Appel Lisa-Marie , Franke Vedran , Benedum Johannes , Grishkovskaya Irina , Strobl Xué , Polyansky Anton , Ammann Gregor , Platzer Sebastian , Neudolt Andrea , Wunder Anna , Walch Lena , Kaiser Stefanie , Zagrovic Bojan , Djinovic-Carugo Kristina , Akalin Altuna , Slade Dea 
Published: January 2023

AbstractThe heptad repeats of the C-terminal domain (CTD) of RNA polymerase II (Pol II) are extensively modified throughout the transcription cycle. The CTD coordinates RNA synthesis and processing by recruiting transcription regulators as well as RNA capping, splicing and 3’end processing factors. The SPOC domain of PHF3 was recently identified as a CTD reader domain specifically binding to phosphorylated serine-2 residues in adjacent CTD repeats. Here, we establish the SPOC domains of the human proteins DIDO, SHARP (also known as SPEN) and RBM15 as phosphoserine binding modules that can act as CTD readers but also recognize other phosphorylated binding partners. We report the crystal structure of SHARP SPOC in complex with CTD and identify the molecular determinants for its specific binding to phosphorylated serine-5. PHF3 and DIDO SPOC domains preferentially interact with the Pol II elongation complex, while RBM15 and SHARP SPOC domains engage with writers and readers of m6A, the most abundant RNA modification. RBM15 positively regulates m6A levels and mRNA stability in a SPOC-dependent manner, while SHARP SPOC is essential for its localization to inactive X-chromosomes. Our findings suggest that the SPOC domain is a major interface between the transcription machinery and regulators of transcription and co-transcriptional processes.
Bio-inspired magnetic-driven folded diaphragm for biomimetic robot
Authors: Lin Dezhao , Yang Fan , Gong Di , Li Ruihong 
Published: January 2023

AbstractFunctional soft materials, exhibiting multiple types of deformation, have shown their potential/abilities to achieve complicated biomimetic behaviors (soft robots). Inspired by the locomotion of earthworm, which is conducted through the contraction and stretching between body segments, this study proposes a type of one-piece-mold folded diaphragm, consisting of the structure of body segments with radial magnetization property, to achieve large 3D and bi-directional deformation with inside-volume change capability subjected to the low homogeneous magnetically driving field (40 mT). Moreover, the appearance based on the proposed magnetic-driven folded diaphragm is able to be easily customized to desired ones and then implanted into different untethered soft robotic systems as soft drivers. To verify the above points, we design the diaphragm pump providing unique properties of lightweight, powerful output and rapid response, and the soft robot including the bio-earthworm crawling robot and swimming robot inspired by squid to exhibit the flexible and rapid locomotion excited by single homogeneous magnetic fields.
Identification of the ageing‐related prognostic gene signature, and the associated regulation axis in skin cutaneous melanoma
Authors: Tian Chonglin , Liu Sujing , Huo Ran 
Published: January 2023

AbstractSkin cutaneous melanoma (SKCM) has substantial malignancy and a poor prognosis. The function of ageing-related genes (ARGs) in SKCM is unknown. In this study, a prognostic risk-scoring model for ARG was constructed based on SKCM RNA-seq, mutation, and clinical data in The Cancer Genome Atlas. Our novel prognostic model, which included four ARGs (IRS2, PDGFRA, TFAP2A, and SOD2), could distinguish between low-risk and high-risk groups. Low-risk patients benefited more from immunotherapy and commonly used targeted and chemotherapy drugs than high-risk patients. There were also considerable differences in immunocyte infiltration and tumour microenvironment between the two groups. Furthermore, multivariate Cox regression analysis revealed that age, pT_stage, pM_stage, body mass index, tumour mutation burden, and risk score were independent factors influencing the prognosis of patients with SKCM; therefore, we devised a prognosis nomogram. Last, a long non-coding (lncRNA) NEAT1/miR-33a-5p/IRS2 regulatory axis of the competing endogenous RNA network was built to investigate the mechanisms of SKCM metastasis progression. Grouping based on the scoring system could predict the prognosis of SKCM and predict the sensitivity of patients to immunotherapy, targeted therapy, and chemotherapy. This could facilitate the formulation of individualised treatment strategies and help drug research and development. These findings highlight the regulatory axis of the lncRNA NEAT1/miR-33a-5p/IRS2, which may play a role in SKCM metastasis.
Investigation of interfacial strength in nacre-mimicking tungsten heavy alloys for nuclear fusion applications
Authors: Haag J. V. , Wang J. , Kruska K. , Olszta M. J. , Henager C. H. , Edwards D. J. , Setyawan W. , Murayama M. 
Published: January 2023

AbstractTungsten heavy alloys have been proposed as plasma facing material components in nuclear fusion reactors and require experimental investigation in their confirmation. For this purpose, a 90W–7Ni–3Fe alloy has been selected and microstructurally manipulated to present a multiphase brick-and-mortar structure of W-phase ‘bricks’ surrounded by a ductile ‘mortar’. This work draws inspiration from nature to artificially imitate the extraordinary combination of strength and stiffness exhibited by mollusks and produce a nacre-mimicking metal matrix composite capable of withstanding the extremely hostile environment of the reactor interior and maintaining structural integrity. The underlying mechanisms behind this integrity have been probed through high-resolution structural and chemical characterization techniques and have revealed chemically diffuse phase boundaries exhibiting unexpected lattice coherency. These features have been attributed to an increase in the energy required for interfacial decohesion in these systems and the simultaneous expression of high strength and toughness in tungsten heavy alloys.
Social and cognitive factors influencing commercial chicken farmers’ antimicrobial usage in Bangladesh
Authors: Imam Tasneem , Gibson Justine S. , Gupta Suman Das , Foysal Mohammad , Das Shetu B. , Hoque Md Ahasanul , Fournié Guillaume , Henning Joerg 
Published: January 2023

AbstractAdapting the Social Cognitive Theory framework, we conducted a cross-sectional study on 137 commercial chicken farms in Bangladesh to investigate factors influencing the behaviour of farmers towards the application of antimicrobials to their birds. Almost all farmers used antimicrobials to treat poultry diseases, while 38.6% also were using them to promote healthy growth of chickens and 10.2% to increase egg production or improve meat quality. Using Structural Equation Modeling (SEM), we identified that inappropriate usage of antimicrobials (behaviour) was strongly driven by farmers’ short-term goals to maintain the health of their chickens in a production cycle (β = 0.813, p = 0.029), rather than long-term concerns. Farmers’ perception about their ability to control antimicrobial administration based on their skills and opportunities (self-efficacy) marginally influenced the short-term goals of antimicrobial usage (β = 0.301, p = 0.073). The results of this study can be used to develop targeted education programs for farmers, to reduce the application of antimicrobials in their poultry flocks.
Global analysis of the association between pig muscle fatty acid composition and gene expression using RNA-Seq
Authors: Valdés-Hernández Jesús , Ramayo-Caldas Yuliaxis , Passols Magí , Sebastià Cristina , Criado-Mesas Lourdes , Crespo-Piazuelo Daniel , Esteve-Codina Anna , Castelló Anna , Sánchez Armand , Folch Josep M. 
Published: January 2023

AbstractFatty acids (FAs) play an essential role as mediators of cell signaling and signal transduction, affecting metabolic homeostasis and determining meat quality in pigs. However, FAs are transformed by the action of several genes, such as those encoding desaturases and elongases of FAs in lipogenic tissues. The aim of the current work was to identify candidate genes, biological processes, and pathways involved in the modulation of intramuscular FA profile fromlongissimus dorsimuscle. FA profile by gas chromatography of methyl esters and gene expression by RNA-Seq were determined in 129 Iberian × Duroc backcrossed pigs. An association analysis between the muscle transcriptome and its FA profile was performed, followed by a concordance and functional analysis. Overall, a list of well-known (e.g.,PLIN1,LEP, ELOVL6, SC5D,NCOA2,ACSL1, MDH1, LPL,LGALS12, TFRC, GOT1,andFBP1) and novel (e.g.,TRARG1, TANK, ENSSSCG00000011196,andENSSSCG00000038429) candidate genes was identified, either in association with specific or several FA traits. Likewise, several of these genes belong to biological processes and pathways linked to energy, lipid, and carbohydrate metabolism, which seem determinants in the modulation of FA compositions. This study can contribute to elucidate the complex relationship between gene expression and FA profile in pig muscle.
A nested bistable module within a negative feedback loop ensures different types of oscillations in signaling systems
Authors: Marrone Juan Ignacio , Sepulchre Jacques-Alexandre , Ventura Alejandra C. 
Published: January 2023

AbstractIn this article, we consider a double phosphorylation cycle, a ubiquitous signaling component, having the ability to display bistability, a behavior strongly related to the existence of positive feedback loops. If this component is connected to other signaling elements, it very likely undergoes some sort of protein–protein interaction. In several cases, these interactions result in a non-explicit negative feedback effect, leading to interlinked positive and negative feedbacks. This combination was studied in the literature as a way to generate relaxation-type oscillations. Here, we show that the two feedbacks together ensure two types of oscillations, the relaxation-type ones and a smoother type of oscillations functioning in a very narrow range of frequencies, in such a way that outside that range, the amplitude of the oscillations is severely compromised. Even more, we show that the two feedbacks are essential for both oscillatory types to emerge, and it is their hierarchy what determines the type of oscillation at work. We used bifurcation analyses and amplitude vs. frequency curves to characterize and classify the oscillations. We also applied the same ideas to another simple model, with the goal of generalizing what we learned from signaling models. The results obtained display the wealth of oscillatory dynamics that exists in a system with a bistable module nested within a negative feedback loop, showing how to transition between different types of oscillations and other dynamical behaviors such as excitability. Our work provides a framework for the study of other oscillatory systems based on bistable modules, from simple two-component models to more complex examples like the MAPK cascade and experimental cases like cell cycle oscillators.
Active particles crossing sharp viscosity gradients
Authors: Gong Jiahao , Shaik Vaseem A. , Elfring Gwynn J. 
Published: January 2023

AbstractActive particles (living or synthetic) often move through inhomogeneous environments, such as gradients in light, heat or nutrient concentration, that can lead to directed motion (or taxis). Recent research has explored inhomogeneity in the rheological properties of a suspending fluid, in particular viscosity, as a mechanical (rather than biological) mechanism for taxis. Theoretical and experimental studies have shown that gradients in viscosity can lead to reorientation due to asymmetric viscous forces. In particular, recent experiments with Chlamydomonas Reinhardtii algae swimming across sharp viscosity gradients have observed that the microorganisms are redirected and scattered due to the viscosity change. Here we develop a simple theoretical model to explain these experiments. We model the swimmers as spherical squirmers and focus on small, but sharp, viscosity changes. We derive a law, analogous to Snell’s law of refraction, that governs the orientation of active particles in the presence of a viscosity interface. Theoretical predictions show good agreement with experiments and provide a mechanistic understanding of the observed reorientation process.
A novel optimization method for belief rule base expert system with activation rate
Authors: Xiang Gang , Wang Jie , Han XiaoXia , Tang Shuaiwen , Hu Guanyu 
Published: January 2023

AbstractAlthough the belief rule base (BRB) expert system has many advantages, such as the effective use of semi-quantitative information, objective description of uncertainty, and efficient nonlinear modeling capability, it is always limited by the problem of combinatorial explosion. The main reason is that the optimization of a BRB with many rules will consume many computing resources, which makes it unable to meet the real-time requirements in some complex systems. Another reason is that the optimization process will destroy the interpretability of those parameters that belong to the inadequately activated rules given by experts. To solve these problems, a novel optimization method for BRB is proposed in this paper. Through the activation rate, the rules that have never been activated or inadequately activated are pruned during the optimization process. Furthermore, even if there is a complete data set and all rules are activated, the activation rate can also be used in the parallel optimization process of the BRB expert system, where the training data set is divided into some subprocesses. The proposed method effectively solves the combinatorial explosion problem of BRB and can make full use of quantitative data without destroying the original interpretability provided by experts. Case studies prove the advantages and effectiveness of the proposed method, which greatly expands the application fields of the BRB expert system.
Distinct patterns of serum and urine macrophage migration inhibitory factor kinetics predict death in sepsis: a prospective, observational clinical study
Authors: Toldi Janos , Kelava Leonardo , Marton Sandor , Muhl Diana , Kustan Peter , Feher Zsolt , Maar Klaudia , Garai Janos , Pakai Eszter , Garami Andras 
Published: January 2023

AbstractMacrophage migration inhibitory factor (MIF) has been considered as a biomarker in sepsis, however the predictive value of the pattern of its kinetics in the serum and in the urine has remained unclarified. It is also unclear whether the kinetics of MIF are different between males and females. We conducted a single-center prospective, observational study with repeated measurements of MIF in serum and urine on days 0, 2, and 4 from admission to the intensive care unit (ICU) in 50 adult septic patients. We found that in patients who died within 90 days, there was an increase in serum MIF level from day 0 to 4, whereas in the survivors there was rather a decrease (p = 0.018). The kinetics were sex-dependent as the same difference in the pattern was present in males (p = 0.014), but not in females (p = 0.418). We also found that urine MIF was markedly lower in patients who died than in survivors of sepsis (p < 0.050). Urine MIF levels did not show temporal changes: there was no meaningful difference between day 0 and 4. These results suggest that kinetics of serum MIF during the initial days from ICU admission can predict death, especially in male patients. Additionally, lower urine MIF levels can also indicate death without showing meaningful temporal kinetics.
Allele-specific expression analysis for complex genetic phenotypes applied to a unique dilated cardiomyopathy cohort
Authors: van Beek Daan , Verdonschot Job , Derks Kasper , Brunner Han , de Kok Theo M. , Arts Ilja C. W. , Heymans Stephane , Kutmon Martina , Adriaens Michiel 
Published: January 2023

AbstractAllele-specific expression (ASE) analysis detects the relative abundance of alleles at heterozygous loci as a proxy for cis-regulatory variation, which affects the personal transcriptome and proteome. This study describes the development and application of an ASE analysis pipeline on a unique cohort of 87 well phenotyped and RNA sequenced patients from the Maastricht Cardiomyopathy Registry with dilated cardiomyopathy (DCM), a complex genetic disorder with a remaining gap in explained heritability. Regulatory processes for which ASE is a proxy might explain this gap. We found an overrepresentation of known DCM-associated genes among the significant results across the cohort. In addition, we were able to find genes of interest that have not been associated with DCM through conventional methods such as genome-wide association or differential gene expression studies. The pipeline offers RNA sequencing data processing, individual and population level ASE analyses as well as group comparisons and several intuitive visualizations such as Manhattan plots and protein–protein interaction networks. With this pipeline, we found evidence supporting the case that cis-regulatory variation contributes to the phenotypic heterogeneity of DCM. Additionally, our results highlight that ASE analysis offers an additional layer to conventional genomic and transcriptomic analyses for candidate gene identification and biological insight.
Assessment of gait and posture characteristics using a smartphone wearable system for persons with osteoporosis with and without falls
Authors: Doshi Krupa B. , Moon Seong Hyun , Whitaker Michael D. , Lockhart Thurmon E. 
Published: January 2023

AbstractWe used smartphone technology to differentiate the gait characteristics of older adults with osteoporosis with falls from those without falls. We assessed gait mannerism and obtained activities of daily living (ADLs) with wearable sensor systems (smartphones and inertial measurement units [IMUs]) to identify fall-risk characteristics. We recruited 49 persons with osteoporosis: 14 who had a fall within a year before recruitment and 35 without falls. IMU sensor signals were sampled at 50 Hz using a customized smartphone app (Lockhart Monitor) attached at the pelvic region. Longitudinal data was collected using MoveMonitor+ (DynaPort) IMU over three consecutive days. Given the close association between serum calcium, albumin, PTH, Vitamin D, and musculoskeletal health, we compared these markers in individuals with history of falls as compared to nonfallers. For the biochemical parameters fall group had significantly lower calcium (P = 0.01*) and albumin (P = 0.05*) and higher parathyroid hormone levels (P = 0.002**) than nonfall group. In addition, persons with falls had higher sway area (P = 0.031*), lower dynamic stability (P < 0.001***), gait velocity (P = 0.012*), and were less able to perform ADLs (P = 0.002**). Thus, persons with osteoporosis with a history of falls can be differentiated by using dynamic real-time measurements that can be easily captured by a smartphone app, thus avoiding traditional postural sway and gait measures that require individuals to be tested in a laboratory setting.