bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the Derivation of Closed‐Form Expressions for Displacements, Strains, and Stresses Inside Poroelastic Reservoirs
Authors: Cornelissen P. , Meulenbroek B. J. , Jansen J. D. 
Published: February 2024

AbstractWe critically review the derivation of closed‐form analytical expressions for elastic displacements, strains, and stresses inside a subsurface reservoir undergoing pore pressure changes using inclusion theory. Although developed decades ago, inclusion theory has been used recently by various authors to obtain fast estimates of depletion‐induced and injection‐induced fault stresses in relation to induced seismicity. We therefore briefly address the current geomechanical relevance of this method, and provide a numerical example to demonstrate its use to compute induced fault stresses. However, the main goal of our paper is to correct some erroneous assumptions that were made in earlier publications. While the final expressions for the poroelastic stresses in these publications were correct, their derivation contained conceptual mistakes due to the mathematical subtleties that arise because of singularities in the Green's functions. The aim of our paper is therefore to present the correct derivation of expressions for the strains and stresses inside an inclusion and to clarify some of the results of the aforementioned studies. Furthermore, we present two conditions that the strain field must satisfy, which can be used to verify the analytical expressions.
TEA domain transcription factor 1 (TEAD1) induces cardiac fibroblasts cells remodeling through BRD4/Wnt4 pathway
Authors: Song Shuai , Zhang Xiaokai , Huang Zihang , Zhao Yongchao , Lu Shuyang , Zeng Linqi , Cai Fengze , Wang Tongyao , Pei Zhiqiang , Weng Xinyu , Luo Wei , Lu Hao , Wei Zilun , Wu Jian , Yu Peng , Shen Li , Zhang Xiaochun , Sun Aijun , Ge Junbo 
Published: February 2024

AbstractCardiac fibroblasts (CFs) are the primary cells tasked with depositing and remodeling collagen and significantly associated with heart failure (HF). TEAD1 has been shown to be essential for heart development and homeostasis. However, fibroblast endogenous TEAD1 in cardiac remodeling remains incompletely understood. Transcriptomic analyses revealed consistently upregulated cardiac TEAD1 expression in mice 4 weeks after transverse aortic constriction (TAC) and Ang-II infusion. Further investigation revealed that CFs were the primary cell type expressing elevated TEAD1 levels in response to pressure overload. Conditional TEAD1 knockout was achieved by crossing TEAD1-floxed mice with CFs- and myofibroblasts-specific Cre mice. Echocardiographic and histological analyses demonstrated that CFs- and myofibroblasts-specific TEAD1 deficiency and treatment with TEAD1 inhibitor, VT103, ameliorated TAC-induced cardiac remodeling. Mechanistically, RNA-seq and ChIP-seq analysis identified Wnt4 as a novel TEAD1 target. TEAD1 has been shown to promote the fibroblast-to-myofibroblast transition through the Wnt signalling pathway, and genetic Wnt4 knockdown inhibited the pro-transformation phenotype in CFs with TEAD1 overexpression. Furthermore, co-immunoprecipitation combined with mass spectrometry, chromatin immunoprecipitation, and luciferase assays demonstrated interaction between TEAD1 and BET protein BRD4, leading to the binding and activation of the Wnt4 promoter. In conclusion, TEAD1 is an essential regulator of the pro-fibrotic CFs phenotype associated with pathological cardiac remodeling via the BRD4/Wnt4 signalling pathway.
Pleiotropic contribution of rbfox1 to psychiatric and neurodevelopmental phenotypes in two zebrafish models
Authors: Antón-Galindo Ester , Adel Maja R. , García-González Judit , Leggieri Adele , López-Blanch Laura , Irimia Manuel , Norton William H. J. , Brennan Caroline H. , Fernàndez-Castillo Noèlia , Cormand Bru 
Published: February 2024

AbstractRBFOX1 is a highly pleiotropic gene that contributes to several psychiatric and neurodevelopmental disorders. Both rare and common variants in RBFOX1 have been associated with several psychiatric conditions, but the mechanisms underlying the pleiotropic effects of RBFOX1 are not yet understood. Here we found that, in zebrafish, rbfox1 is expressed in spinal cord, mid- and hindbrain during developmental stages. In adults, expression is restricted to specific areas of the brain, including telencephalic and diencephalic regions with an important role in receiving and processing sensory information and in directing behaviour. To investigate the contribution of rbfox1 to behaviour, we used rbfox1sa15940, a zebrafish mutant line with TL background. We found that rbfox1sa15940 mutants present hyperactivity, thigmotaxis, decreased freezing behaviour and altered social behaviour. We repeated these behavioural tests in a second rbfox1 mutant line with a different genetic background (TU), rbfox1del19, and found that rbfox1 deficiency affects behaviour similarly in this line, although there were some differences. rbfox1del19 mutants present similar thigmotaxis, but stronger alterations in social behaviour and lower levels of hyperactivity than rbfox1sa15940 fish. Taken together, these results suggest that mutations in rbfox1 lead to multiple behavioural changes in zebrafish that might be modulated by environmental, epigenetic and genetic background effects, and that resemble phenotypic alterations present in Rbfox1-deficient mice and in patients with different psychiatric conditions. Our study, thus, highlights the evolutionary conservation of rbfox1 function in behaviour and paves the way to further investigate the mechanisms underlying rbfox1 pleiotropy on the onset of neurodevelopmental and psychiatric disorders.
Inhibition of the ILK-AKT pathway by upregulation of PARVB contributes to the cochlear cell death in Fascin2 gene knockout mice
Authors: Liu Rongrong , Shang Wenjing , Liu Yingying , Xie Yi , Luan Jun , Zhang Ting , Ma Ying , Wang Zengxian , Sun Yan , Song Xicheng , Han Fengchan 
Published: February 2024

AbstractThe Fscn2 (Fascin2) gene encodes an actin cross-linking protein that is involved in the formation of hair cell stereocilia and retina structure. Mutations in Fscn2 gene have been linked to hearing impairment and retinal degeneration in humans and mice. To understand the function of the Fscn2 gene, we generated the Fscn2 knockout mice, which showed progressive loss of hearing and hair cells. Our goal of the present study was to investigate the mechanism underlying cochlear cell death in the Fscn2 knockout mice. Microarray analysis revealed upregulation of expression of PARVB, a local adhesion protein, in the inner ears of Fscn2 knockout mice at 8 weeks of age. Further studies showed increased levels of PARVB together with cleaved-Caspase9 and decreased levels of ILK, p-ILK, p-AKT, and Bcl-2 in the inner ears of Fscn2 knockout mice of the same age. Knockdown of Fscn2 in HEI-OCI cells led to decreased cell proliferation ability and migration rate, along with increased levels of PARVB and decreased levels of ILK, p-ILK, p-AKT, Bcl-2 and activated Rac1 and Cdc42. Overexpression of Fscn2 or inhibition of Parvb expression in HEI-OC1 cells promoted cell proliferation and migration, with increased levels of ILK, p-ILK, p-AKT, and Bcl-2. Finally, FSCN2 binds with PPAR-γ to reduce its nuclear translocation in HEI-OC1 cells, and inhibition of PPAR-γ by GW9662 decreased the level of PARVB and increased the levels of p-AKT, p-ILK, and Bcl-2. Our results suggest that FSCN2 negatively regulates PARVB expression by inhibiting the entry of PPAR-γ into the cell nucleus, resulting in inhibition of ILK-AKT related pathways and of cochlear cell survival in Fscn2 knockout mice. Our findings provide new insights and ideas for the prevention and treatment of genetic hearing loss.
Onset of double subduction controls plate motion reorganisation
Authors: Zhang Kuidi , Liao Jie , Gerya Taras 
Published: February 2024

AbstractFace-to-face double subduction systems, in which two oceanic plates subduct toward each other, are essential elements of plate tectonics. Two subduction zones in such systems are typically uneven in age and their spatially and temporally variable dynamics remain enigmatic. Here, with 2D numerical modelling, we demonstrate that the onset of the younger subduction zone strongly changes the dynamics of the older subduction zone. The waxing younger subduction may gradually absorb plate convergence from the older one, resulting in older subduction waning featured by the dramatic decrease in subduction rate and trench retreat. The dynamical transformation of subduction predominance alters the intraplate stress and mantle flow, regulating the relative motion among the three different plates. The process of waxing and waning of subduction zones controls plate motion reorganisation, providing a reference to interpret the past, present, and future evolution of several key double subduction regions found on the modern Earth.
Articular surface interactions distinguish dinosaurian locomotor joint poses
Authors: Manafzadeh Armita R. , Gatesy Stephen M. , Bhullar Bhart-Anjan S. 
Published: February 2024

AbstractOur knowledge of vertebrate functional evolution depends on inferences about joint function in extinct taxa. Without rigorous criteria for evaluating joint articulation, however, such analyses risk misleading reconstructions of vertebrate animal motion. Here we propose an approach for synthesizing raycast-based measurements of 3-D articular overlap, symmetry, and congruence into a quantitative “articulation score” for any non-interpenetrating six-degree-of-freedom joint configuration. We apply our methodology to bicondylar hindlimb joints of two extant dinosaurs (guineafowl, emu) and, through comparison with in vivo kinematics, find that locomotor joint poses consistently have high articulation scores. We then exploit this relationship to constrain reconstruction of a pedal walking stride cycle for the extinct dinosaur Deinonychus antirrhopus, demonstrating the utility of our approach. As joint articulation is investigated in more living animals, the framework we establish here can be expanded to accommodate additional joints and clades, facilitating improved understanding of vertebrate animal motion and its evolution.
Causes of death among people living with metastatic cancer
Authors: Mani Kyle , Deng Daxuan , Lin Christine , Wang Ming , Hsu Melinda L. , Zaorsky Nicholas G. 
Published: February 2024

AbstractStudying survivorship and causes of death in patients with advanced or metastatic cancer remains an important task. We characterize the causes of death among patients with metastatic cancer, across 13 cancer types and 25 non-cancer causes and predict the risk of death after diagnosis from the diagnosed cancer versus other causes (e.g., stroke, heart disease, etc.). Among 1,030,937 US (1992–2019) metastatic cancer survivors, 82.6% of patients (n = 688,529) died due to the diagnosed cancer, while 17.4% (n = 145,006) died of competing causes. Patients with lung, pancreas, esophagus, and stomach tumors are the most likely to die of their metastatic cancer, while those with prostate and breast cancer have the lowest likelihood. The median survival time among patients living with metastases is 10 months; our Fine and Gray competing risk model predicts 1 year survival with area under the receiver operating characteristic curve of 0.754 (95% CI [0.754, 0.754]). Leading non-cancer deaths are heart disease (32.4%), chronic obstructive and pulmonary disease (7.9%), cerebrovascular disease (6.1%), and infection (4.1%).
Rejuvenation as the origin of planar defects in the CrCoNi medium entropy alloy
Authors: Yang Yang , Yin Sheng , Yu Qin , Zhu Yingxin , Ding Jun , Zhang Ruopeng , Ophus Colin , Asta Mark , Ritchie Robert O. , Minor Andrew M. 
Published: February 2024

AbstractHigh or medium- entropy alloys (HEAs/MEAs) are multi-principal element alloys with equal atomic elemental composition, some of which have shown record-breaking mechanical performance. However, the link between short-range order (SRO) and the exceptional mechanical properties of these alloys has remained elusive. The local destruction of SRO by dislocation glide has been predicted to lead to a rejuvenated state with increased entropy and free energy, creating softer zones within the matrix and planar fault boundaries that enhance the ductility, but this has not been verified. Here, we integrate in situ nanomechanical testing with energy-filtered four-dimensional scanning transmission electron microscopy (4D-STEM) and directly observe the rejuvenation during cyclic mechanical loading in single crystal CrCoNi at room temperature. Surprisingly, stacking faults (SFs) and twin boundaries (TBs) are reversible in initial cycles but become irreversible after a thousand cycles, indicating SF energy reduction and rejuvenation. Molecular dynamics (MD) simulation further reveals that the local breakdown of SRO in the MEA triggers these SF reversibility changes. As a result, the deformation features in HEAs/MEAs remain planar and highly localized to the rejuvenated planes, leading to the superior damage tolerance characteristic in this class of alloys.
A signal processing and deep learning framework for methylation detection using Oxford Nanopore sequencing
Authors: Ahsan Mian Umair , Gouru Anagha , Chan Joe , Zhou Wanding , Wang Kai 
Published: February 2024

AbstractOxford Nanopore sequencing can detect DNA methylations from ionic current signal of single molecules, offering a unique advantage over conventional methods. Additionally, adaptive sampling, a software-controlled enrichment method for targeted sequencing, allows reduced representation methylation sequencing that can be applied to CpG islands or imprinted regions. Here we present DeepMod2, a comprehensive deep-learning framework for methylation detection using ionic current signal from Nanopore sequencing. DeepMod2 implements both a bidirectional long short-term memory (BiLSTM) model and a Transformer model and can analyze POD5 and FAST5 signal files generated on R9 and R10 flowcells. Additionally, DeepMod2 can run efficiently on central processing unit (CPU) through model pruning and can infer epihaplotypes or haplotype-specific methylation calls from phased reads. We use multiple publicly available and newly generated datasets to evaluate the performance of DeepMod2 under varying scenarios. DeepMod2 has comparable performance to Guppy and Dorado, which are the current state-of-the-art methods from Oxford Nanopore Technologies that remain closed-source. Moreover, we show a high correlation (r = 0.96) between reduced representation and whole-genome Nanopore sequencing. In summary, DeepMod2 is an open-source tool that enables fast and accurate DNA methylation detection from whole-genome or adaptive sequencing data on a diverse range of flowcell types.
Neoadjuvant cobimetinib and atezolizumab with or without vemurafenib for high-risk operable Stage III melanoma: the Phase II NeoACTIVATE trial
Authors: Hieken Tina J. , Nelson Garth D. , Flotte Thomas J. , Grewal Eric P. , Chen Jun , McWilliams Robert R. , Kottschade Lisa A. , Yang Lu , Domingo-Musibay Evidio , Dronca Roxana S. , Yan Yiyi , Markovic Svetomir N. , Dimou Anastasios , Montane Heather N. , Erskine Courtney L. , Piltin Mara A. , Price Daniel L. , Khariwala Samir S. , Hui Jane , Strand Carrie A. , Harrington Susan M. , Suman Vera J. , Dong Haidong , Block Matthew S. 
Published: February 2024

AbstractBoth targeted therapies and immunotherapies provide benefit in resected Stage III melanoma. We hypothesized that the combination of targeted and immunotherapy given prior to therapeutic lymph node dissection (TLND) would be tolerable and drive robust pathologic responses. In NeoACTIVATE (NCT03554083), a Phase II trial, patients with clinically evident resectable Stage III melanoma received either 12 weeks of neoadjuvant vemurafenib, cobimetinib, and atezolizumab (BRAF-mutated, Cohort A, n = 15), or cobimetinib and atezolizumab (BRAF-wild-type, Cohort B, n = 15) followed by TLND and 24 weeks of adjuvant atezolizumab. Here, we report outcomes from the neoadjuvant portion of the trial. Based on intent to treat analysis, pathologic response (≤50% viable tumor) and major pathologic response (complete or near-complete, ≤10% viable tumor) were observed in 86.7% and 66.7% of BRAF-mutated and 53.3% and 33.3% of BRAF-wild-type patients, respectively (primary outcome); these exceeded pre-specified benchmarks of 50% and 30% for major pathologic response. Grade 3 and higher toxicities, primarily dermatologic, occurred in 63% during neoadjuvant treatment (secondary outcome). No surgical delays nor progression to regional unresectability occurred (secondary outcome). Peripheral blood CD8 + TCM cell expansion associated with favorable pathologic responses (exploratory outcome).
Deep photonic network platform enabling arbitrary and broadband optical functionality
Authors: Najjar Amiri Ali , Vit Aycan Deniz , Gorgulu Kazim , Magden Emir Salih 
Published: February 2024

AbstractExpanding applications in optical communications, computing, and sensing continue to drive the need for high-performance integrated photonic components. Designing these on-chip systems with arbitrary functionality requires beyond what is possible with physical intuition, for which machine learning-based methods have recently become popular. However, computational demands for physically accurate device simulations present critical challenges, significantly limiting scalability and design flexibility of these methods. Here, we present a highly-scalable, physics-informed design platform for on-chip optical systems with arbitrary functionality, based on deep photonic networks of custom-designed Mach-Zehnder interferometers. Leveraging this platform, we demonstrate ultra-broadband power splitters and a spectral duplexer, each designed within two minutes. The devices exhibit state-of-the-art experimental performance with insertion losses below 0.66 dB, and 1-dB bandwidths exceeding 120 nm. This platform provides a tractable path towards systematic, large-scale photonic system design, enabling custom power, phase, and dispersion profiles for high-throughput communications, quantum information processing, and medical/biological sensing applications.
Effects of human disturbances on wildlife behaviour and consequences for predator-prey overlap in Southeast Asia
Authors: Lee Samuel Xin Tham , Amir Zachary , Moore Jonathan H. , Gaynor Kaitlyn M. , Luskin Matthew Scott 
Published: February 2024

AbstractSome animal species shift their activity towards increased nocturnality in disturbed habitats to avoid predominantly diurnal humans. This may alter diel overlap among species, a precondition to most predation and competition interactions that structure food webs. Here, using camera trap data from 10 tropical forest landscapes, we find that hyperdiverse Southeast Asian wildlife communities shift their peak activity from early mornings in intact habitats towards dawn and dusk in disturbed habitats (increased crepuscularity). Our results indicate that anthropogenic disturbances drive opposing behavioural adaptations based on rarity, size and feeding guild, with more nocturnality among the 59 rarer specialists’ species, more diurnality for medium-sized generalists, and less diurnality for larger hunted species. Species turnover also played a role in underpinning community- and guild-level responses, with disturbances associated with markedly more detections of diurnal generalists and their medium-sized diurnal predators. However, overlap among predator-prey or competitor guilds does not vary with disturbance, suggesting that net species interactions may be conserved.
VO2 memristor-based frequency converter with in-situ synthesize and mix for wireless internet-of-things
Authors: Liu Chang , Tiw Pek Jun , Zhang Teng , Wang Yanghao , Cai Lei , Yuan Rui , Pan Zelun , Yue Wenshuo , Tao Yaoyu , Yang Yuchao 
Published: February 2024

AbstractWireless internet-of-things (WIoT) with data acquisition sensors are evolving rapidly and the demand for transmission efficiency is growing rapidly. Frequency converter that synthesizes signals at different frequencies and mixes them with sensor datastreams is a key component for efficient wireless transmission. However, existing frequency converters employ separate synthesize and mix circuits with complex digital and analog circuits using complementary metal-oxide semiconductor (CMOS) devices, naturally incurring excessive latency and energy consumption. Here we report a highly uniform and calibratable VO2 memristor oscillator, based on which we build memristor-based frequency converter using 8$$\times$$
×
8 VO2 array that can realize in-situ frequency synthesize and mix with help of compact periphery circuits. We investigate the self-oscillation based on negative differential resistance of VO2 memristors and the programmability with different driving currents and calibration resistances, demonstrating capabilities of such frequency converter for in-situ frequency synthesize and mix for 2 ~ 8 channels with frequencies up to 48 kHz for low frequency transmission link. When transmitting classical sensor data (acoustic, vision and spatial) in an end-to-end WIoT experimental setup, our VO2-based memristive frequency converter presents up to 1.45× ~ 1.94× power enhancement with only 0.02 ~ 0.21 dB performance degradations compared with conventional CMOS-based frequency converter. This work highlights the potential in solving frequency converter’s speed and energy efficiency problems in WIoT using high crystalline quality epitaxially grown VO2 and calibratable VO2-based oscillator array, revealing a promising direction for next-generation WIoT system design.
Digital PCR quantification of ultrahigh ERBB2 copy number identifies poor breast cancer survival after trastuzumab
Authors: Meng Pei , Dalal Hina , Chen Yilun , Brueffer Christian , Gladchuk Sergii , Alcaide Miguel , Ehinger Anna , Saal Lao H. 
Published: February 2024

AbstractHER2/ERBB2 evaluation is necessary for treatment decision-making in breast cancer (BC), however current methods have limitations and considerable variability exists. DNA copy number (CN) evaluation by droplet digital PCR (ddPCR) has complementary advantages for HER2/ERBB2 diagnostics. In this study, we developed a single-reaction multiplex ddPCR assay for determination of ERBB2 CN in reference to two control regions, CEP17 and a copy-number-stable region of chr. 2p13.1, validated CN estimations to clinical in situ hybridization (ISH) HER2 status, and investigated the association of ERBB2 CN with clinical outcomes. 909 primary BC tissues were evaluated and the area under the curve for concordance to HER2 status was 0.93 and 0.96 for ERBB2 CN using either CEP17 or 2p13.1 as reference, respectively. The accuracy of ddPCR ERBB2 CN was 93.7% and 94.1% in the training and validation groups, respectively. Positive and negative predictive value for the classic HER2 amplification and non-amplification groups was 97.2% and 94.8%, respectively. An identified biological “ultrahigh” ERBB2 ddPCR CN group had significantly worse survival within patients treated with adjuvant trastuzumab for both recurrence-free survival (hazard ratio, HR: 3.3; 95% CI 1.1–9.6; p = 0.031, multivariable Cox regression) and overall survival (HR: 3.6; 95% CI 1.1–12.6; p = 0.041). For validation using RNA-seq data as a surrogate, in a population-based SCAN-B cohort (NCT02306096) of 682 consecutive patients receiving adjuvant trastuzumab, the ultrahigh-ERBB2 mRNA group had significantly worse survival. Multiplex ddPCR is useful for ERBB2 CN estimation and ultrahigh ERBB2 may be a predictive factor for decreased long-term survival after trastuzumab treatment.