bluuebunny/crossref_metadata_2025_split huggingface dataset:
HER2 + breast cancers evade anti-HER2 therapy via a switch in driver pathway
Authors: Smith Alison E. , Ferraro Emanuela , Safonov Anton , Morales Cristina Bernado , Lahuerta Enrique J. Arenas , Li Qing , Kulick Amanda , Ross Dara , Solit David B. , de Stanchina Elisa , Reis-Filho Jorge , Rosen Neal , Arribas Joaquín , Razavi Pedram , Chandarlapaty Sarat 
Published: November 2021

AbstractInhibition of HER2 in HER2-amplified breast cancer has been remarkably successful clinically, as demonstrated by the efficacy of HER-kinase inhibitors and HER2-antibody treatments. Whilst resistance to HER2 inhibition is common in the metastatic setting, the specific programs downstream of HER2 driving resistance are not established. Through genomic profiling of 733 HER2-amplified breast cancers, we identify enrichment of somatic alterations that promote MEK/ERK signaling in metastatic tumors with shortened progression-free survival on anti-HER2 therapy. These mutations, including NF1 loss and ERBB2 activating mutations, are sufficient to mediate resistance to FDA-approved HER2 kinase inhibitors including tucatinib and neratinib. Moreover, resistant tumors lose AKT dependence while undergoing a dramatic sensitization to MEK/ERK inhibition. Mechanistically, this driver pathway switch is a result of MEK-dependent activation of CDK2 kinase. These results establish genetic activation of MAPK as a recurrent mechanism of anti-HER2 therapy resistance that may be effectively combated with MEK/ERK inhibitors.
Temporal variability in quantitative human gut microbiome profiles and implications for clinical research
Authors: Vandeputte Doris , De Commer Lindsey , Tito Raul Y. , Kathagen Gunter , Sabino João , Vermeire Séverine , Faust Karoline , Raes Jeroen 
Published: November 2021

AbstractWhile clinical gut microbiota research is ever-expanding, extending reference knowledge of healthy between- and within-subject gut microbiota variation and its drivers remains essential; in particular, temporal variability is under-explored, and a comparison with cross-sectional variation is missing. Here, we perform daily quantitative microbiome profiling on 713 fecal samples from 20 Belgian women over six weeks, combined with extensive anthropometric measurements, blood panels, dietary data, and stool characteristics. We show substantial temporal variation for most major gut genera; we find that for 78% of microbial genera, day-to-day absolute abundance variation is substantially larger within than between individuals, with up to 100-fold shifts over the study period. Diversity, and especially evenness indicators also fluctuate substantially. Relative abundance profiles show similar but less pronounced temporal variation. Stool moisture, and to a lesser extent diet, are the only significant host covariates of temporal microbiota variation, while menstrual cycle parameters did not show significant effects. We find that the dysbiotic Bact2 enterotype shows increased between- and within-subject compositional variability. Our results suggest that to increase diagnostic as well as target discovery power, studies could adopt a repeated measurement design and/or focus analysis on community-wide microbiome descriptors and indices.
Modulation of pancreatic cancer cell sensitivity to FOLFIRINOX through microRNA-mediated regulation of DNA damage
Authors: Carotenuto Pietro , Amato Francesco , Lampis Andrea , Rae Colin , Hedayat Somaieh , Previdi Maria C. , Zito Domenico , Raj Maya , Guzzardo Vincenza , Sclafani Francesco , Lanese Andrea , Parisi Claudia , Vicentini Caterina , Said-Huntingford Ian , Hahne Jens C. , Hallsworth Albert , Kirkin Vladimir , Young Kate , Begum Ruwaida , Wotherspoon Andrew , Kouvelakis Kyriakos , Azevedo Sergio Xavier , Michalarea Vasiliki , Upstill-Goddard Rosie , Rao Sheela , Watkins David , Starling Naureen , Sadanandam Anguraj , Chang David K. , Biankin Andrew V. , Jamieson Nigel B. , Scarpa Aldo , Cunningham David , Chau Ian , Workman Paul , Fassan Matteo , Valeri Nicola , Braconi Chiara 
Published: November 2021

AbstractFOLFIRINOX, a combination of chemotherapy drugs (Fluorouracil, Oxaliplatin, Irinotecan -FOI), provides the best clinical benefit in pancreatic ductal adenocarcinoma (PDAC) patients. In this study we explore the role of miRNAs (MIR) as modulators of chemosensitivity to identify potential biomarkers of response. We find that 41 and 84 microRNA inhibitors enhance the sensitivity of Capan1 and MiaPaCa2 PDAC cells respectively. These include a MIR1307-inhibitor that we validate in further PDAC cell lines. Chemotherapy-induced apoptosis and DNA damage accumulation are higher in MIR1307 knock-out (MIR1307KO) versus control PDAC cells, while re-expression of MIR1307 in MIR1307KO cells rescues these effects. We identify binding of MIR1307 to CLIC5 mRNA through covalent ligation of endogenous Argonaute-bound RNAs cross-linking immunoprecipitation assay. We validate these findings in an in vivo model with MIR1307 disruption. In a pilot cohort of PDAC patients undergoing FOLFIRONX chemotherapy, circulating MIR1307 correlates with clinical outcome.
Temperature effects on carbon storage are controlled by soil stabilisation capacities
Authors: Hartley Iain P. , Hill Tim C. , Chadburn Sarah E. , Hugelius Gustaf 
Published: November 2021

AbstractPhysical and chemical stabilisation mechanisms are now known to play a critical role in controlling carbon (C) storage in mineral soils, leading to suggestions that climate warming-induced C losses may be lower than previously predicted. By analysing > 9,000 soil profiles, here we show that, overall, C storage declines strongly with mean annual temperature. However, the reduction in C storage with temperature was more than three times greater in coarse-textured soils, with limited capacities for stabilising organic matter, than in fine-textured soils with greater stabilisation capacities. This pattern was observed independently in cool and warm regions, and after accounting for potentially confounding factors (plant productivity, precipitation, aridity, cation exchange capacity, and pH). The results could not, however, be represented by an established Earth system model (ESM). We conclude that warming will promote substantial soil C losses, but ESMs may not be predicting these losses accurately or which stocks are most vulnerable.
Quantum mechanical rotation of a photon polarization by Earth’s gravitational field
Authors: Noh Hansol , Alsing Paul M. , Ahn Doyeol , Miller Warner A. , Park Namkyoo 
Published: November 2021

AbstractWe describe the quantum mechanical rotation of a photon state, the Wigner rotation—a quantum effect that couples a transformation of a reference frame to a particle’s spin, to investigate geometric phases induced by Earth’s gravitational field for observers in various orbits. We find a potentially measurable quantum phase of the Wigner rotation angle in addition to the rotation of standard fame, the latter of which is computed and agrees well with the geodetic rotation. When an observer is in either a circular or a spiraling orbit containing non-zero angular momentum, the additional quantum phase contributes 10−6 degree to 10−4 degree respectively, depending on the altitude of the Earth orbit. In the former case, the additional quantum phase is dominant over the near-zero classical geodetic rotation. Our results show that the Wigner rotation represents a non-trivial semi-classical effect of quantum field theory on a background classical gravitational field.
Sauropodomorph evolution across the Triassic–Jurassic boundary: body size, locomotion, and their influence on morphological disparity
Authors: Apaldetti Cecilia , Pol Diego , Ezcurra Martín D. , Martínez Ricardo N. 
Published: November 2021

AbstractSauropodomorph dinosaurs were the dominant medium to large-sized herbivores of most Mesozoic continental ecosystems, being characterized by their long necks and reaching a size unparalleled by other terrestrial animals (> 60 tonnes). Our study of morphological disparity across the entire skeleton shows that during the Late Triassic the oldest known sauropodomorphs occupied a small region of morphospace, subsequently diversifying both taxonomically and ecologically, and shifting to a different and broader region of the morphospace. After the Triassic–Jurassic boundary event, there are no substancial changes in sauropodomorph morphospace occupation. Almost all Jurassic sauropodomorph clades stem from ghost lineages that cross the Triassic–Jurassic boundary, indicating that variations after the extinction were more related to changes of pre-existing lineages (massospondylids, non-gravisaurian sauropodiforms) rather than the emergence of distinct clades or body plans. Modifications in the locomotion (bipedal to quadrupedal) and the successive increase in body mass seem to be the main attributes driving sauropodomorph morphospace distribution during the Late Triassic and earliest Jurassic. The extinction of all non-sauropod sauropodomorphs by the Toarcian and the subsequent diversification of gravisaurian sauropods represent a second expansion of the sauropodomorph morphospace, representing the onset of the flourishing of these megaherbivores that subsequently dominated in Middle and Late Jurassic terrestrial assemblages.
Effects of size and position of an unconnected aluminum electrode on bipolar anodization in an AC electric field
Authors: Takeuchi Ryo , Asoh Hidetaka 
Published: November 2021

AbstractThe effects of the size and position of an aluminum bipolar electrode (BPE) on the uniformity of formation of anodic porous alumina in an alternating current electric field were investigated. Anodized specimens were dyed, and the resistance was measured after the specimens were anodized again. Phenomena observed during film formation indicated that the BPEs had unique potential distributions that strongly depended on their length and width. The color variations and electrical resistance of the BPEs were symmetrical and varied from the centers of the BPEs to their ends. When multiple BPEs were processed at the same time, their position in the non-uniform electric field was demonstrated to be an important factor for controlling the uniformity of film formation. The best results were obtained when the BPE was placed at the center of the defined space.
Behavioural effects of task-relevant neuromodulation by rTMS on giving-up
Authors: Miyauchi Eri , Kawasaki Masahiro 
Published: November 2021

AbstractRecent studies suggest that online repetitive transcranial magnetic stimulation (rTMS) can induce local entrainment of ongoing endogenous oscillatory activity during a task. This effect may impact cognitive performance, depending on the function of the oscillation. In this study, we aimed to investigate the effects of stimulation frequency and target location that are relevant to the cognitive processes of giving-up. We first investigated the correlations between the EEG oscillations and cognitive giving-up processes during problem-solving tasks (Experiment 1). We then conducted online rTMS to examine the frequency-dependent stimulation effects of rTMS on the performance of problem-solving tasks and ongoing oscillations (Experiment 2). The results of Experiment 1 suggested that the frontal theta rhythm is associated with the giving-up processes and that the frontal alpha rhythm is associated with problem-solving behaviour. Accordingly, we hypothesised that rTMS at the theta frequency would induce ongoing theta activity and accelerate the giving-up behaviour, while rTMS at the alpha frequency would induce ongoing alpha activity and slow down the giving-up behaviour in Experiment 2. The results showed that theta-frequency rTMS application induced an increase in theta amplitudes and shortened the giving-up response. Alpha-frequency rTMS application induced an increase in alpha amplitudes, but did not change giving-up responses. Considering the close resemblance between giving-up behaviour and rumination in depression, neuromodulation of cognitive giving-up processes may lead to a new intervention to treat depression by rTMS. Furthermore, this study strengthens the hypothesis that modulating task-relevant oscillations by rTMS could induce behavioural changes related to cognitive performance.
The mechanisms and mechanical energy of human gait initiation from the lower-limb joint level perspective
Authors: Zhao Guoping , Grimmer Martin , Seyfarth Andre 
Published: November 2021

AbstractThis study aims to improve our understanding of gait initiation mechanisms and the lower-limb joint mechanical energy contributions. Healthy subjects were instructed to initiate gait on an instrumented track to reach three self-selected target velocities: slow, normal and fast. Lower-limb joint kinematics and kinetics of the first five strides were analyzed. The results show that the initial lateral weight shift is achieved by hip abduction torque on the lifting leg (leading limb). Before the take-off of the leading limb, the forward body movement is initiated by decreasing ankle plantarflexion torque, which results in an inverted pendulum-like passive forward fall. The hip flexion/extension joint has the greatest positive mechanical energy output in the first stride of the leading limb, while the ankle joint contributes the most positive mechanical energy in the first stride of the trailing limb (stance leg). Our results indicate a strong correlation between control of the frontal plane and the sagittal plane joints during gait initiation. The identified mechanisms and the related data can be used as a guideline for improving gait initiation with wearable robots such as exoskeletons and prostheses.
Urinary concentrations of neonicotinoid insecticides were related to renal tubular dysfunction and neuropsychological complaints in Dry-zone of Sri Lanka
Authors: Taira Kumiko , Kawakami Tomonori , Weragoda Sujithra Kaushaliya , Herath H. M. Ayala S. , Ikenaka Yoshinori , Fujioka Kazutoshi , Hemachandra Madhubhani , Pallewatta Nirmalie , Aoyama Yoshiko , Ishizuka Mayumi , Bonmatin Jean-Marc , Komori Makiko 
Published: November 2021

AbstractNeonicotinoids are systemic insecticides used since the 1990’s , that possess renal tubular toxicity. We conducted a field-based descriptive study in the North Central Dry-zone of Sri Lanka, where chronic kidney disease (CKD) of unknown etiology has been increasing since the 1990’s. To elucidate the relationship between renal tubular dysfunctions and urinary neonicotinoids concentrations, we collected spot urine samples from15 CKD patients, 15 family members, and 62 neighbors in 2015, analyzed two renal tubular biomarkers, Cystatin-C and L-FABP, quantified seven neonicotinoids and a metabolite N-desmethyl-acetamiprid by LC–MS/MS; and we investigated their symptoms using a questionnaire. Cystatin-C and L-FABP had a positive correlation (p < 0.001). N-Desmethyl-acetamiprid was detected in 92.4% of the urine samples, followed by dinotefuran (17.4%), thiamethoxam (17.4%), clothianidin (9.8%), thiacloprid and imidacloprid. Dinotefuran and thiacloprid have never been registered in Sri Lanka. In High Cystatin-C group (> 70 μg/gCre, n = 7), higher urinary concentration of dinotefuran (p = 0.009), and in Zero Cystatin-C group (< LOQ, n = 7), higher N-desmethyl-acetamiprid (p = 0.013), dinotefuran (p = 0.049), and thiacloprid (p = 0.035), and more complaints of chest pains, stomachache, skin eruption and diarrhea (p < 0.05) were found than in Normal Cystatin-C group (n = 78). Urinary neonicotinoids may be one of the potential risk factors for renal tubular dysfunction in this area.
Facial threat affects trust more strongly than facial attractiveness in women than it does in men
Authors: Brustkern Johanna , Heinrichs Markus , Walker Mirella , Schiller Bastian 
Published: November 2021

AbstractTrust is essential in initiating social relationships. Due to the differential evolution of sex hormones as well as the fitness burdens of producing offspring, evaluations of a potential mating partner’s trustworthiness likely differ across sexes. Here, we explore unknown sex-specific effects of facial attractiveness and threat on trusting other-sex individuals. Ninety-three participants (singles; 46 women) attracted by the other sex performed an incentivized trust game. They had to decide whether to trust individuals of the other sex represented by a priori-created face stimuli gradually varying in the intensities of both attractiveness and threat. Male and female participants trusted attractive and unthreatening-looking individuals more often. However, whereas male participants’ trust behavior was affected equally by attractiveness and threat, female participants’ trust behavior was more strongly affected by threat than by attractiveness. This indicates that a partner’s high facial attractiveness might compensate for high facial threat in male but not female participants. Our findings suggest that men and women prioritize attractiveness and threat differentially, with women paying relatively more attention to threat cues inversely signaling parental investment than to attractiveness cues signaling reproductive fitness. This difference might be attributable to an evolutionary, biologically sex-specific decision regarding parental investment and reproduction behavior.
Transpiration rates of red maple (Acer rubrum L.) differ between management contexts in urban forests of Maryland, USA
Authors: Ponte Sarah , Sonti Nancy F. , Phillips Tuana H. , Pavao-Zuckerman Mitchell A. 
Published: November 2021

AbstractThe hydrological functioning of urban trees can reduce stormwater runoff, mitigate the risk of flood, and improve water quality in developed areas. Tree canopies intercept rainfall and return water to the atmosphere through transpiration, while roots increase infiltration and storage in the soil. Despite this, the amount of stormwater that trees remove through these functions in urban settings is not well characterized, limiting the use of urban forests as practical stormwater management strategies. To address this gap, we use ecohydrological approaches to assess the transpiration rates of urban trees in different management settings. Our research questions are: Do transpiration rates of trees of the same species vary among different management contexts? Do relationships between environmental drivers and transpiration change among management contexts? These management settings included single trees over turfgrass and a cluster of trees over turfgrass in Montgomery County, MD, and closed canopy forest with a leaf litter layer in Baltimore, MD. We used sap flux sensors installed in 18 mature red maple (Acer rubrum L.) trees to characterize transpiration rates during the growing season. We also measured soil volumetric water content, air temperature, relative humidity, and precipitation at each site. In agreement with our initial hypothesis, we found that single trees had nearly three times the daily sum of sap flux density (JS) of closed canopy trees. When averaged over the entire measurement period, JS was approximately 260, 195, and 91 g H2O cm−2 day−1 for single trees, cluster trees and closed canopy trees, respectively. Additionally, single trees were more responsive to VPD than closed canopy and cluster trees. These results provide a better understanding of the influence of management context on urban tree transpiration and can help to identify targets to better manage urban forest settings to reduce urban stormwater runoff.
An exceptional G(2) extension of the Standard Model from the correspondence with Cayley–Dickson algebras automorphism groups
Authors: Masi Nicolò 
Published: November 2021

AbstractIn this article I propose a new criterion to extend the Standard Model of particle physics from a straightforward algebraic conjecture: the symmetries of physical microscopic forces originate from the automorphism groups of main Cayley–Dickson algebras, from complex numbers to octonions and sedenions. This correspondence leads to a natural enlargement of the Standard Model color sector, from aSU(3) gauge group to an exceptional Higgs-brokenG(2) group, following the octonionic automorphism relation guideline. In this picture, an additional ensemble of massiveG(2)-gluons emerges, which is separated from the particle dynamics of the Standard Model.
Comprehensive molecular-genetic analysis of mid-frequency sensorineural hearing loss
Authors: Pavlenkova Zuzana , Varga Lukas , Borecka Silvia , Karhanek Miloslav , Huckova Miloslava , Skopkova Martina , Profant Milan , Gasperikova Daniela 
Published: November 2021

AbstractThe genetic heterogeneity of sensorineural hearing loss (SNHL) is a major hurdle to the detection of disease-causing variants. We aimed to identify underlying causal genes associated with mid-frequency hearing loss (HL), which contributes to less than about 1% of SNHL cases, by whole exome sequencing (WES). Thirty families segregating mid-frequency SNHL, in whom biallelic GJB2 mutations had been previously excluded, were selected from among 851 families in our DNA repository of SNHL. DNA samples from the probands were subjected to WES analysis and searched for candidate variants associated with SNHL. We were able to identify the genetic aetiology in six probands (20%). In total, we found three pathogenic and three likely pathogenic variants in four genes (COL4A5, OTOGL, TECTA, TMPRSS3). One more proband was a compound heterozygote for a pathogenic variant and a variant of uncertain significance (VUS) in MYO15A gene. To date, MYO15A and TMPRSS3 have not yet been described in association with mid-frequency SNHL. In eight additional probands, eight candidate VUS variants were detected in five genes (DIAPH1, MYO7A, TECTA, TMC1, TSPEAR). Seven of these 16 variants have not yet been published or mentioned in the available databases. The most prevalent gene was TECTA, identified in 23% of all tested families. Furthermore, we confirmed the hypothesis that a substantive portion of cases with this conspicuous audiogram shape is a consequence of a genetic disorder.
Deep learning-based histopathological segmentation for whole slide images of colorectal cancer in a compressed domain
Authors: Kim Hyeongsub , Yoon Hongjoon , Thakur Nishant , Hwang Gyoyeon , Lee Eun Jung , Kim Chulhong , Chong Yosep 
Published: November 2021

AbstractAutomatic pattern recognition using deep learning techniques has become increasingly important. Unfortunately, due to limited system memory, general preprocessing methods for high-resolution images in the spatial domain can lose important data information such as high-frequency information and the region of interest. To overcome these limitations, we propose an image segmentation approach in the compressed domain based on principal component analysis (PCA) and discrete wavelet transform (DWT). After inference for each tile using neural networks, a whole prediction image was reconstructed by wavelet weighted ensemble (WWE) based on inverse discrete wavelet transform (IDWT). The training and validation were performed using 351 colorectal biopsy specimens, which were pathologically confirmed by two pathologists. For 39 test datasets, the average Dice score, the pixel accuracy, and the Jaccard score were 0.804 ± 0.125, 0.957 ± 0.025, and 0.690 ± 0.174, respectively. We can train the networks for the high-resolution image with the large region of interest compared to the result in the low-resolution and the small region of interest in the spatial domain. The average Dice score, pixel accuracy, and Jaccard score are significantly increased by 2.7%, 0.9%, and 2.7%, respectively. We believe that our approach has great potential for accurate diagnosis.