bluuebunny/crossref_metadata_2025_split huggingface dataset:
Geometric constraints on human brain function
Authors: Pang James C. , Aquino Kevin M. , Oldehinkel Marianne , Robinson Peter A. , Fulcher Ben D. , Breakspear Michael , Fornito Alex 
Published: May 2023

AbstractThe anatomy of the brain necessarily constrains its function, but precisely how remains unclear. The classical and dominant paradigm in neuroscience is that neuronal dynamics are driven by interactions between discrete, functionally specialized cell populations connected by a complex array of axonal fibres1–3. However, predictions from neural field theory, an established mathematical framework for modelling large-scale brain activity4–6, suggest that the geometry of the brain may represent a more fundamental constraint on dynamics than complex interregional connectivity7,8. Here, we confirm these theoretical predictions by analysing human magnetic resonance imaging data acquired under spontaneous and diverse task-evoked conditions. Specifically, we show that cortical and subcortical activity can be parsimoniously understood as resulting from excitations of fundamental, resonant modes of the brain’s geometry (that is, its shape) rather than from modes of complex interregional connectivity, as classically assumed. We then use these geometric modes to show that task-evoked activations across over 10,000 brain maps are not confined to focal areas, as widely believed, but instead excite brain-wide modes with wavelengths spanning over 60 mm. Finally, we confirm predictions that the close link between geometry and function is explained by a dominant role for wave-like activity, showing that wave dynamics can reproduce numerous canonical spatiotemporal properties of spontaneous and evoked recordings. Our findings challenge prevailing views and identify a previously underappreciated role of geometry in shaping function, as predicted by a unifying and physically principled model of brain-wide dynamics.
Myelin dysfunction drives amyloid-β deposition in models of Alzheimer’s disease
Authors: Depp Constanze , Sun Ting , Sasmita Andrew Octavian , Spieth Lena , Berghoff Stefan A. , Nazarenko Taisiia , Overhoff Katharina , Steixner-Kumar Agnes A. , Subramanian Swati , Arinrad Sahab , Ruhwedel Torben , Möbius Wiebke , Göbbels Sandra , Saher Gesine , Werner Hauke B. , Damkou Alkmini , Zampar Silvia , Wirths Oliver , Thalmann Maik , Simons Mikael , Saito Takashi , Saido Takaomi , Krueger-Burg Dilja , Kawaguchi Riki , Willem Michael , Haass Christian , Geschwind Daniel , Ehrenreich Hannelore , Stassart Ruth , Nave Klaus-Armin 
Published: May 2023

AbstractThe incidence of Alzheimer’s disease (AD), the leading cause of dementia, increases rapidly with age, but why age constitutes the main risk factor is still poorly understood. Brain ageing affects oligodendrocytes and the structural integrity of myelin sheaths1, the latter of which is associated with secondary neuroinflammation2,3. As oligodendrocytes support axonal energy metabolism and neuronal health4–7, we hypothesized that loss of myelin integrity could be an upstream risk factor for neuronal amyloid-β (Aβ) deposition, the central neuropathological hallmark of AD. Here we identify genetic pathways of myelin dysfunction and demyelinating injuries as potent drivers of amyloid deposition in mouse models of AD. Mechanistically, myelin dysfunction causes the accumulation of the Aβ-producing machinery within axonal swellings and increases the cleavage of cortical amyloid precursor protein. Suprisingly, AD mice with dysfunctional myelin lack plaque-corralling microglia despite an overall increase in their numbers. Bulk and single-cell transcriptomics of AD mouse models with myelin defects show that there is a concomitant induction of highly similar but distinct disease-associated microglia signatures specific to myelin damage and amyloid plaques, respectively. Despite successful induction, amyloid disease-associated microglia (DAM) that usually clear amyloid plaques are apparently distracted to nearby myelin damage. Our data suggest a working model whereby age-dependent structural defects of myelin promote Aβ plaque formation directly and indirectly and are therefore an upstream AD risk factor. Improving oligodendrocyte health and myelin integrity could be a promising target to delay development and slow progression of AD.
Pan-KRAS inhibitor disables oncogenic signalling and tumour growth
Authors: Kim Dongsung , Herdeis Lorenz , Rudolph Dorothea , Zhao Yulei , Böttcher Jark , Vides Alberto , Ayala-Santos Carlos I. , Pourfarjam Yasin , Cuevas-Navarro Antonio , Xue Jenny Y. , Mantoulidis Andreas , Bröker Joachim , Wunberg Tobias , Schaaf Otmar , Popow Johannes , Wolkerstorfer Bernhard , Kropatsch Katrin Gabriele , Qu Rui , de Stanchina Elisa , Sang Ben , Li Chuanchuan , McConnell Darryl B. , Kraut Norbert , Lito Piro 
Published: May 2023

AbstractKRAS is one of the most commonly mutated proteins in cancer, and efforts to directly inhibit its function have been continuing for decades. The most successful of these has been the development of covalent allele-specific inhibitors that trap KRAS G12C in its inactive conformation and suppress tumour growth in patients1–7. Whether inactive-state selective inhibition can be used to therapeutically target non-G12C KRAS mutants remains under investigation. Here we report the discovery and characterization of a non-covalent inhibitor that binds preferentially and with high affinity to the inactive state of KRAS while sparing NRAS and HRAS. Although limited to only a few amino acids, the evolutionary divergence in the GTPase domain of RAS isoforms was sufficient to impart orthosteric and allosteric constraints for KRAS selectivity. The inhibitor blocked nucleotide exchange to prevent the activation of wild-type KRAS and a broad range of KRAS mutants, including G12A/C/D/F/V/S, G13C/D, V14I, L19F, Q22K, D33E, Q61H, K117N and A146V/T. Inhibition of downstream signalling and proliferation was restricted to cancer cells harbouring mutant KRAS, and drug treatment suppressed KRAS mutant tumour growth in mice, without having a detrimental effect on animal weight. Our study suggests that most KRAS oncoproteins cycle between an active state and an inactive state in cancer cells and are dependent on nucleotide exchange for activation. Pan-KRAS inhibitors, such as the one described here, have broad therapeutic implications and merit clinical investigation in patients with KRAS-driven cancers.
In situ tumour arrays reveal early environmental control of cancer immunity
Authors: Ortiz-Muñoz Guadalupe , Brown Markus , Carbone Catherine B. , Pechuan-Jorge Ximo , Rouilly Vincent , Lindberg Henrik , Ritter Alex T. , Raghupathi Gautham , Sun Qianbo , Nicotra Tess , Mantri Shreya R. , Yang Angela , Doerr Jonas , Nagarkar Deepti , Darmanis Spyros , Haley Benjamin , Mariathasan Sanjeev , Wang Yulei , Gomez-Roca Carlos , de Andrea Carlos Eduardo , Spigel David , Wu Thomas , Delamarre Lelia , Schöneberg Johannes , Modrusan Zora , Price Richard , Turley Shannon J. , Mellman Ira , Moussion Christine 
Published: May 2023

AbstractThe immune phenotype of a tumour is a key predictor of its response to immunotherapy1–4. Patients who respond to checkpoint blockade generally present with immune-inflamed5–7 tumours that are highly infiltrated by T cells. However, not all inflamed tumours respond to therapy, and even lower response rates occur among tumours that lack T cells (immune desert) or that spatially exclude T cells to the periphery of the tumour lesion (immune excluded)8. Despite the importance of these tumour immune phenotypes in patients, little is known about their development, heterogeneity or dynamics owing to the technical difficulty of tracking these features in situ. Here we introduce skin tumour array by microporation (STAMP)—a preclinical approach that combines high-throughput time-lapse imaging with next-generation sequencing of tumour arrays. Using STAMP, we followed the development of thousands of arrayed tumours in vivo to show that tumour immune phenotypes and outcomes vary between adjacent tumours and are controlled by local factors within the tumour microenvironment. Particularly, the recruitment of T cells by fibroblasts and monocytes into the tumour core was supportive of T cell cytotoxic activity and tumour rejection. Tumour immune phenotypes were dynamic over time and an early conversion to an immune-inflamed phenotype was predictive of spontaneous or therapy-induced tumour rejection. Thus, STAMP captures the dynamic relationships of the spatial, cellular and molecular components of tumour rejection and has the potential to translate therapeutic concepts into successful clinical strategies.
Effects of the order of exposure to antimicrobials on the incidence of multidrug-resistant Pseudomonas aeruginosa
Authors: Yasuda Nami , Fujita Tomoko , Fujioka Takahiro , Tagawa Mei , Kohira Naoki , Torimaru Kensho , Shiota Sumiko , Kumagai Takanori , Morita Daichi , Ogawa Wakano , Tsuchiya Tomofusa , Kuroda Teruo 
Published: May 2023

AbstractMultidrug-resistant Pseudomonas aeruginosa (MDRP) is one of the most important pathogens in clinical practice. To clarify the mechanisms contributing to its emergence, we isolated MDRPs using the P. aeruginosa PAO1, the whole genome sequence of which has already been elucidated. Mutant strains resistant to carbapenems, aminoglycosides, and new quinolones, which are used to treat P. aeruginosa infections, were isolated; however, none met the criteria for MDRPs. Then, PAO1 strains were exposed to these antimicrobial agents in various orders and the appearance rate of MDRP varied depending on the order of exposure; MDRPs more frequently appeared when gentamicin was applied before ciprofloxacin, but were rarely isolated when ciprofloxacin was applied first. Exposure to ciprofloxacin followed by gentamicin increased the expression of MexCD-OprJ, an RND-type multidrug efflux pump, due to the NfxB mutation. In contrast, exposure to gentamicin followed by ciprofloxacin resulted in more mutations in DNA gyrase. These results suggest that the type of quinolone resistance mechanism is related to the frequency of MDRP and that the risk of MDRP incidence is highly dependent on the order of exposure to gentamicin and ciprofloxacin.
Compact high-resolution FBG strain interrogator based on laser-written 3D scattering structure in flat optical fiber
Authors: Falak Przemyslaw , Lee Timothy , Zahertar Shahrzad , Shi Bo , Moog Bruno , Brambilla Gilberto , Holmes Christopher , Beresna Martynas 
Published: May 2023

AbstractWe demonstrate a fiber Bragg grating (FBG) strain interrogator based on a scattering medium to generate stable and deterministic speckle patterns, calibrated with applied strain, which are highly dependent on the FBG back-reflection spectral components. The strong wavelength-dependency of speckle patterns was previously used for high resolution wavemeters where scattering effectively folds the optical path, but instability makes practical realization of such devices difficult. Here, a new approach is demonstrated by utilizing femtosecond laser-written scatterers inside flat optical fiber, to enhance mechanical stability. By inscribing 15 planes of pseudo-randomized nanovoids (714 $$\times$$
×
500 voids per plane) as a 3D array in a 1 $$\times$$
×
0.7 $$\times$$
×
0.16 mm volume, the intrinsic stability and compactness of the device was improved. Operating as a wavemeter, it remained stable for at least 60 h with 45 pm resolution over the wavelength range of 1040–1056 nm. As a reflection mode FBG interrogator, after calibrating speckle patterns by applying tensile strain to the FBG, the device is capable of detecting microstrain changes in the range of 0–200 $$\mu \epsilon$$

μ
ϵ

with a standard error of 4 $$\mu \epsilon$$

μ
ϵ

, limited by the translation stage step size. All these characteristics make it an interesting technology for filling the niche of low-cost, high-resolution wavemeters and interrogators which offer the best available trade-off between resolution, compactness, price and stability.
Low energy nebulization preserves integrity of SARS-CoV-2 mRNA vaccines for respiratory delivery
Authors: van Rijn Cees J. M. , Vlaming Killian E. , Bem Reinout A. , Dekker Rob J. , Poortinga Albert , Breit Timo , van Leeuwen Selina , Ensink Wim A. , van Wijnbergen Kelly , van Hamme John L. , Bonn Daniel , Geijtenbeek Teunis B. H. 
Published: May 2023

AbstractNebulization of mRNA therapeutics can be used to directly target the respiratory tract. A promising prospect is that mucosal administration of lipid nanoparticle (LNP)-based mRNA vaccines may lead to a more efficient protection against respiratory viruses. However, the nebulization process can rupture the LNP vehicles and degrade the mRNA molecules inside. Here we present a novel nebulization method able to preserve substantially the integrity of vaccines, as tested with two SARS-CoV-2 mRNA vaccines. We compare the new method with well-known nebulization methods used for medical respiratory applications. We find that a lower energy level in generating LNP droplets using the new nebulization method helps safeguard the integrity of the LNP and vaccine. By comparing nebulization techniques with different energy dissipation levels we find that LNPs and mRNAs can be kept largely intact if the energy dissipation remains below a threshold value, for LNP integrity 5–10 J/g and for mRNA integrity 10–20 J/g for both vaccines.
Assisted damage closure and healing in soft robots by shape memory alloy wires
Authors: Kashef Tabrizian Seyedreza , Terryn Seppe , Cornellà Aleix Costa , Brancart Joost , Legrand Julie , Van Assche Guy , Vanderborght Bram 
Published: May 2023

AbstractSelf-healing soft robots show enormous potential to recover functional performance after healing the damages. However, healing in these systems is limited by the recontact of the fracture surfaces. This paper presents for the first time a shape memory alloy (SMA) wire-reinforced soft bending actuator made out of a castor oil-based self-healing polymer, with the incorporated ability to recover from large incisions via shape memory assisted healing. The integrated SMA wires serve three major purposes; (i) Large incisions are closed by contraction of the current-activated SMA wires that are integrated into the chamber. These pull the fracture surfaces into contact, enabling the healing. (ii) The heat generated during the activation of the SMA wires is synergistically exploited for accelerating the healing. (iii) Lastly, during pneumatic actuation, the wires constrain radial expansion and one-side longitudinal extension of the soft chamber, effectuating the desired actuator bending motion. This novel approach of healing is studied via mechanical and ultrasound tests on the specimen level, as well as via bending characterization of the pneumatic robot in multiple damage healing cycles. This technology allows soft robots to become more independent in terms of their self-healing capabilities from human intervention.
Restoration of the gut barrier integrity and restructuring of the gut microbiome in aging by angiotensin-(1–7)
Authors: Chittimalli Kishore , Jahan Jesmin , Sakamuri Anil , McAdams Zachary L. , Ericsson Aaron C. , Jarajapu Yagna P.R. 
Published: May 2023

Abstract
Compromised barrier function of colon epithelium with aging is largely due to gut microbial dysbiosis. Recent studies implicate an important role for angiotensin converting enzymes, ACE and ACE2, angiotensins, and the receptors, AT1 receptor (AT1R) and Mas receptor (MasR), in the regulation of colon functions. The present study tested the hypothesis that leaky gut in aging is associated with an imbalance in ACE2/ACE and that the treatment with angiotenisn-(1–7) (Ang-(1–7)) will restore gut barrier integrity and microbiome. Studies were carried out in Young (3–4 months) and old (20–24 months) male mice. Ang-(1–7) was administered by using osmotic pumps. Outcome measures included expressions of ACE, ACE2, AT1R, and MasR, intestinal permeability by using FITC-dextran, and immunohistochemistry of claudin 1 and occludin, and intestinal stem cells (ISCs). ACE2 protein and activity were decreased in Old group while that of ACE were unchanged. Increased intestinal permeability and plasma levels of zonulin-1 in the Old group were normalized by Ang-(1–7). Epithelial disintegrity, reduced number of goblet cells and ISCs in the old group were restored by Ang-(1–7). Expression of claudin 1 and occludin in the aging colon was increased by Ang-(1–7). Infiltration of CD11b+ or F4/80+ inflammatory cells in the old colons were decreased by Ang-(1–7). Gut microbial dysbiosis in aging was evident by decreased richness and altered beta diversity that were reversed by Ang-(1–7) with increased abundance of Lactobacillus or Lachnospiraceae. The present study shows that Ang-(1–7) restores gut barrier integrity and reduces inflammation in the aging colon by restoring the layer of ISCs and by restructuring the gut microbiome.
Hearing Impairment, Mental Health Services Use, and Perceived Unmet Needs Among Adults With Serious Mental Illness: A Cross-Sectional Study
Authors: Xie Zhigang , Tanner Rebecca , Striley Catherine L. , Sheffield Sterling W. , Marlow Nicole M. 
Published: May 2023

Purpose:Individuals with hearing impairment have higher risks of mental illnesses. We sought to develop a richer understanding of how the presence of any hearing impairment affects three types (prescription medication, outpatient services, and inpatient services) of mental health services utilization (MHSU) and perceived unmet needs for mental health care; also, we aimed to identify sociodemographic factors associated with outpatient mental health services use among those with hearing impairment and discuss potential implications under the U.S. health care system.Method:Using secondary data from the 2015–2019 National Survey on Drug Use and Health, our study included U.S. adults aged ≥ 18 years who reported serious mental illnesses (SMIs) in the past year. Multivariable logistic regression was used to examine associations of hearing impairment with MHSU and perceived unmet mental health care needs.Results:The study sample comprised 12,541 adults with SMIs. Prevalence of MHSU (medication: 55.5% vs. 57.5%; outpatient: 37.1% vs. 44.2%; inpatient: 6.6% vs.7.1%) and unmet needs for mental health care (47.5% vs. 43.3%) were estimated among survey respondents who reported hearing impairment and those who did not, respectively. Those with hearing impairment were significantly less likely to report outpatient MHSU (OR= 0.73, 95% CI [0.60, 0.90]).Conclusions:MHSU was low while perceived unmet needs for mental health care were high among individuals with SMIs, regardless of hearing status. In addition, patients with hearing impairment were significantly less likely to report outpatient MHSU than their counterparts. Enhancing communication is essential to improve access to mental health care for those with hearing impairment.
Collective fabrication of guided longitudinal SAW resonator without Bragg grating mirror
Authors: Baron Thomas , Oliveri Stefania , Richard Thomas , Soumann Valerie , Belharet Djaffar , Robert Laurent , Raschetti Marina , Salut Roland , Courjon Emilie , Laroche Thierry , Bernard Florent , Clairet Alexandre , Ballandras Sylvain 
Published: May 2023

AbstractThis Research article document discussed about a new structure composed of a sub‐micron‐thick layer of a single‐crystal piezoelectric material on a substrate. Longitudinal waves are used for experimental demonstration with 4’’ collective processes. Electrical experimental–computation validate the concept with Q × f products near 1012.
Classification method for multiple power quality disturbances via label distribution enhancement and multi‐granular feature optimization
Authors: Ruan Zihang , Hu Wenxi , Ma Xing , Xiao Xianyong , Lei Lei , Liu Huizi 
Published: May 2023

AbstractLarge‐scale integration of distributed generation and widespread use of power electronic equipment make power quality disturbances (PQDs) more complicated. There are still unsolved problems for the classification of multiple power quality disturbances (MPQDs) that consist of various kinds of single disturbances: (1) since the difference between the contribution degrees of every contained single disturbance to the composite disturbance is ignored, the logical labels cannot completely describe the composite disturbance; (2) the optimal feature in one granular space may not be optimal in another. These drawbacks lead to the degradation of MPQD classification, which should be considered a multi‐label model rather than single‐label model used in existing methods. Therefore, this paper proposes a novel method to improve the classification performance of MPQDs. The label distribution, representing the contribution degree of a single disturbance to the composite disturbance, is introduced. In addition, the high‐dimensional feature space is reduced by multigranular optimization, where the fuzziness and redundancy are removed by the modified rough‐set method. To improve the performance of the classifier, the ensemble classification model based on homogeneous classifier integration is proposed to integrate the base classifiers constructed by the feature vectors from different granularity spaces. A large number of field recordings are applied to validate the proposed method. The results show that the proposed method performs better than traditional methods, especially under noisy environments.
Scalable multi‐site photovoltaic power forecasting based on stream computing
Authors: Sun Yuxi , Yu Heyang , Geng Guangchao , Chen Changyu , Jiang Quanyuan 
Published: May 2023

AbstractPhotovoltaic (PV) is essential for global carbon neutrality, it is imperative to forecast PV generation accurately for power operation. With the rapid growth of distributed PV sites, a scalable cloud service tends to play a vital role in PV forecasting to address the increasing cost of computing resources and data subscriptions. Such a scheme creates a possibility to further enhance forecasting performance by re‐using forecasting model, data, and computing resources all in the cloud. In order to achieve this goal, this work proposes a multi‐site PV forecasting system design with a message queue (MQ) and stream computing engine, where a hybrid neural network model is trained and continuously updated using real‐time data. A performance benchmark with up to 60 sites served simultaneously was performed to verify the scalability of the stream computing based approach. Moreover, after incremental updating of the forecasting model, a decrease in normalized root mean square error and normalized mean absolute error of PV forecasting were observed, demonstrating that better short‐term forecasting accuracy was achieved.
Traversée adolescente et rencontre de l’objet
Authors: Bonnichon Delphine 
Published: May 2023

Nous émettons l’hypothèse que le recours à l’homoérotisme à l’adolescence constitue une pièce maîtresse dans le cheminement qui mène à la rencontre de l’objet en revêtant plusieurs fonctions. Mais ce recours peut buter sur le travail de perte que toute adolescence exige. Nous déploierons les spécificités de ce recours et ses potentiels empêchements dans le développement psychosexuel du garçon. Nous mettrons ces éléments à l’épreuve, à partir du roman « Call me by your name » d’André Aciman (2007).
Le corps vécu et la « fabrique du temps »
Authors: Crespo Inés , Sirmai Claire 
Published: May 2023

Nous explorons des façons dont le corps vécu impacte l’expérience psychique du temps, que nous nommons la « fabrique du temps » en suivant l’analyse de la phénoménologie de la conscience intime du temps élaborée par E. Husserl et reprise par M. Merleau-Ponty. Pour ce faire, nous proposons de relater la prise en charge en psychomotricité d’un jeune adulte, patient en hôpital de jour, et d’étoffer ce récit conceptuellement en nous appuyant sur des notions provenant de la phénoménologie.