bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spectral control of nonclassical light pulses using an integrated thin-film lithium niobate modulator
Authors: Zhu Di , Chen Changchen , Yu Mengjie , Shao Linbo , Hu Yaowen , Xin C. J. , Yeh Matthew , Ghosh Soumya , He Lingyan , Reimer Christian , Sinclair Neil , Wong Franco N. C. , Zhang Mian , Lončar Marko 
Published: November 2022

AbstractManipulating the frequency and bandwidth of nonclassical light is essential for implementing frequency-encoded/multiplexed quantum computation, communication, and networking protocols, and for bridging spectral mismatch among various quantum systems. However, quantum spectral control requires a strong nonlinearity mediated by light, microwave, or acoustics, which is challenging to realize with high efficiency, low noise, and on an integrated chip. Here, we demonstrate both frequency shifting and bandwidth compression of heralded single-photon pulses using an integrated thin-film lithium niobate (TFLN) phase modulator. We achieve record-high electro-optic frequency shearing of telecom single photons over terahertz range (±641 GHz or ±5.2 nm), enabling high visibility quantum interference between frequency-nondegenerate photon pairs. We further operate the modulator as a time lens and demonstrate over eighteen-fold (6.55 nm to 0.35 nm) bandwidth compression of single photons. Our results showcase the viability and promise of on-chip quantum spectral control for scalable photonic quantum information processing.
Thin ceramic PZT dual- and multi-frequency pMUT arrays for photoacoustic imaging
Authors: Zheng Qincheng , Wang Haoran , Yang Hao , Jiang Huabei , Chen Zhenfang , Lu Yao , Feng Philip X.-L. , Xie Huikai 
Published: November 2022

AbstractMiniaturized ultrasonic transducer arrays with multiple frequencies are key components in endoscopic photoacoustic imaging (PAI) systems to achieve high spatial resolution and large imaging depth for biomedical applications. In this article, we report on the development of ceramic thin-film PZT-based dual- and multi-frequency piezoelectric micromachined ultrasonic transducer (pMUT) arrays and the demonstration of their PAI applications. With chips sized 3.5 mm in length or 10 mm in diameter, square and ring-shaped pMUT arrays incorporating as many as 2520 pMUT elements and multiple frequencies ranging from 1 MHz to 8 MHz were developed for endoscopic PAI applications. Thin ceramic PZT with a thickness of 9 μm was obtained by wafer bonding and chemical mechanical polishing (CMP) techniques and employed as the piezoelectric layer of the pMUT arrays, whose piezoelectric constant d31 was measured to be as high as 140 pm/V. Benefiting from this high piezoelectric constant, the fabricated pMUT arrays exhibited high electromechanical coupling coefficients and large vibration displacements. In addition to electrical, mechanical, and acoustic characterization, PAI experiments with pencil leads embedded into an agar phantom were conducted with the fabricated dual- and multi-frequency pMUT arrays. Photoacoustic signals were successfully detected by pMUT elements with different frequencies and used to reconstruct single and fused photoacoustic images, which clearly demonstrated the advantages of using dual- and multi-frequency pMUT arrays to provide comprehensive photoacoustic images with high spatial resolution and large signal-to-noise ratio simultaneously.
Effects of stress on neural processing of combat-related stimuli in deployed soldiers: an fMRI study
Authors: Lorenz Robert C. , Butler Oisin , Willmund Gerd , Wesemann Ulrich , Zimmermann Peter , Gallinat Jürgen , Kühn Simone 
Published: November 2022

AbstractSevere trauma exposure may lead to symptoms of both posttraumatic stress disorder and depression. Neuroanatomical theories suggest that both disorders may share imbalances in fronto-limbic circuits. Longitudinal studies are necessary to better understand the impact of a stressful life situation on potential long-term fronto-limbic imbalances. Here we investigated soldiers neural processing of combat-related stimuli versus negative affective stimuli before and after the deployment in different war zones. In the final analysis we included 104 deployed soldiers (combat group) and 36 soldiers that were not deployed (control group). Behaviorally, we found a significant group by time interaction regarding depression symptom scores with an increase in the combat group. Depressive symptoms were subclinical. On the neural level, neither the whole brain analysis nor the region of interest (ROI) analyses including frontal and limbic ROIs revealed any significant results in the group by time interaction. However, extracted ROI values of the group by time interaction of amygdala and hippocampus were positively associated with the change in depression symptom scores in the combat group, but not in the control group. These results highlight the role of depression in individuals that experience stressful life situations. Future studies may need to investigate the role of depressive symptoms after trauma exposure with different tasks that may be particularly sensitive to changes due to depressive symptoms.
Incorporating weekly carboplatin in anthracycline and paclitaxel-containing neoadjuvant chemotherapy for triple-negative breast cancer: propensity-score matching analysis and TIL evaluation
Authors: Dieci Maria Vittoria , Carbognin Luisa , Miglietta Federica , Canino Fabio , Giorgi Carlo Alberto , Cumerlato Enrico , Amato Ottavia , Massa Davide , Griguolo Gaia , Genovesi Elisa , Garufi Giovanna , Giannarelli Diana , Tornincasa Antonio , Trudu Lucia , Michieletto Silvia , Saibene Tania , Lo Mele Marcello , Fassan Matteo , Zarrilli Giovanni , Piacentini Federico , Bria Emilio , Guarneri Valentina 
Published: November 2022

Abstract
Background
The generation of data capturing the risk-benefit ratio of incorporating carboplatin (Cb) to neoadjuvant chemotherapy (NACT) for triple-negative breast cancer (TNBC) in a clinical practice setting is urgently needed. Tumour-infiltrating lymphocytes (TILs) have an established role in TNBC receiving NACT, however, the role of TIL dynamics under NACT exposure in patients receiving the current standard of care is largely uncharted.

Methods
Consecutive TNBC patients receiving anthracycline-taxane [A-T] +/− Cb NACT at three Institutions were enrolled. Stromal-TILs were evaluated on pre-NACT and residual disease (RD) specimens. In the clinical cohort, propensity-score-matching was used to control selection bias.

Results
In total, 247 patients were included (A-T = 40.5%, A-TCb = 59.5%). After propensity-score-matching, pCR was significantly higher for A-TCb vs A-T (51.9% vs 34.2%, multivariate: OR = 2.40, P = 0.01). No differences in grade ≥3 haematological toxicities were observed. TILs increased from baseline to RD in the overall population and across A-T/A-TCb subgroups. TIL increase from baseline to RD was positively and independently associated with distant disease-free survival (multivariate: HR = 0.43, P = 0.05).

Conclusions
We confirmed in a clinical practice setting of TNBC patients receiving A-T NACT that the incorporation of weekly Cb significantly improved pCR. In addition, A-T +/− Cb enhanced immune infiltration from baseline to RD. Finally, we reported a positive independent prognostic role of TIL increase after NACT exposure.
SphK-produced S1P in somatic cells is indispensable for LH-EGFR signaling-induced mouse oocyte maturation
Authors: Yuan Feifei , Hao Xiaoqiong , Cui Yanying , Huang FuXin , Zhang Xiaodan , Sun Yanli , Hao Tiantian , Wang Zhijuan , Xia Wei , Su Youqiang , Zhang Meijia 
Published: November 2022

AbstractGerm cell division and differentiation require intimate contact and interaction with the surrounding somatic cells. Luteinizing hormone (LH) triggers epidermal growth factor (EGF)-like growth factors to promote oocyte maturation and developmental competence by activating EGF receptor (EGFR) in somatic cells. Here, we showed that LH-EGFR signaling-activated sphingosine kinases (SphK) in somatic cells. The activation of EGFR by EGF increased S1P and calcium levels in cumulus-oocyte complexes (COCs), and decreased the binding affinity of natriuretic peptide receptor 2 (NPR2) for natriuretic peptide type C (NPPC) to release the cGMP-mediated meiotic arrest. These functions of EGF were blocked by the SphK inhibitor SKI-II, which could be reversed by the addition of S1P. S1P also activated the Akt/mTOR cascade reaction in oocytes and promoted targeting protein for Xklp2 (TPX2) accumulation and oocyte developmental competence. Specifically depleting Sphk1/2 in somatic cells reduced S1P levels and impaired oocyte meiotic maturation and developmental competence, resulting in complete female infertility. Collectively, SphK-produced S1P in somatic cells serves as a functional transmitter of LH-EGFR signaling from somatic cells to oocytes: acting on somatic cells to induce oocyte meiotic maturation, and acting on oocytes to improve oocyte developmental competence.
BNIP3 phosphorylation by JNK1/2 promotes mitophagy via enhancing its stability under hypoxia
Authors: He Yun-Ling , Li Jian , Gong Sheng-Hui , Cheng Xiang , Zhao Ming , Cao Yan , Zhao Tong , Zhao Yong-Qi , Fan Ming , Wu Hai-Tao , Zhu Ling-Ling , Wu Li-Ying 
Published: November 2022

AbstractMitophagy is an important metabolic mechanism that modulates mitochondrial quality and quantity by selectively removing damaged or unwanted mitochondria. BNIP3 (BCL2/adenovirus e1B 19 kDa protein interacting protein 3), a mitochondrial outer membrane protein, is a mitophagy receptor that mediates mitophagy under various stresses, particularly hypoxia, since BNIP3 is a hypoxia-responsive protein. However, the underlying mechanisms that regulate BNIP3 and thus mediate mitophagy under hypoxic conditions remain elusive. Here, we demonstrate that in hypoxia JNK1/2 (c-Jun N-terminal kinase 1/2) phosphorylates BNIP3 at Ser 60/Thr 66, which hampers proteasomal degradation of BNIP3 and drives mitophagy by facilitating the direct binding of BNIP3 to LC3 (microtubule-associated protein 1 light chain 3), while PP1/2A (protein phosphatase 1/2A) represses mitophagy by dephosphorylating BNIP3 and triggering its proteasomal degradation. These findings reveal the intrinsic mechanisms cells use to regulate mitophagy via the JNK1/2-BNIP3 pathway in response to hypoxia. Thus, the JNK1/2-BNIP3 signaling pathway strongly links mitophagy to hypoxia and may be a promising therapeutic target for hypoxia-related diseases.
An AI approach for managing financial systemic risk via bank bailouts by taxpayers
Authors: Petrone Daniele , Rodosthenous Neofytos , Latora Vito 
Published: November 2022

AbstractBank bailouts are controversial governmental decisions, putting taxpayers’ money at risk to avoid a domino effect through the network of claims between financial institutions. Yet very few studies address quantitatively the convenience of government investments in failing banks from the taxpayers’ standpoint. We propose a dynamic financial network framework incorporating bailout decisions as a Markov Decision Process and an artificial intelligence technique that learns the optimal bailout actions to minimise the expected taxpayers’ losses. Considering the European global systemically important institutions, we find that bailout decisions become optimal only if the taxpayers’ stakes exceed some critical level, endogenously determined by all financial network’s characteristics. The convenience to intervene increases with the network’s distress, taxpayers’ stakes, bank bilateral credit exposures and crisis duration. Moreover, the government should optimally keep bailing-out banks that received previous investments, creating moral hazard for rescued banks that could increase their risk-taking, reckoning on government intervention.
The endocannabinoid anandamide is an airway relaxant in health and disease
Authors: Simon Annika , von Einem Thomas , Seidinger Alexander , Matthey Michaela , Bindila Laura , Wenzel Daniela 
Published: November 2022

AbstractChronic obstructive airway diseases are a global medical burden that is expected to increase in the near future. However, the underlying mechanistic processes are poorly understood so far. Herein, we show that the endocannabinoid anandamide (AEA) induces prominent airway relaxation in vitro and in vivo. In contrast to 2-arachidonlyglycerol-induced airway relaxation, this is mediated by fatty acid amide hydrolase (FAAH)-dependent metabolites. In particular, we identify mouse and also human epithelial and airway smooth muscle cells as source of AEA-induced prostaglandin E2 production and cAMP as direct mediator of AEA-dependent airway relaxation. Mass spectrometry experiments demonstrate reduced levels of endocannabinoid-like compounds in lungs of ovalbumin-sensitized mice indicating a pathophysiological relevance of endocannabinoid signalling in obstructive airway disease. Importantly, AEA inhalation protects against airway hyper-reactivity after ovalbumin sensitization. Thus, this work highlights the AEA/FAAH axis as a critical regulator of airway tone that could provide therapeutic targets for airway relaxation.
Ciliary neurotrophic factor-mediated neuroprotection involves enhanced glycolysis and anabolism in degenerating mouse retinas
Authors: Do Rhee Kun , Wang Yanjie , ten Hoeve Johanna , Stiles Linsey , Nguyen Thao Thi Thu , Zhang Xiangmei , Vergnes Laurent , Reue Karen , Shirihai Orian , Bok Dean , Yang Xian-Jie 
Published: November 2022

AbstractCiliary neurotrophic factor (CNTF) acts as a potent neuroprotective cytokine in multiple models of retinal degeneration. To understand mechanisms underlying its broad neuroprotective effects, we have investigated the influence of CNTF on metabolism in a mouse model of photoreceptor degeneration. CNTF treatment improves the morphology of photoreceptor mitochondria, but also leads to reduced oxygen consumption and suppressed respiratory chain activities. Molecular analyses show elevated glycolytic pathway gene transcripts and active enzymes. Metabolomics analyses detect significantly higher levels of ATP and the energy currency phosphocreatine, elevated glycolytic pathway metabolites, increased TCA cycle metabolites, lipid biosynthetic pathway intermediates, nucleotides, and amino acids. Moreover, CNTF treatment restores the key antioxidant glutathione to the wild type level. Therefore, CNTF significantly impacts the metabolic status of degenerating retinas by promoting aerobic glycolysis and augmenting anabolic activities. These findings reveal cellular mechanisms underlying enhanced neuronal viability and suggest potential therapies for treating retinal degeneration.
Neutrophil breaching of the blood vessel pericyte layer during diapedesis requires mast cell-derived IL-17A
Authors: Joulia Régis , Guerrero-Fonseca Idaira María , Girbl Tamara , Coates Jonathon A. , Stein Monja , Vázquez-Martínez Laura , Lynam Eleanor , Whiteford James , Schnoor Michael , Voehringer David , Roers Axel , Nourshargh Sussan , Voisin Mathieu-Benoit 
Published: November 2022

AbstractNeutrophil diapedesis is an immediate step following infections and injury and is driven by complex interactions between leukocytes and various components of the blood vessel wall. Here, we show that perivascular mast cells (MC) are key regulators of neutrophil behaviour within the sub-endothelial space of inflamed venules. Using confocal intravital microscopy, we observe directed abluminal neutrophil motility along pericyte processes towards perivascular MCs, a response that created neutrophil extravasation hotspots. Conversely, MC-deficiency and pharmacological or genetic blockade of IL-17A leads to impaired neutrophil sub-endothelial migration and breaching of the pericyte layer. Mechanistically, identifying MCs as a significant cellular source of IL-17A, we establish that MC-derived IL-17A regulates the enrichment of key effector molecules ICAM-1 and CXCL1 in nearby pericytes. Collectively, we identify a novel MC-IL-17A-pericyte axis as modulator of the final steps of neutrophil diapedesis, with potential translational implications for inflammatory disorders driven by increased neutrophil diapedesis.
Activation and signaling mechanism revealed by GPR119-Gs complex structures
Authors: Qian Yuxia , Wang Jiening , Yang Linlin , Liu Yanru , Wang Lina , Liu Wei , Lin Yun , Yang Hong , Ma Lixin , Ye Sheng , Wu Shan , Qiao Anna 
Published: November 2022

AbstractAgonists selectively targeting cannabinoid receptor-like G-protein-coupled receptor (GPCR) GPR119 hold promise for treating metabolic disorders while avoiding unwanted side effects. Here we present the cryo-electron microscopy (cryo-EM) structures of the human GPR119-Gssignaling complexes bound to AR231453 and MBX-2982, two representative agonists reported for GPR119. The structures reveal a one-amino acid shift of the conserved proline residue of TM5 that forms an outward bulge, opening up a hydrophobic cavity between TM4 and TM5 at the middle of the membrane for its endogenous ligands-monounsaturated lipid metabolites. In addition, we observed a salt bridge between ICL1 of GPR119 and Gβs. Disruption of the salt bridge eliminates the cAMP production of GPR119, indicating an important role of Gβsin GPR119-mediated signaling. Our structures, together with mutagenesis studies, illustrate the conserved binding mode of the chemically different agonists, and provide insights into the conformational changes in receptor activation and G protein coupling.
Cryo-EM structure of ex vivo fibrils associated with extreme AA amyloidosis prevalence in a cat shelter
Authors: Schulte Tim , Chaves-Sanjuan Antonio , Mazzini Giulia , Speranzini Valentina , Lavatelli Francesca , Ferri Filippo , Palizzotto Carlo , Mazza Maria , Milani Paolo , Nuvolone Mario , Vogt Anne-Cathrine , Vogel Monique , Palladini Giovanni , Merlini Giampaolo , Bolognesi Martino , Ferro Silvia , Zini Eric , Ricagno Stefano 
Published: November 2022

AbstractAA amyloidosis is a systemic disease characterized by deposition of misfolded serum amyloid A protein (SAA) into cross-β amyloid in multiple organs in humans and animals. AA amyloidosis occurs at high SAA serum levels during chronic inflammation. Prion-like transmission was reported as possible cause of extreme AA amyloidosis prevalence in captive animals, e.g. 70% in cheetah and 57–73% in domestic short hair (DSH) cats kept in zoos and shelters, respectively. Herein, we present the 3.3 Å cryo-EM structure of AA amyloid extracted post-mortem from the kidney of a DSH cat with renal failure, deceased in a shelter with extreme disease prevalence. The structure reveals a cross-β architecture assembled from two 76-residue long proto-filaments. Despite >70% sequence homology to mouse and human SAA, the cat SAA variant adopts a distinct amyloid fold. Inclusion of an eight-residue insert unique to feline SAA contributes to increased amyloid stability. The presented feline AA amyloid structure is fully compatible with the 99% identical amino acid sequence of amyloid fragments of captive cheetah.
Somatic mutation distribution across tumour cohorts provides a signal for positive selection in cancer
Authors: Boström Martin , Larsson Erik 
Published: November 2022

AbstractCancer gene discovery is reliant on distinguishing driver mutations from a multitude of passenger mutations in tumour genomes. While driver genes may be revealed based on excess mutation recurrence or clustering, there is a need for orthogonal principles. Here, we take advantage of the fact that non-cancer genes, containing only passenger mutations under neutral selection, exhibit a likelihood of mutagenesis in a given tumour determined by the tumour’s mutational signature and burden. This relationship can be disrupted by positive selection, leading to a difference in the distribution of mutated cases across a cohort for driver and passenger genes. We apply this principle to detect cancer drivers independently of recurrence in large pan-cancer cohorts, and show that our method (SEISMIC) performs comparably to traditional approaches and can provide resistance to known confounding mutational phenomena. Being based on a different principle, the approach provides a much-needed complement to existing methods for detecting signals of selection.
CHD7 regulates otic lineage specification and hair cell differentiation in human inner ear organoids
Authors: Nie Jing , Ueda Yoshitomo , Solivais Alexander J. , Hashino Eri 
Published: November 2022

AbstractMutations in CHD7 cause CHARGE syndrome, affecting multiple organs including the inner ear in humans. We investigate how CHD7 mutations affect inner ear development using human pluripotent stem cell-derived organoids as a model system. We find that loss of CHD7 or its chromatin remodeling activity leads to complete absence of hair cells and supporting cells, which can be explained by dysregulation of key otic development-associated genes in mutant otic progenitors. Further analysis of the mutant otic progenitors suggests that CHD7 can regulate otic genes through a chromatin remodeling-independent mechanism. Results from transcriptome profiling of hair cells reveal disruption of deafness gene expression as a potential underlying mechanism of CHARGE-associated sensorineural hearing loss. Notably, co-differentiating CHD7 knockout and wild-type cells in chimeric organoids partially rescues mutant phenotypes by restoring otherwise severely dysregulated otic genes. Taken together, our results suggest that CHD7 plays a critical role in regulating human otic lineage specification and hair cell differentiation.
Compact artificial neuron based on anti-ferroelectric transistor
Authors: Cao Rongrong , Zhang Xumeng , Liu Sen , Lu Jikai , Wang Yongzhou , Jiang Hao , Yang Yang , Sun Yize , Wei Wei , Wang Jianlu , Xu Hui , Li Qingjiang , Liu Qi 
Published: November 2022

AbstractNeuromorphic machines are intriguing for building energy-efficient intelligent systems, where spiking neurons are pivotal components. Recently, memristive neurons with promising bio-plausibility have been developed, but with limited reliability, bulky capacitors or additional reset circuits. Here, we propose an anti-ferroelectric field-effect transistor neuron based on the inherent polarization and depolarization of Hf0.2Zr0.8O2 anti-ferroelectric film to meet these challenges. The intrinsic accumulated polarization/spontaneous depolarization of Hf0.2Zr0.8O2 films implements the integration/leaky behavior of neurons, avoiding external capacitors and reset circuits. Moreover, the anti-ferroelectric neuron exhibits low energy consumption (37 fJ/spike), high endurance (>1012), high uniformity and high stability. We further construct a two-layer fully ferroelectric spiking neural networks that combines anti-ferroelectric neurons and ferroelectric synapses, achieving 96.8% recognition accuracy on the Modified National Institute of Standards and Technology dataset. This work opens the way to emulate neurons with anti-ferroelectric materials and provides a promising approach to building high-efficient neuromorphic hardware.