bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of COVID-19 and associated lockdowns on traumatic spinal cord injury incidence: a population based study
Authors: McCaughey Euan J. , Ho Frederick K. , Mackay Daniel F. , Pell Jill P. , Humburg Peter , Purcell Mariel 
Published: November 2023

Abstract
Study design
Natural experiment

Objectives
To determine whether COVID-19 restrictions were associated with changes in the incidence of traumatic spinal cord injury (TSCI) in Scotland.

Setting
The Queen Elizabeth National Spinal Injuries Unit (QENSIU), the sole provider of treatment for TSCI in Scotland.

Methods
Time series analysis of all admissions for TSCI between 1st January 2015 and 31st August 2022.

Results
Over the 8-year study period, 745 patients were admitted to the QENSIU with a TSCI. Interrupted time series analysis showed that level 3 and 4 COVID-19 lockdown restrictions (the most severe levels) were associated with lower incidence of TSCI (RR 0.63, CI% CI 0.47, 0.82, p < 0.001). The associations were stronger in people aged over 45 (additive interaction p = 0.001), males (additive interaction p = 0.01) and non-tetraplegia (additive interaction p = 0.002). The incidence of TSCI due to deliberate self-harm was higher (0.41 versus 0.23 per month) during restrictions.

Conclusions
Overall, TSCI incidence reduced in Scotland when lockdowns were implemented, presumably due to lower engagement in risky activities. The increase in TSCI due to deliberate self-harm may reflect increased mental health problems and social isolation and should be anticipated and targeted in future pandemics. The change in incidence during the COVID-19 pandemic may have an economic impact and see a temporary reduction in the burden on health and social care. The results of this study will be useful for resource planning in future pandemics.
Transport of bound quasiparticle states in a two-dimensional boundary superfluid
Authors: Autti Samuli , Haley Richard P. , Jennings Asher , Pickett George R. , Poole Malcolm , Schanen Roch , Soldatov Arkady A. , Tsepelin Viktor , Vonka Jakub , Zavjalov Vladislav V. , Zmeev Dmitry E. 
Published: November 2023

AbstractThe B phase of superfluid 3He can be cooled into the pure superfluid regime, where the thermal quasiparticle density is negligible. The bulk superfluid is surrounded by a quantum well at the boundaries of the container, confining a sea of quasiparticles with energies below that of those in the bulk. We can create a non-equilibrium distribution of these states within the quantum well and observe the dynamics of their motion indirectly. Here we show that the induced quasiparticle currents flow diffusively in the two-dimensional system. Combining this with a direct measurement of energy conservation, we conclude that the bulk superfluid 3He is effectively surrounded by an independent two-dimensional superfluid, which is isolated from the bulk superfluid but which readily interacts with mechanical probes. Our work shows that this two-dimensional quantum condensate and the dynamics of the surface bound states are experimentally accessible, opening the possibility of engineering two-dimensional quantum condensates of arbitrary topology.
Double-strand breaks induce inverted duplication chromosome rearrangements by a DNA polymerase δ-dependent mechanism
Authors: Al-Zain Amr M. , Nester Mattie R. , Ahmed Iffat , Symington Lorraine S. 
Published: November 2023

AbstractInverted duplications, also known as foldback inversions, are commonly observed in cancers and are the major class of chromosome rearrangement recovered from yeast cells lacking Mre11 nuclease activity. Foldback priming at DNA double-strand breaks (DSBs) is one mechanism proposed for the generation of inverted duplications. However, the other pathway steps have not been fully elucidated. Here, we show that a DSB induced near natural inverted repeats drives high frequency inverted duplication in Sae2 and Mre11-deficient cells. We find that DNA polymerase δ proof-reading activity, but not Rad1 nuclease, trims the heterologous flaps formed after foldback annealing. Additionally, Pol32 is required for the generation of inverted duplications, suggesting that Pol δ catalyzes fill-in synthesis primed from the foldback to create a hairpin-capped chromosome that is subsequently replicated to form a dicentric inversion chromosome. Finally, we show that stabilization of the dicentric chromosome after breakage involves telomere capture by non-reciprocal translocation mediated by repeat sequences or by deletion of one centromere.
Glycoengineered keratinocyte library reveals essential functions of specific glycans for all stages of HSV-1 infection
Authors: Bagdonaite Ieva , Marinova Irina N. , Rudjord-Levann Asha M. , Pallesen Emil M. H. , King-Smith Sarah L. , Karlsson Richard , Rømer Troels B. , Chen Yen-Hsi , Miller Rebecca L. , Olofsson Sigvard , Nordén Rickard , Bergström Tomas , Dabelsteen Sally , Wandall Hans H. 
Published: November 2023

AbstractViral and host glycans represent an understudied aspect of host-pathogen interactions, despite potential implications for treatment of viral infections. This is due to lack of easily accessible tools for analyzing glycan function in a meaningful context. Here we generate a glycoengineered keratinocyte library delineating human glycosylation pathways to uncover roles of specific glycans at different stages of herpes simplex virus type 1 (HSV-1) infectious cycle. We show the importance of cellular glycosaminoglycans and glycosphingolipids for HSV-1 attachment, N-glycans for entry and spread, and O-glycans for propagation. While altered virion surface structures have minimal effects on the early interactions with wild type cells, mutation of specific O-glycosylation sites affects glycoprotein surface expression and function. In conclusion, the data demonstrates the importance of specific glycans in a clinically relevant human model of HSV-1 infection and highlights the utility of genetic engineering to elucidate the roles of specific viral and cellular carbohydrate structures.
Paclitaxel plus carboplatin and durvalumab with or without oleclumab for women with previously untreated locally advanced or metastatic triple-negative breast cancer: the randomized SYNERGY phase I/II trial
Authors: Buisseret Laurence , Loirat Delphine , Aftimos Philippe , Maurer Christian , Punie Kevin , Debien Véronique , Kristanto Paulus , Eiger Daniel , Goncalves Anthony , Ghiringhelli François , Taylor Donatienne , Clatot Florent , Van den Mooter Tom , Ferrero Jean-Marc , Bonnefoi Hervé , Canon Jean-Luc , Duhoux Francois P. , Mansi Laura , Poncin Renaud , Barthélémy Philippe , Isambert Nicolas , Denis Zoë , Catteau Xavier , Salgado Roberto , Agostinetto Elisa , de Azambuja Evandro , Rothé Françoise , Craciun Ligia , Venet David , Romano Emanuela , Stagg John , Paesmans Marianne , Larsimont Denis , Sotiriou Christos , Ignatiadis Michail , Piccart-Gebhart Martine 
Published: November 2023

AbstractChemo-immunotherapy is the first-line standard of care for patients with PD-L1 positive metastatic triple-negative breast cancer (mTNBC). SYNERGY (NCT03616886) is a dose-finding phase I and a randomized phase II, open-label trial evaluating if targeting the immunosuppressive adenosine pathway can enhance the antitumor activity of chemo-immunotherapy. The phase I part included 6 patients with untreated locally-advanced or mTNBC to determine the safety and recommended phase II dose of the anti-CD73 antibody oleclumab in combination with the anti-PD-L1 durvalumab and 12 cycles of weekly carboplatin and paclitaxel. In the phase II part, 127 women were randomized 1:1 to receive chemo-immunotherapy, with (arm A) or without (arm B) oleclumab. The primary endpoint was the clinical benefit rate at week 24, defined as stable disease, partial or complete response per RECIST v1.1. Secondary endpoints included objective response rate, duration of response, survival outcomes (progression-free survival and overall survival), and safety. The trial did not meet its primary endpoint, as the 24-week clinical benefit rate was not significantly improved by adding oleclumab (43% vs. 44%, p = 0.61). Exploratory median progression-free survival was 5.9 months in arm A as compared to 7.0 months in arm B (p = 0.90). The safety profile was manageable in both arms.
Screening the Coulomb interaction leads to a prethermal regime in two-dimensional bad conductors
Authors: Stanley L. J. , Lin Ping V. , Jaroszyński J. , Popović Dragana 
Published: November 2023

AbstractThe absence of thermalization in certain isolated many-body systems is of great fundamental interest. Many-body localization (MBL) is a widely studied mechanism for thermalization to fail in strongly disordered quantum systems, but it is still not understood precisely how the range of interactions affects the dynamical behavior and the existence of MBL, especially in dimensions D > 1. By investigating nonequilibrium dynamics in strongly disordered D = 2 electron systems with power-law interactions ∝ 1/rα and poor coupling to a thermal bath, here we observe MBL-like, prethermal dynamics for α = 3. In contrast, for α = 1, the system thermalizes, although the dynamics is glassy. Our results provide important insights for theory, especially since we obtained them on systems that are much closer to the thermodynamic limit than synthetic quantum systems employed in previous studies of MBL. Thus, our work is a key step towards further studies of ergodicity breaking and quantum entanglement in real materials.
Emergent superconductivity in topological-kagome-magnet/metal heterostructures
Authors: Wang He , Liu Yanzhao , Gong Ming , Jiang Hua , Gao Xiaoyue , Ma Wenlong , Luo Jiawei , Ji Haoran , Ge Jun , Jia Shuang , Gao Peng , Wang Ziqiang , Xie X. C. , Wang Jian 
Published: November 2023

AbstractItinerant kagome lattice magnets exhibit many novel correlated and topological quantum electronic states with broken time-reversal symmetry. Superconductivity, however, has not been observed in this class of materials, presenting a roadblock in a promising path toward topological superconductivity. Here, we report that novel superconductivity can emerge at the interface of kagome Chern magnet TbMn6Sn6 and metal heterostructures when elemental metallic thin films are deposited on either the top (001) surface or the side surfaces. Superconductivity is also successfully induced and systematically studied by using various types of metallic tips on different TbMn6Sn6 surfaces in point-contact measurements. The anisotropy of the superconducting upper critical field suggests that the emergent superconductivity is quasi-two-dimensional. Remarkably, the interface superconductor couples to the magnetic order of the kagome metal and exhibits a hysteretic magnetoresistance in the superconducting states. Taking into account the spin-orbit coupling, the observed interface superconductivity can be a surprising and more realistic realization of the p-wave topological superconductors theoretically proposed for two-dimensional semiconductors proximity-coupled to s-wave superconductors and insulating ferromagnets. Our findings of robust superconductivity in topological-Chern-magnet/metal heterostructures offer a new direction for investigating spin-triplet pairing and topological superconductivity.
Evidence for two dimensional anisotropic Luttinger liquids at millikelvin temperatures
Authors: Yu Guo , Wang Pengjie , Uzan-Narovlansky Ayelet J. , Jia Yanyu , Onyszczak Michael , Singha Ratnadwip , Gui Xin , Song Tiancheng , Tang Yue , Watanabe Kenji , Taniguchi Takashi , Cava Robert J. , Schoop Leslie M. , Wu Sanfeng 
Published: November 2023

AbstractInteracting electrons in one dimension (1D) are governed by the Luttinger liquid (LL) theory in which excitations are fractionalized. Can a LL-like state emerge in a 2D system as a stable zero-temperature phase? This question is crucial in the study of non-Fermi liquids. A recent experiment identified twisted bilayer tungsten ditelluride (tWTe2) as a 2D host of LL-like physics at a few kelvins. Here we report evidence for a 2D anisotropic LL state down to 50 mK, spontaneously formed in tWTe2 with a twist angle of ~ 3o. While the system is metallic-like and nearly isotropic above 2 K, a dramatically enhanced electronic anisotropy develops in the millikelvin regime. In the anisotropic phase, we observe characteristics of a 2D LL phase including a power-law across-wire conductance and a zero-bias dip in the along-wire differential resistance. Our results represent a step forward in the search for stable LL physics beyond 1D.
A general large-scale synthesis approach for crystalline porous materials
Authors: Liu Xiongli , Wang An , Wang Chunping , Li Jinli , Zhang Zhiyuan , Al-Enizi Abdullah M. , Nafady Ayman , Shui Feng , You Zifeng , Li Baiyan , Wen Yangbing , Ma Shengqian 
Published: November 2023

AbstractCrystalline porous materials such as covalent organic frameworks (COFs), metal-organic frameworks (MOFs) and porous organic cages (POCs) have been widely applied in various fields with outstanding performances. However, the lack of general and effective methodology for large-scale production limits their further industrial applications. In this work, we developed a general approach comprising high pressure homogenization (HPH), which can realize large-scale synthesis of crystalline porous materials including COFs, MOFs, and POCs under benign conditions. This universal strategy, as illustrated in the proof of principle studies, has prepared 4 COFs, 4 MOFs, and 2 POCs. It can circumvent some drawbacks of existing approaches including low yield, high energy consumption, low efficiency, weak mass/thermal transfer, tedious procedures, poor reproducibility, and high cost. On the basis of this approach, an industrial homogenizer can produce 0.96 ~ 580.48 ton of high-performance COFs, MOFs, and POCs per day, which is unachievable via other methods.
Inhibition of glycolysis-driven immunosuppression with a nano-assembly enhances response to immune checkpoint blockade therapy in triple negative breast cancer
Authors: Ren Xijiao , Cheng Zhuo , He Jinming , Yao Xuemei , Liu Yingqi , Cai Kaiyong , Li Menghuan , Hu Yan , Luo Zhong 
Published: November 2023

AbstractImmune-checkpoint inhibitors (ICI) are promising modalities for treating triple negative breast cancer (TNBC). However, hyperglycolysis, a hallmark of TNBC cells, may drive tumor-intrinsic PD-L1 glycosylation and boost regulatory T cell function to impair ICI efficacy. Herein, we report a tumor microenvironment-activatable nanoassembly based on self-assembled aptamer-polymer conjugates for the targeted delivery of glucose transporter 1 inhibitor BAY-876 (DNA-PAE@BAY-876), which remodels the immunosuppressive TME to enhance ICI response. Poly β-amino ester (PAE)-modified PD-L1 and CTLA-4-antagonizing aptamers (aptPD-L1 and aptCTLA-4) are synthesized and co-assembled into supramolecular nanoassemblies for carrying BAY-876. The acidic tumor microenvironment causes PAE protonation and triggers nanoassembly dissociation to initiate BAY-876 and aptamer release. BAY-876 selectively inhibits TNBC glycolysis to deprive uridine diphosphate N-acetylglucosamine and downregulate PD-L1 N-linked glycosylation, thus facilitating PD-L1 recognition of aptPD-L1 to boost anti-PD-L1 therapy. Meanwhile, BAY-876 treatment also elevates glucose supply to tumor-residing regulatory T cells (Tregs) for metabolically rewiring them into an immunostimulatory state, thus cooperating with aptCTLA-4-mediated immune-checkpoint inhibition to abolish Treg-mediated immunosuppression. DNA-PAE@BAY-876 effectively reprograms the immunosuppressive microenvironment in preclinical models of TNBC in female mice and provides a distinct approach for TNBC immunotherapy in the clinics.
Causal identification of single-cell experimental perturbation effects with CINEMA-OT
Authors: Dong Mingze , Wang Bao , Wei Jessica , de O. Fonseca Antonio H. , Perry Curtis J. , Frey Alexander , Ouerghi Feriel , Foxman Ellen F. , Ishizuka Jeffrey J. , Dhodapkar Rahul M. , van Dijk David 
Published: November 2023

AbstractRecent advancements in single-cell technologies allow characterization of experimental perturbations at single-cell resolution. While methods have been developed to analyze such experiments, the application of a strict causal framework has not yet been explored for the inference of treatment effects at the single-cell level. Here we present a causal-inference-based approach to single-cell perturbation analysis, termed CINEMA-OT (causal independent effect module attribution + optimal transport). CINEMA-OT separates confounding sources of variation from perturbation effects to obtain an optimal transport matching that reflects counterfactual cell pairs. These cell pairs represent causal perturbation responses permitting a number of novel analyses, such as individual treatment-effect analysis, response clustering, attribution analysis, and synergy analysis. We benchmark CINEMA-OT on an array of treatment-effect estimation tasks for several simulated and real datasets and show that it outperforms other single-cell perturbation analysis methods. Finally, we perform CINEMA-OT analysis of two newly generated datasets: (1) rhinovirus and cigarette-smoke-exposed airway organoids, and (2) combinatorial cytokine stimulation of immune cells. In these experiments, CINEMA-OT reveals potential mechanisms by which cigarette-smoke exposure dulls the airway antiviral response, as well as the logic that governs chemokine secretion and peripheral immune cell recruitment.
Age-related dysregulation of homeostatic control in neuronal microcircuits
Authors: Radulescu Carola I. , Doostdar Nazanin , Zabouri Nawal , Melgosa-Ecenarro Leire , Wang Xingjian , Sadeh Sadra , Pavlidi Pavlina , Airey Joe , Kopanitsa Maksym , Clopath Claudia , Barnes Samuel J. 
Published: November 2023

AbstractNeuronal homeostasis prevents hyperactivity and hypoactivity. Age-related hyperactivity suggests homeostasis may be dysregulated in later life. However, plasticity mechanisms preventing age-related hyperactivity and their efficacy in later life are unclear. We identify the adult cortical plasticity response to elevated activity driven by sensory overstimulation, then test how plasticity changes with age. We use in vivo two-photon imaging of calcium-mediated cellular/synaptic activity, electrophysiology and c-Fos-activity tagging to show control of neuronal activity is dysregulated in the visual cortex in late adulthood. Specifically, in young adult cortex, mGluR5-dependent population-wide excitatory synaptic weakening and inhibitory synaptogenesis reduce cortical activity following overstimulation. In later life, these mechanisms are downregulated, so that overstimulation results in synaptic strengthening and elevated activity. We also find overstimulation disrupts cognition in older but not younger animals. We propose that specific plasticity mechanisms fail in later life dysregulating neuronal microcircuit homeostasis and that the age-related response to overstimulation can impact cognitive performance.
Molecular blueprints for spinal circuit modules controlling locomotor speed in zebrafish
Authors: Pallucchi Irene , Bertuzzi Maria , Madrid David , Fontanel Pierre , Higashijima Shin-ichi , El Manira Abdeljabbar 
Published: November 2023

AbstractThe flexibility of motor actions is ingrained in the diversity of neurons and how they are organized into functional circuit modules, yet our knowledge of the molecular underpinning of motor circuit modularity remains limited. Here we use adult zebrafish to link the molecular diversity of motoneurons (MNs) and the rhythm-generating V2a interneurons (INs) with the modular circuit organization that is responsible for changes in locomotor speed. We show that the molecular diversity of MNs and V2a INs reflects their functional segregation into slow, intermediate or fast subtypes. Furthermore, we reveal shared molecular signatures between V2a INs and MNs of the three speed circuit modules. Overall, by characterizing how the molecular diversity of MNs and V2a INs relates to their function, connectivity and behavior, our study provides important insights not only into the molecular mechanisms for neuronal and circuit diversity for locomotor flexibility but also for charting circuits for motor actions in general.
Chloroplast transformation for bioencapsulation and oral delivery using the immunoglobulin G fragment crystallizable (Fc) domain
Authors: LaManna Lisa , Chou Chih-Hsuan , Lei Hanqin , Barton Elisabeth R. , Maliga Pal 
Published: November 2023

AbstractProinsulin Like Growth Factor I (prolGF-I) and myostatin (Mstn) regulate muscle regeneration and mass when intravenously delivered. We tested if chloroplast bioencapsulated forms of these proteins may serve as a non-invasive means of drug delivery through the digestive system. We created tobacco (Nicotiana tabacum) plants carrying GFP-Fc1, proIGF-I-Fc1, and Mstn-Fc1 fusion genes, in which fusion with the immunoglobulin G Fc domain improved both protein stability and absorption in the small intestine. No transplastomic plants were obtained with the Mstn-Fc1 gene, suggesting that the protein is toxic to plant cells. proIGF-I-Fc1 protein levels were too low to enable in vivo testing. However, GFP-Fc1 accumulated at a high level, enabling evaluation of chloroplast-made Fc fusion proteins for oral delivery. Tobacco leaves were lyophilized for testing in a mouse system. We report that the orally administered GFP-Fc1 fusion protein (5.45 µg/g GFP-Fc1) has been taken up by the intestinal epithelium cells, evidenced by confocal microscopy. GFP-Fc1 subsequently entered the circulation where it was detected by ELISA. Data reported here confirm that chloroplast expression and oral administration of lyophilized leaves is a potential delivery system of therapeutic proteins fused with Fc1, with the advantage that the proteins may be stored at room temperature.
A novel immune-related gene signature for predicting immunotherapy outcomes and survival in clear cell renal cell carcinoma
Authors: Gu Jie , Zhang Xiaobo , Peng ZhangZhe , Peng Zhuoming , Liao Zhouning 
Published: November 2023

AbstractClear cell renal carcinoma (ccRCC) is one of the most common cancers worldwide. In this study, a new model of immune-related genes was developed to predict the overall survival and immunotherapy efficacy in patients with ccRCC. Immune-related genes were obtained from the ImmPort database. Clinical data and transcriptomics of ccRCC samples were downloaded from GSE29609 and The Cancer Genome Atlas. An immune-related gene-based prognostic model (IRGPM) was developed using the least absolute shrinkage and selection operator regression algorithm and multivariate Cox regression. The reliability of the developed models was evaluated by Kaplan–Meier survival curves and time-dependent receiver operating characteristic curves. Furthermore, we constructed a nomogram based on the IRGPM and multiple clinicopathological factors, along with a calibration curve to examine the predictive power of the nomogram. Overall, this study investigated the association of IRGPM with immunotherapeutic efficacy, immune checkpoints, and immune cell infiltration. Eleven IRGs based on 528 ccRCC samples significantly associated with survival were used to construct the IRGPM. Remarkably, the IRGPM, which consists of 11 hub genes (SAA1, IL4, PLAUR, PLXNB3, ANGPTL3, AMH, KLRC2, NR3C2, KL, CSF2, and SEMA3G), was found to predict the survival of ccRCC patients accurately. The calibration curve revealed that the nomogram developed with the IRGPM showed high predictive performance for the survival probability of ccRCC patients. Moreover, the IRGPM subgroups showed different levels of immune checkpoints and immune cell infiltration in patients with ccRCC. IRGPM might be a promising biomarker of immunotherapeutic responses in patients with ccRCC. Overall, the established IRGPM was valuable for predicting survival, reflecting the immunotherapy response and immune microenvironment in patients with ccRCC.