bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of cyclopeptide inhibitors of cGAS targeting protein-DNA interaction and phase separation
Authors: Wang Xiaoquan , Wang Youqiao , Cao Anqi , Luo Qinhong , Chen Daoyuan , Zhao Weiqi , Xu Jun , Li Qinkai , Bu Xianzhang , Quan Junmin 
Published: October 2023

AbstractCyclic GMP-AMP synthase (cGAS) is an essential sensor of aberrant cytosolic DNA for initiating innate immunity upon invading pathogens and cellular stress, which is considered as a potential drug target for autoimmune and autoinflammatory diseases. Here, we report the discovery of a class of cyclopeptide inhibitors of cGAS identified by an in vitro screening assay from a focused library of cyclic peptides. These cyclopeptides specifically bind to the DNA binding site of cGAS and block the binding of dsDNA with cGAS, subsequently inhibit dsDNA-induced liquid phase condensation and activation of cGAS. The specificity and potency of one optimal lead XQ2B were characterized in cellular assays. Concordantly, XQ2B inhibited herpes simplex virus-1 (HSV-1)-induced antiviral immune responses and enhanced HSV-1 infection in vitro and in vivo. Furthermore, XQ2B significantly suppressed the elevated levels of type I interferon and proinflammatory cytokines in primary macrophages from Trex1-/- mice and systemic inflammation in Trex1-/- mice. XQ2B represents the specific cGAS inhibitor targeting protein-DNA interaction and phase separation and serves as a scaffold for the development of therapies in the treatment of cGAS-dependent inflammatory diseases.
Ecological mechanisms and current systems shape the modular structure of the global oceans’ prokaryotic seascape
Authors: Milke Felix , Meyerjürgens Jens , Simon Meinhard 
Published: October 2023

AbstractMajor biogeographic features of the microbial seascape in the oceans have been established and their underlying ecological mechanisms in the (sub)tropical oceans and the Pacific Ocean identified. However, we still lack a unifying understanding of how prokaryotic communities and biogeographic patterns are affected by large-scale current systems in distinct ocean basins and how they are globally shaped in line with ecological mechanisms. Here we show that prokaryotic communities in the epipelagic Pacific and Atlantic Ocean, in the southern Indian Ocean, and the Mediterranean Sea are composed of modules of co-occurring taxa with similar environmental preferences. The relative partitioning of these modules varies along latitudinal and longitudinal gradients and are related to different hydrographic and biotic conditions. Homogeneous selection and dispersal limitation were identified as the major ecological mechanisms shaping these communities and their free-living (FL) and particle-associated (PA) fractions. Large-scale current systems govern the dispersal of prokaryotic modules leading to the highest diversity near subtropical fronts.
Fitness cost associated with cell phenotypic switching drives population diversification dynamics and controllability
Authors: Henrion Lucas , Martinez Juan Andres , Vandenbroucke Vincent , Delvenne Mathéo , Telek Samuel , Zicler Andrew , Grünberger Alexander , Delvigne Frank 
Published: October 2023

AbstractIsogenic cell populations can cope with stress conditions by switching to alternative phenotypes. Even if it can lead to increased fitness in a natural context, this feature is typically unwanted for a range of applications (e.g., bioproduction, synthetic biology, and biomedicine) where it tends to make cellular response unpredictable. However, little is known about the diversification profiles that can be adopted by a cell population. Here, we characterize the diversification dynamics for various systems (bacteria and yeast) and for different phenotypes (utilization of alternative carbon sources, general stress response and more complex development patterns). Our results suggest that the diversification dynamics and the fitness cost associated with cell switching are coupled. To quantify the contribution of the switching cost on population dynamics, we design a stochastic model that let us reproduce the dynamics observed experimentally and identify three diversification regimes, i.e., constrained (at low switching cost), dispersed (at medium and high switching cost), and bursty (for very high switching cost). Furthermore, we use a cell-machine interface called Segregostat to demonstrate that different levels of control can be applied to these diversification regimes, enabling applications involving more precise cellular responses.
Generative complex networks within a dynamic memristor with intrinsic variability
Authors: Guo Yunpeng , Duan Wenrui , Liu Xue , Wang Xinxin , Wang Lidan , Duan Shukai , Ma Cheng , Li Huanglong 
Published: October 2023

AbstractArtificial neural networks (ANNs) have gained considerable momentum in the past decade. Although at first the main task of the ANN paradigm was to tune the connection weights in fixed-architecture networks, there has recently been growing interest in evolving network architectures toward the goal of creating artificial general intelligence. Lagging behind this trend, current ANN hardware struggles for a balance between flexibility and efficiency but cannot achieve both. Here, we report on a novel approach for the on-demand generation of complex networks within a single memristor where multiple virtual nodes are created by time multiplexing and the non-trivial topological features, such as small-worldness, are generated by exploiting device dynamics with intrinsic cycle-to-cycle variability. When used for reservoir computing, memristive complex networks can achieve a noticeable increase in memory capacity a and respectable performance boost compared to conventional reservoirs trivially implemented as fully connected networks. This work expands the functionality of memristors for ANN computing.
Control of metal oxides’ electronic conductivity through visual intercalation chemical reactions
Authors: Zhang Yuanyuan , Zhang Xiaohua , Pang Quanquan , Yan Jianhua 
Published: October 2023

AbstractCation intercalation is an effective method to optimize the electronic structures of metal oxides, but tuning intercalation structure and conductivity by manipulating ion movement is difficult. Here, we report a visual topochemical synthesis strategy to control intercalation pathways and structures and realize the rapid synthesis of flexible conductive metal oxide films in one minute at room temperature. Using flexible TiO2 nanofiber films as the prototype, we design three charge-driven models to intercalate preset Li+-ions into the TiO2 lattice slowly (µm/s), rapidly (mm/s), or ultrafast (cm/s). The Li+-intercalation causes real-time color changes of the TiO2 films from white to blue and then black, corresponding to the structures of LixTiO2 and LixTiO2-δ, and the enhanced conductivity from 0 to 1 and 40 S/m. This work realizes large-scale and rapid synthesis of flexible TiO2 nanofiber films with tunable conductivity and is expected to extend the synthesis to other conductive metal oxide films.
Defeating depolarizing fields with artificial flux closure in ultrathin ferroelectrics
Authors: Gradauskaite Elzbieta , Meier Quintin N. , Gray Natascha , Sarott Martin F. , Scharsach Tizian , Campanini Marco , Moran Thomas , Vogel Alexander , Del Cid-Ledezma Karla , Huey Bryan D. , Rossell Marta D. , Fiebig Manfred , Trassin Morgan 
Published: October 2023

AbstractMaterial surfaces encompass structural and chemical discontinuities that often lead to the loss of the property of interest in so-called dead layers. It is particularly problematic in nanoscale oxide electronics, where the integration of strongly correlated materials into devices is obstructed by the thickness threshold required for the emergence of their functionality. Here we report the stabilization of ultrathin out-of-plane ferroelectricity in oxide heterostructures through the design of an artificial flux-closure architecture. Inserting an in-plane-polarized ferroelectric epitaxial buffer provides the continuity of polarization at the interface; despite its insulating nature, we observe the emergence of polarization in our out-of-plane-polarized model of ferroelectric BaTiO3 from the very first unit cell. In BiFeO3, the flux-closure approach stabilizes a 251° domain wall. Its unusual chirality is probably associated with the ferroelectric analogue to the Dzyaloshinskii–Moriya interaction. We, thus, see that in an adaptively engineered geometry, the depolarizing-field-screening properties of an insulator can even surpass those of a metal and be a source of functionality. This could be a useful insight on the road towards the next generation of oxide electronics.
Acousto-optic modulation of gigawatt-scale laser pulses in ambient air
Authors: Schrödel Yannick , Hartmann Claas , Zheng Jiaan , Lang Tino , Steudel Max , Rutsch Matthias , Salman Sarper H. , Kellert Martin , Pergament Mikhail , Hahn-Jose Thomas , Suppelt Sven , Dörsam Jan Helge , Harth Anne , Leemans Wim P. , Kärtner Franz X. , Hartl Ingmar , Kupnik Mario , Heyl Christoph M. 
Published: October 2023

AbstractControl over the intensity, shape, direction and phase of coherent light is essential in numerous fields, from gravitational wave astronomy, quantum metrology and ultrafast sciences to semiconductor fabrication. Modern photonics, however, can involve parameter regimes where the wavelength or high optical powers involved restrict control due to absorption, light-induced damage or optical nonlinearity in solid media. Here we propose to circumvent these constraints using gaseous media tailored by high-intensity ultrasound waves. We demonstrate an implementation of this approach by efficiently deflecting ultrashort laser pulses using ultrasound waves in ambient air, without the use of transmissive solid media. At optical peak powers of 20 GW, exceeding previous limits of solid-based acousto-optic modulation by about three orders of magnitude, we reach a deflection efficiency greater than 50% while preserving excellent beam quality. Our approach is not limited to laser pulse deflection; gas-phase photonic schemes controlled by sonic waves could potentially be useful for realizing a new class of optical elements such as lenses or waveguides, which are effectively invulnerable against damage and can operate in new spectral regions.
Gemcitabine and cisplatin plus nivolumab as organ-sparing treatment for muscle-invasive bladder cancer: a phase 2 trial
Authors: Galsky Matthew D. , Daneshmand Siamak , Izadmehr Sudeh , Gonzalez-Kozlova Edgar , Chan Kevin G. , Lewis Sara , Achkar Bassam El , Dorff Tanya B. , Cetnar Jeremy Paul , Neil Brock O. , D’Souza Anishka , Mamtani Ronac , Kyriakopoulos Christos , Jun Tomi , Gogerly-Moragoda Mahalya , Brody Rachel , Xie Hui , Nie Kai , Kelly Geoffrey , Horowitz Amir , Kinoshita Yayoi , Ellis Ethan , Nose Yohei , Ioannou Giorgio , Cabal Rafael , Del Valle Diane M. , Haines G. Kenneth , Wang Li , Mouw Kent W. , Samstein Robert M. , Mehrazin Reza , Bhardwaj Nina , Yu Menggang , Zhao Qianqian , Kim-Schulze Seunghee , Sebra Robert , Zhu Jun , Gnjatic Sacha , Sfakianos John , Pal Sumanta K. 
Published: October 2023

AbstractCystectomy is a standard treatment for muscle-invasive bladder cancer (MIBC), but it is life-altering. We initiated a phase 2 study in which patients with MIBC received four cycles of gemcitabine, cisplatin, plus nivolumab followed by clinical restaging. Patients achieving a clinical complete response (cCR) could proceed without cystectomy. The co-primary objectives were to assess the cCR rate and the positive predictive value of cCR for a composite outcome: 2-year metastasis-free survival in patients forgoing immediate cystectomy or <ypT1N0 in patients electing immediate cystectomy. Seventy-six patients were enrolled; of these, 33 achieved a cCR (43%, 95% confidence interval (CI): 32%, 55%), and 32 of 33 who achieved a cCR opted to forgo immediate cystectomy. The positive predictive value of cCR was 0.97 (95% CI: 0.91, 1), meeting the co-primary objective. The most common adverse events were fatigue, anemia, neutropenia and nausea. Somatic alterations in pre-specified genes (ATM,RB1,FANCCandERCC2) or increased tumor mutational burden did not improve the positive predictive value of cCR. Exploratory analyses of peripheral blood mass cytometry and soluble protein analytes demonstrated an association between the baseline and on-treatment immune contexture with clinical outcomes. Stringently defined cCR after gemcitabine, cisplatin, plus nivolumab facilitated bladder sparing and warrants further study. ClinicalTrials.gov identifier:NCT03558087.
AZD5582 plus SIV-specific antibodies reduce lymph node viral reservoirs in antiretroviral therapy-suppressed macaques
Authors: Dashti Amir , Sukkestad Sophia , Horner Anna M. , Neja Margaret , Siddiqi Zain , Waller Chevaughn , Goldy Jordan , Monroe Dominique , Lin Alice , Schoof Nils , Singh Vidisha , Mavigner Maud , Lifson Jeffrey D. , Deleage Claire , Tuyishime Marina , Falcinelli Shane D. , King Hannah A. D. , Ke Ruian , Mason Rosemarie D. , Archin Nancie M. , Dunham Richard M. , Safrit Jeffrey T. , Jean Sherrie , Perelson Alan S. , Margolis David M. , Ferrari Guido , Roederer Mario , Silvestri Guido , Chahroudi Ann 
Published: October 2023

AbstractThe main barrier to HIV cure is a persistent reservoir of latently infected CD4+ T cells harboring replication-competent provirus that fuels rebound viremia upon antiretroviral therapy (ART) interruption. A leading approach to target this reservoir involves agents that reactivate latent HIV proviruses followed by direct clearance of cells expressing induced viral antigens by immune effector cells and immunotherapeutics. We previously showed that AZD5582, an antagonist of inhibitor of apoptosis proteins and mimetic of the second mitochondrial-derived activator of caspases (IAPi/SMACm), induces systemic reversal of HIV/SIV latency but with no reduction in size of the viral reservoir. In this study, we investigated the effects of AZD5582 in combination with four SIV Env-specific Rhesus monoclonal antibodies (RhmAbs) ± N-803 (an IL-15 superagonist) in SIV-infected, ART-suppressed rhesus macaques. Here we confirm the efficacy of AZD5582 in inducing SIV reactivation, demonstrate enhancement of latency reversal when AZD5582 is used in combination with N-803 and show a reduction in total and replication-competent SIV-DNA in lymph-node-derived CD4+ T cells in macaques treated with AZD5582 + RhmAbs. Further exploration of this therapeutic approach may contribute to the goal of achieving an HIV cure.
Elranatamab in relapsed or refractory multiple myeloma: the MagnetisMM-1 phase 1 trial
Authors: Bahlis Nizar J. , Costello Caitlin L. , Raje Noopur S. , Levy Moshe Y. , Dholaria Bhagirathbhai , Solh Melhem , Tomasson Michael H. , Damore Michael A. , Jiang Sibo , Basu Cynthia , Skoura Athanasia , Chan Edward M. , Trudel Suzanne , Jakubowiak Andrzej , Gasparetto Cristina , Chu Michael P. , Dalovisio Andrew , Sebag Michael , Lesokhin Alexander M. 
Published: October 2023

AbstractMultiple myeloma (MM) is a plasma cell malignancy expressing B cell maturation antigen (BCMA). Elranatamab, a bispecific antibody, engages BCMA on MM and CD3 on T cells. The MagnetisMM-1 trial evaluated its safety, pharmacokinetics and efficacy. Primary endpoints, including the incidence of dose-limiting toxicities as well as objective response rate (ORR) and duration of response (DOR), were met. Secondary efficacy endpoints included progression-free survival (PFS) and overall survival (OS). Eighty-eight patients with relapsed or refractory MM received elranatamab monotherapy, and 55 patients received elranatamab at efficacious doses. Patients had received a median of five prior regimens; 90.9% were triple-class refractory, 29.1% had high cytogenetic risk and 23.6% received prior BCMA-directed therapy. No dose-limiting toxicities were observed during dose escalation. Adverse events included cytopenias and cytokine release syndrome. Exposure was dose proportional. With a median follow-up of 12.0 months, the ORR was 63.6% and 38.2% of patients achieving complete response or better. For responders, the median DOR was 17.1 months. All 13 patients evaluable for minimal residual disease achieved negativity. Even after prior BCMA-directed therapy, 53.8% achieved response. For all 55 patients, median PFS was 11.8 months, and median OS was 21.2 months. Elranatamab achieved durable responses, manageable safety and promising survival for patients with MM. ClinicalTrials.gov Identifier: NCT03269136.
An open dataset with electrohysterogram records of pregnancies ending in induced and cesarean section delivery
Authors: Jager Franc 
Published: October 2023

AbstractThe existing non-invasive automated preterm birth prediction methods rely on the use of uterine electrohysterogram (EHG) records coming from spontaneous preterm and term deliveries, and are indifferent to term induced and cesarean section deliveries. In order to enhance current publicly available pool of term EHG records, we developed a new EHG dataset, Induced Cesarean EHG DataSet (ICEHG DS), containing 126 30-minute EHG records, recorded early (23rd week), and/or later (31st week) during pregnancy, of those pregnancies that were expected to end in spontaneous term delivery, but ended in induced or cesarean section delivery. The records were collected at the University Medical Center Ljubljana, Ljubljana, Slovenia. The dataset includes 38 and 43, early and later, induced; 11 and 8, early and later, cesarean; and 13 and 13, early and later, induced and cesarean EHG records. This dataset enables better understanding of the underlying physiological mechanisms involved during pregnancies ending in induced and cesarean deliveries, and provides a robust and more realistic assessment of the performance of automated preterm birth prediction methods.
Examinations of effects of socio-demographic features and disease-related data of patients with hemodialysis on the quality of life
Authors: Togay Elif , Akyüz Hatice Öntürk 
Published: October 2023

Abstract
This study aimed to detect the effects of demographic features and disease-related data of individuals with hemodialysis treatment on quality of life. The research universe consisted of 113 patients who received dialysis treatment in three state hospitals. Sampling was not used in this research with 97 volunteer patients who complied with the study criteria. The data collection process was performed face-to-face between 15 March and 15 April 2021. Data was collected using the Participant Information Form and the Quality of Life Scale (Short From-36). In our research, 50.5% of participants were male and 49.5% were female. The age of 61.9% of participants was ≥ 51 years and 78.4% were married. Most participants (67%) had ≥ 3 children, 35.1% received dialysis treatment for 3–10 years, 90.7% had dialysis three times a week, and 64.9% had an arterio-venous fistula vascular access line. In addition, 24% had another family member who received dialysis treatment, with hypertension as the etiology in 35.6% of chronic renal failure (CRF). The findings showed that 93.8% patients had no previous transplantation, and 62.9% considered future transplantation.Within the scope of this research, the findings suggest that the quality of life of dialysis patients was poor. Demographic features and disease data affected the quality of life at different levels.
Moisture mitigation using a vented liner and a vented socket system for individuals with transfemoral amputation
Authors: Gnyawali Surya C. , Denune Jeffrey A. , Hockman Bryce , Kristjánsdóttir Jóna Valgerður , Ragnarsdóttir Margrét Sól , Timsina Lava R. , Ghatak Subhadip , Lechler Knut , Sen Chandan K. , Roy Sashwati 
Published: October 2023

AbstractSweating and heat buildup at the skin-liner interface is a major challenge for persons with limb loss. Liners made of heat-non-conducting materials may cause sweating of the residual limb and may result in liners slipping off the skin surface especially on a warm day or during high activity, causing skin breakdown and affecting limb health. To address this, we evaluated the efficacy of the vented liner-socket system (VS, Össur) compared to Seal-In silicone liner and non-vented socket (nVS, Össur) in reducing relative humidity (RH) during increased sweat. Nine individuals with limb loss using nVS were randomized to VS or nVS and asked for activity in a 20-min treadmill walk. RH was significantly attenuated (p = 0.0002) and perceived sweating, as reported by prosthesis users, improved (p = 0.028) with VS, patient-reported comprehensive lower limb amputee socket survey (CLASS) outcomes to determine the suspension, stability, and comfort were not significantly different between VS and nVS. There are limited rigorous scientific studies that clearly provide evidence-based guidelines to the prosthetist in the selection of liners from numerous available options. The present study is innovative in clearly establishing objective measures for assessing humidity and temperatures at the skin-liner interface while performing activity. As shown by the measured data and perceived sweat scores provided by the subjects based on their daily experience, this study provided clear evidence establishing relative humidity at the skin-liner interface is reduced with the use of a vented liner-socket system when compared to a similar non-vented system.
Prediction of lithium-ion battery SOC based on the fusion of MHA and ConvolGRU
Authors: Tang Pei , Hua Jusen , Wang Pengchen , QU Zhonghui , Jiang Minnan 
Published: October 2023

AbstractIf the charging state of the lithium-ion battery can be accurately predicted, overcharge and overdischarge of the battery can be avoided, and the service life of the battery can be improved. In order to improve the prediction accuracy of SOC, a prediction method combined with convolutional layer, multi-head attention mechanism and gated cycle unit is proposed to extract data feature information from different dimensions of space and time. Using the data set of the University of Maryland, we simulated the battery in real vehicle operating conditions at different temperatures (0 °C, 25 °C, 45 °C). The test results showed that the mean absolute error, root mean square error and maximum prediction error of the model were 0.53%, 0.67% and 0.4% respectively. The results show that the model can predict SOC accurately. At the same time, the comparison with other prediction models shows that the prediction accuracy of this model is the highest.
Coupled catalytic states and the role of metal coordination in Cas9
Authors: Das Anuska , Rai Jay , Roth Mitchell O. , Shu Yuerong , Medina Megan L. , Barakat Mackenzie R. , Li Hong 
Published: October 2023

AbstractControlling the activity of the CRISPR–Cas9 system is essential to its safe adoption for clinical and research applications. Although the conformational dynamics of Cas9 are known to control its enzymatic activity, details of how Cas9 influences the catalytic processes at both nuclease domains remain elusive. Here we report five cryo-electron microscopy structures of the active Acidothermus cellulolyticus Cas9 complex along the reaction path at 2.2–2.9 Å resolution. We observed that a large movement in one nuclease domain, triggered by the cognate DNA, results in noticeable changes in the active site of the other domain that is required for metal coordination and catalysis. Furthermore, the conformations synchronize the reaction intermediates, enabling coupled cutting of the two DNA strands. Consistent with the roles of conformations in organizing the active sites, adjustments to the metal-coordination residues lead to altered metal specificity of A. cellulolyticus Cas9 and commonly used Streptococcus pyogenes Cas9 in cells.