bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term survival benefit of anti-PD-1 therapy in patients with relapsed or refractory classical Hodgkin lymphoma
Authors: Liu Weiping , Lin Ningjing , Feng Xinqin , Xie Yan , You Chong , Zhou Xiaohua , Song Yuqin , Zhu Jun 
Published: September 2023

AbstractAnti-programmed cell death-1 (anti-PD-1) therapies have shown a favorable efficacy and good tolerance for relapsed or refractory (r/r) classical Hodgkin lymphoma (cHL). However, there are limited data on long-term outcomes among patients with r/r cHL who achieve an objective response to anti-PD-1 therapies. A total of 260 responders from four, phase 2 clinical trials were included in this study. The median age was 32 years with a male/female ratio of 1.3:1. After a median follow-up period of 31.1 months, 116 (44.6%) responders experienced disease progression and 18 (6.9%) died. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 55.1% and 89.7% overall. Patients with partial remission (PR) had inferior outcomes compared with those who achieved complete remission (3-year PFS, 29.5% vs. 72.3%, P < 0.001; 3-year OS, 81.5% vs. 94.4%, P = 0.017). Moreover, the survival outcome was inferior for patients with refractory disease compared with those with relapsed disease. Multivariate Cox regression analysis showed PR and refractory disease were independent risk factors for PFS. In conclusion, PR and refractory disease have a negative impact on the survival benefit of anti-PD-1 therapeutics in patients with r/r cHL, which highlights the need for multimodal treatment strategies.
Water-assisted hydrogen spillover in Pt nanoparticle-based metal–organic framework composites
Authors: Gu Zhida , Li Mengke , Chen Cheng , Zhang Xinglong , Luo Chengyang , Yin Yutao , Su Ruifa , Zhang Suoying , Shen Yu , Fu Yu , Zhang Weina , Huo Fengwei 
Published: September 2023

AbstractHydrogen spillover is the migration of activated hydrogen atoms from a metal particle onto the surface of catalyst support, which has made significant progress in heterogeneous catalysis. The phenomenon has been well researched on oxide supports, yet its occurrence, detection method and mechanism on non-oxide supports such as metal–organic frameworks (MOFs) remain controversial. Herein, we develop a facile strategy for efficiency enhancement of hydrogen spillover on various MOFs with the aid of water molecules. By encapsulating platinum (Pt) nanoparticles in MOF-801 for activating hydrogen and hydrogenation of C=C in the MOF ligand as activated hydrogen detector, a research platform is built with Pt@MOF-801 to measure the hydrogenation region for quantifying the efficiency and spatial extent of hydrogen spillover. A water-assisted hydrogen spillover path is found with lower migration energy barrier than the traditional spillover path via ligand. The synergy of the two paths explains a significant boost of hydrogen spillover in MOF-801 from imperceptible existence to spanning at least 100-nm-diameter region. Moreover, such strategy shows universality in different MOF and covalent organic framework materials for efficiency promotion of hydrogen spillover and improvement of catalytic activity and antitoxicity, opening up new horizons for catalyst design in porous crystalline materials.
NET4 and RabG3 link actin to the tonoplast and facilitate cytoskeletal remodelling during stomatal immunity
Authors: Hawkins Timothy J. , Kopischke Michaela , Duckney Patrick J. , Rybak Katarzyna , Mentlak David A. , Kroon Johan T. M. , Bui Mai Thu , Richardson A. Christine , Casey Mary , Alexander Agnieszka , De Jaeger Geert , Kalde Monika , Moore Ian , Dagdas Yasin , Hussey Patrick J. , Robatzek Silke 
Published: September 2023

AbstractMembers of the NETWORKED (NET) family are involved in actin-membrane interactions. Here we show that two members of the NET family, NET4A and NET4B, are essential for normal guard cell actin reorganization, which is a process critical for stomatal closure in plant immunity. NET4 proteins interact with F-actin and with members of the Rab7 GTPase RABG3 family through two distinct domains, allowing for simultaneous localization to actin filaments and the tonoplast. NET4 proteins interact with GTP-bound, active RABG3 members, suggesting their function being downstream effectors. We also show that RABG3b is critical for stomatal closure induced by microbial patterns. Taken together, we conclude that the actin cytoskeletal remodelling during stomatal closure involves a molecular link between actin filaments and the tonoplast, which is mediated by the NET4-RABG3b interaction. We propose that stomatal closure to microbial patterns involves the coordinated action of immune-triggered osmotic changes and actin cytoskeletal remodelling likely driving compact vacuolar morphologies.
A R-loop sensing pathway mediates the relocation of transcribed genes to nuclear pore complexes
Authors: Penzo Arianna , Dubarry Marion , Brocas Clémentine , Zheng Myriam , Mangione Raphaël M. , Rougemaille Mathieu , Goncalves Coralie , Lautier Ophélie , Libri Domenico , Simon Marie-Noëlle , Géli Vincent , Dubrana Karine , Palancade Benoit 
Published: September 2023

AbstractNuclear pore complexes (NPCs) have increasingly recognized interactions with the genome, as exemplified in yeast, where they bind transcribed or damaged chromatin. By combining genome-wide approaches with live imaging of model loci, we uncover a correlation between NPC association and the accumulation of R-loops, which are genotoxic structures formed through hybridization of nascent RNAs with their DNA templates. Manipulating hybrid formation demonstrates that R-loop accumulation per se, rather than transcription or R-loop-dependent damages, is the primary trigger for relocation to NPCs. Mechanistically, R-loop-dependent repositioning involves their recognition by the ssDNA-binding protein RPA, and SUMO-dependent interactions with NPC-associated factors. Preventing R-loop-dependent relocation leads to lethality in hybrid-accumulating conditions, while NPC tethering of a model hybrid-prone locus attenuates R-loop-dependent genetic instability. Remarkably, this relocation pathway involves molecular factors similar to those required for the association of stalled replication forks with NPCs, supporting the existence of convergent mechanisms for sensing transcriptional and genotoxic stresses.
NLRP3 selectively drives IL-1β secretion by Pseudomonas aeruginosa infected neutrophils and regulates corneal disease severity
Authors: Minns Martin S. , Liboro Karl , Lima Tatiane S. , Abbondante Serena , Miller Brandon A. , Marshall Michaela E. , Tran Chau Jolynn , Roistacher Alicia , Rietsch Arne , Dubyak George R. , Pearlman Eric 
Published: September 2023

AbstractMacrophages infected with Gram-negative bacteria expressing Type III secretion system (T3SS) activate the NLRC4 inflammasome, resulting in Gasdermin D (GSDMD)-dependent, but GSDME independent IL-1β secretion and pyroptosis. Here we examine inflammasome signaling in neutrophils infected with Pseudomonas aeruginosa strain PAO1 that expresses the T3SS effectors ExoS and ExoT. IL-1β secretion by neutrophils requires the T3SS needle and translocon proteins and GSDMD. In macrophages, PAO1 and mutants lacking ExoS and ExoT (ΔexoST) require NLRC4 for IL-1β secretion. While IL-1β release from ΔexoST infected neutrophils is also NLRC4-dependent, infection with PAO1 is instead NLRP3-dependent and driven by the ADP ribosyl transferase activity of ExoS. Genetic and pharmacologic approaches using MCC950 reveal that NLRP3 is also essential for bacterial killing and disease severity in a murine model of P. aeruginosa corneal infection (keratitis). Overall, these findings reveal a function for ExoS ADPRT in regulating inflammasome subtype usage in neutrophils versus macrophages and an unexpected role for NLRP3 in P. aeruginosa keratitis.
A CCL2+DPP4+ subset of mesenchymal stem cells expedites aberrant formation of creeping fat in humans
Authors: Wu Fengfei , Wu Fangting , Zhou Qian , Liu Xi , Fei Jieying , Zhang Da , Wang Weidong , Tao Yi , Lin Yubing , Lin Qiaoqiao , Pan Xinghua , Sun Kai , Xie Fang , Bai Lan 
Published: September 2023

AbstractCreeping fat is a typical feature of Crohn’s disease. It refers to the expansion of mesenteric adipose tissue around inflamed and fibrotic intestines and is associated with stricture formation and intestinal obstruction. In this study, we characterize creeping fat as pro-adipogenic and pro-fibrotic. Lipidomics analysis of Crohn’s disease patients (sixteen males, six females) and healthy controls (five males, ten females) reveals abnormal lipid metabolism in creeping fat. Through scRNA-seq analysis on mesenteric adipose tissue from patients (five males, one female) and healthy controls (two females), we identify a CCL2+DPP4+ subset of mesenchymal stem cells that expands in creeping fat and expedites adipogenic differentiation into dystrophic adipocytes in response to CCL20+CD14+ monocytes and IL-6, leading to the formation of creeping fat. Ex vivo experiments (tissues from five males, one female) confirm that both CCL20+CD14+ monocytes and IL-6 activate DPP4+ mesenchymal stem cells towards a pro-adipogenic phenotype. This study provides a comprehensive investigation of creeping fat formation and offers a conceptual framework for discovering therapeutic targets for treatment of Crohn’s disease.
Observation of suppressed viscosity in the normal state of 3He due to superfluid fluctuations
Authors: Baten Rakin N. , Tian Yefan , Smith Eric N. , Mueller Erich J. , Parpia Jeevak M. 
Published: September 2023

AbstractEvidence of fluctuations in transport have long been predicted in 3He. They are expected to contribute only within 100μK of Tc and play a vital role in the theoretical modeling of ordering; they encode details about the Fermi liquid parameters, pairing symmetry, and scattering phase shifts. It is expected that they will be of crucial importance for transport probes of the topologically nontrivial features of superfluid 3He under strong confinement. Here we characterize the temperature and pressure dependence of the fluctuation signature, by monitoring the quality factor of a quartz tuning fork oscillator. We have observed a fluctuation-driven reduction in the viscosity of bulk 3He, finding data collapse consistent with the predicted theoretical behavior.
Chronic cough relief by allosteric modulation of P2X3 without taste disturbance
Authors: Guo Chang-Run , Zhang Zhong-Zhe , Zhou Xing , Sun Meng-Yang , Li Tian-Tian , Lei Yun-Tao , Gao Yu-Hao , Li Qing-Quan , Yue Chen-Xi , Gao Yu , Lin Yi-Yu , Hao Cui-Yun , Li Chang-Zhu , Cao Peng , Zhu Michael X. , Rong Ming-Qiang , Wang Wen-Hui , Yu Ye 
Published: September 2023

AbstractP2X receptors are cation channels that sense extracellular ATP. Many therapeutic candidates targeting P2X receptors have begun clinical trials or acquired approval for the treatment of refractory chronic cough (RCC) and other disorders. However, the present negative allosteric modulation of P2X receptors is primarily limited to the central pocket or the site below the left flipper domain. Here, we uncover a mechanism of allosteric regulation of P2X3 in the inner pocket of the head domain (IP-HD), and show that the antitussive effects of quercetin and PSFL2915 (our nM-affinity P2X3 inhibitor optimized based on quercetin) on male mice and guinea pigs were achieved by preventing allosteric changes of IP-HD in P2X3. While being therapeutically comparable to the newly licensed P2X3 RCC drug gefapixant, quercetin and PSFL2915 do not have an adverse effect on taste as gefapixant does. Thus, allosteric modulation of P2X3 via IP-HD may be a druggable strategy to alleviate RCC.
Synergism between CMG helicase and leading strand DNA polymerase at replication fork
Authors: Xu Zhichun , Feng Jianrong , Yu Daqi , Huo Yunjing , Ma Xiaohui , Lam Wai Hei , Liu Zheng , Li Xiang David , Ishibashi Toyotaka , Dang Shangyu , Zhai Yuanliang 
Published: September 2023

AbstractThe replisome that replicates the eukaryotic genome consists of at least three engines: the Cdc45-MCM-GINS (CMG) helicase that separates duplex DNA at the replication fork and two DNA polymerases, one on each strand, that replicate the unwound DNA. Here, we determined a series of cryo-electron microscopy structures of a yeast replisome comprising CMG, leading-strand polymerase Polε and three accessory factors on a forked DNA. In these structures, Polε engages or disengages with the motor domains of the CMG by occupying two alternative positions, which closely correlate with the rotational movement of the single-stranded DNA around the MCM pore. During this process, the polymerase remains stably coupled to the helicase using Psf1 as a hinge. This synergism is modulated by a concerted rearrangement of ATPase sites to drive DNA translocation. The Polε-MCM coupling is not only required for CMG formation to initiate DNA replication but also facilitates the leading-strand DNA synthesis mediated by Polε. Our study elucidates a mechanism intrinsic to the replisome that coordinates the activities of CMG and Polε to negotiate any roadblocks, DNA damage, and epigenetic marks encountered during translocation along replication forks.
Breastfeeding and impact on childhood hospital admissions: a nationwide birth cohort in South Korea
Authors: Lee Jeong-Seon , Shin Jae Il , Kim Sunyeup , Choi Yong-Sung , Shin Youn Ho , Hwang Jimin , Shin Jung U , Koyanagi Ai , Jacob Louis , Smith Lee , Jeong Han Eol , Noh Yunha , Oh In-Sun , Rhee Sang Youl , Min Chanyang , Cho Seong Ho , Turner Steve , Fond Guillaume , Boyer Laurent , Suh Dong In , Acharya Krishna Prasad , Shin Ju-Young , Lee Seung Won , Yon Dong Keon 
Published: September 2023

AbstractBenefits of breastfeeding for both the mother and the child are well established, but a comprehensive and robust study to investigate the protective effect of breastfeeding and attenuated time effect stratified by cause of morbidity are lacking. This study is based on the nationwide birth cohort in Korea that includes data on all infants born from 2009 to 2015. Of 1,608,540 children, the median follow-up period was 8.41 years (interquartile range, 6.76-10.06). When compared to children with fully formula feeding, the hospital admission rate was 12% lower in those with partially breastfeeding and 15% lower in those with exclusive breastfeeding. The apparent protective effect of breastfeeding was reduced with increasing age. Our study provides potential evidence of the beneficial association of breastfeeding on subsequent hospital admissions. The protective effect declined over time as the children grew older. Encouraging any breastfeeding for at least the first 6 months among infants is an important public health strategy to improve overall child health.
Neural representation of goal direction in the monarch butterfly brain
Authors: Beetz M. Jerome , Kraus Christian , el Jundi Basil 
Published: September 2023

AbstractNeural processing of a desired moving direction requires the continuous comparison between the current heading and the goal direction. While the neural basis underlying the current heading is well-studied, the coding of the goal direction remains unclear in insects. Here, we used tetrode recordings in tethered flying monarch butterflies to unravel how a goal direction is represented in the insect brain. While recording, the butterflies maintained robust goal directions relative to a virtual sun. By resetting their goal directions, we found neurons whose spatial tuning was tightly linked to the goal directions. Importantly, their tuning was unaffected when the butterflies changed their heading after compass perturbations, showing that these neurons specifically encode the goal direction. Overall, we here discovered invertebrate goal-direction neurons that share functional similarities to goal-direction cells reported in mammals. Our results give insights into the evolutionarily conserved principles of goal-directed spatial orientation in animals.
Large T cell clones expressing immune checkpoints increase during multiple myeloma evolution and predict treatment resistance
Authors: Botta Cirino , Perez Cristina , Larrayoz Marta , Puig Noemi , Cedena Maria-Teresa , Termini Rosalinda , Goicoechea Ibai , Rodriguez Sara , Zabaleta Aintzane , Lopez Aitziber , Sarvide Sarai , Blanco Laura , Papetti Daniele M. , Nobile Marco S. , Besozzi Daniela , Gentile Massimo , Correale Pierpaolo , Siragusa Sergio , Oriol Albert , González-Garcia Maria Esther , Sureda Anna , de Arriba Felipe , Rios Tamayo Rafael , Moraleda Jose-Maria , Gironella Mercedes , Hernandez Miguel T. , Bargay Joan , Palomera Luis , Pérez-Montaña Albert , Goldschmidt Hartmut , Avet-Loiseau Hervé , Roccaro Aldo , Orfao Alberto , Martinez-Lopez Joaquin , Rosiñol Laura , Lahuerta Juan-José , Blade Joan , Mateos Maria-Victoria , San-Miguel Jesús F. , Martinez Climent Jose-Angel , Paiva Bruno ,   the Programa Para el Estudio de la Terapéutica en Hemopatías Malignas/Grupo Español de Mieloma (PETHEMA/GEM) cooperative group,   the iMMunocell study group
Published: September 2023

AbstractTumor recognition by T cells is essential for antitumor immunity. A comprehensive characterization of T cell diversity may be key to understanding the success of immunomodulatory drugs and failure of PD-1 blockade in tumors such as multiple myeloma (MM). Here, we use single-cell RNA and T cell receptor sequencing to characterize bone marrow T cells from healthy adults (n = 4) and patients with precursor (n = 8) and full-blown MM (n = 10). Large T cell clones from patients with MM expressed multiple immune checkpoints, suggesting a potentially dysfunctional phenotype. Dual targeting of PD-1 + LAG3 or PD-1 + TIGIT partially restored their function in mice with MM. We identify phenotypic hallmarks of large intratumoral T cell clones, and demonstrate that the CD27− and CD27+ T cell ratio, measured by flow cytometry, may serve as a surrogate of clonal T cell expansions and an independent prognostic factor in 543 patients with MM treated with lenalidomide-based treatment combinations.
Anionic ring-opening polymerization of functional epoxide monomers in the solid state
Authors: Park Jihye , Kim Ahyun , Kim Byeong-Su 
Published: September 2023

AbstractDespite recent advancements in mechanochemical polymerization, understanding the unique mechanochemical reactivity during the ball milling polymerization process still requires extensive investigations. Herein, solid-state anionic ring-opening polymerization is used to synthesize polyethers from various functional epoxide monomers. The critical parameters of the monomers are investigated to elucidate the unique reactivity of ball milling polymerization. The controllable syntheses of the desired polyethers are characterized via NMR, GPC, and MALDI-ToF analyses. Interestingly, bulky monomers exhibit faster conversions in the solid-state in clear contrast to that observed for solution polymerization. Particularly, a close linear correlation is observed between the conversion of the ball milling polymerization and melting point of the functional epoxide monomers, indicating melting point as a critical predictor of mechanochemical polymerization reactivity. This study provides insights into the efficient design and understanding of mechanochemical polymerization.
An entropy-controlled objective chip for reflective confocal microscopy with subdiffraction-limit resolution
Authors: He Jun , Zhao Dong , Liu Hong , Teng Jinghua , Qiu Cheng-Wei , Huang Kun 
Published: September 2023

AbstractPlanar diffractive lenses (PDLs) with optimized but disordered structures can focus light beyond the diffraction limit. However, these disordered structures have inevitably destroyed wide-field imaging capability, limiting their applications in microscopy. Here, we introduce information entropy S to evaluate the disorder of an objective chip by using the probability of its structural deviation from standard Fresnel zone plates. Inspired by the theory of entropy change, we predict an equilibrium point $${S}_{0}=0.5$$

S

0

=
0.5
to balance wide-field imaging (theoretically evaluated by the Strehl ratio) and subdiffraction-limit focusing. To verify this, a $${NA}=0.9$$
N
A
=
0.9
objective chip with a record-long focal length of 1 mm is designed with $$S=0.535$$
S
=
0.535
, which is the nearest to the equilibrium point among all reported PDLs. Consequently, our fabricated chip can focus light with subdiffraction-limit size of 0.44 λ and image fine details with spatial frequencies up to 4000 lp/mm experimentally. These unprecedented performances enable ultracompact reflective confocal microscopy for superresolution imaging.
The effect of high perioperative inspiratory oxygen fraction for abdominal surgery on surgical site infection: a systematic review and meta-analysis
Authors: Kuh Jae Hee , Jung Woo-Seok , Lim Leerang , Yoo Hae Kyung , Ju Jae-Woo , Lee Ho-Jin , Kim Won Ho 
Published: September 2023

AbstractGuidelines from the World Health Organization strongly recommend the use of a high fraction of inspired oxygen (FiO2) in adult patients undergoing general anesthesia to reduce surgical site infection (SSI). However, previous meta-analyses reported inconsistent results. We aimed to address this controversy by focusing specifically on abdominal surgery with relatively high risk of SSI. Medline, EMBASE, and Cochrane CENTRAL databases were searched. Randomized trials of abdominal surgery comparing high to low perioperative FiO2 were included, given that the incidence of SSI was reported as an outcome. Meta-analyses of risk ratios (RR) were performed using a fixed effects model. Subgroup analysis and meta-regression were employed to explore sources of heterogeneity. We included 27 trials involving 15977 patients. The use of high FiO2 significantly reduced the incidence of SSI (n = 27, risk ratio (RR): 0.87; 95% confidence interval (CI): 0.79, 0.95; I2 = 49%, Z = 3.05). Trial sequential analysis (TSA) revealed that z-curve crossed the trial sequential boundary and data are sufficient. This finding held true for the subgroup of emergency operations (n = 2, RR: 0.54; 95% CI: 0.35, 0.84; I2 = 0%, Z = 2.75), procedures using air as carrier gas (n = 9, RR: 0.79; 95% CI: 0.69, 0.91; I2 = 60%, Z = 3.26), and when a high level of FiO2 was maintained for a postoperative 6 h or more (n = 9, RR: 0.68; 95% CI: 0.56, 0.83; I2 = 46%, Z = 3.83). Meta-regression revealed no significant interaction between SSI with any covariates including age, sex, body-mass index, diabetes mellitus, duration of surgery, and smoking. Quality of evidence was assessed to be moderate to very low. Our pooled analysis revealed that the application of high FiO2 reduced the incidence of SSI after abdominal operations. Although TSA demonstrated sufficient data and cumulative analysis crossed the TSA boundary, our results should be interpreted cautiously given the low quality of evidence.Registration: https://www.crd.york.ac.uk/prospero (CRD42022369212) on October 2022.