bluuebunny/crossref_metadata_2025_split huggingface dataset:
The contribution of affective content to cue-response correspondence in a word association task: Focus on emotion words and emotion-laden words
Authors: Betancourt Ángel-Armando , Guasch Marc , Ferré Pilar 
Published: October 2023

AbstractThis study aimed at examining the contribution of affective content to the organization of words in the lexicon. Based on existing free association norms and on a series of questionnaires we developed, we examined the characteristics of the words produced as associates to 840 Spanish cue words. Half of them were affective words and the other half were neutral (non-affective) words. Among the affective cue words, some words directly labeled an emotion (emotion words, EM) and others did not label an emotion but could elicit it (emotion-laden words, EL). The words produced as associates were also classified according to this distinction. Furthermore, we examined the relationship between the lexico-semantic and affective properties of the cue words and the associated words. The results revealed that EM, EL, and neutral associated words were elicited to a greater extent by cue words of the same type than by other types of cue words. Furthermore, the degree of correspondence between the affective properties of the cues and their associates was higher than that of lexico-semantic variables. These results have methodological implications for research on semantic memory and are of interest for applied studies focused on affective word organization in specific populations.
Hybrid deep learning model-based human action recognition in indoor environment
Authors: Sain Manoj Kumar , Laskar Rabul Hussain , Singha Joyeeta , Saini Sandeep 
Published: October 2023

AbstractHuman activity recognition (HAR) is an emerging challenge among researchers. HAR has many possible uses in various fields, including healthcare, sports, and security. Furthermore, there are only a few publicly accessible datasets for classifying and recognizing physical activity in the literature, and these datasets comprise fewer activities. We created and compared our dataset with available datasets, that is, NTU-RGBD, UP-FALL, UR-Fall, WISDM, and UCI HAR. The proposed dataset consists of seven activities: eating, exercise, handshake, situps, vomiting, headache, and walking. The activities were collected from 20 people between the ages of 25 and 40 years using Kinect V2 sensor at 30 FPS. For classification, we use deep learning architectures based on convolutional neural network (CNN) and long short-term memory (LSTM). Additionally, we developed a novel hybrid deep learning model by combining a CNN, a bidirectional LSTM unit, and a fully connected layer for activity identification. The suggested model builds unique guided features using the preprocessed skeleton coordinates and their distinctive geometrical and kinematic aspects. Results from the experiment are contrasted with the performance of stand-alone CNNs, LSTMs, and ConvLSTM. The proposed model’s accuracy of 99.5% surpasses that of CNN, LSTM, and ConvLSTM, which have accuracy rates of 95.76%, 97%, and 98.89%, respectively. Our proposed technique is invariant of stance, speed, individual, clothes, etc. The proposed dataset sample is accessible to the general public.
Pyruvate kinase M2 regulates mitochondrial homeostasis in cisplatin-induced acute kidney injury
Authors: Xie Wenjia , He Qingyun , Zhang Yan , Xu Xinxin , Wen Ping , Cao Hongdi , Zhou Yang , Luo Jing , Yang Junwei , Jiang Lei 
Published: October 2023

AbstractAn important pathophysiological process of acute kidney injury (AKI) is mitochondrial fragmentation in renal tubular epithelial cells, which leads to cell death. Pyruvate kinase M2 (PKM2) is an active protein with various biological functions that participates in regulating glycolysis and plays a key role in regulating cell survival. However, the role and mechanism of PKM2 in regulating cell survival during AKI remain unclear. Here, we found that the phosphorylation of PKM2 contributed to the formation of the PKM2 dimer and translocation of PKM2 into the mitochondria after treatment with staurosporine or cisplatin. Mitochondrial PKM2 binds myosin heavy chain 9 (MYH9) to promote dynamin-related protein 1 (DRP1)-mediated mitochondrial fragmentation. Both in vivo and in vitro, PKM2-specific loss or regulation PKM2 activity partially limits mitochondrial fragmentation, alleviating renal tubular injury and cell death, including apoptosis, necroptosis, and ferroptosis. Moreover, staurosporine or cisplatin-induced mitochondrial fragmentation and cell death were reversed in cultured cells by inhibiting MYH9 activity. Taken together, our results indicate that the regulation of PKM2 abundance and activity to inhibit mitochondrial translocation may maintain mitochondrial integrity and provide a new therapeutic strategy for treating AKI.
Impact of global climate cooling on Ordovician marine biodiversity
Authors: Ontiveros Daniel Eliahou , Beaugrand Gregory , Lefebvre Bertrand , Marcilly Chloe Markussen , Servais Thomas , Pohl Alexandre 
Published: October 2023

AbstractGlobal cooling has been proposed as a driver of the Great Ordovician Biodiversification Event, the largest radiation of Phanerozoic marine animal Life. Yet, mechanistic understanding of the underlying pathways is lacking and other possible causes are debated. Here we couple a global climate model with a macroecological model to reconstruct global biodiversity patterns during the Ordovician. In our simulations, an inverted latitudinal biodiversity gradient characterizes the late Cambrian and Early Ordovician when climate was much warmer than today. During the Mid-Late Ordovician, climate cooling simultaneously permits the development of a modern latitudinal biodiversity gradient and an increase in global biodiversity. This increase is a consequence of the ecophysiological limitations to marine Life and is robust to uncertainties in both proxy-derived temperature reconstructions and organism physiology. First-order model-data agreement suggests that the most conspicuous rise in biodiversity over Earth’s history – the Great Ordovician Biodiversification Event – was primarily driven by global cooling.
Signature-driven repurposing of Midostaurin for combination with MEK1/2 and KRASG12C inhibitors in lung cancer
Authors: Macaya Irati , Roman Marta , Welch Connor , Entrialgo-Cadierno Rodrigo , Salmon Marina , Santos Alba , Feliu Iker , Kovalski Joanna , Lopez Ines , Rodriguez-Remirez Maria , Palomino-Echeverria Sara , Lonfgren Shane M. , Ferrero Macarena , Calabuig Silvia , Ludwig Iziar A. , Lara-Astiaso David , Jantus-Lewintre Eloisa , Guruceaga Elizabeth , Narayanan Shruthi , Ponz-Sarvise Mariano , Pineda-Lucena Antonio , Lecanda Fernando , Ruggero Davide , Khatri Purvesh , Santamaria Enrique , Fernandez-Irigoyen Joaquin , Ferrer Irene , Paz-Ares Luis , Drosten Matthias , Barbacid Mariano , Gil-Bazo Ignacio , Vicent Silve 
Published: October 2023

AbstractDrug combinations are key to circumvent resistance mechanisms compromising response to single anti-cancer targeted therapies. The implementation of combinatorial approaches involving MEK1/2 or KRASG12C inhibitors in the context of KRAS-mutated lung cancers focuses fundamentally on targeting KRAS proximal activators or effectors. However, the antitumor effect is highly determined by compensatory mechanisms arising in defined cell types or tumor subgroups. A potential strategy to find drug combinations targeting a larger fraction of KRAS-mutated lung cancers may capitalize on the common, distal gene expression output elicited by oncogenic KRAS. By integrating a signature-driven drug repurposing approach with a pairwise pharmacological screen, here we show synergistic drug combinations consisting of multi-tyrosine kinase PKC inhibitors together with MEK1/2 or KRASG12C inhibitors. Such combinations elicit a cytotoxic response in both in vitro and in vivo models, which in part involves inhibition of the PKC inhibitor target AURKB. Proteome profiling links dysregulation of MYC expression to the effect of both PKC inhibitor-based drug combinations. Furthermore, MYC overexpression appears as a resistance mechanism to MEK1/2 and KRASG12C inhibitors. Our study provides a rational framework for selecting drugs entering combinatorial strategies and unveils MEK1/2- and KRASG12C-based therapies for lung cancer.
CSTF2 mediated mRNA N6-methyladenosine modification drives pancreatic ductal adenocarcinoma m6A subtypes
Authors: Zheng Yanfen , Li Xingyang , Deng Shuang , Zhao Hongzhe , Ye Ying , Zhang Shaoping , Huang Xudong , Bai Ruihong , Zhuang Lisha , Zhou Quanbo , Li Mei , Su Jiachun , Li Rui , Bao Xiaoqiong , Zeng Lingxing , Chen Rufu , Zheng Jian , Lin Dongxin , He Chuan , Zhang Jialiang , Zuo Zhixiang 
Published: October 2023

AbstractN6-methyladenosine (m6A) modification of gene transcripts plays critical roles in cancer. Here we report transcriptomic m6A profiling in 98 tissue samples from 65 individuals with pancreatic ductal adenocarcinoma (PDAC). We identify 17,996 m6A peaks with 195 hyper-methylated and 93 hypo-methylated in PDAC compared with adjacent normal tissues. The differential m6A modifications distinguish two PDAC subtypes with different prognosis outcomes. The formation of the two subtypes is driven by a newly identified m6A regulator CSTF2 that co-transcriptionally regulates m6A installation through slowing the RNA Pol II elongation rate during gene transcription. We find that most of the CSTF2-regulated m6As have positive effects on the RNA level of host genes, and CSTF2-regulated m6As are mainly recognized by IGF2BP2, an m6A reader that stabilizes mRNAs. These results provide a promising PDAC subtyping strategy and potential therapeutic targets for precision medicine of PDAC.
Structure-based design of a phosphotyrosine-masked covalent ligand targeting the E3 ligase SOCS2
Authors: Ramachandran Sarath , Makukhin Nikolai , Haubrich Kevin , Nagala Manjula , Forrester Beth , Lynch Dylan M. , Casement Ryan , Testa Andrea , Bruno Elvira , Gitto Rosaria , Ciulli Alessio 
Published: October 2023

AbstractThe Src homology 2 (SH2) domain recognizes phosphotyrosine (pY) post translational modifications in partner proteins to trigger downstream signaling. Drug discovery efforts targeting the SH2 domains have long been stymied by the poor drug-like properties of phosphate and its mimetics. Here, we use structure-based design to target the SH2 domain of the E3 ligase suppressor of cytokine signaling 2 (SOCS2). Starting from the highly ligand-efficient pY amino acid, a fragment growing approach reveals covalent modification of Cys111 in a co-crystal structure, which we leverage to rationally design a cysteine-directed electrophilic covalent inhibitor MN551. We report the prodrug MN714 containing a pivaloyloxymethyl (POM) protecting group and evidence its cell permeability and capping group unmasking using cellular target engagement and in-cell 19F NMR spectroscopy. Covalent engagement at Cys111 competitively blocks recruitment of cellular SOCS2 protein to its native substrate. The qualified inhibitors of SOCS2 could find attractive applications as chemical probes to understand the biology of SOCS2 and its CRL5 complex, and as E3 ligase handles in proteolysis targeting chimera (PROTACs) to induce targeted protein degradation.
Multi-species atlas resolves an axolotl limb development and regeneration paradox
Authors: Zhong Jixing , Aires Rita , Tsissios Georgios , Skoufa Evangelia , Brandt Kerstin , Sandoval-Guzmán Tatiana , Aztekin Can 
Published: October 2023

AbstractHumans and other tetrapods are considered to require apical-ectodermal-ridge (AER) cells for limb development, and AER-like cells are suggested to be re-formed to initiate limb regeneration. Paradoxically, the presence of AER in the axolotl, a primary model organism for regeneration, remains controversial. Here, by leveraging a single-cell transcriptomics-based multi-species atlas, composed of axolotl, human, mouse, chicken, and frog cells, we first establish that axolotls contain cells with AER characteristics. Further analyses and spatial transcriptomics reveal that axolotl limbs do not fully re-form AER cells during regeneration. Moreover, the axolotl mesoderm displays part of the AER machinery, revealing a program for limb (re)growth. These results clarify the debate about the axolotl AER and the extent to which the limb developmental program is recapitulated during regeneration.
FAM210A is essential for cold-induced mitochondrial remodeling in brown adipocytes
Authors: Qiu Jiamin , Yue Feng , Zhu Peipei , Chen Jingjuan , Xu Fan , Zhang Lijia , Kim Kun Ho , Snyder Madigan M. , Luo Nanjian , Xu Hao-wei , Huang Fang , Tao W. Andy , Kuang Shihuan 
Published: October 2023

AbstractCold stimulation dynamically remodels mitochondria in brown adipose tissue (BAT) to facilitate non-shivering thermogenesis in mammals, but what regulates mitochondrial plasticity is poorly understood. Comparing mitochondrial proteomes in response to cold revealed FAM210A as a cold-inducible mitochondrial inner membrane protein. An adipocyte-specific constitutive knockout ofFam210a(Fam210aAKO) disrupts mitochondrial cristae structure and diminishes the thermogenic activity of BAT, rendering theFam210aAKOmice vulnerable to lethal hypothermia under acute cold exposure. Induced knockout ofFam210ain adult adipocytes (Fam210aiAKO) does not affect steady-state mitochondrial structure under thermoneutrality, but impairs cold-induced mitochondrial remodeling, leading to progressive loss of cristae and reduction of mitochondrial density. Proteomics reveals an association between FAM210A and OPA1, whose cleavage governs cristae dynamics and mitochondrial remodeling. Mechanistically, FAM210A interacts with mitochondrial protease YME1L and modulates its activity toward OMA1 and OPA1 cleavage. These data establish FAM210A as a key regulator of mitochondrial cristae remodeling in BAT and shed light on the mechanism underlying mitochondrial plasticity in response to cold.
HIV-1 treatment timing shapes the human intestinal memory B-cell repertoire to commensal bacteria
Authors: Planchais Cyril , Molinos-Albert Luis M. , Rosenbaum Pierre , Hieu Thierry , Kanyavuz Alexia , Clermont Dominique , Prazuck Thierry , Lefrou Laurent , Dimitrov Jordan D. , Hüe Sophie , Hocqueloux Laurent , Mouquet Hugo 
Published: October 2023

AbstractHIV-1 infection causes severe alterations of gut mucosa, microbiota and immune system, which can be curbed by early antiretroviral therapy. Here, we investigate how treatment timing affects intestinal memory B-cell and plasmablast repertoires of HIV-1-infected humans. We show that only class-switched memory B cells markedly differ between subjects treated during the acute and chronic phases of infection. Intestinal memory B-cell monoclonal antibodies show more prevalent polyreactive and commensal bacteria-reactive clones in late- compared to early-treated individuals. Mirroring this, serum IgA polyreactivity and commensal-reactivity are strongly increased in late-treated individuals and correlate with intestinal permeability and systemic inflammatory markers. Polyreactive blood IgA memory B cells, many of which egressed from the gut, are also substantially enriched in late-treated individuals. Our data establish gut and systemic B-cell polyreactivity to commensal bacteria as hallmarks of chronic HIV-1 infection and suggest that initiating treatment early may limit intestinal B-cell abnormalities compromising HIV-1 humoral response.
Light-driven nucleation, growth, and patterning of biorelevant crystals using resonant near-infrared laser heating
Authors: Bistervels Marloes H. , Antalicz Balázs , Kamp Marko , Schoenmaker Hinco , Noorduin Willem L. 
Published: October 2023

AbstractSpatiotemporal control over crystal nucleation and growth is of fundamental interest for understanding how organisms assemble high-performance biominerals, and holds relevance for manufacturing of functional materials. Many methods have been developed towards static or global control, however gaining simultaneously dynamic and local control over crystallization remains challenging. Here, we show spatiotemporal control over crystallization of retrograde (inverse) soluble compounds induced by locally heating water using near-infrared (NIR) laser light. We modulate the NIR light intensity to start, steer, and stop crystallization of calcium carbonate and laser-write with micrometer precision. Tailoring the crystallization conditions overcomes the inherently stochastic crystallization behavior and enables positioning single crystals of vaterite, calcite, and aragonite. We demonstrate straightforward extension of these principles toward other biorelevant compounds by patterning barium-, strontium-, and calcium carbonate, as well as strontium sulfate and calcium phosphate. Since many important compounds exhibit retrograde solubility behavior, NIR-induced heating may enable light-controlled crystallization with precise spatiotemporal control.
Supramolecular catalysis with ethers enabled by dual chalcogen bonding activation
Authors: Zhao Zhiguo , Pang Yuanling , Zhao Ziqiang , Zhou Pan-Pan , Wang Yao 
Published: October 2023

AbstractThe activation of ethers by weak interactions is a long-standing objective in supramolecular catalysis, but yet it remains an underdeveloped topic. The obstacles towards solving this problem are prominent since it is difficult for a weak interaction to cleave a relatively strong C-O σ-bond and moreover, the ionic intermediate composing of an alkoxide ion and an electrophilic carbocation would deactivate weak interaction donors. Herein, we describe a distinctive activation mode, dual Se···π and Se···O bonding, that could activate benzylic as well as allylic ether C-O σ-bonds to achieve cyclization, coupling and elimination reactions. This dual Se···π and Se···O bonding catalysis approach could tolerate various alkoxide leaving groups, while the other representative weak interaction donors showed no catalytic activity.
NAT10-dependent N4‐acetylcytidine modification mediates PAN RNA stability, KSHV reactivation, and IFI16-related inflammasome activation
Authors: Yan Qin , Zhou Jing , Wang Ziyu , Ding Xiangya , Ma Xinyue , Li Wan , Jia Xuemei , Gao Shou-Jiang , Lu Chun 
Published: October 2023

AbstractN-acetyltransferase 10 (NAT10) is an N4‐acetylcytidine (ac4C) writer that catalyzes RNA acetylation at cytidine N4 position on tRNAs, rRNAs and mRNAs. Recently, NAT10 and the associated ac4C have been reported to increase the stability of HIV-1 transcripts. Here, we show that NAT10 catalyzes ac4C addition to the polyadenylated nuclear RNA (PAN), a long non-coding RNA encoded by the oncogenic DNA virus Kaposi’s sarcoma-associated herpesvirus (KSHV), triggering viral lytic reactivation from latency. Mutagenesis of ac4C sites in PAN RNA in the context of KSHV infection abolishes PAN ac4C modifications, downregulates the expression of viral lytic genes and reduces virion production. NAT10 knockdown or mutagenesis erases ac4C modifications of PAN RNA and increases its instability, and prevents KSHV reactivation. Furthermore, PAN ac4C modification promotes NAT10 recruitment of IFN-γ-inducible protein-16 (IFI16) mRNA, resulting in its ac4C acetylation, mRNA stability and translation, and eventual inflammasome activation. These results reveal a novel mechanism of viral and host ac4C modifications and the associated complexes as a critical switch of KSHV replication and antiviral immunity.
Oblique lateral interbody fusion with internal fixations in the treatment for cross-segment degenerative lumbar spine disease (L2-3 and L4-5) finite element analysis
Authors: Zhang Shuyi , Zhang Yilong , Huang Licai , Zhang Shuao , Lu Chenshui , Liu Zhengpeng , Kang Chan , Wang Zhao 
Published: October 2023

AbstractMulti-segmental lumbar degenerative disease, including intersegmental disc degeneration, is found in clinical practice. Controversy still exists regarding the treatment for cross-segment degeneration. Oblique Lateral Interbody Fusion (OLIF) with several internal fixations was used to treat cross-segment lumbar degenerative disease. A whole lumbar spine model was extracted from CT images of the whole lumbar spine of patients with lumbar degeneration. The L2-3 and L4-5 intervertebral spaces were fused with OLIF using modeling software, the Pedicle screws were performed on L2-3 and L4-5, and different internal fixations were performed on L3-4 in Finite Element (FE) software. Among the six 10 Nm moments of different directions, the L3-4 no surgery (NS) group had the relatively largest Range of Motion (ROM) in the whole lumbar spine, while the L2-5 Long segmental fixation (LSF)group had the smallest ROM and the other groups had similar ROM. The ROM in the L1-2 and L5-S1 was relatively close in the six group models, and the articular cartilage stress and disc stress on the L1-2 and L5-S1 were relatively close. In contrast, the L3-4 ROM differed relatively greatly, with the LSF ROM the smallest and the NS ROM the largest, and the L3-4 Coflex (Coflex) group more active than the L3-4 Bacfuse (Bacfuse) group and the L3-4 translaminar facet screw fixation (TFSF) group. The stress on the articular cartilage and disc at L3-4 was relatively greater in the NS disc and articular cartilage, and greater in the Coflex group than in the Bacfuse and TFSF groups, with the greatest stress on the internal fixation in the TFSF group, followed by the Coflex group, and relatively similar stress in the Bacfuse, LSF, and NS groups. In the TFSF group, the stress on the internal fixation was greater than the yield strength among different directional moments of 10 Nm, which means it is unsuitable to be an internal fixation. The LSF group had the greatest overall ROM, which may lead to postoperative low back discomfort. The NS group has the greatest overall ROM, but its increased stress on the L3-4 disc and articular cartilage may lead to accelerated degeneration of the L3-4 disc and articular cartilage. The Coflex and Bacfuse groups had a reduced L3-4 ROM but a greater stress on disc compared to the LSF group, which may lead to disc degeneration in the long term. However, their stress on the articular cartilage was relatively low. Coflex and Bacfuse can still be considered better surgical options.
Comparison of 2-octyl cyanoacrylate and n-octyl cyanoacrylate topical skin adhesives for wound closure after ankle fracture surgery: a prospective randomized trial
Authors: Park Young Hwan , Son Sei Wook , Han Sang Roc , Kim Hak Jun 
Published: October 2023

AbstractTo date, only a few clinical studies have investigated the differences between 2-octyl cyanoacrylate and n-octyl cyanoacrylate topical skin adhesives (TSAs). This study aimed to compare the outcomes of the two TSAs for wound closure after ankle fracture surgeries. Fifty-six patients were randomized to receive either a 2-octyl or n-octyl cyanoacrylate TSA. At 3 and 6 months after surgery, wound cosmetic outcomes were assessed using the Hollander Wound Evaluation Scale (HWES), and patient satisfaction for wound cosmesis was assessed using the visual analog scale (VAS) and 5-item Likert scale. Functional outcomes at 6 months after surgery were assessed using the Olerud–Molander Ankle Score (OMAS). Fifty-five patients completed the study protocol. Within the follow-up period, no differences were found between the two groups in terms of HWES, VAS, 5-item Likert scale, and OMAS. 2-octyl cyanoacrylate TSA and n-octyl cyanoacrylate TSA were comparable options for wound closure after ankle fracture surgeries in terms of wound cosmesis, patient satisfaction, and functional outcome.