bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying the role of (dis)inhibition in the vicious cycle of substance use through ecological momentary assessment and resting-state fMRI
Authors: Chirokoff Valentine , Berthoz Sylvie , Fatseas Melina , Misdrahi David , Dupuy Maud , Abdallah Majd , Serre Fuschia , Auriacombe Marc , Pfefferbaum Adolf , Sullivan Edith V. , Chanraud Sandra 
Published: June 2024

AbstractFunctional inhibition is known to improve treatment outcomes in substance use disorder (SUD), potentially through craving management enabled by underlying cerebral integrity. Whereas treatment is challenged by a multitude of substances that patients often use, no study has yet unraveled if inhibition and related cerebral integrity could prevent relapse from multiples substances, that is, one’s primary drug of choice and secondary ones. Individuals with primary alcohol, cannabis, or tobacco use disorders completed intensive Ecological Momentary Assessment (EMA) coupled with resting-state functional MRI (rs-fMRI) to characterize the extent to which inhibition and cerebral substrates interact with craving and use of primary and any substances. Participants were 64 patients with SUD and 35 healthy controls who completed one week EMA using Smartphones to report 5 times daily their craving intensity and substance use and to complete Stroop inhibition testing twice daily. Subsamples of 40 patients with SUD and 34 control individuals underwent rs-fMRI. Mixed Model Analysis revealed that reported use of any substance by SUD individuals predicted later use of any and primary substance, whereas use of the primary substance only predicted higher use of that same substances. Craving and inhibition level independently predicted later use but did not significantly interact. Preserved inhibition performance additionally influenced use indirectly by mediating the link between subsequent uses and by being linked to rs-fMRI connectivity strength in fronto-frontal and cerebello-occipital connections. As hypothesized, preserved inhibition performance, reinforced by the integrity of inhibitory neurofunctional substrates, may partake in breaking an unhealthy substance use pattern for a primary substance but may not generalize to non-target substances or to craving management.
Healthcare professionals’ perspectives on oral health care in acute stroke patients: a qualitative study
Authors: Konadu Akua Boakyewaa , Iwuozo Emmanuel U. , Sunkwa-Mills Gifty , Ayoola Yekeen A. , Manu Ewura A. , Hewlett Sandra A. , Dedey Florence , Abdulkadir Mohammed B. , Ogedegbe Olugbenga 
Published: June 2024

Abstract
Background
Stroke is a major public health problem, with the disabilities of the patients increasing their risk of poor oral health. Currently, in Ghana and Nigeria, no guideline exists for oral health care in stroke patients, while most of our acute stroke care settings have no documented protocol.

Aim
This study sought to understand the perspectives of healthcare professionals in Ghana and Nigeria about oral healthcare in acute stroke patients.

Methods
A qualitative inductive approach was employed to explore healthcare professionals’ perspectives. After obtaining informed consent, in-depth interviews were conducted among doctors, nurses, and physiotherapists using semi-structured question guides. Participants’ responses were audiotaped for transcription and analysis. Interviews were conducted until data saturation was reached. Data were analyzed thematically to generate themes and sub-themes using an inductive approach.

The results
Twenty-five (25) health care professionals (HCP) aged 25–60 years with a mean age of 36.2 ± 4.2 years were interviewed. There were 15 (60.0%) males and 10 (40.0%) females. HCP included nurse practitioners 14 (56.0%), medical doctors 7 (28.0%), and physiotherapists 4 (16.0%). The HCP demonstrated adequate knowledge of stroke and considered oral health important for esthetic and clinical reasons. They, however, reported being unable to give it the required attention due to inadequate collaboration between the various professional cadres, insufficient equipment, and a skewed focus on other clinical needs of the acute stroke patients.

Conclusions
The findings indicate that HCPs perceived oral health care as very important among patients with acute stroke. However, they reported a lack of collaboration and integration of oral health care in routine stroke care as a major impediment.
CXCR7 activation evokes the anti-PD-L1 antibody against glioblastoma by remodeling CXCL12-mediated immunity
Authors: Liu Chan-Chuan , Yang Wen-Bin , Chien Chia-Hung , Wu Cheng-Lin , Chuang Jian-Ying , Chen Pin-Yuan , Chu Jui-Mei , Cheng Siao Muk , Qiu Li-Ying , Chang Yung-Chieh , Hwang Daw-Yang , Huang Chih-Yuan , Lee Jung-Shun , Chang Kwang-Yu 
Published: June 2024

AbstractThe interaction between glioblastoma cells and glioblastoma-associated macrophages (GAMs) influences the immunosuppressive tumor microenvironment, leading to ineffective immunotherapies. We hypothesized that disrupting the communication between tumors and macrophages would enhance the efficacy of immunotherapies. Transcriptomic analysis of recurrent glioblastoma specimens indicated an enhanced neuroinflammatory pathway, with CXCL12 emerging as the top-ranked gene in secretory molecules. Single-cell transcriptome profiling of naïve glioblastoma specimens revealed CXCL12 expression in tumor and myeloid clusters. An analysis of public glioblastoma datasets has confirmed the association of CXCL12 with disease and PD-L1 expression. In vitro studies have demonstrated that exogenous CXCL12 induces pro-tumorigenic characteristics in macrophage-like cells and upregulated PD-L1 expression through NF-κB signaling. We identified CXCR7, an atypical receptor for CXCL12 predominantly present in tumor cells, as a negative regulator of CXCL12 expression by interfering with extracellular signal-regulated kinase activation. CXCR7 knockdown in a glioblastoma mouse model resulted in worse survival outcomes, increased PD-L1 expression in GAMs, and reduced CD8+ T-cell infiltration compared with the control group. Ex vivo T-cell experiments demonstrated enhanced cytotoxicity against tumor cells with a selective CXCR7 agonist, VUF11207, reversing GAM-induced immunosuppression in a glioblastoma cell-macrophage-T-cell co-culture system. Notably, VUF11207 prolonged survival and potentiated the anti-tumor effect of the anti-PD-L1 antibody in glioblastoma-bearing mice. This effect was mitigated by an anti-CD8β antibody, indicating the synergistic effect of VUF11207. In conclusion, CXCL12 conferred immunosuppression mediated by pro-tumorigenic and PD-L1-expressing GAMs in glioblastoma. Targeted activation of glioblastoma-derived CXCR7 inhibits CXCL12, thereby eliciting anti-tumor immunity and enhancing the efficacy of anti-PD-L1 antibodies.
CSTF3 contributes to platinum resistance in ovarian cancer through alternative polyadenylation of lncRNA NEAT1 and generating the short isoform NEAT1_1
Authors: Luo Xin , Wei Qinglv , Jiang Xiaoyan , Chen Ningxuan , Zuo Xinzhao , Zhao Hongyan , Liu Yujiao , Liu Xiaoyi , Xie Lingcui , Yang Yu , Liu Tao , Yi Ping , Xu Jing 
Published: June 2024

AbstractPlatinum-based chemotherapy is the standard postoperative adjuvant treatment for ovarian cancer (OC). Despite the initial response to chemotherapy, 85% of advanced OC patients will have recurrent disease. Relapsed disease and platinum resistance are the major causes of death in OC patients. In this study, we compared the global regulation of alternative polyadenylation (APA) in platinum-resistant and platinum-sensitive tissues of OC patients by analyzing a set of single-cell RNA sequencing (scRNA-seq) data from public databases and found that platinum-resistant patients exhibited global 3’ untranslated region (UTR) shortening due to the different usage of polyadenylation sites (PASs). The APA regulator CSTF3 was the most significantly upregulated gene in epithelial cells of platinum-resistant OC. CSTF3 knockdown increased the sensitivity of OC cells to platinum. The lncRNA NEAT1 has two isoforms, short (NEAT1_1) and long (NEAT1_2) transcript, because of the APA processing in 3’UTR. We found that CSTF3 knockdown reduced the usage of NEAT1 proximal PAS to lengthen the transcript and facilitate the expression of NEAT1_2. Downregulation of the expression of NEAT1 (NEAT1_1/_2), but not only NEAT1_2, also increased the sensitivity of OC cells to platinum. Overexpressed NEAT1_1 reversed the platinum resistance of OC cells after knocking down CSTF3 expression. Furthermore, downregulated expression of CSTF3 and NEAT1_1, rather than NEAT1_2, was positively correlated with inactivation of the PI3K/AKT/mTOR pathway in OC cells. Together, our findings revealed a novel mechanism of APA regulation in platinum-resistant OC. CSTF3 directly bound downstream of the NEAT1 proximal PAS to generate the short isoform NEAT1_1 and was conducive to platinum resistance, which provides a potential biomarker and therapeutic strategy for platinum-resistant OC patients.
Hippo kinases Mst1 and Mst2 maintain NK cell homeostasis by orchestrating metabolic state and transcriptional activity
Authors: Feng Peiran , Luo Liang , Yang Quanli , Meng Wanqing , Guan Zerong , Li Zhizhong , Sun Guodong , Dong Zhongjun , Yang Meixiang 
Published: June 2024

AbstractNatural killer (NK) cells play a crucial role in immune response against viral infections and tumors. However, further investigation is needed to better understand the key molecules responsible for determining the fate and function of NK cells. In this study, we made an important discovery regarding the involvement of the Hippo kinases Mst1 and Mst2 as novel regulators in maintaining mouse NK cell homeostasis. The presence of high Mst1 and Mst2 (Mst1/2) activity in NK cells is essential for their proper development, survival and function in a canonical Hippo signaling independent mode. Mechanistically, Mst1/2 induce cellular quiescence by regulating the processes of proliferation and mitochondrial metabolism, thereby ensuring the development and survival of NK cells. Furthermore, Mst1/2 effectively sense IL-15 signaling and facilitate the activation of pSTAT3-TCF1, which contributes to NK cell homeostasis. Overall, our investigation highlights the crucial role of Mst1/2 as key regulators in metabolic reprogramming and transcriptional regulation for mouse NK cell survival and function, emphasizing the significance of cellular quiescence during NK cell development and functional maturation.
Mechanism of motoneuronal and pyramidal cell death in amyotrophic lateral sclerosis and its potential therapeutic modulation
Authors: Nógrádi Bernát , Nógrádi-Halmi Dóra , Erdélyi-Furka Barbara , Kádár Zalán , Csont Tamás , Gáspár Renáta 
Published: June 2024

AbstractAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder clinically characterized by muscle atrophy and progressive paralysis. Loss of motoneurons and pyramidal cells is thought to be the center piece of the complex and multifaceted ALS pathology, however, the exact mechanisms laying behind motoneuronal cell death in the spinal cord and motor cortex are still unknown. It was originally proposed that apoptosis plays a fundamental role in motoneuronal demise, nonetheless, later it became clear that other forms of regulated cell death, including necroptosis, pyroptosis, ferroptosis, and autophagy-dependent cell death, may also contribute to motoneuron loss. Over the past years, multiple studies aimed to improve our understanding of the contributory role of these mechanisms as well as to offer novel targets for potential therapeutic interventions. The pharmacological inhibition of the ferroptotic pathway and the modulation of the autophagic machinery seem to have particularly promising effects, reducing motoneuron loss and slowing disease progression in transgenic models of ALS. Nevertheless, the potential beneficial effects of necroptosis-targeting interventions were mostly disproven in the latest studies. In this review we aim to summarize the current view on regulated cell death mechanisms that lead to motoneuronal and pyramidal cell degeneration in ALS and showcase their applicability as future drug targets.
High-entropy relaxor ferroelectric ceramics for ultrahigh energy storage
Authors: Peng Haonan , Wu Tiantian , Liu Zhen , Fu Zhengqian , Wang Dong , Hao Yanshuang , Xu Fangfang , Wang Genshui , Chu Junhao 
Published: June 2024

AbstractDielectric ceramic capacitors with ultrahigh power densities are fundamental to modern electrical devices. Nonetheless, the poor energy density confined to the low breakdown strength is a long-standing bottleneck in developing desirable dielectric materials for practical applications. In this instance, we present a high-entropy tungsten bronze-type relaxor ferroelectric achieved through an equimolar-ratio element design, which realizes a giant recoverable energy density of 11.0 J·cm−3 and a high efficiency of 81.9%. Moreover, the atomic-scale microstructural study confirms that the excellent comprehensive energy storage performance is attributed to the increased atomic-scale compositional heterogeneity from high configuration entropy, which modulates the relaxor features as well as induces lattice distortion, resulting in reduced polarization hysteresis and enhanced breakdown endurance. This study provides evidence that developing high-entropy relaxor ferroelectric material via equimolar-ratio element design is an effective strategy for achieving ultrahigh energy storage characteristics. Our results also uncover the immense potential of tetragonal tungsten bronze-type materials for advanced energy storage applications.
Broad-spectrum activity against mosquito-borne flaviviruses achieved by a targeted protein degradation mechanism
Authors: Liu Han-Yuan , Li Zhengnian , Reindl Theresia , He Zhixiang , Qiu Xueer , Golden Ryan P. , Donovan Katherine A. , Bailey Adam , Fischer Eric S. , Zhang Tinghu , Gray Nathanael S. , Yang Priscilla L. 
Published: June 2024

AbstractViral genetic diversity presents significant challenges in developing antivirals with broad-spectrum activity and high barriers to resistance. Here we report development of proteolysis targeting chimeras (PROTACs) targeting the dengue virus envelope (E) protein through coupling of known E fusion inhibitors to ligands of the CRL4CRBN E3 ubiquitin ligase. The resulting small molecules block viral entry through inhibition of E-mediated membrane fusion and interfere with viral particle production by depleting intracellular E in infected Huh 7.5 cells. This activity is retained in the presence of point mutations previously shown to confer partial resistance to the parental inhibitors due to decreased inhibitor-binding. The E PROTACs also exhibit broadened spectrum of activity compared to the parental E inhibitors against a panel of mosquito-borne flaviviruses. These findings encourage further exploration of targeted protein degradation as a differentiated and potentially advantageous modality for development of broad-spectrum direct-acting antivirals.
Proteome allocation is linked to transcriptional regulation through a modularized transcriptome
Authors: Patel Arjun , McGrosso Dominic , Hefner Ying , Campeau Anaamika , Sastry Anand V. , Maurya Svetlana , Rychel Kevin , Gonzalez David J. , Palsson Bernhard O. 
Published: June 2024

AbstractIt has proved challenging to quantitatively relate the proteome to the transcriptome on a per-gene basis. Recent advances in data analytics have enabled a biologically meaningful modularization of the bacterial transcriptome. We thus investigate whether matched datasets of transcriptomes and proteomes from bacteria under diverse conditions can be modularized in the same way to reveal novel relationships between their compositions. We find that; (1) the modules of the proteome and the transcriptome are comprised of a similar list of gene products, (2) the modules in the proteome often represent combinations of modules from the transcriptome, (3) known transcriptional and post-translational regulation is reflected in differences between two sets of modules, allowing for knowledge-mapping when interpreting module functions, and (4) through statistical modeling, absolute proteome allocation can be inferred from the transcriptome alone. Quantitative and knowledge-based relationships can thus be found at the genome-scale between the proteome and transcriptome in bacteria.
Effectiveness of COVID-19 vaccines against severe COVID-19 among patients with cancer in Catalonia, Spain
Authors: Lazar Neto Felippe , Mercadé-Besora Núria , Raventós Berta , Pérez-Crespo Laura , Castro Junior Gilberto , Ranzani Otavio T. , Duarte-Salles Talita 
Published: June 2024

AbstractPatients with cancer were excluded from pivotal randomized clinical trials of COVID-19 vaccine products, and available observational evidence on vaccine effectiveness (VE) focused mostly on mild, and not severe COVID-19, which is the ultimate goal of vaccination for high-risk groups. Here, using primary care electronic health records from Catalonia, Spain (SIDIAP), we built two large cohorts of vaccinated and matched control cancer patients with a primary vaccination scheme (n = 184,744) and a booster (n = 108,534). Most patients received a mRNA-based product in primary (76.2%) and booster vaccination (99.9%). Patients had 51.8% (95% CI 40.3%−61.1%) and 58.4% (95% CI 29.3%−75.5%) protection against COVID-19 hospitalization and COVID-19 death respectively after full vaccination (two-doses) and 77.9% (95% CI 69.2%−84.2%) and 80.2% (95% CI 63.0%−89.4%) after booster. Compared to primary vaccination, the booster dose provided higher peak protection during follow-up. Calibration of VE estimates with negative outcomes, and sensitivity analyses with slight different population and COVID-19 outcomes definitions provided similar results. Our results confirm the role of primary and booster COVID-19 vaccination in preventing COVID-19 severe events in patients with cancer and highlight the need for the additional dose in this population.
C(sp3)–H sulfinylation of light hydrocarbons with sulfur dioxide via hydrogen atom transfer photocatalysis in flow
Authors: Nagornîi Dmitrii , Raymenants Fabian , Kaplaneris Nikolaos , Noël Timothy 
Published: June 2024

AbstractSulfur-containing scaffolds originating from small alkyl fragments play a crucial role in various pharmaceuticals, agrochemicals, and materials. Nonetheless, their synthesis using conventional methods presents significant challenges. In this study, we introduce a practical and efficient approach that harnesses hydrogen atom transfer photocatalysis to activate volatile alkanes, such as isobutane, butane, propane, ethane, and methane. Subsequently, these nucleophilic radicals react with SO2 to yield the corresponding sulfinates. These sulfinates then serve as versatile building blocks for the synthesis of diverse sulfur-containing organic compounds, including sulfones, sulfonamides, and sulfonate esters. Our use of flow technology offers a robust, safe and scalable platform for effectively activating these challenging gaseous alkanes, facilitating their transformation into valuable sulfinates.
Birefringence-induced phase delay enables Brillouin mechanical imaging in turbid media
Authors: Antonacci Giuseppe , Vanna Renzo , Ventura Marco , Schiavone Maria Lucia , Sobacchi Cristina , Behrouzitabar Morteza , Polli Dario , Manzoni Cristian , Cerullo Giulio 
Published: June 2024

AbstractAcoustic vibrations of matter convey fundamental viscoelastic information that can be optically retrieved by hyperfine spectral analysis of the inelastic Brillouin scattered light. Increasing evidence of the central role of the viscoelastic properties in biological processes has stimulated the rise of non-contact Brillouin microscopy, yet this method faces challenges in turbid samples due to overwhelming elastic background light. Here, we introduce a common-path Birefringence-Induced Phase Delay (BIPD) filter to disentangle the polarization states of the Brillouin and Rayleigh signals, enabling the rejection of the background light using a polarizer. We demonstrate a 65 dB extinction ratio in a single optical pass collecting Brillouin spectra in extremely scattering environments and across highly reflective interfaces. We further employ the BIPD filter to image bone tissues from a mouse model of osteopetrosis, highlighting altered biomechanical properties compared to the healthy control. Results herald new opportunities in mechanobiology where turbid biological samples remain poorly characterized.
A programmable seekRNA guides target selection by IS1111 and IS110 type insertion sequences
Authors: Siddiquee Rezwan , Pong Carol H. , Hall Ruth M. , Ataide Sandro F. 
Published: June 2024

AbstractIS1111 and IS110 insertion sequence (IS) family members encode an unusual DEDD transposase type and exhibit specific target site selection. The IS1111 group include identifiable subterminal inverted repeats (sTIR) not found in the IS110 type1. IS in both families include a noncoding region (NCR) of significant length and, as each individual IS or group of closely related IS selects a different site, we had previously proposed that an NCR-derived RNA was involved in target selection2. Here, we find that the NCR is usually downstream of the transposase gene in IS1111 family IS and upstream in the IS110 type. Four IS1111 and one IS110 family members that target different sequences are used to demonstrate that the NCR determines a short seeker RNA (seekRNA) that co-purified with the transposase. The seekRNA is essential for transposition of the IS or a cargo flanked by IS ends from and to the preferred target. Short sequences matching both top and bottom strands of the target are present in the seekRNA but their order in IS1111 and IS110 family IS is reversed. Reprogramming the seekRNA and donor flank to target a different site is demonstrated, indicating future biotechnological potential for these systems.
Master corepressor inactivation through multivalent SLiM-induced polymerization mediated by the oncogene suppressor RAI2
Authors: Goradia Nishit , Werner Stefan , Mullapudi Edukondalu , Greimeier Sarah , Bergmann Lina , Lang Andras , Mertens Haydyn , Węglarz Aleksandra , Sander Simon , Chojnowski Grzegorz , Wikman Harriet , Ohlenschläger Oliver , von Amsberg Gunhild , Pantel Klaus , Wilmanns Matthias 
Published: June 2024

AbstractWhile the elucidation of regulatory mechanisms of folded proteins is facilitated due to their amenability to high-resolution structural characterization, investigation of these mechanisms in disordered proteins is more challenging due to their structural heterogeneity, which can be captured by a variety of biophysical approaches. Here, we used the transcriptional master corepressor CtBP, which binds the putative metastasis suppressor RAI2 through repetitive SLiMs, as a model system. Using cryo-electron microscopy embedded in an integrative structural biology approach, we show that RAI2 unexpectedly induces CtBP polymerization through filaments of stacked tetrameric CtBP layers. These filaments lead to RAI2-mediated CtBP nuclear foci and relieve its corepressor function in RAI2-expressing cancer cells. The impact of RAI2-mediated CtBP loss-of-function is illustrated by the analysis of a diverse cohort of prostate cancer patients, which reveals a substantial decrease in RAI2 in advanced treatment-resistant cancer subtypes. As RAI2-like SLiM motifs are found in a wide range of organisms, including pathogenic viruses, our findings serve as a paradigm for diverse functional effects through multivalent interaction-mediated polymerization by disordered proteins in healthy and diseased conditions.