bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a tool to support general practitioners to help adolescents with knee pain: an analysis using the Theoretical Domains Framework
Authors: Guldhammer Clara , Holden Sinead , Audreucci Alessandro , Johansen Simon Kristoffer , Thomsen Janus Nikolaj Laust , Rathleff Michael Skovdal 
Published: April 2023

Abstract

Aim:
Using the Theoretical Domains Framework (TDF) and COM-B model, this study aimed to determine the facilitators to a support tool for adolescent non-traumatic knee pain in general practice.

Background:
Many children and adolescents with non-traumatic knee pain consult their general practice. Currently, there are no tools to support general practitioners in the diagnosis and management of this group. There is a need to identify behavioural targets that would facilitate further development and implementation of such a tool.

Methods:
This study was designed as a qualitative study using focus group interviews with 12 medical doctors working in general practice. The semi-structured focus group interviews conducted online and followed an interview guide based on the TDF and COM-B model. Data were analysed via thematic text analysis.

Findings:
One of the biggest challenges from the general practitioner’s perspective was how to manage and guide adolescents with non-traumatic knee pain. The doctors had doubts in their capability to diagnose knee pain and saw opportunity to help structure the consultation. The doctors felt motivated to use a tool but considered access a potential barrier. Increasing opportunity and motivation by creating access in the community among general practitioners was considered important. We identified several barriers and facilitators for a support tool for the management of adolescent non-traumatic knee pain in general practice. To align with user needs, future tools should support diagnostic workup, structure the consultation and be easily available among doctors working in general practice.
Defining regorafenib as a senomorphic drug: therapeutic potential in the age-related lung disease emphysema
Authors: Park Jung-Jin , Oh Kwangseok , Lee Gun-Wu , Bang Geul , Park Jin-Hee , Kim Han-Byeol , Kim Jin Young , Shin Eun-Young , Kim Eung-Gook 
Published: April 2023

AbstractSenescence, a hallmark of aging, is a factor in age-related diseases (ARDs). Therefore, targeting senescence is widely regarded as a practicable method for modulating the effects of aging and ARDs. Here, we report the identification of regorafenib, an inhibitor of multiple receptor tyrosine kinases, as a senescence-attenuating drug. We identified regorafenib by screening an FDA-approved drug library. Treatment with regorafenib at a sublethal dose resulted in effective attenuation of the phenotypes of βPIX knockdown- and doxorubicin-induced senescence and replicative senescence in IMR-90 cells; cell cycle arrest, and increased SA-β-Gal staining and senescence-associated secretory phenotypes, particularly increasing the secretion of interleukin 6 (IL-6) and IL-8. Consistent with this result, slower progression of βPIX depletion-induced senescence was observed in the lungs of mice after treatment with regorafenib. Mechanistically, the results of proteomics analysis in diverse types of senescence indicated that growth differentiation factor 15 and plasminogen activator inhibitor-1 are shared targets of regorafenib. Analysis of arrays for phospho-receptors and kinases identified several receptor tyrosine kinases, including platelet-derived growth factor receptor α and discoidin domain receptor 2, as additional targets of regorafenib and revealed AKT/mTOR, ERK/RSK, and JAK/STAT3 signaling as the major effector pathways. Finally, treatment with regorafenib resulted in attenuation of senescence and amelioration of porcine pancreatic elastase-induced emphysema in mice. Based on these results, regorafenib can be defined as a novel senomorphic drug, suggesting its therapeutic potential in pulmonary emphysema.
Targeting glutamine metabolism as a therapeutic strategy for cancer
Authors: Jin Jonghwa , Byun Jun-Kyu , Choi Yeon-Kyung , Park Keun-Gyu 
Published: April 2023

AbstractProliferating cancer cells rely largely on glutamine for survival and proliferation. Glutamine serves as a carbon source for the synthesis of lipids and metabolites via the TCA cycle, as well as a source of nitrogen for amino acid and nucleotide synthesis. To date, many studies have explored the role of glutamine metabolism in cancer, thereby providing a scientific rationale for targeting glutamine metabolism for cancer treatment. In this review, we summarize the mechanism(s) involved at each step of glutamine metabolism, from glutamine transporters to redox homeostasis, and highlight areas that can be exploited for clinical cancer treatment. Furthermore, we discuss the mechanisms underlying cancer cell resistance to agents that target glutamine metabolism, as well as strategies for overcoming these mechanisms. Finally, we discuss the effects of glutamine blockade on the tumor microenvironment and explore strategies to maximize the utility of glutamine blockers as a cancer treatment.
BAP1 as a guardian of genome stability: implications in human cancer
Authors: Kwon Jongbum , Lee Daye , Lee Shin-Ai 
Published: April 2023

AbstractBAP1 is a ubiquitin C-terminal hydrolase domain-containing deubiquitinase with a wide array of biological activities. Studies in which advanced sequencing technologies were used have uncovered a link between BAP1 and human cancer. Somatic and germline mutations of the BAP1 gene have been identified in multiple human cancers, with a particularly high frequency in mesothelioma, uveal melanoma and clear cell renal cell carcinoma. BAP1 cancer syndrome highlights that all carriers of inherited BAP1-inactivating mutations develop at least one and often multiple cancers with high penetrance during their lifetime. These findings, together with substantial evidence indicating the involvement of BAP1 in many cancer-related biological activities, strongly suggest that BAP1 functions as a tumor suppressor. Nonetheless, the mechanisms that account for the tumor suppressor function of BAP1 have only begun to be elucidated. Recently, the roles of BAP1 in genome stability and apoptosis have drawn considerable attention, and they are compelling candidates for key mechanistic factors. In this review, we focus on genome stability and summarize the details of the cellular and molecular functions of BAP1 in DNA repair and replication, which are crucial for genome integrity, and discuss the implications for BAP1-associated cancer and relevant therapeutic strategies. We also highlight some unresolved issues and potential future research directions.
Abnormal global signal topography of self modulates emotion dysregulation in major depressive disorder
Authors: Keskin Kaan , Eker Mehmet Çağdaş , Gönül Ali Saffet , Northoff Georg 
Published: April 2023

AbstractMajor depressive disorder (MDD) is a complex mental disorder featured by an increased focus on the self and emotion dysregulation whose interaction remains unclear, though. At the same time, various studies observed abnormal representation of global fMRI brain activity in specifically those regions, e.g., cortical midline structure (CMS) in MDD that are associated with the self. Are the self and its impact on emotion regulation related to global brain activity unevenly represented in CMS relative to non-CMS? Addressing this yet open question is the main goal of our study. We here investigate post-acute treatment responder MDD and healthy controls in fMRI during an emotion task involving both attention and reappraisal of negative and neutral stimuli. We first demonstrate abnormal emotion regulation with increased negative emotion severity on the behavioral level. Next, focusing on a recently established three-layer topography of self, we show increased representation of global fMRI brain activity in specifically those regions mediating the mental (CMS) and exteroceptive (Right temporo-parietal junction and mPFC) self in post-acute MDD during the emotion task. Applying a complex statistical model, namely multinomial regression analyses, we show that increased global infra-slow neural activity in the regions of the mental and exteroceptive self modulates the behavioral measures of specifically negative emotion regulation (emotion attention and reappraisal/suppression). Together, we demonstrate increased representation of global brain activity in regions of the mental and exteroceptive self, including their modulation of negative emotion dysregulation in specifically the infra-slow frequency range (0.01 to 0.1 Hz) of post-acute MDD. These findings support the assumption that the global infra-slow neural basis of the increased self-focus in MDD may take on the role as basic disturbance in that it generates the abnormal regulation of negative emotions.
A new glance at autophagolysosomal-dependent or -independent function of transcriptional factor EB in human cancer
Authors: Wang Ting , Qin Yi , Ye Zeng , Jing De-sheng , Fan Gui-xiong , Liu Meng-qi , Zhuo Qi-feng , Ji Shun-rong , Chen Xue-min , Yu Xian-jun , Xu Xiao-wu , Li Zheng 
Published: April 2023

AbstractAutophagy-lysosome system plays a variety of roles in human cancers. In addition to being implicated in metabolism, it is also involved in tumor immunity, remodeling the tumor microenvironment, vascular proliferation, and promoting tumor progression and metastasis. Transcriptional factor EB (TFEB) is a major regulator of the autophagy-lysosomal system. With the in-depth studies on TFEB, researchers have found that it promotes various cancer phenotypes by regulating the autophagolysosomal system, and even in an autophagy-independent way. In this review, we summarize the recent findings about TFEB in various types of cancer (melanoma, pancreatic ductal adenocarcinoma, renal cell carcinoma, colorectal cancer, breast cancer, prostate cancer, ovarian cancer and lung cancer), and shed some light on the mechanisms by which it may serve as a potential target for cancer treatment.
Differential effects of CMV infection on the viability of cardiac cells
Authors: Yadav Santosh K. , Gawargi Flobater I. , Hasan Mohammad H. , Tandon Ritesh , Upton Jason W. , Mishra Paras K. 
Published: April 2023

AbstractCytomegalovirus (CMV) is a widely prevalent herpesvirus that reaches seroprevalence rates of up to 95% in several parts of the world. The majority of CMV infections are asymptomatic, albeit they have severe detrimental effects on immunocompromised individuals. Congenital CMV infection is a leading cause of developmental abnormalities in the USA. CMV infection is a significant risk factor for cardiovascular diseases in individuals of all ages. Like other herpesviruses, CMV regulates cell death for its replication and establishes and maintains a latent state in the host. Although CMV-mediated regulation of cell death is reported by several groups, it is unknown how CMV infection affects necroptosis and apoptosis in cardiac cells. Here, we infected primary cardiomyocytes, the contractile cells in the heart, and primary cardiac fibroblasts with wild-type and cell-death suppressor deficient mutant CMVs to determine how CMV regulates necroptosis and apoptosis in cardiac cells. Our results reveal that CMV infection prevents TNF-induced necroptosis in cardiomyocytes; however, the opposite phenotype is observed in cardiac fibroblasts. CMV infection also suppresses inflammation, reactive oxygen species (ROS) generation, and apoptosis in cardiomyocytes. Furthermore, CMV infection improves mitochondrial biogenesis and viability in cardiomyocytes. We conclude that CMV infection differentially affects the viability of cardiac cells.
3-sulfonyloxyaryl(mesityl)iodonium triflates as 1,2-benzdiyne precursors with activation via ortho-deprotonative elimination strategy
Authors: Yuan Haoyin , Yin Wenhao , Hu Jili , Li Yang 
Published: April 2023

AbstractBenzyne has long captivated the attention of chemists and has gained numerous synthetic achievements. Among typical benzyne generation methods, removal of two vicinal substituents from 1,2-difunctionalized benzenes, i.e., Kobayashi’s protocol, are prevailing, while ortho-deprotonative elimination from mono-substituted benzene lags far behind. Despite the advantages of atom economy and ready achievability of precursors, a bottle neck for ortho-deprotonative elimination strategy resides in the weak acidity of the ortho-hydrogen, which normally demands strong bases as the activating reagents. Here, an efficient aryne generation protocol is developed, where ortho-deprotonative elimination on 3-sulfonyloxyaryl(mesityl)iodonium triflates occurs under mild conditions and the generated 3-sulfonyloxyarynes can serve as efficient 1,2-benzdiyne synthons. This array of 1,2-benzdiyne precursors can be conveniently prepared with high functional group tolerance, and densely substituted scaffolds can be accessed as well. Carbonate and fluoride salts are found to serve as efficient activating reagents, which are the weakest bases used in ortho-deprotonative elimination strategies. Particularly, this scaffold has predictable chemoselective generation of the designated aryne intermediates. The success of this ortho-deprotonative elimination protocol sets up a unique platform with a broad spectrum of synthetic applications.
Spatial probabilistic mapping of metabolite ensembles in mass spectrometry imaging
Authors: Abu Sammour Denis , Cairns James L. , Boskamp Tobias , Marsching Christian , Kessler Tobias , Ramallo Guevara Carina , Panitz Verena , Sadik Ahmed , Cordes Jonas , Schmidt Stefan , Mohammed Shad A. , Rittel Miriam F. , Friedrich Mirco , Platten Michael , Wolf Ivo , von Deimling Andreas , Opitz Christiane A. , Wick Wolfgang , Hopf Carsten 
Published: April 2023

AbstractMass spectrometry imaging vows to enable simultaneous spatially resolved investigation of hundreds of metabolites in tissues, but it primarily relies on traditional ion images for non-data-driven metabolite visualization and analysis. The rendering and interpretation of ion images neither considers nonlinearities in the resolving power of mass spectrometers nor does it yet evaluate the statistical significance of differential spatial metabolite abundance. Here, we outline the computational framework moleculaR (https://github.com/CeMOS-Mannheim/moleculaR) that is expected to improve signal reliability by data-dependent Gaussian-weighting of ion intensities and that introduces probabilistic molecular mapping of statistically significant nonrandom patterns of relative spatial abundance of metabolites-of-interest in tissue. moleculaR also enables cross-tissue statistical comparisons and collective molecular projections of entire biomolecular ensembles followed by their spatial statistical significance evaluation on a single tissue plane. It thereby fosters the spatially resolved investigation of ion milieus, lipid remodeling pathways, or complex scores like the adenylate energy charge within the same image.
Dynamical latent state computation in the male macaque posterior parietal cortex
Authors: Lakshminarasimhan Kaushik J. , Avila Eric , Pitkow Xaq , Angelaki Dora E. 
Published: April 2023

AbstractSuccess in many real-world tasks depends on our ability to dynamically track hidden states of the world. We hypothesized that neural populations estimate these states by processing sensory history through recurrent interactions which reflect the internal model of the world. To test this, we recorded brain activity in posterior parietal cortex (PPC) of monkeys navigating by optic flow to a hidden target location within a virtual environment, without explicit position cues. In addition to sequential neural dynamics and strong interneuronal interactions, we found that the hidden state - monkey’s displacement from the goal - was encoded in single neurons, and could be dynamically decoded from population activity. The decoded estimates predicted navigation performance on individual trials. Task manipulations that perturbed the world model induced substantial changes in neural interactions, and modified the neural representation of the hidden state, while representations of sensory and motor variables remained stable. The findings were recapitulated by a task-optimized recurrent neural network model, suggesting that task demands shape the neural interactions in PPC, leading them to embody a world model that consolidates information and tracks task-relevant hidden states.
Transition-metal-free silylboronate-mediated cross-couplings of organic fluorides with amines
Authors: Zhou Jun , Zhao Zhengyu , Shibata Norio 
Published: April 2023

AbstractC–N bond cross-couplings are fundamental in the field of organic chemistry. Herein, silylboronate-mediated selective defluorinative cross-coupling of organic fluorides with secondary amines via a transition-metal-free strategy is disclosed. The cooperation of silylboronate and potassium tert-butoxide enables the room-temperature cross-coupling of C–F and N–H bonds, effectively avoiding the high barriers associated with thermally induced SN2 or SN1 amination. The significant advantage of this transformation is the selective activation of the C–F bond of the organic fluoride by silylboronate without affecting potentially cleavable C–O, C–Cl, heteroaryl C–H, or C–N bonds and CF3 groups. Tertiary amines with aromatic, heteroaromatic, and/or aliphatic groups were efficiently synthesized in a single step using electronically and sterically varying organic fluorides and N-alkylanilines or secondary amines. The protocol is extended to the late-stage syntheses of drug candidates, including their deuterium-labeled analogs.
The Trypanosoma cruzi Antigen and Epitope Atlas: antibody specificities in Chagas disease patients across the Americas
Authors: Ricci Alejandro D. , Bracco Leonel , Salas-Sarduy Emir , Ramsey Janine M. , Nolan Melissa S. , Lynn M. Katie , Altcheh Jaime , Ballering Griselda E. , Torrico Faustino , Kesper Norival , Villar Juan C. , Marcipar Iván S. , Marco Jorge D. , Agüero Fernán 
Published: April 2023

AbstractDuring an infection the immune system produces pathogen-specific antibodies. These antibody repertoires become specific to the history of infections and represent a rich source of diagnostic markers. However, the specificities of these antibodies are mostly unknown. Here, using high-density peptide arrays we examined the human antibody repertoires of Chagas disease patients. Chagas disease is a neglected disease caused by Trypanosoma cruzi, a protozoan parasite that evades immune mediated elimination and mounts long-lasting chronic infections. We describe a proteome-wide search for antigens, characterised their linear epitopes, and show their reactivity on 71 individuals from diverse human populations. Using single-residue mutagenesis we revealed the core functional residues for 232 of these epitopes. Finally, we show the diagnostic performance of identified antigens on challenging samples. These datasets enable the study of the Chagas antibody repertoire at an unprecedented depth and granularity, while also providing a rich source of serological biomarkers.
Interfacial assembly of binary atomic metal-Nx sites for high-performance energy devices
Authors: Jiang Zhe , Liu Xuerui , Liu Xiao-Zhi , Huang Shuang , Liu Ying , Yao Ze-Cheng , Zhang Yun , Zhang Qing-Hua , Gu Lin , Zheng Li-Rong , Li Li , Zhang Jianan , Fan Youjun , Tang Tang , Zhuang Zhongbin , Hu Jin-Song 
Published: April 2023

AbstractAnion-exchange membrane fuel cells and Zn–air batteries based on non-Pt group metal catalysts typically suffer from sluggish cathodic oxygen reduction. Designing advanced catalyst architectures to improve the catalyst’s oxygen reduction activity and boosting the accessible site density by increasing metal loading and site utilization are potential ways to achieve high device performances. Herein, we report an interfacial assembly strategy to achieve binary single-atomic Fe/Co-Nx with high mass loadings through constructing a nanocage structure and concentrating high-density accessible binary single-atomic Fe/Co–Nx sites in a porous shell. The prepared FeCo-NCH features metal loading with a single-atomic distribution as high as 7.9 wt% and an accessible site density of around 7.6 × 1019 sites g−1, surpassing most reported M–Nx catalysts. In anion exchange membrane fuel cells and zinc–air batteries, the FeCo-NCH material delivers peak power densities of 569.0 or 414.5 mW cm−2, 3.4 or 2.8 times higher than control devices assembled with FeCo-NC. These results suggest that the present strategy for promoting catalytic site utilization offers new possibilities for exploring efficient low-cost electrocatalysts to boost the performance of various energy devices.
Current-driven writing process in antiferromagnetic Mn2Au for memory applications
Authors: Reimers S. , Lytvynenko Y. , Niu Y. R. , Golias E. , Sarpi B. , Veiga L. S. I. , Denneulin T. , Kovács A. , Dunin-Borkowski R. E. , Bläßer J. , Kläui M. , Jourdan M. 
Published: April 2023

AbstractCurrent pulse driven Néel vector rotation in metallic antiferromagnets is one of the most promising concepts in antiferromagnetic spintronics. We show microscopically that the Néel vector of epitaxial thin films of the prototypical compound Mn2Au can be reoriented reversibly in the complete area of cross shaped device structures using single current pulses. The resulting domain pattern with aligned staggered magnetization is long term stable enabling memory applications. We achieve this switching with low heating of ≈20 K, which is promising regarding fast and efficient devices without the need for thermal activation. Current polarity dependent reversible domain wall motion demonstrates a Néel spin-orbit torque acting on the domain walls.
Ecological change of the gut microbiota during pregnancy and progression to dyslipidemia
Authors: Yang Xu , Zhang Mingzhi , Zhang Yuqing , Wei Hongcheng , Guan Quanquan , Dong Chao , Deng Siting , Tun Hein Min , Xia Yankai 
Published: April 2023

AbstractThe composition of the gut microbiome was previously found to be associated with clinical responses to dyslipidemia, but there is limited consensus on the dynamic change of the gut microbiota during pregnancy and the specific microbiome characteristics linked to dyslipidemia in pregnant women. We collected fecal samples from 513 pregnant women at multiple time points during pregnancy in a prospective cohort. Taxonomic composition and functional annotations were determined by 16S rRNA amplicon sequencing and shotgun metagenomic sequencing. The predictive potential of gut microbiota on the risk of dyslipidemia was determined. The gut microbiome underwent dynamic changes during pregnancy, with significantly lower alpha diversity observed in dyslipidemic patients compared to their healthy counterparts. Several genera, including Bacteroides, Paraprevotella, Alistipes, Christensenellaceae R7 group, Clostridia UCG-014, and UCG-002 were negatively associated with lipid profiles and dyslipidemia. Further metagenomic analysis recognized a common set of pathways involved in gastrointestinal inflammation, where disease-specific microbes played an important role. Machine learning analysis confirmed the link between the microbiome and its progression to dyslipidemia, with a micro-averaged AUC of 0.824 (95% CI: 0.782-0.855) combined with blood biochemical data. Overall, the human gut microbiome, including Alistipes and Bacteroides, was associated with the lipid profile and maternal dyslipidemia during pregnancy by perturbing inflammatory functional pathways. Gut microbiota combined with blood biochemical data at the mid-pregnancy stage could predict the risk of dyslipidemia in late pregnancy. Therefore, the gut microbiota may represent a potential noninvasive diagnostic and therapeutic strategy for preventing dyslipidemia in pregnancy.