bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stress Granules Underlie Acute Myeloid Leukemia Stem Cell Survival and Stress Adaptation
Authors: Tajik Amanda , Tsao Emily , Jahangiri Soheil , Seale Brendon , Yee Brian A. , Naritomi Jack T. , Balde Zaldy , Cathelin Severine , Chahi Ava Keyvani , Li Lance , Chen He Tian , Wong Nicholas , Liu Lina , Joshi Pratik , Moreira Steven , McCloskey Curtis W. , Khan Shahbaz , Rothamel Katherine L. , Boutzen Helena , Bansal Suraj , Zeng Andy G.X. , Aigner Stefan , Lu Yu , Dick John E. , Kislinger Thomas , Khokha Rama , Minden Mark D. , Gingras Anne-Claude , Yeo Gene W. , Hope Kristin J. 
Published: January 2025

ABSTRACTThe link between cancer maintenance and an ability to sustain continued growth through stresses conferred by the cancer state itself is growing. However, there are significant gaps in our understanding of how this stress is managed, particularly at the level of cancer initiating cells. Here, we identify proteins comprising the dynamic, stress-adaptive ribonucleoprotein complexes known as stress granules (SG) to be enriched among the factors essential for leukemic stem cell (LSC)-driven leukemic propagation. Focusing on core SG nucleator G3BP1, we dissect the role of SGs in human acute myeloid leukemia (AML), their targetability, and the mechanisms they govern to uncover a novel propensity for AML, and in particular LSC-enriched fractions, to prime the expression of SG components, form SGs with greater fidelity and to be reliant on their establishment and continued integrity for LSC maintenance. We further unveil the transcript and protein interactome of G3BP1 in the AML context and show that consolidated control of innate immune signaling, and apoptosis repression is executed through regional binding specificity of G3BP1 to highly structured 3’UTRs and cooperation with the RNA helicase UPF1 to mediate transcript decay in SGs. Altogether our findings advance novel fundamental principles of stress adaptation exploited in AML and LSCs that may extend to other cancers and uncover SGs as a novel axis for therapy development.
Plectin Regulates Focal Adhesion Dynamics and Cytoskeletal Organization in Mouse Astrocytes: Implications for Reactive Astrogliosis
Authors: Furlani Borut , Potokar Maja , Pozo Devoto Victorio Martin , Wiche Gerhard , Zorec Robert , Jorgačevski Jernej 
Published: January 2025

ABSTRACTReactive astrogliosis, a hallmark of central nervous system pathologies, involves cellular responses, including morphological remodelling and upregulation of intermediate filaments such as vimentin. These changes are driven by cytoskeletal dynamics and are mediated by focal adhesions (FAs). Our study identifies plectin, a versatile cytoskeletal linker protein, as a critical modulator of FA-associated processes in mouse astrocytes. We demonstrate that plectin localizes to astrocyte FAs, where it regulates their number, maturation, turnover, and the mobility of FA components. Plectin also polarizes within FAs, depending on their maturation state, and controls the recruitment of key cytoskeletal elements particularly vimentin. In plectin-deficient astrocytes, the vimentin network exhibits impaired connectivity, accompanied by altered viscoelastic properties of the cells. In a model of reactive astrocytes FA number and size were elevated along with the expression of plectin, highlighting involvement of plectin in pathological conditions.
Microglia regulate nucleus accumbens synaptic development and circuit function underlying threat avoidance behaviors
Authors: Gongwer Michael W. , Etienne Fanny , Moca Eric N. , Chappell Megan S. , Blagburn-Blanco Sara V. , Riley Jack P. , Enos Alexander S. , Haratian Melody , Qi Alex , Rojo Rocio , Wilke Scott A. , Pridans Clare , DeNardo Laura A. , De Biase Lindsay M. 
Published: January 2025

AbstractWhile CNS microglia have well-established roles in synapse pruning during neurodevelopment, only a few studies have identified roles for microglia in synapse formation. These studies focused on the cortex and primary sensory circuits during restricted developmental time periods, leaving substantial gaps in our understanding of the early developmental functions of microglia. Here we investigated how the absence of microglia impacts synaptic development in the nucleus accumbens (NAc), a region critical for emotional regulation and motivated behaviors and where dysfunction is implicated in psychiatric disorders that arise early in life. Using a genetically modified mouse that lacks microglia (Csf1rΔFIRE/ΔFIRE), we found blunted excitatory synapse formation in the NAc. This effect was most prominent during the second and third postnatal weeks, when we previously found microglia to be overproduced, and was accompanied by an increase in presynaptic release probability and alterations in postsynaptic kinetics. Tissue-level NAc proteomics confirmed that microglial absence impacted numerous proteins involved in synapse structure, trans-synaptic signaling, and pre-synaptic function. However, microglial absence did not perturb levels of astrocyte-derived cues and adhesive proteins that promote synaptogenesis, suggesting that reduced synapse number may be caused by absence of a microglial-derived synaptogenic cue. Although observed electrophysiological synaptic changes were largely normalized by adulthood, we identified lasting effects of microglial absence on threat avoidance behavior, and these behavioral effects were directly associated with alterations of NAc neuronal activity. Together, these results indicate a critical role for microglia in regulating the synaptic landscape of the developing NAc and in establishing functional circuits underlying adult behavioral repertoires.
Built-environment professionals welcome prescriptive ecology evidence to enhance communication with stakeholders for biodiversity-inclusive cities: Insights from professionals in both the Global North and South
Authors: Lu Jing , Li Li , Hernando Ana , Manzanera Jose Antonio 
Published: January 2025

AbstractIn our urbanized world, cities pose threats and opportunities for global biodiversity. The Kunming-Montreal Global Biodiversity Framework advocates for biodiversity-inclusive urban planning and design (BIPD) to enhance native biodiversity and sustainable urbanization. However, creating effective biodiversity-inclusive urban landscapes is challenging. Despite the growing knowledge advances in urban ecology, its effective application in urban planning practices remains inadequate. Therefore, understanding the perspectives of Built-environment professionals (BEPs), who are typically responsible for urban transformations, towards BIPD is essential. This study employs Q-Methodology to explore a broad profile of BEPs’ perspectives in the United States, Spain, China and Ethiopia, across the Global North and South, using citizen-science-based species distribution modeling (SDM) mapping as an example. We identified four perspectives among BEPs:Pluralist,Enthusiast,PragmatistandContextualist, offering insights into the challenges and opportunities of implementing BIPD. A key challenge for BEPs is their limited awareness of critical ecological knowledge, alongside two other issues: structural barriers and misaligned values and attitudes with stakeholders. Importantly, our study highlights promising opportunities. BEPs’ positive attitudes toward BIPD reflect their readiness for adaptive innovations. Their diverse value patterns and professional norms suggest a willingness to pursue transformative changes. BEPs particularly welcome applicable evidence-based tools to facilitate effective stakeholder communications and trade-off decisions, whilePluralistsandEnthusiastsalso show interest in multidisciplinary collaborations. This nuanced understanding of challenges and opportunities can facilitate transdisciplinary knowledge awareness and foster knowledge advancement, ultimately paving the way for mainstreaming BIPD as a key innovation for urban sustainability.Highlights1. Built-environment professionals (BEPs) encompass four distinct perspectives:Pluralist,Enthusiast,Pragmatist, andContextualist, revealing diverse outlooks on planning for biodiversity-inclusive cities.2. A significant challenge identified is BEPs’ limited awareness of critical ecological knowledge.3. BEPs demonstrate both readiness and willingness to embrace transformative innovations.4. BEPs particularly welcome prescriptive ecology evidence to facilitate effective stakeholder communications and trade-off decisions.5. This study advances the empirical understanding of integrating biodiversity into urban sustainability practices.
Integrated single-cell analyses of affinity-tested B-cells enable the identification of a gene signature to predict antibody affinity
Authors: Chirichella Michele , Ratcliff Matthew , Gu Shuang , Miragaia Ricardo , Sammito Massimo , Cutano Valentina , Cohen Suzanne , Angeletti Davide , Romero-Ros Xavier , Schofield Darren J. 
Published: January 2025

AbstractAdvancements in single-cell technologies and deep sequencing have revealed the vast B-cell repertoire arising from immunisation, enhancing the number of antibodies available for testing. However, selecting the highest affinity antibodies from many sequences is not a straightforward feat, as mechanisms sustaining affinity maturation and related markers remain under-studied. Here, we generated datasets of antigen-specific B-cells after mouse immunisation as well as re-analysed public data to identify a novel transcriptomic signature, "High Signature" (HS), with predictive power for high-affinity antibodies. HS, derived by integrating antibody sequences, gene expression, and affinity measurements, enabled sub-nanomolar affinity antibody selection without sequence pre-analysis. Notably, HS-expressing B-cells were 2.5 times more likely to yield high-affinity antibodies than randomly picked cells. Mechanistically, we identified RUVBL2, an AAA+ ATPase, as a primary HS modulator, suggesting its involvement in affinity maturation. Furthermore, HS applied to human PBMC data enriched high-affinity antibody expression, underscoring its potential in antibody discovery.
Plasma Proteomic Signatures of Physical Activity Provide Insights into Biological Impacts of Physical Activity and its Protective Role Against Dementia
Authors: Arani Gayatri , Arora Amit , Yang Shuai , Wu Jingyue , Kraszewski Jennifer N. , Martins Amy , Miller Alexandra , Zeba Zebunnesa , Jafri Ayan , Hu Chengcheng , Farland Leslie V. , Bea Jennifer W. , Coletta Dawn K. , Aslan Daniel H. , Sayre M Katherine , Bharadwaj Pradyumna K , Ally Madeline , Maltagliati Silvio , Lai Mark H C , Wilcox Rand , de Geus Eco , Alexander Gene E. , Raichlen David A. , Klimentidis Yann C. 
Published: January 2025

ABSTRACTPhysical activity (PA), including sedentary behavior, is associated with many diseases, including Alzheimer’s disease and all-cause dementia. However, the specific biological mechanisms through which PA protects against disease are not entirely understood. To address this knowledge gap, we first assessed the conventional observational associations of three self-reported and three device-based PA measures with circulating levels of 2,911 plasma proteins measured in the UK Biobank (nmax=39,160) and assessed functional enrichment of identified proteins. We then used bi-directional Mendelian randomization (MR) to further evaluate the evidence for causal relationships of PA with protein levels. Finally, we performed mediation analyses to identify proteins that may mediate the relationship of PA with incident all-cause dementia. Our findings revealed 41 proteins consistently associated with all PA measures and 1,027 proteins associated with at least one PA measure. Both conventional observational and MR study designs converged on proteins that appear to increase as a result of PA, including integrin proteins such as ITGAV and ITGAM, as well as MXRA8, CLEC4A, CLEC4M, GFRA1, and ADGRG2; and on proteins that appear to decrease as a result of PA such as LEP, LPL, INHBC, CLMP, PTGDS, ADM, OGN, and PI3. Functional enrichment analyses revealed several relevant processes, including cell-matrix adhesion, integrin-mediated signaling, and collagen binding. Finally, several proteins, including GDF15, ITGAV, HPGDS, BCAN, and MENT, were found to mediate the relationship of PA with all-cause dementia, implicating processes such as synaptic plasticity, neurogenesis and inflammation, through which PA protects against dementia. Our results provide insights into how PA may affect biological processes and protect from all-cause dementia, and provide avenues for future research into the health-promoting effects of PA.
A Comparison of In-Person and Telehealth Treatment Modalities using the SpeechVive Device
Authors: Covert Renee , Snyder Sandy , Lambert Ashleigh , Spremulli Mary , Blandford Brianna , Dwenger Kaitlyn , Malandraki Georgia , McDonough Meghan , Brosseau-Lapre Françoise , Huber Jessica E. 
Published: January 2025

ABSTRACTTelehealth is increasing popular as a treatment option for people with Parkinson disease (PD). The SpeechVive device is a wearable device that uses the Lombard effect to help patients speak more loudly, slowly, and clearly. This study sought to examine the effectiveness of the device to improve communication in people with PD, delivered over a telehealth modality as compared to in-person, using implementation science design. 66 people with PD were enrolled for 12 weeks with 34 choosing the in-person group and 32 in the telehealth group. Participants were assessed pre-, mid-, and post-treatment. Participants produced continuous speech samples on and off the device at each timepoint. Sound pressure level (SPL), utterance length, pause frequency, and total pause duration were measured. Psychosocial surveys were administered to evaluate the effects of treatment on depression, self-efficacy, and participation. The in-person group increased SPL when wearing the device while the telehealth group did not. Both groups paused less often while wearing the device. Utterance length increased post-treatment for the telehealth group, but not for the in-person group. An increase in communication participation ratings in the telehealth group, but not the in-person group, was the only significant change in the psychosocial metrics. The in-person group showed similar treatment effects as previous studies. The device was not as effective in the telehealth group. One limitation was data loss due to recording issues that impacted the telehealth group more than the in-person group.
Interplay of Host and Viral Genetic Variations in Modulating Antibody Responses to Genotype 3a Hepatitis C Virus: Implications for Vaccine Design
Authors: Wang Zhiqing , Humphreys Isla , Quistrebert Jocelyn , Chai Haiting , Dhir Josh , Nisioi Alexandru , Radford Paul ,   STOP-HCV consortium, Ball Jonathan K. , Irving William L. , Klenerman Paul , Barnes Eleanor , McKeating Jane A. , Tarr Alexander W. , Ansari M. Azim 
Published: January 2025

AbstractHepatitis C virus (HCV) exhibits significant genetic diversity and is a of cause severe liver complications, including liver failure and hepatocellular carcinoma. The envelope glycoproteins E1 and E2 of HCV are the primary targets for the humoral immune response and have the highest sequence diversity in the HCV genome. The humoral immune response to HCV infection may be modulated by host and virus genetic factors. Here, using virus sequencing and host genetic data, as well as antibody binding and neutralization assays from 54 patients infected with HCV subtype 3a virus, we investigated the factors associated with antibody binding and neutralization. Genetic variation in the hostIFNL4gene were associated with antibody binding response, with the IFNλ4-P70 variant associated with reduced binding relative to IFNλ4-Null variant. Testing for association between all variable amino acids in HCV E1 and E2 glycoproteins and antibody response, we discovered two sites in or near the CD81 binding sites in E2 (sites 501 and 533) that were associated with neutralization sensitivity, along with an additional site in E2 (653) that was associated with binding. Additionally, motifs at two glycosylation sites (N476 and N234) were associated with binding and/or neutralisation. Furthermore, an increase in intra-patient hypervariable region 1 (HVR1) diversity was associated with stronger binding response. By considering the complex factors that influence antibody binding and neutralization, future vaccine strategies can be designed to elicit a robust immune response against a diverse range of HCV strains, addressing the needs of a diverse population.
Effectiveness of first line therapy forHelicobacter pyloriinfection in children and adolescents: a multicenter study in the United Arab Emirates
Authors: Al Atrash Eman , Al-Marzooq Farah , AbdelMassih Antoine , Bakro Amina , Azzaz Amer 
Published: January 2025

AbstractGlobally, gastric infection withHelicobacter pylorihas a high prevalence. Bacterial eradication is crucial to prevent long-term complications such as gastric cancer. There is a standard recommended first-line therapy with a desirable eradication goal of 90%, but this is non-achievable in most trials in children. Thus, it is recommended to evaluate first-line therapy at national centres, especially in areas where antimicrobial susceptibility testing is limited. This study aimed to examine the effectiveness of first-line regimen in eradicatingH. pyloriinfection in the pediatric population in the United Arab Emirates. This retrospective study was conducted in 2017-2023, involving patients aged 1-16 years. Patients diagnosed with and treated forH. pyloriinfection were included, specifically those who completed 2-week treatment with documented adequate compliance. Confirmation ofH. pylorieradication was done 4 weeks after the completion of antimicrobial therapy.H. pyloriwas detected among 447 patients, while 413 patients underwent complete treatment. Only 345 patients (77%) were evaluated for confirmed eradication via stoolH. pyloriantigen test (44%) or urea breath test (39%) which were the most used diagnostic modalities. Most patients (285/345; 83%) were treated with Proton Pump Inhibitor/Amoxicillin/Clarithromycin (PAC). Eradication was successful in 226 patients (65%), mostly in patients treated with the PAC regimen (193/285; 68%), compared to 20-55% eradication rates for patients treated with other regimens including metronidazole. Antibiotic regimen was the only significant predictor of eradication success (p<0.001), with non-significant correlation with other factors as age and gender. The overall eradication rate for the first-line therapy forH. pylorifalls below the recommended primary success rate for eradication (>90%). Factors influencing treatment success and adherence should be carefully considered to optimize the management ofH. pyloriinfection in pediatric patients. Further prospective studies are warranted to validate these findings and explore additional strategies for improving treatment outcomes.
Evaluating rapid water excitation techniques for 5D whole-heart fat-suppressed free-running cardiac MRI at 1.5T scanner
Authors: Safarkhanlo Yasaman , Yerly Jérôme , Falcão Mariana B. L. , Mackowiak Adèle LC , Piccini Davide , Stuber Matthias , Jung Bernd , Gräni Christoph , Bastiaansen Jessica AM 
Published: January 2025

AbstractBackgroundBalanced steady-state free precession (bSSFP) sequences offer high SNR and excellent tissue contrast for whole-heart MRI. However, inadequate fat suppression can introduce artifacts, particularly with non-Cartesian readouts. This study aimed to compare novel rapid water-excitation (WE) pulses for 3D radial whole-heart free-running MRI at 1.5T, specifically Binomial Off-Resonant Rectangular (BORR), Lipid Insensitive Binomial Off-Resonant RF Excitation (LIBRE), and Lipid Insensitive Binomial Off-Resonant (LIBOR) pulses, alongside a Fast Interrupted Steady-State (FISS) and non-fat suppressed free-running bSSFP sequence.MethodsThree free-running MRI protocols (BORR, LIBRE, LIBOR) were optimized for fat suppression at 1.5T using a phantom. These protocols, along with FISS and non-fat suppressed bSSFP, were tested in phantom and five volunteers, with each acquisition lasting 3min and 41sec.SNR and CNRWater-Fatwere measured in phantom data, while SNR and CNRBlood-Myocardiumwere assessed in volunteers using static gridded reconstructions. Motion-resolved reconstructions were used for qualitative assessments. SAR values were measured for each sequence, and statistical differences were analyzed using one-way ANOVA (p < 0.05). The pulse with the best combination of high SNR and low SAR was identified for further applications.ResultsIn phantom studies, LIBOR had the highest CNRWater-Fat(276.8 ± 2.5), followed by LIBRE (268.1 ± 2.6), BORR (249.9 ± 2.2), and FISS (212.7 ± 2.7), though these differences were not statistically significant (p > 0.05). FISS showed the highest SAR (1.41 W.kg-1), while LIBOR had the lowest (0.23 W.kg-1). In volunteers, BORR had the highest SNR in the ventricular blood pool (17.0 ± 1.5), and LIBRE had the highest CNRBlood-Fat(29.4 ± 9.3). FISS had the highest CNRBlood-Myocardium(29.0 ± 8.9), but the differences were not significant (p > 0.05). LIBOR consistently had the lowest SAR (0.26 W.kg-1).ConclusionThis study compared various fat-signal-suppression approaches in 3D contrast-free whole-heart free-running bSSFP MRI at 1.5T. Although the sequences performed similarly in SNR and CNR, LIBOR offered the lowest SAR, making it a promising candidate for future whole-heart MRI applications, particularly where RF energy deposition is a concern.
The effect of adult psychological therapies on employment and earnings: Evidence from England
Authors: Rzepnicka Klaudia , Sharland Emma , Rossa Marta , Dolby Ted , Oparina Ekaterina , Saunders Rob , Ayoubkhani Daniel , Nafilyan Vahé 
Published: January 2025

AbstractPeople suffering from common mental disorders (CMD) such as depression and anxiety are more likely to be economically inactive. Psychological therapies are highly effective at treating CMDs, but less is known about their impact on long-term labour market outcomes. Using national treatment programme data in England, NHS Talking Therapies (NHSTT), with unique linkage to administration data on employment and census records, we estimated the causal effects of NHSTT on employment and earnings.Overall, completing treatment led to a maximum average increase of £17 in monthly earnings (year two) and likelihood of paid employment by 1.5 percentage points (year seven). Those “Not working, seeking work’ saw a maximum average increase in pay of £63 per month (year seven) and likelihood of paid employment by 3.1 percentage points (year four). Our findings demonstrate the economic benefits of treating CMDs, and how investing in mental health can impact labour market participation.