bluuebunny/crossref_metadata_2025 huggingface dataset:
Neighbourhood characteristics and loneliness in later life: The role of ‘person-environment fit’
Authors: Lam Jack , Baxter Janeen
Published: January 2025

Background and Objectives

There is increasing acknowledgment that loneliness is associated with neighbourhood characteristics in addition to individual characteristics. We use four waves of geocoded data to examine longitudinal associations between neighbourhood characteristics and loneliness of older adults.

Research Design and Methods

We draw on ‘person-environment fit’ theory, utilizing individual assessments of neighbourhoods, but also create aggregate assessments of neighbourhood by combining responses from other respondents from the same geographic area to test associations with loneliness.

Results

Random-effects models demonstrate individual and aggregate assessments of neighbourhoods are related to loneliness, though in models inclusive of control variables, the associations between aggregate assessments of neighbourhood and loneliness were attenuated. Fixed-effects models show only individual assessments of the neighbourhood are associated with variations in loneliness.

Discussion and Implications

Consistent with the ‘person-environment fit’ theory, loneliness appears more sensitive to individual assessments of neighbourhood, irrespective of others’ assessments. Our findings point to the subjective nature of loneliness and suggest that measures to improve loneliness should focus on understanding and addressing individual perceptions of neighbourhoods, highlighting the importance of promoting age-friendly environments.
Characteristics and antimicrobial susceptibility of bacteria causing acute otitis media in children at Vietnam National Children’s Hospital: a cross-sectional study
Authors: Đỗ Hồng Điệp , Trần Minh Điển , Nguyễn Tuyết Xương , Thủy Phùng Thị Bích , Ngọc Hoàng Thị Bích , Liên Phạm Thị Lan , Nguyen Minh , DeAngelis Elena , Thân Hữu Tiệp , Nguyễn Khắc Trưởng , Guzman-Holst Adriana
Published: January 2025

Background

Acute otitis media (AOM) is a leading cause of healthcare visits, antibiotic prescription and complications in children aged under 5 years. Following the introduction of pneumococcal conjugate vaccines (PCVs), non-typeable Haemophilus influenzae (NTHi) has become the most common causative agent for AOM, followed by Streptococcus pneumoniae and Moraxella catarrhalis. PCVs are not yet included in the National Immunization Program in Vietnam.

Objectives

To determine the frequency and characteristics of the pathogens related to AOM in Vietnam in children ≤5 years old.

Methods

This was a cross-sectional study performed at the Vietnam National Children’s Hospital from October 2021 to December 2023 in children ≤5 years old diagnosed with acute suppurative otitis media. Clinical features of the children were described. Pathogens of interest were identified by culture or real-time PCR (rtPCR). The antibiotic susceptibility profiles of H. influenzae and S. pneumoniae isolates were determined.

Results

In total, 482 children ≤5 years old were included, of which 70.8% were ≤2 years old and 61% had an history of AOM. The most frequent bacteria isolated were H. influenzae (52.1%, 99.6% of which were NTHi) and S. pneumoniae (41.1%). Most S. pneumoniae isolates were resistant to azithromycin, clarithromycin and cefuroxime. Most H. influenzae isolates were resistant to amoxicillin, cefixime, cefuroxime, azithromycin and clarithromycin.

Conclusions

The pathogens most frequently associated with AOM in this study were in line with previous findings. Many isolates were resistant to commonly given oral antibiotics. These results can inform decision-making on AOM prevention and treatment strategies in Vietnam.
Geographic profiling of psychosis prevalence by ethnic group: an application of ecological inference to London neighbourhoods
Authors: Congdon Peter
Published: January 2025

In view of ethnic and geographic heterogeneity in psychosis, establishing varying psychosis prevalence both by neighbourhood, and by ethnic group, is important for mental health needs assessment and service planning. This paper uses an ecological inference framework to estimate neighbourhood psychosis rates by ethnic group, when the available information is limited to totals of diagnosed psychosis by neighbourhood. To assess sensitivity in inferences, and possible spatial confounding, alternative models for ethnic-area psychosis rates are used. In an application to 4,835 micro-neighbourhoods across London, the highest psychosis rates are among Black ethnic groups, with a rate ratio averaging 2.35 compared with prevalence among Whites. There is evidence for an ethnic density effect: lower psychosis rates than expected in neighbourhoods with high non-White ethnic concentration.
A rare case of endo-bronchial lipoma presenting with vague cardiac symptoms
Authors: Asghar Zoha , Irfani Muhammad Mehdi , Fatimi Alizeh , Sohail Abdul Ahad , Fatimi Saulat Hasnain
Published: January 2025

Endobronchial lipoma is an extremely rare benign tumor, accounting for 0.1%–0.5% of all lung tumors. This case report presents a patient diagnosed with endobronchial lipoma, a condition that can lead to significant bronchial obstruction and subsequent parenchymal damage. Patients usually exhibit symptoms including cough, dyspnea, and recurrent respiratory infections, which initially mimic more common pulmonary conditions such as chronic obstructive pulmonary disease. However, in our case patient presented with non-specific cardiac symptoms. Diagnosis was confirmed through bronchoscopy, revealing a well-circumscribed mass obstructing the bronchus. Due to severe parenchymal inflammation, treatment involved left-sided thoracotomy and upper lobectomy which successfully relieved the obstruction and alleviated the patient’s symptoms. Histopathological examination identified the tumor as a lipoma. This case underscores the importance of considering endobronchial lipoma in differential diagnoses for patients with unexplained cardiac or respiratory symptoms, as early detection and treatment can prevent significant complications.
Impersonal experiential constructions in ancient Northwest Semitic languages in a diachronic perspective
Authors: Notarius Tania
Published: January 2025

This paper scrutinizes the impersonal usage of experiential constructions in ancient Northwest Semitic (NWS) languages. A methodological distinction is made between affective and evaluative types of the impersonal experiential usage, where the affective type communicates the physical and emotive condition of the Experiencer (Hebrew ḥam lô ‘he feels warm’), and the evaluative type communicates an attitude towards particular proposition (Hebrew ˀim ˁal PN ṭôḇ ‘if PN would like …’). These types are distributed differently in the ancient NWS languages. The Old Canaanite of El-Amarna demonstrates both usages of the impersonal experiential construction, while Akkadian has only the evaluative usage. Ugaritic avoids the impersonal usage, except for some diagnostic cases in the language of prose. Biblical Hebrew consistently demonstrates both types. Official Aramaic exemplifies the evalua tive type only, while the affective type emerges at the Middle and Late Aramaic stages. In this paper, it is hypothesized that the impersonal experiential construction, and its affective type in particular, may be an areal Canaanite feature. The affective experiential usage appears in Ugaritic and then a thousand years later in Aramaic, as a result of contact with Canaanite languages.
Descriptive complexity for distributed computing with circuits
Authors: Ahvonen Veeti , Heiman Damian , Hella Lauri , Kuusisto Antti
Published: January 2025

We investigate distributed computing with identifiers in the realistic scenario where the local computations in a distributed message passing setting are operated by Boolean circuits. We call this framework the message passing circuit model. We capture the expressive power of the model with a recursive rule-based logic called modal substitution calculus MSC. The result is established via constructing translations that are highly efficient in relation to size and computation time. In particular, the worst size blow-up is quadratic and becomes linear in the bounded-degree scenario. Computation time delays are similarly modest. As a concrete demonstration of how our setting works, we establish that a very fast coloring algorithm based on Cole–Vishkin can be specified by logarithmic size programs (and thus also logarithmic size circuits) in the bounded-degree scenario.
Discovery of 26 new Galactic radio transients by MeerTRAP
Authors: Turner J D , Stappers B W , Tian J , Bezuidenhout M C , Caleb M , Driessen L N , Jankowski F , Pastor-Marazuela I , Rajwade K M , Surnis M , Kramer M , Barr E D , Berezina M
Published: January 2025

Radio searches for single pulses provide the opportunity to discover one-off events, fast transients and some pulsars that might otherwise be missed by conventional periodicity searches. The MeerTRAP real-time search pipeline operates commensally to observations with the MeerKAT telescope. Here, we report on 26 new Galactic radio transients, mostly rotating radio transients (RRATs) and also the detection of one RRAT and two pulsars that were independently discovered by other surveys. The dispersion measures of two of the new sources marginally exceed the Galactic contribution depending on the electron density model used. Using a simple method of fitting a Gaussian function to individual pulses, and obtaining positions of arcsecond accuracy from image-based localisations using channelised voltage data from our transient buffer, we have derived timing solutions spanning multiple years for five sources. The timing parameters imply ages of several Myr and low surface magnetic field strengths which is characteristic of RRATs. We were able to measure spin periods for eight more transients, including one source which appears to rotate every 17.5 seconds. A majority of the sources have only been seen in one observation, sometimes despite multiple return visits to the field. Some sources exhibit complex emission features like component switching and periodic microstructure.
The Racialized Sexism of Migration and Asylum Regimes Pregnancy, Migration, and Borders in France
Authors: Freedman Jane , Sahraoui Nina , Tyszler Elsa
Published: January 2025

The gendered implications of migration and asylum regimes require further attention in an era of border militarization and increasingly hostile environments, especially across the Global North, a region in which many countries pride themselves on standing for gender equality, whereas they in fact perpetuate gendered forms of discrimination and violence against irregularized migrant women. This article examines the experiences in France of pregnant women and recent mothers from Global South countries and their encounters with the asylum and migration regimes and the healthcare sector. We argue that the administrative precarity and material destitution that contemporary asylum and migration policies enact need to be analyzed as racialized sexism because of their specifically gendered implications as well as their racist premises. This research stems from fieldwork carried out in France in 2020 and 2021 in the capital, as well as at the “air borders” and at the French–Italian border in the Alps.
Climate friendly MOFs synthesis for drug delivery systems by integrating AI, intelligent manufacturing, and quantum solutions in industry 6.0 sustainable approach
Authors: Akhtar Maryam , Majeed Hammad , Iftikhar Tehreema , Ahmad Khalil
Published: January 2025

Since the Industrial Revolution, ecological damage, ecosystem disruption, and climate change acceleration have frequently resulted from human advancement at the price of the environment. Due to the rise in illnesses, Industry 6.0 calls for a renewed dedication to sustainability with latest technologies. Focused research and creative solutions are needed to achieve the UN Sustainable Development Goals (SDGs), especially 3, 9, 13, 14, 15, 17. A promising sustainable technology for enhancing healthcare while reducing environmental effect is Metal Organic Frameworks (MOFs). MOFs are perfect for drug administration because of their high surface areas, adjustable pore sizes, and remarkable drug-loading capacities. They are created by combining advanced artificial intelligence, intelligent manufacturing, and quantum computing. Researchers can create MOFs with functional groups or ligands that bind selectively to target cells or tissues, minimizing off-target effects, thanks to the distinct benefits that families like MIL, HKUST, UiO, and ZIF etc. offer for targeted drug delivery. Combining MOFs with other nanomaterials results in multipurpose systems that can handle challenging biomedical issues. Despite its promise, there are still issues with MOFs’ possible toxicity and long-term stability in physiological settings. To advance their medicinal applications, these problems must be resolved. Researchers can increase the usefulness of MOFs in medicine by critically analysing these limitations and putting up creative alternatives. The creation of MOFs especially with advanced technologies (additive manufacturing etc.) for drug delivery is a prime example of how scientific advancement and environmental stewardship may coexist to provide healthcare solutions that are advantageous to both people and the environment.
Enhancement of adipose stem cell quality via Cu‐MON: Transcriptome and bioinformatics analysis of normal and diabetic stem cells
Authors: Pang Ruixin , Liu Kaijing , Liu Biou , Yang Jing
Published: January 2025

Transplanted adipose stem cells (ASC) have a low survival rate in the body, and there are not many ASC that can be effectively used, which weakens their tissue repair function. Based on this status quo, a new type of copper‐based metal–organic network (Cu‐MON) was used to pretreat cells to regulate cell activity in order to improve the efficacy of cell therapy or reduce the number of cells used, thus reducing the cost of clinical treatment. Gene expression changes before and after Cu‐MON treatment of normal donor adipose stem cells (ND‐ASC) and type 2 diabetes mellitus adipose stem cells (T2DM‐ASC) were evaluated through RNA sequencing, KEGG and GO enrichment analysis. The results showed that Cu‐MON improved ASC cell quality by regulating immune response and promoting paracrine secretion. IL‐17 signaling pathway and IL‐6, CXCL8, and MMP‐9 were key pathways and necessary genes that affected the ability of stem cells. In addition, Cu‐MON also improved stem cell antiviral ability through Type I interferon signaling pathway. Our research showed that Cu‐MON had improved the cell quality of ASC by regulating immune response, promoting paracrine secretion, and improving antiviral capabilities. This approach to biomaterial pretreatment is fast, convenient, and relatively safe, and provides new strategies for improving the efficiency of cell therapies.
Sodium tanshinone IIA sulfonate alleviates fetal growth restriction by mediating aquaporin‐3 expression in placental trophoblast cells
Authors: Pan Shuangjia , Xu Anjian , Chen Baoyi , Lu Xinyue , Zou Jieni , Hua Ying
Published: January 2025

Fetal growth restriction (FGR) is characterized by the inability of the fetus to achieve its growth potential due to pathological factors, most commonly impaired placental trophoblast cell function. Currently, effective prevention and treatment methods of FGR are limited. We aimed to explore the pathogenesis of FGR and provide potential strategies for mitigating its occurrence. The case–control study compared AQP3 expression in placental trophoblast cells of pregnant women with FGR and those with normal pregnancies. Then mouse FGR models were induced via cadmium exposure, and placental trophoblast cells (JEG‐3) were similarly treated. The study assessed the effects of Sodium tanshinone IIA sulfonate (STS) and the role of the PI3K/Akt pathway in improving AQP3 expression and trophoblast cell function. Placental trophoblast cells in FGR cases exhibited significantly reduced AQP3 expression. AQP3‐knockdown cells displayed dysfunction. Cadmium exposure in mice and JEG‐3 cells led to decreased AQP3 expression and trophoblast cell dysfunction, both of which were ameliorated by STS. Fetal mouse weight increased with STS treatment. STS upregulated AQP3 expression and improved trophoblast cell function in AQP3‐knockdown cells. Inhibiting the PI3K/Akt pathway diminished STS's beneficial effects. ThereforeSTS may enhance AQP3 expression in placental trophoblast cells affected by FGR through the activation of the PI3K/Akt pathway, ultimately bolstering placental trophoblast cell function and alleviating FGR. As above, STS appears to be a potential therapeutic agent for alleviating FGR.
Longitudinal T cell repertoire analysis reveals dynamic clonal T cell populations in Ulcerative Colitis
Authors: Briggs Kristi C. , Lin Jessica S. , Chaaban Lara , Parian Alyssa , Lazarev Mark , Selaru Florin , Housseau Franck , Smith Kellie N. , Melia Joanna M. P.
Published: January 2025

Background

Ulcerative Colitis (UC) is characterized by chronic, relapsing and remitting inflammation in the colon and rectum. Pathogenic T cell activity is thought to play a major role in this process. T cell effector function is determined by the T cell receptor (TCR) and the antigen it recognizes. Examining the TCR repertoire can provide key insights into the adaptive immune response.

Objective

To characterize the longitudinal TCR repertoire of patients with UC across disease activity to determine if recurrent antigen(s) are responsible for active inflammation.

Design

Bulk TCR Vβ sequencing was done on colon tissue of 20 patients with UC across multiple time points of disease. Corresponding clinical metadata was also obtained over the same time period for each patient to map their clinical disease course. The top ten most highly abundant clones from each time point were longitudinally tracked and correlated with disease phenotype.

Results

Seventy-five percent of patients did not have overlapping abundant TCR clones across multiple time points of disease. The remaining 25% of patients had one to five TCR clones present in high abundance in their tissue during every time point analyzed.

Conclusion

These results demonstrate that most patients with UC do not share a similar TCR repertoire over time, indicating that times of inflammation are associated with unique antigen exposures. A smaller group of patients have persistent, private TCR clones with high abundance, 60% of whom had more unremitting, active disease.
Matrix stiffness modulated release of spheroid-derived extracellular vesicles and discovery of Piezo1 cargo
Authors: Sheth Maulee , Sharma Manju , Kongsomros Supasek , Lehn Maria , Takebe Takanori , Takiar Vinita , Wise-Draper Trisha , Chutipongtanate Somchai , Esfandiari Leyla
Published: January 2025

Augmented extracellular matrix (ECM) stiffness is a mechanical hallmark of cancer. Mechanotransduction studies have extensively probed the mechanisms by which ECM stiffness regulates intracellular communication. However, the influence of stiffness on intercellular communication aiding tumor progression in three-dimensional microenvironments remains unknown. Small extracellular vesicles (EVs) are communicators of altered biophysical cues to distant sites through EV-ECM interactions and EV-mediated recipient cell-ECM interactions. Here we demonstrate stiffness-mediated modulation of small EVs secretion and cargo from three-dimensional oral squamous cell carcinoma spheroids. Using a spheroid culture platform with varying matrix stiffness properties, we show that small EVs carry parental biomolecular cargo, including mechanosensitive Piezo1 ion channel and adhesion molecule CD44. We comprehensively validate the presence of both markers in our EV populations using proteomic and genetic analysis. Transcriptomic analysis of microRNA and long non-coding RNA cargo of small EVs released from soft and stiff ECM spheroids revealed enrichment of tumorigenic and metastatic profiles in EVs from stiff ECM cultures compared to that of soft ones. Gene set enrichment analysis of a comparative dataset obtained by overlaying spheroid mRNA and EV miRNA profiles identified key oncogenic pathways involved in cell-EV crosstalk in the spheroid model.
The Dark Side of Photosymbiosis: Elaborate Repeats with TEs and Unknown ORFs in Photosymbiotic Bivalves Made Exceptionally Big Metazoan Mitogenomes
Authors: Tan Andy D. Y. , Li Ruiqi , Li Jingchun
Published: January 2025

Limited truly “complete”mitogenomes have been published for marine invertebrates, with many being partial and focused on protein-coding genes. Dispelling the traditional myth of “metazoan mitogenomes being highly conserved in size and gene order”, long-read technologies have revealed novel structures and complexities in animal mitogenomes. Our investigation of PacBio-assembled mitogenomes of several marine bivalve species (family Cardiidae), revealed a photosymbiotic bivalve,Fragum sueziense, possesses one of the largest circular metazoan mitogenome (92,770 bp). Additionally, mitogenomes of photosymbiotic bivalves from the generaFragumandTridacnaranged from 22 to 92.8 kb, surpassing the more typical sizes in non-photosymbiotic cardiids (∼14 to 19 kb). Those expansions in mitogenomes are attributed to elaborate, species-specific repetitive sequences in the major non-coding region (NCR) which manifest an inability to assemble “complete” mitogenomes from Illumina short reads (at 150 bp) alone; divergent nature of those NCRs also hinder interspecies alignment. However, we annotated supernumerary tRNAs, transposable element fragments and open reading frames in NCRs despite their hitherto unknown functions. We postulate that NCR inflation in these photosymbiotic species may be associated with elevated reactive oxygen species in their mantle and altered immune states due to host-symbiont interactions involving photosymbionts. More complete mitogenomes are needed to uncover novel genetic elements and their functions otherwise undocumented to science.

SIGNIFICANCE STATEMENT

Many published animal mitogenomes does not truly span the entirety of the major non-coding region (NCR), often due to the inability of short-read sequencing to confidently cover highly repetitive sequences. In this study, long-read sequencing enabled us to access “more complete” mitogenomes for a comparative analysis focused on the nature of the NCRs between photosymbiotic and non-photosymbiotic bivalves, and the elements within them. We not only uncovered one of the largest circular metazoan mitogenomes (Fragum sueziense), but also found ample genetic elements within the conventionally “non-coding” regions, including extensive elaborate repeat patterns, transposable elements and unknown open reading frames. To our knowledge, this is the first time extensive transposable elements have been reported in animal mitogenomes. Our study revealed extreme mitogenome expansions and complexities as potential costs to bivalve-algal photosymbiosis, and provide insights into metazoan symbiosis evolution.
What is the best brain state to predict autistic traits?
Authors: Horien Corey , Mandino Francesca , Greene Abigail S. , Shen Xilin , Powell Kelly , Vernetti Angelina , O’Connor David , McPartland James C. , Volkmar Fred R. , Chun Marvin , Chawarska Katarzyna , Lake Evelyn M.R. , Rosenberg Monica D. , Satterthwaite Theodore , Scheinost Dustin , Finn Emily , Constable R. Todd
Published: January 2025

Autism is a heterogeneous condition, and functional magnetic resonance imaging-based studies have advanced understanding of neurobiological correlates of autistic features. Nevertheless, little work has focused on the optimal brain states to reveal brain-phenotype relationships. In addition, there is a need to better understand the relevance of attentional abilities in mediating autistic features. Using connectome-based predictive modelling, we interrogate three datasets to determine scanning conditions that can boost prediction of clinically relevant phenotypes and assess generalizability. In dataset one, a sample of youth with autism and neurotypical participants, we find that a sustained attention task (the gradual onset continuous performance task) results in high prediction performance of autistic traits compared to a free-viewing social attention task and a resting-state condition. In dataset two, we observe the predictive network model of autistic traits generated from the sustained attention task generalizes to predict measures of attention in neurotypical adults. In dataset three, we show the same predictive network model of autistic traits from dataset one further generalizes to predict measures of social responsiveness in data from the Autism Brain Imaging Data Exchange. In sum, our data suggest that an in-scanner sustained attention challenge can help delineate robust markers of autistic traits and support the continued investigation of the optimal brain states under which to predict phenotypes in psychiatric conditions.
Rehabilitation your way: A randomized trial comparing home-based and self-managed web versus paper programs to improve arm and hand function after stroke
Authors: Westlake Kelly P. , Waller Sandy McCombe , Magdar Lawrence , Akinsolotu Ruth , Udo Jean , Burridge Jane , Whitall Jill
Published: January 2025

Background

Home-based, self-managed stroke rehabilitation can complement limited healthcare resources. Computer-based programs offer a potential for rehabilitation without the need for complex technology or direct therapist supervision.

Objective

To compare effectiveness of a home-based web rehabilitation program (STRONG) versus a paper exercise program (PEP) for stroke-related upper extremity disability.

Methods

In this single-blind randomized controlled trial 43 participants with stroke were stratified by motor ability and motivation, then randomly assigned to either STRONG (n=22) or PEP (n=21). Training consisted of a 6-week intervention phase (at least 1 hour daily, 5 days weekly), followed by a 6-week follow-up phase with optional training. Primary outcomes were Fugl-Meyer Upper Extremity Assessment (FMA) and the streamlined timed Wolf Motor Function Test (WMFT-T). Secondary outcomes Motor Activity Log (MAL), WMFT-Function (WMFT-F), Stroke Motivation Scale, and Self-Efficacy Scale.

Results

Neither program showed superiority in FMA or WMFT-T. Within-group FMA improvements were similar (Strong: 1.8 points vs PEP: 2.1 points at post-training; 3.3 vs 1.9 at follow-up). However, STRONG participants reported better arm and hand use in daily activities (MAL) at post-training and follow-up. Additionally, STRONG participants showed higher self-efficacy at post-training, though this difference was not maintained at follow-up.

Conclusion

Both programs led to modest motor improvements. While STRONG did not outperform PEP in the primary outcomes, participants reported using their affected arm and hand more in daily activities and higher program continuation after the intervention period. Results suggest that home-based, self-managed rehabilitation combining exercises with daily tasks appears beneficial for stroke survivors post-standard rehabilitation.

Clinicaltrials.govidentifier:NCT03484182
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

The 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

Reactive 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

While 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

In 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.

Highlights

1. 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

Advancements 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

Physical 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

Telehealth 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

Hepatitis 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

Globally, 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.