bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 neutralizing antibody specificities differ dramatically between recently infected infants and immune-imprinted individuals
Authors: Dadonaite Bernadeta , Burrell Allison R. , Logue Jenni , Chu Helen Y. , Payne Daniel C. , Haslam David B. , Staat Mary A. , Bloom Jesse D. 
Published: January 2025

AbstractThe immune response to viral infection is shaped by past exposures to related virus strains, a phenomenon known as imprinting. For SARS-CoV-2, much of the population has been imprinted by a viral spike from an early strain, either through vaccination or infection during the early stages of the COVID-19 pandemic. As a consequence of this imprinting, infection with more recent SARS-CoV-2 strains primarily boosts cross-reactive antibodies elicited by the imprinting strain. Here we compare the neutralizing antibody specificities of imprinted individuals versus infants infected with a recent strain. Specifically, we use pseudovirus-based deep mutational scanning to measure how spike mutations affect neutralization by the serum antibodies of adults and children imprinted by the original vaccine versus infants with a primary infection by a XBB* variant. While the serum neutralizing activity of the imprinted individuals primarily targets the spike receptor-binding domain (RBD), serum neutralizing activity of infants only infected with XBB* mostly targets the spike N-terminal domain (NTD). In these infants, secondary exposure to the XBB* spike via vaccination shifts more of the neutralizing activity towards the RBD, although the specific RBD sites targeted are different than for imprinted adults. The dramatic differences in neutralization specificities among individuals with different exposure histories likely impact SARS-CoV-2 evolution.
Short-term Outcomes of Trabeculectomy with Mitomycin-C in a Tertiary Eye Hospital in Nepal: A Prospective Descriptive Study
Authors: Thinley  , Paudyal Indhira , Joshi Pratibha Lama 
Published: January 2025

AbstractObjectiveThis study evaluated the short-term outcomes of trabeculectomy with mitomycin-C in glaucoma patients at Tilganga Institute of Ophthalmology, Kathmandu, Nepal, between June 2021 and May 2022.MethodsThis was a prospective descriptive study, conducted on 56 eyes of 51 consecutive glaucoma patients who underwent trabeculectomy with mitomycin-C (0.02%). Follow-up assessments were carried out on postoperative day 1, week 1, month 1, month 3, and month 6. Statistical analysis was done using SPSS version 20 software.ResultsThe study included 38 male (74.5%) and 13 female (25.5%) patients with an average age of 43.50 ± 15.45 years. A significant reduction in median intraocular pressure (IOP) from 24.33 mmHg preoperatively to 12.00 mmHg at 6 months postoperatively was observed (P < 0.01). The median number of anti-glaucoma medications decreased from 3.0 preoperatively to 0.0 at all postoperative visits. Complete surgical success was achieved in 85.7% of eyes. Common complications included shallow anterior chamber, hypotony, and IOP elevation.ConclusionTrabeculectomy with mitomycin-C demonstrated high surgical success rate with low complication rates in the short term, making it an effective and safe treatment option for glaucoma patients not medically controlled. It may benefit glaucoma patients facing challenges with long-term anti-glaucoma medication use and frequent follow-up visits, thus improving the management outcomes of this chronic condition.
The effects of alcohol use severity and polygenic risk on gray matter volumes in young adults
Authors: Chen Yu , Li Huey-Ting , Luo Xingguang , Li Guangfei , Ide Jaime S. , Li Chiang-Shan R. 
Published: January 2025

AbstractGenetic factors contribute to alcohol misuse. Chronic alcohol consumption is associated with decreases in gray matter volumes (GMVs) of the brain. However, it remains unclear whether or how genetic risks may alter GMVs independent of the effects of alcohol exposure. Here, we employed the Human Connectome Project data of neurotypical adults (n = 995; age 22-35; 618 women) and, with voxel-based morphometry analysis, computed the GMVs of 166 regions in the automated anatomical atlas 3. Alcohol use behaviors were assessed with the Semi-Structured Assessment for the Genetics of Alcoholism. Alcohol use severity was quantified by the first principal component (PC1) identified of principal component analysis of 15 drinking measures. Polygenic risk scores (PRS) for alcohol dependence were computed for all subjects using the Psychiatric Genomics Consortium study of alcohol dependence as the base sample. With age, sex, race, and total intracranial volume as covariates, we evaluated the relationships of regional GMVs with PC1 and PRS together in a linear regression. PC1 was negatively correlated with GMVs of right insula and Heschl’s gyrus, and PRS was positively correlated with GMVs of left posterior orbitofrontal cortex, bilateral intralaminar nuclei of the thalamus and lingual gyri. These findings suggest distinct volumetric neural markers of drinking severity and genetic risks of alcohol misuse. Notably, in contrast to volumetric reduction, the genetic risks of dependent drinking may involve larger regional volumes in the reward, emotion, and saliency circuits.
Evaluation of plasma p-tau217 for detecting amyloid pathology in a diverse and heterogeneous community-based cohort
Authors: Rudolph Marc D. , Sutphen Courtney L. , Register Thomas C. , Lockhart Samuel N. , Rundle Melissa M. , Hughes Timothy M. , Bateman James R. , Solingapuram Sai Kiran K. , Whitlow Christopher T. , Craft Suzanne , Mielke Michelle M. 
Published: January 2025

ABSTRACTINTRODUCTIONStudies suggest excellent performance of plasma p-tau217 for detecting amyloid pathology, though studies in more diverse populations are needed to validate previously determined cutpoints.METHODSPlasma p-tau217 utility for detecting amyloid pathology (Aβ) via amyloid PET (n=598) and/or cerebrospinal fluid (CSF;n=154) was assessed in a heterogeneous, community-based cohort in the Wake Forest Alzheimer’s Disease Research Center (WFADRC). Participants (n=598) were 21% Black; 313 cognitive unimpaired (CU), 214 mild cognitive impairment (MCI), and 64 dementia (DEM); 49% prediabetic, 44% hypertensive; 29% overweight/obese; and 64% with mild-to-moderate kidney disease. Gaussian-mixture models, logistic regression, and receiver operating curve analyses were performed.RESULTSPlasma p-tau217 was associated with elevated Aβ deposition and accurately classified Aβ-positive participants (PET: AUC: 94%-97%, cutpoint≥.338 pg/mL; CSF: AUC = .84, cutpoint ≥.307 pg/mL).DISCUSSIONPlasma p-tau217 is an accurate indicator of amyloid pathology in a heterogeneous cohort, and superior to other plasma biomarkers assessed. Longitudinal analyses assessing impact of comorbidities on p-tau217 utility for disease progression are underway.HIGHLIGHTSThe WFADRC is a diverse and heterogeneous cohort.P-tau217 levels were lower, on average, in cognitively unimpaired participants, females, and Black participants.Plasma p-tau217 classified amyloid PET positive individuals with high precision and performed better than p-tau181.Cutpoints and reference ranges of plasma p-tau217 were lower compared to recently published thresholds.Combining cutpoint approaches, a 4-tier system captured cohort heterogeneity.
Static and dynamic intracerebral signal analysis reveals protective networks against seizures in drug-resistant focal epilepsy
Authors: Di Giacomo Roberta , Núñez Pablo , Poza Jesús , Rodríguez-González Victor , Gómez Carlos , Burini Alessandra , Castana Laura , de Curtis Marco , Tassi Laura , Varotto Giulia 
Published: January 2025

AbstractBackgroundEpilepsy research increasingly emphasizes the role of brain network dynamics in seizure generation and propagation. This study explores static and dynamic functional networks in subjects with drug-resistant epilepsy, to identify mechanisms that enhance or inhibit seizure initiation. To this aim, we analyzed functional connectivity of brain networks preceding ictal minor electrical discharges and major seizures in epileptogenic and non-epileptogenic zones explored with intracerebral electrodes.Material and methodsStereo-electroencephalographic signals were recorded from 39 patients with focal drug-resistant epilepsy during presurgical monitoring. Static functional connectivity was analyzed using graph theory metrics, whereas dynamic connectivity through the analysis of the complexity and dwell times of brain meta-states activations.ResultsStatic connectivity analysis revealed significant alterations in network centrality, integration, and segregation properties, with distinct patterns observed in resting conditions just ahead minor electrical discharges and major seizures. Specifically, network analysis before minor electrical discharges exhibited increased nodal strength and reduced betweenness centrality in the epileptogenic zone, associated with increased integration and reduced segregation in non-epileptogenic zones. Dynamic connectivity analysis showed lower complexity and longer stability of meta-states before minor electrical discharges, particularly in high-frequency signals of non-epileptogenic zones.ConclusionsOur findings provide novel and valuable insights into the dynamic reconfiguration of brain networks before epileptic seizures, suggesting an inhibitory/protective mechanism mainly involving the non-epileptogenic zones. Understanding these network changes is pivotal for improving epilepsy treatment strategies targeting dynamic network alterations.
GacA regulates symbiosis and mediates lifestyle transitions inPseudomonas
Authors: Luo Youqing , Srinivas Apsara , Guidry Casey , Bull Carolee , Haney Cara H. , Hamilton Corri 
Published: January 2025

ABSTRACTThrough horizontal gene transfer, closely related bacterial strains have assimilated distinct sets of genes, resulting in significantly varied lifestyles. However, it is not clear how strains are able to properly regulate horizontally transferred virulence genes. We hypothesized that strains may use components of the core genome to regulate diverse horizontally acquired genes. To investigate how closely related bacteria assimilate and activate horizontally acquired DNA, we used a model ofPseudomonas fluorescenssubspeciesbrassicacearumstrains, N2E2 and N2C3, which exhibit contrasting lifestyles on the model plant Arabidopsis.P. brassicacearumstrain N2E2 is a plant commensal and contains the genes that encode biosynthetic enzymes for the anti-fungal compound 2,4-Diacetylphloroglucinol (DAPG). In contrast, N2C3 lacks DAPG biosynthesis and has gained a pathogenic island encoding syringomycin (SYR)-and syringopeptin (SYP)-like toxins from the plant pathogenP. syringae.This causes a transition in lifestyle from plant-protective N2E2 to plant pathogenic N2C3. We found that N2E2 and N2C3 share a highly conserved two-component system GacA/S, a known regulator of DAPG and SYR/SYP. Using knockout mutations, we found that aΔgacAmutation resulted in loss of expression of SYR/SYP virulence genes and returned pathogenic N2C3 to a plant commensal lifestyle. Our study further explored the conservation of regulatory control across strains by demonstrating that GacA genes from both distant and closely relatedPseudomonasstrains could functionally complement one another across the genus.IMPORTANCEEmerging pathogens represent a significant threat to humans, agriculture, and natural ecosystems. Bacterial horizontal gene transfer aids in the acquisition of novel genes that facilitate bacterial adaptation to new environments. Our work shows a novel role for GacA in orchestrating the regulatory changes necessary for virulence and lifestyle transitions facilitated by HGT. These findings suggest that the GacA/S system plays a key role in mediating transitions across diversePseudomonassymbiotic lifestyles. It provides insights into the mechanisms that drive the emergence of pathogenic strains and highlights potential targets for managing bacterial threats to plant health.
Mapping the complete influenza A virus infection cycle through single vRNP imaging
Authors: Rabouw Huib H. , Schokolowski Janin , Müller Micha , Baars Matthijs J.D. , Dost Antonella F.M. , Bestebroer Theo M. , Püschel Jakob , Clevers Hans , Fouchier Ron A.M. , Tanenbaum Marvin E. 
Published: January 2025

AbstractCell-to-cell heterogeneity is a common feature of viral infection that can generate enormous complexity, complicating understanding of infection progression and interpretation of differences between viral variants. To overcome these challenges, we developed a technology to visualize the infection cycle of human influenza A virus (IAV) from start-to-finish in individual living cells with unprecedented spatial and temporal resolution, which identified numerous distinct pathways through which infection can progress. We show that heterogeneous viral gene expression drives infection cycle heterogeneity, and identified genome packaging, vRNP transcriptional activation and host cell division as major determinants of gene expression variability. Our work maps out the complete IAV infection cycle, identifies the origin of infection heterogeneity and provides a broadly-applicable technology for studying IAV and other viruses.
A comparative metagenomic analysis of antibiotic resistance in the fecal microbiome of pigs raised with and without antibiotics
Authors: Pillay Stephanie , Abeel Thomas 
Published: January 2025

AbstractPurposeThe use of antibiotics in swine production has raised concerns about its impact on animal health, microbial ecology, and the emergence of antibiotic resistance. The gut microbiome, a critical component of animal health, is susceptible to disruptions caused by antibiotic use. The fecal microbiome can provide a snapshot of changes in the gut microbiome and provide information on the spread of antibiotic resistance from pig feces to the environment.MethodsWe investigated the differences between the fecal microbiome of pigs raised with (AB+) and without (AB-) antibiotics to assess how antibiotic exposure influenced the microbial community, antibiotic resistance genes (ARGs), and mobile genetic elements (MGEs).ResultsOur findings revealed that the use of antibiotics combined with study-specific conditions alters the fecal microbiome. Antibiotic usage in pigs explains 20% of the variation in the diversity of bacterial species detected between AB+ and AB- pigs. Similarly, variations in ARGs were observed in the two groups. The RND efflux pump gene family was abundant in both groups. The OXAβ-lactamase gene and associated plasmids were more prevalent in the AB- group. We also identified integrons linked to chloramphenicol resistance and transposon-associated integrative elements that can facilitate the spread of antibiotic resistance genes within and between bacterial species.ConclusionThese findings highlight that antibiotics influence both the microbial community and the antibiotic resistance gene repertoire, regardless of study-specific or environmental conditions. This emphasises the potential for fecal matter to contribute to the spread of antibiotic resistance in the environment, underscoring the need for more research to fully understand these dynamics in agricultural settings.
OT-Mation: an open-source code for parsing CSV files into python scripts for control of OT-2 liquid handling robotics
Authors: Laverick Alex , Convey Katherine , Harrison Catherine , Tomlinson Jenny , Stach Jem , Howard Thomas P. 
Published: January 2025

AbstractOT-Mation is an open-source Python script designed to automate the programming of OT-2 liquid handling robots, making combinatorial experiments more accessible to researchers. By parsing user-defined CSV files containing information on labware, reagents, pipettes, and experimental design, OT-Mation generates a bespoke Python script compatible with the OT-2 system. OT-Mation enhances reproducibility, reduces human error, and streamlines workflows, making it a valuable addition to any laboratory utilising OT-2 robotics for liquid handling. While OT-Mation can be used for setting up any type of experiment on the OT-2, its real utility lies in making the connection between multifactorial experimental design software outputs (i.e. Design of Experiments arrays) and liquid-handling robot executable code. As such, OT-Mation helps bridge the gap between code-based flexibility and user-friendly operation, allowing researchers with limited programming skills to design and execute complex experiments efficiently.
Quieting the Storm: Hypoxia as a Strategy to Boost UC-MSC Therapies for Neonatal Hypoxic-Ischemic Encephalopathy
Authors: Serrenho Inês , Mendes Vera , Caramelo Inês , Cardoso Carla M. , Manadas Bruno , Baltazar Graça 
Published: January 2025

AbstractIntegrating stem cell therapies into clinical settings faces several challenges, particularly in achieving the high cell yields necessary for attaining therapeutic doses. Preconditioning with hypoxic conditions has shown promise in enhancing the UC-MSCs reparative capabilities of the central nervous system. Recent evidence suggests that oxygen concentration and exposure duration can shape MSCs’ phenotypes, supporting the need for further optimization of this strategy in a way to achieve maximal repair. In this study, we assessed the effects of both prolonged mild hypoxia (MH; 5% oxygen for 48 hours) and short severe hypoxia (SSH; 0.1% oxygen for 24 hours) on UC-MSCs’ ability to alleviate motor and cognitive deficits in a rodent model of neonatal HIE. Our results show that short, severe hypoxia led to more improvements in functional recovery than prolonged mild hypoxia, supporting that specific preconditioning parameters are crucial in maximizing UC-MSC therapeutic potential. To investigate the molecular effects of hypoxia-preconditioned MSCs in the neonatal brain post-HIE, we employed untargeted proteomics on ipsilesional brain samples from control, HIE, HIE treated with naïve UC-MSCs, and HIE treated with SSH-preconditioned UC-MSCs groups, 30 days after lesion induction. This approach identified protein signatures related to injury and therapeutic intervention. Pathway enrichment analysis further revealed that administration of UC-MSCs preconditioned with short severe hypoxia significantly impacted neural signaling, protein synthesis, and energy metabolism pathways, pointing to long-term mechanisms that may support neuronal repair. These findings enhance our understanding of hypoxia-preconditioning in MSCs therapy in driving a positive therapeutic response, supporting the development of more effective and feasible treatments for neonatal HIE.
The periphery as a critical project: towards an architectural pedagogy for the Anthropocene
Authors: McEwan Cameron 
Published: January 2025

PurposeThe aim of this paper is to advance a critical pedagogical framework, combining critical pedagogy, design research, architectural theory and experiential learning. It addresses global challenges at the intersection between urban peripheries and the Anthropocene – the centre of the climate crisis is a spatial crisis – preparing students as engaged architect citizens capable of reshaping collective life.Design/methodology/approachThe framework is examined through a case study of the author’s final year architectural theory module, “The Periphery as a Critical Project”, elucidating its theoretical underpinning and presenting a visual analysis of student projects. Methods include reflective module design, fieldwork, close-reading of literature across disciplines, design research, experiential learning strategies and an inventive “theorypractice”.FindingsThe research demonstrates that theorypractice articulates a transformative and experiential learning experience, articulating architectural education as a site for critical engagement with urgent challenges. The approach equips students with critical thinking and making skills, cultivates a commitment to civic responsibility and encourages alternative visions for the Anthropocene. The paper concludes with concepts and practices to define an emerging architectural pedagogy for the Anthropocene.Practical implicationsThe research provides guidance for educators in architecture, aligning with RIBA reforms emphasising “history, theories, methodologies” and experiential learning in allied fields such as urban studies, environmental planning and social policy, focused on climate and social resilience, spatial justice and critical literacy. More broadly it aims at preparing engaged architect citizens who can work on and with the world.Originality/valueThis paper contributes an original framework and novel methodology, bringing together theoretical and design research from architecture, urban studies, design, critical pedagogy and environmental humanities to expand experiential learning within architectural theory, an underexplored position. It addresses urgent issues related to urban peripheries, climate change, and how we educate future architects in times of crisis, offering a model for allied fields facing similar societal challenges.
Numerical investigation of wave dynamics in laminar falling films: influence of Kapitza number and inclination angle
Authors: Chen Yuanxiang , Zheng Jian , Liu Yue , Oliva Llena Asensio , Castro Gonzalez Jesus 
Published: January 2025

Purpose
This study aims to optimize the design of falling film heat exchangers by providing a deeper understanding of wave characteristics and capillary flow in laminar inclined falling films at low Reynolds numbers. The focus is on the effects of different Kapitza numbers, influenced by fluid properties and inclination, on the interfacial wave behavior.

Design/methodology/approach
A numerical investigation was conducted using the volume of fluid method within OpenFOAM’s interFoam solver. This study examined the effects of Kapitza number, inclination angle and inlet disturbances on wave formation and flow dynamics, analyzing how these factors influence interfacial wave amplitude, wavelength and flow in the capillary region.

Findings
The results revealed that higher Kapitza numbers lead to the formation of stronger capillary waves. Flow separation was observed in the capillary wave region for materials with high Kapitza numbers. An improved Nosoko correlation model was developed, incorporating the inclination angle to more accurately predict the relationship between wave peaks and wavelengths in inclined cases.

Originality/value
This research investigates the impact of low Kapitza number on inclined falling film flow, and a correlation model was derived that provides a broader range for evaluating wave behavior in inclined conditions, offering extended references for the design of falling film heat exchangers.