bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic Signatures of Adaptation to Stress Reveal Shared Evolutionary Trends Between Tetrahymena utriculariae and Its Algal Endosymbiont, Micractinium tetrahymenae
Authors: Kelly Joseph B , Carlson David E , Reuter Manuela , Sommershof Annette , Adamec Lubomír , Becks Lutz 
Published: February 2025

Abstract
The evolution of intracellular endosymbiosis marks a major transition in the biology of the host and endosymbiont. Yet, how adaptation manifests in the genomes of the participants remains relatively understudied. We investigated this question by sequencing the genomes of Tetrahymena utriculariae, a commensal of the aquatic carnivorous bladderwort Utricularia reflexa, and its intracellular algae, Micractinium tetrahymenae. We discovered an expansion in copy number and negative selection in a TLD domain-bearing gene family in the genome of T. utriculariae, identifying it as a candidate for being an adaptive response to oxidative stress resulting from the physiology of its endosymbionts. We found that the M. tetrahymenae genome is larger than those of other Micractinium and Chlorella and contains a greater number of rapidly expanding orthogroups. These were enriched for Gene Ontology terms relevant to the regulation of intracellular signal transduction and cellular responses to stress and stimulus. Single-exon tandem repeats were overrepresented in paralogs belonging to these rapidly expanding orthogroups, which implicates long terminal repeat retrotransposons (LTRs) as potential agents of adaptation. We additionally performed a comparative transcriptomic analysis of M. tetrahymenae in a free-living state and in endosymbiosis with T. utriculariae and discovered that the genes that are differentially expressed were enriched for pathways that evidence shifts in energy generation and storage and in cellular protection strategies. Together, our results elucidate the axes along which the participants must adapt in this young endosymbiosis and highlight evolutionary responses to stress as a shared trend.
mRNA-LM: full-length integrated SLM for mRNA analysis
Authors: Li Sizhen , Noroozizadeh Shahriar , Moayedpour Saeed , Kogler-Anele Lorenzo , Xue Zexin , Zheng Dinghai , Montoya Fernando Ulloa , Agarwal Vikram , Bar-Joseph Ziv , Jager Sven 
Published: February 2025

Abstract
The success of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) messenger RNA (mRNA) vaccine has led to increased interest in the design and use of mRNA for vaccines and therapeutics. Still, selecting the most appropriate mRNA sequence for a protein remains a challenge. Several recent studies have shown that the specific mRNA sequence can have a significant impact on the translation efficiency, half-life, degradation rates, and other issues that play a major role in determining vaccine efficiency. To enable the selection of the most appropriate sequence, we developed mRNA-LM, an integrated small language model for modeling the entire mRNA sequence. mRNA-LM uses the contrastive language–image pretraining integration technology to combine three separate language models for the different mRNA segments. We trained mRNA-LM on millions of diverse mRNA sequences from several different species. The unsupervised model was able to learn meaningful biology related to evolution and host–pathogen interactions. Fine-tuning of mRNA-LM allowed us to use it in several mRNA property prediction tasks. As we show, using the full-length integrated model led to accurate predictions, improving on prior methods proposed for this task.
The membrane-targeting-sequence motif is required for exhibition of recessive resurrection in Escherichia coli RNase E
Authors: Basak Papri , Ekka Manjula , Pandiyan Apuratha , Tandon Smriti , Gowrishankar Jayaraman 
Published: February 2025

Abstract
The essential homotetrameric endoribonuclease RNase E of Escherichia coli participates in global RNA turnover as well as stable RNA maturation. The protomer’s N-terminal half (residues 1–529) bears the catalytic, allosteric, and tetramerization domains, including the active site residues D303 and D346. The C-terminal half (CTH, residues 530–1061) is dispensable for viability. We have previously described a phenomenon of recessive resurrection in RNase E that requires the CTH, wherein the wild-type homotetramer apparently displays nearly identical activity in vivo as a heterotetramer comprising three catalytically dead subunits (with D303A or D346A substitutions) and one wild-type subunit. Here, we show that recessive resurrection is exhibited even in dimeric RNase E with the CTH, and that it is largely dependent on the presence of a membrane-targeting-sequence motif (residues 565–582). A single F575E substitution also impaired recessive resurrection, whereas other CTH motifs (such as those for binding of RNA or of partner proteins) were dispensable. The phenomenon was independent of RNA 5′-monophosphate sensing by the enzyme. We propose that membrane-anchoring of RNase E renders it processive for endoribonucleolytic action, and that recessive resurrection and dominant negativity associated with mutant protomers are mutually exclusive manifestations of, respectively, processive and distributive catalytic mechanisms in a homo-oligomeric enzyme.
Structural and mechanistic insights into the activation of a short prokaryotic argonaute system from archaeon Sulfolobus islandicus
Authors: Dai Zhikang , Chen Yu , Guan Zeyuan , Chen Xueting , Tan Keyi , Yang Kaiyue , Yan Xuhui , Liu Yidong , Gong Zhou , Han Wenyuan , Zou Tingting 
Published: February 2025

Abstract
Prokaryotic Argonaute proteins (pAgos) defend the host against invading nucleic acids, including plasmids and viruses. Short pAgo systems confer immunity by inducing cell death upon detecting invading nucleic acids. However, the activation mechanism of the SiAgo system, comprising a short pAgo from the archaeon Sulfolobus islandicus and its associated proteins SiAga1 and SiAga2, remains largely unknown. Here, we determined the cryo-electron microscopy structures of the SiAgo–Aga1 apo complex and the RNA–DNA-bound SiAgo–Aga1 complex at resolutions of 2.7 and 3.0 Å, respectively. Our results revealed that a positively charged pocket is generated from the interaction between SiAgo and SiAga1, exhibiting an architecture similar to APAZ-pAgo of short pAgo systems and accommodating the nucleic acids. Further investigation elucidated the conserved mechanism of nucleic acid recognition by SiAgo–Aga1. Both the SiAgo–Aga1 interaction and nucleic acid recognition by the complex are essential for antiviral defense. Biochemical and structural analyses demonstrated that SiAgo–Aga1 undergoes extensive conformational changes upon binding to the RNA–DNA duplex, thereby licensing its interaction with the effector SiAga2 to trigger the immune response. Overall, our findings highlight the evolutionary conservation of Agos across phylogenetic clades and provide structural insights into the activation mechanism of the SiAgo system.
Screening for brain metastases in patients with advanced non-small cell lung cancer and an actionable genomic alteration: a structured literature review
Authors: Huijs Jarno W J , Bortolot Martina , Berghoff Anna S , Brastianos Priscilla K , Degens Juliette H R J , De Ruysscher Dirk K M , Compter Annette , Hendriks Lizza E L 
Published: February 2025

Abstract

Background
Brain metastases (BM) frequently occur in patients with non-small cell lung cancer (NSCLC) with actionable genomic alterations (AGA). Targeted therapies (TTs) improve outcomes, but differences in BM screening and eligibility criteria across trials make comparisons challenging. While stage IV NSCLC guidelines recommend BM screening, it is not mandatory, and imaging techniques vary.

Methods
Registrational and phase II/III trials of FDA/EMA-approved TTs for advanced NSCLC with AGA, published since 2012, were included. Main focus of the review was evaluation of baseline brain screening practices across trials. Information on BM follow-up, BM incidence, and BM-related outcomes was retrieved.

Results
Of 51 trials, 71% mandated baseline BM screening, and 27% mandated follow-up imaging for all patients. MRI was specified for BM assessment in 31% of the trials. BM incidence at baseline was high, up to 40% in the first-line setting. While most trials included patients with BM, eligibility criteria varied, and 43% of trials pre-specified BM-related outcomes; 56% of phase III trials used BM as a stratification factor.

Conclusion
This review highlights the increasing attention to BM screening in NSCLC TT trials. However, substantial heterogeneity remains in BM eligibility, screening, outcomes, and follow-up. Standardizing these aspects in future trials is essential.
Oseltamivir Reduces 30-Day Mortality in Older Adults With Influenza: A Pooled Analysis From the 2012–2019 Serious Outcomes Surveillance Network of the Canadian Immunization Research Network
Authors: Pott Henrique , Andrew Melissa K , Shaffelburg Zachary , Nichols Michaela K , Ye Lingyun , ElSherif May , Hatchette Todd F , LeBlanc Jason J , Ambrose Ardith , Boivin Guy , Bowie William , Johnstone Jennie , Katz Kevin , Lagacé-Wiens Phillipe , Loeb Mark , McCarthy Anne , McGeer Allison , Poirier Andre , Powis Jeff , Richardson David , Semret Makeda , Smith Stephanie , Smyth Daniel , Stiver Grant , Trottier Sylvie , Valiquette Louis , Webster Duncan , McNeil Shelly A 
Published: February 2025

Abstract

Background
Oseltamivir is recommended for the treatment of adults hospitalized with influenza, but adherence is often suboptimal. This may be due to doubts about the reliability of the evidence supporting its benefits, particularly when initiation is delayed. We aimed to assess the effectiveness of oseltamivir in reducing mortality in older adults hospitalized with influenza, with a focus on the timing of initiation.

Methods
The CIRN-SOS Network gathered data on severe respiratory illnesses across 5 Canadian provinces during the influenza seasons 2012–2019. Individuals aged ≥65 years with confirmed influenza and available antiviral prescription data were included. We compared the 30-day survival rates of hospitalized patients based on oseltamivir prescription status. Kaplan-Meier estimated survival probability and inverse probability of treatment (IPT)–weighted Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. The analyses considered the time to antiviral initiation (&gt;48 vs ≤48 hours).

Results
Among the 8135 influenza patients studied, 2126 did not receive antiviral treatment, whereas 6009 were treated with oseltamivir. A total of 395 patients were hospitalized for &gt;30 days. The overall mortality rate was 8.32 per 1000 person-days, with 53.9% of the deaths occurring within the first week. Oseltamivir recipients had a 18% lower risk of 30-day mortality (IPT-weighted HR, 0.82 [95% CI, .69–.98]). The benefit was significant for influenza A (IPT-weighted HR, 0.74 [95% CI, .61–.91]) but not for influenza B (IPT-weighted HR, 1.12 [95% CI, .81–1.56]). Oseltamivir remained effective even when initiated after 48 hours (IPT-weighted HR, 0.66 [95% CI, .49–.90]). Influenza vaccination did not mediate the effectiveness of oseltamivir in reducing mortality.

Conclusions
Oseltamivir significantly reduces mortality risk in older adults hospitalized with influenza, even when administered after 48 hours, independent of vaccination status.
Clinical Trials Registration. NCT01517191.
Can Pollution Markets Work in Developing Countries? Experimental Evidence from India
Authors: Greenstone Michael , Pande Rohini , Ryan Nicholas , Sudarshan Anant 
Published: February 2025

Abstract
Market-based environmental regulations are seldom used in low-income countries, where pollution is highest but state capacity is often low. We collaborated with the Gujarat Pollution Control Board (GPCB) to design and experimentally evaluate the world’s first particulate matter emissions market, which covered industrial plants in a large Indian city. There are three main findings. First, the market functioned well. Treatment plants, randomly assigned to the emissions market, traded permits to become significant net sellers or buyers. After trading, treatment plants held enough permits to cover their emissions 99% of the time, compared to just 66% compliance with standards under the command-and-control status quo. Second, treatment plants reduced pollution emissions, relative to control plants, by 20% to 30%. Third, the market reduced abatement costs by an estimated 11%, holding constant emissions. This cost-savings estimate is based on plant-specific marginal cost curves that we estimate from the universe of bids to buy and sell permits in the market. The combination of pollution reductions and low costs imply that the emissions market has mortality benefits that exceed its costs by at least twenty-five times.
Teledidactic peer-tutored musculoskeletal ultrasound training for medical students—the TELMUS study
Authors: Neubauer Ricarda , Recker Florian , Bauer Claus-Juergen , Petzinna Simon , Karakostas Pantelis , Behning Charlotte , Schäfer Valentin Sebastian 
Published: February 2025

Abstract

Objectives
Despite growing interest in musculoskeletal ultrasound (MSUS), training opportunities are often limited due to staff shortages and disbalances of expertise between rural and urban areas. Teledidactic approaches have the potential to expand access to training opportunities. This study aims to compare the effectiveness of teledidactic peer-tutored MSUS training to a conventional approach.

Methods
A teledidactic course was held by a student tutor following a validated MSUS curriculum. An on-campus MSUS training taught by physician lecturers served as a control. Students were randomly assigned to one of both study groups. Objective structured clinical examinations (OSCE) were conducted before and after the training to objectively measure the learning outcome of the participants. Handheld ultrasound devices (ButterflyIQ®) and iPads (Apple Inc., eighth generation) were provided to the students for the MSUS course.

Results
Thirty medical students participated in the study. Prior to the course, baseline OSCE scores were recorded as 13.03/63 (SD ± 4.20) for the on-campus cohort and 13.00/63 (SD ± 6.04) for the teledidactic group. In the post-training OSCE evaluation, the on-campus cohort attained an average score of 56.80/63 (SD ± 4.22), while the TELMUS group averagely achieved 58.53/63 points (SD ± 3.52). While all students’ skills increased over time, there was no significant difference between the two cohorts either before or after the course.

Conclusion
Peer-tutored, teledidactic MSUS training showed to be non-inferior to the conventional approach and is a promising approach to reduce local and global disparities in educational opportunities regarding MSUS.
Association between large vessel vasculitis and inflammatory bowel disease: a case-control study
Authors: Maillet François , Nguyen Yann , Espitia Olivier , Perard Laurent , Salvarani Carlo , Rivière Etienne , Ndiaye Dieynaba , Durel Cécile-Audrey , Guilpain Philippe , Mouthon Luc , Kernder Anna , Loricera Javier , Cohen Pascal , Melki Isabelle , de Moreuil Claire , Limal Nicolas , Mékinian Arsène , Costedoat-Chalumeau Nathalie , Morel Nathalie , Boutemy Jonathan , Raffray Loïc , Allain Jean-Sébastien , Devauchelle Valérie , Kone-Paut Isabelle , Fabre Marc , Durel Marie , Dossier Antoine , Abad Sébastien , Visentini Marcella , Bigot Adrien , Yildiz Halil , Fain Olivier , Samson Maxime , Gondran Guillaume , Abitbol Vered , Terrier Benjamin 
Published: February 2025

Abstract

Objectives
To describe the characteristics and outcome of patients with the association of large vessel vasculitis (LVV, Takayasu arteritis [TA] or GCA) and IBD.

Methods
An observational, multicentre, retrospective case-control study. Cases were LVV-IBD patients from European countries, whereas controls had isolated LVV (iLVV).

Results
A total of 39 TA-IBD and 12 GCA-IBD cases were enrolled, compared with 52 isolated GCA (iGCA) and 93 isolated TA (iTA) controls. LVV occurred after IBD in 56% in TA-IBD and 75% in GCA-IBD, with a median interval of 1 year (interquartile range [IQR] 1–7) in TA-IBD and 8.6 years (IQR 1–17.7) in GCA-IBD. Crohn’s disease was more common in TA-IBD (67%), whereas ulcerative colitis was more common in GCA-IBD (58%). Compared with iTA, TA-IBD were significantly younger at diagnosis of TA (median age 27 vs 37 years, P &lt; 0.001) and had more upper limb claudication (36% vs 12%, P = 0.006). GCA-IBD patients had more frequent arterial thickening or stenosis than controls (75% vs 30%, respectively, P = 0.044) and tended to more frequently involve gastrointestinal arteries (20% vs 0%, respectively, P = 0.06). LVV occurred in IBD patients despite treatment with glucocorticoids (36%), azathioprine (25%) or TNF-alpha blockers (29%). The presence of the IBD was not associated with a higher LVV relapse rate in multivariate analysis (adjusted hazard ratio [aHR] 0.62 [0.13–2.83] for GCA and aHR 0.92 [0.44–1.89] for TA).

Conclusion
This study identifies specific clinical and imaging characteristics of LVV-IBD patients, in particular a more severe vascular presentation of GCA-IBD patients compared with iGCA patients.
Generational variations in wellbeing: suicide rates, cohort characteristics, and national socio-political context over seven decades
Authors: Stockard Jean 
Published: February 2025

Abstract
Over recent decades, the relative wellbeing of younger birth cohorts declined in many western countries, indicating growing generational inequality. Building on Durkheimian theory, this paper examines explanations for these changes, hypothesizing that differences in cohort wellbeing are related to variations in social integration associated with birth cohorts and national socio-political contexts. Age–period-specific suicide rates of men and women from 1950 to 2020 in 19 highly developed western nations, including 26 birth cohorts, born from 1875 to 2004, are examined using estimable function analysis and age–period–cohort characteristic (APCC) models. Cohort variations in wellbeing are significantly greater in English-speaking nations, which have traditionally provided less institutionalized support and social integration than continental European nations. Age-specific suicide rates are larger for cohorts with childhood demographic characteristics associated with less social integration (relative cohort size and family structure). Major historical events associated with social integration in formative years of late adolescence and young adulthood also influence cohort wellbeing, with higher age-specific rates for cohorts experiencing the Great Depression of the 1930s and health pandemics of the early 20th and 21st centuries and lower rates for those experiencing periods of war and national conflict. However, the magnitude of these associations is strongly influenced by socio-political context. Negative effects of cohort characteristics are muted and positive effects are enhanced in the continental nations. In addition, patterns of associations vary by age and gender. Results remain with strong controls for the pace of change, additional measures of national context, and sensitivity analyses.
New branch on the tree of life of Gastrotricha: establishment of a new genus for limno-terrestrial species
Authors: Minowa Axell Kou , Kieneke Alexander , Campos Ariane , Balsamo Maria , Plewka Michael , Guidi Loretta , Araújo Thiago Quintão , Garraffoni André RinaldoSenna 
Published: February 2025

Abstract
Gastrotricha encompass a diversity of free-living micrometazoans typically associated with aquatic or semi-aquatic environments. The discovery of a gastrotrich species in limno-terrestrial habitats challenges existing taxonomic classifications and expands our understanding of their ecological diversity. This study describes Dendroichthydium ibyrapora gen. et sp. nov., a new gastrotrich from epiphytic mosses found in Atlantic rainforest within Serra do Japi biological reserve, and establishes its taxonomic status through morphological and molecular analyses. Morphological characterization was conducted using light microscopy, scanning electron microscopy, and confocal laser scanning microscopy, revealing that D. ibyrapora exhibits distinctive adaptations suited to limno-terrestrial environments, including unique cuticular adaptations and rearrangement of locomotory cilia. Molecular phylogenetics, using 18S and 28S ribosomal DNA sequences, supports the recognition of Dendroichthydium as a new genus, distinctly separated from known genera within Paucitubulatina. Furthermore, we propose reclassifying Chaetonotus (Chaetonotus) silvaticus to Dendroichthydium silvaticus comb. nov. based on shared morphological traits. The establishment of the genus Dendroichthydium reflects the ongoing need to re-evaluate gastrotrich diversity and taxonomy, highlighting the role of underexplored limno-terrestrial habitats in hosting unique life forms. This study underscores the importance of integrating morphology and genetics to improve our understanding of phylogenetics and the evolutionary dynamics of Gastrotricha.
Quantitative Analysis of Relationship between Paraspinal Muscle Degeneration and Degree of Degenerative Lumbar Spondylolisthesis
Authors: Da Weiwei , Jian Qiang , Evan Joiner , Chan Andrew K. , McCormick Paul C. , Mandigo Christopher E. , Neira Justin Anthony , Angevine Peter D. , Li Xiaofeng , Chou Dean 
Published: February 2025

Study Design.
Clinical retrospective study.

Objective.
The authors aim to analyze the relationship between paraspinal muscle degeneration and degree of L4-5 Degenerative lumbar spondylolisthesis (DLS).

Summary of Background Data.
While paraspinal muscle degeneration is thought to contribute to spondylolisthesis severity, this relationship has yet to be fully characterized.

Methods.
A retrospective analysis was performed of all neurosurgical patients admitted to the Columbia Neurosurgery Spine Division for treatment of L4-5 DLS between January 2018 and March 2024. Preoperative lumbopelvic parameters and slip percentage (SP) were calculated from standing radiographs; paraspinal muscle volume (MV), fatty volume (FV) and fatty infiltration (FI) of posterior paraspinal muscle were derived from MRI images using 3D Slicer (Earth, TX). Correlation and multiple linear regression analyses were used to assess the relationship between SP and paraspinal MV, FV, FI, and spinopelvic parameters.

Results.
221 patients with average SP of 23.74±0.09% were included. The female patients had higher SP, lumbar lordosis (LL), pelvic incidence (PI) and lower IVA than the male patients. However, paraspinal MV was lower and FI was higher in the Meyerding Grade II and female groups compared to the Grade I and male groups (P<0.01). There was a positive correlation between SP and metrics of fat replacement (P<0.01) and a negative correlation between SP and metrics of paraspinal muscles volume (P<0.01) at the L4-5 level. A stepwise multivariate regression ultimately included MFI, IVA, and LL and accounted for 15.2% of the variance in SP.

Conclusion.
In this single center retrospective study, greater degree of spondylolisthesis was modestly associated with lower MV and increased FI of the lumbar paraspinal muscles, suggesting that paraspinal muscle degeneration may be one of several important factors in the development of spondylolisthesis.