bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of soft tissue volume on estimates of skeletal pneumaticity: implications for fossil archosaurs
Authors: Burton Maria Grace , Benito Juan , Mellor Kirsty , Smith Emily , Martin-Silverstone Elizabeth , O'Connor Patrick , Field Daniel J. 
Published: February 2025

Air space proportion (ASP), the volume fraction in bone that is occupied by air, is frequently applied as a measure for quantifying the extent of skeletal pneumaticity in extant and fossil archosaurs. Nonetheless, ASP estimates rely on a key assumption: that the soft tissue mass within pneumatic bones is negligible, an assumption that has rarely been explicitly acknowledged or tested. Here, we provide the first comparisons between estimated air space proportion (where the internal cavity of a pneumatic bone is assumed to be completely air-filled) and true air space proportion (ASPt, where soft tissues present within the internal cavities of fresh specimens are considered). Using birds as model archosaurs exhibiting postcranial skeletal pneumaticity, we find that estimates of ASPt are significantly lower than estimates of ASP, raising an important consideration that should be acknowledged in investigations of the evolution of skeletal pneumaticity and bulk skeletal density in extinct archosaurs, as well as in volume-based estimates of archosaur body mass. We advocate for the difference between ASP and ASPt to be explicitly acknowledged in studies seeking to quantify the extent of skeletal pneumaticity in extinct archosaurs, to avoid the risk of systematically overestimating the volume fraction of pneumatic bones composed of air.
This article is part of the theme issue ‘The biology of the avian respiratory system’.
A synchrotron X-ray CT-based 3D atlas of the songbird syrinx with single muscle fibre resolution implies fine motor control of syringeal vocal folds
Authors: Adam Iris , Zai Anja T. , Stepien Anna E. , Yamahachi Homare , Schlepütz Christian M. , Hahnloser Richard H. R. , Elemans Coen P. H. 
Published: February 2025

Avian vocalizations are produced by precisely coordinated motion of the respiratory, syringeal and upper vocal tract systems. Syringeal muscles are controlled with unprecedented resolution, down to independent control of individual muscle fibres. However, we currently lack an anatomical description of syrinx muscles at single fibre resolution. Here, we combined a micron-resolution synchrotron X-ray CT scan of the zebra finch syrinx with micro-dissections of independent specimens to resolve syrinx muscle morphology at individual muscle fibre level. We define two new, previously unknown muscles and update the fibre trajectories and attachment sites of three previously described muscles. Our new insights into the fine anatomy of syrinx muscles show that not one, but both avian vocal folds can be directly controlled by contracting syrinx muscles. Thus, our data reveal novel anatomical complexity with consequences for the biomechanics and motor control of sound production.
This article is part of the theme issue 'The biology of the avian respiratory system'.
Respiratory contributions to birdsong—evolutionary considerations and open questions
Authors: Goller Franz 
Published: February 2025

Respiration plays a central role in avian vocal behaviour by providing the airstream that induces vibration of vocal folds. In this role, respiratory movements dictate the coarse temporal pattern of song, while simultaneously fulfilling its vital functions. Whereas these aspects have been investigated in oscines, little information exists in other taxa. Broad taxonomic information is, however, necessary for addressing questions regarding evolutionary specializations of the respiratory system. Acoustic recordings of unstudied taxa suggest that rapid action by respiratory muscles is a basal trait within birds. In addition to controlling the timing of vocalization, respiratory activity also influences acoustic features such as sound amplitude and frequency. The latter is more strongly influenced by respiratory driving pressure in non-vocal learners. Singing, as a highly dynamic respiratory activity presents an opportunity for studying detailed ventilation patterns and thus could give insight into the basic control of airflow in the avian lung–air sac system. Although we have learned many details of how respiratory control is tied into cortical song control, many open questions remain. Control of respiratory pacemaker circuitry by upstream vocal control centres, respiratory input in initiation of vocalization and the use of online feedback from the respiratory system are all incompletely understood.
This article is part of the theme issue ‘The biology of the avian respiratory system’.
Colonic inflammation modulates the intestinal circadian landscape
Authors: Butler Thomas D , Downton Polly , Dickson Suzanna H , Luengas-Martinez Andrea , Simpkins Devin A , Khoo Isabel , Veal Sarah , West Alexander C , Adamson Antony D , Bechtold David A , McLaughlin John T , Gibbs Julie E 
Published: February 2025

SummaryInflammatory bowel disease (IBD) is a chronic inflammatory condition that carries significant morbidity. The circadian (24h) clock regulates many aspects of immunity and circadian disruption is implicated in inflammatory disease. We examined the impact of acute dextran sulphate sodium-induced colitis on the intestinal circadian landscape and investigated consequences of intestinal epithelial cell (IEC) clock disruption on immune function in health and under inflammatory stress. Within the inflamed colon, we observed attenuated IEC clock function. Furthermore,de novooscillations in numbers of colonic regulatory T cells emerged, associated with diurnal variation in proliferation and activation markers. IEC-specific deletion of core clock geneBmal1drove alterations in the rhythmic colonic transcriptome (impacting key immune pathways) and marked damping of microbiota rhythmicity. IEC-specificBmal1deletion did not impact colitis severity. These results highlight the impact of colonic inflammation on circadian processes and suggest that circadian logic could be applied in IBD treatment.
Quantitative systems pharmacology modeling of pyrrolobenzodiazepine antibody-drug conjugates targeting BCMA
Authors: Lam Inez , Dai David , Arends Rosalinda H. , Reddy Venkatesh Pilla , Ball Kathryn , Gabhann Feilim Mac 
Published: February 2025

AbstractAntibody-drug conjugates (ADCs) are novel therapeutics combining two molecules linked together: an antibody that provides targeting to specific cells, and a cytotoxic drug (warhead) that can deconjugate from the antibody and kill those cells. The warhead by itself would be too nonspecific and toxic; the antibody by itself would be insufficiently effective at killing the cells. As more and more ADCs enter the drug development pipeline, understanding the mechanistic reasons behind efficacy and toxicity is critical to evaluating both successful and failed trials. Here, we have developed a mechanistic computational model of ADCs, and specifically parameterize it using data for MEDI2228, an anti-BCMA antibody conjugated to pyrrolobenzodiazepine (PBD) warheads. We build the model to track not only the concentrations of ADC and its released warhead drug inside and outside the cell, but also to track the recent history of the warhead, so that we can distinguish between pathways for on-target and bystander (nontargeted) cell killing. We show that this effect is predicted to be small underin vitroconditions due to dilution in large volumes of media, but likely to form a significant part of both targeted and nontargeted cell killingin vivo, where the extracellular volume has less of a dilution effect. We also explore the impact of key design parameters of ADCs, including drug to antibody ratio (DAR), warhead potency, and lipophilicity; this analysis demonstrates the balance needed between killing of targeted and nontargeted cells. Using this quantitative systems pharmacology model, we can generate insights for optimization of ADC design and determine which factors are most critical to efficacy and toxicity, leading to more informed and rational development of cancer therapies.
Differential Avian Responses to Coffee Farming Lead to Community Homogenization in a Working Landscape in Jardín, Colombia
Authors: Cediel Fernando , Ruíz-Gutiérrez Viviana , Echeverri Alejandra , Parra Juan. Luis 
Published: February 2025

AbstractIn Colombia, coffee production has an ingrained cultural and economic importance. Coffee is cultivated in biodiverse areas using a variety of practices ranging from sun-exposed monocultures to mixed and shaded plantations. Management practices on this working landscape alter the composition of bird communities. We hypothesize that coffee agroecosystems homogenize bird communities by favoring the occupancy of non-forest dependent bird species and deterring forest dependent birds. We evaluate the effects of coffee plantations and associated metrics of vegetation structure on a subset of bird species in an agroforestry landscape in the Western Andes in Colombia and evaluate the hypothesis of community homogenization. We collected data in two consecutive years in 153 sites in coffee plantations and other habitats in Jardín, Colombia. In order to evaluate birds’ response to changes in the working landscape we made single-season occupancy models and used five covariates: coffee (binary covariate), foliage height diversity (FHD) and canopy height (CH) as proxies for coffee management practices, human footprint (LHFI), and elevation. Finally, we used generalized dissimilarity models (GDM) with the same covariates and geographical distance to evaluate the homogenization hypothesis among coffee sites. We identified 193 species (six endangered and five endemics) and modeled occupancy of 74 species. Coffee plantations significantly decreased the occupancy of 14 species while 13 were favored. In general, non-forest dependent species preferred lower FHD and lower CH values, and occurred at lower elevations with high LHFI. On the contrary, forest dependent species preferred higher FHD and CH, and were found at higher elevations. The GDM with best fit supported the hypothesis that coffee sites tend to be more similar than no-coffee sites, and that elevation and FHD explained most of the variation in dissimilarity. The working landscape in Jardín holds an important community of birds but coffee plantations are driving its homogenization. We anticipate that non-forest dependent birds will continue to colonize working landscapes, unless structural vegetation changes are promoted. Increasing FHD and CH is a potential strategy to improve forest dependent bird occupancy and reduce homogenization in Jardín.
Changes in the health-related ecosystem services and disservices provided by urban trees over multiple decades in a small city
Authors: Kwong Russell , Victor Thomas E. , Dijstelbloem Noa , Dong Zhou Y. , Robillard Ava M. , Gagnon Willa A. , Simon Christina S. , Radhakrishnan Camille I. , Peralta Keily A. , Youngstrom Elan C. , Terjesen Emma C. , Tsignadze Maia , Okuyama Daphne , Ma Moheng , Katz Daniel S.W. 
Published: February 2025

AbstractThe effects of urban trees on public health should change over decades due to shifts in tree composition and abundance, environmental conditions, human demography, and disease incidence. However, there are few case studies documenting changes in the health-related ecosystem services and disservices provided by trees over time. Here we use seven tree censuses to quantify changes in the effects of city-owned trees on air pollution, allergenic pollen, hydrology, and heat due to shifts in tree abundance and environmental conditions in Ithaca, New York, a small city in the Northeastern United States. We also review how shifts in disease incidence have affected these trees’ health consequences. From 2005 to 2021, trees removed 20% more ozone and 268% more PM2.5; they also removed substantially more runoff and had higher cooling capacity. In contrast, the amount of certain air pollutants removed by trees dropped from 2005 to 2021 for sulfur dioxide (361 kg/yr to 8 kg/yr), carbon monoxide (65 kg/yr to 32 kg/yr), and nitrogen dioxide (380 kg/yr to 298 kg/yr) as their ambient concentrations dropped. Pollen production by street trees from 1947 to 2021 initially dropped due to Dutch elm disease but has quadrupled since the 1980s due to increases in several high-pollen producing genera. Overall, this study illustrates how the public health effects of trees vary over decades due to changes in tree composition and abundance, environmental conditions, and changes in disease incidence and human demography, emphasizing the importance of incorporating long-term perspectives into contemporary tree management decisions.Highlights● Urban trees health-related ecosystem services changed over decades in a case study● The removal of SO2, NO2, and CO by urban trees is diminishing due to cleaner air● Shifts in tree composition have had large effects on allergenic pollen production● Changes in human disease incidence over decades mediate trees health effects
STAT3 Sustains Tumorigenicity Following Mutant KRAS Ablation
Authors: D’Amico Stephen , Kirillov Varvara , Liu Jingxuan , Qiu Zhijuan , Lei Xinyuan , Qin Hong , Sheridan Brian S. , Reich Nancy C. 
Published: February 2025

AbstractOncogenic KRAS mutations underlie some of the deadliest human cancers. Genetic or pharmacological inactivation of mutant KRAS is not sufficient for long-term control of advanced tumors. Using a conceptual framework of pancreatic ductal adenocarcinoma, we find that CRISPR-mediated ablation of mutant KRAS can terminate tumor progression contingent on the concomitant inactivation of STAT3. STAT3 inactivation is needed to ensure that KRAS-ablated tumor cells lose their malignant identity. Mechanistically, the combined loss of mutant KRAS and STAT3 disrupts a core transcriptional program of cancer cells critical to oncogenic competence. This in turn impairs tumor growth in mice and enhances immune rejection, leading to tumor clearance. We propose that the STAT3 transcriptional program operating in cancer cells enforces their malignant identity, rather than providing classical features of transformation, and shapes cancer persistence following KRAS inactivation. Our findings establish STAT3 as a critical enforcer of oncogenic identity in KRAS-ablated tumors, revealing a key vulnerability that could be exploited for combination therapies.SignificanceThe limited clinical success of KRAS inhibitors points to the need to identify means by which tumor cells maintain stemness and immune evasion. We make an unprecedented finding that the STAT3 transcription factor can sustain tumorigenicity of pancreatic cancer cells following depletion of the KRAS oncogenic driver. The results have important implications for successful therapeutic intervention.
Improving allometric models to estimate the proboscis length of tropical bees
Authors: Frühholz Kilian , Kuba Kenneth , Pitz Maximilian , Windl Julia , Keller Alexander , Brehm Gunnar , Rasmussen Claus , Leonhardt Sara Diana , Mendes Diniz Ugo 
Published: February 2025

ABSTRACTThe proboscis length of bees is a key morphological trait shaping communities, pollination networks, and likely their responses to habitat loss. Despite its importance, it is rarely considered in ecological studies because of logistic limitations in obtaining accurate measurements across many different species. In two previous studies, the proboscis length of temperate bee species was estimated based on body size and bee family. However, bee taxa partially occurring in the tropics might deviate from this allometric relationship due to different functional constraints. Thus, we tested if equations developed for temperate bees can accurately predict the proboscis length in Meliponini, Euglossini (both Apidae), and Augochlorini (Halictidae), three ubiquitous and highly important tribes of tropical bees. We measured the intertegular distance (as a proxy of body size measurement) and the proboscis length of 892 specimens of 105 tropical species. We used these measurements to evaluate the previous model and found that its estimations lacked accuracy when applied to tropical bees, particularly to Meliponini and Euglossini. We developed new allometric equations estimating the proboscis length based on the intertegular distance, using (sub-) genera as an additional predictive variable to refine the estimations. We tested our approach by creating a test model for Meliponini, trained with only 80 % of the data, and evaluated this model using the remaining 20 %, resulting in a high accuracy of estimates. Our results shed additional light on the nature of the proboscis length-body size allometric relationship in tropical bees and provide a tool for future studies on the functional ecology of bees and their interactions with plants.
Advancing Heterospecific Sterile Insect Technique AgainstDrosophila suzukii:selection of the optimal irradiation dose forD. melanogastermales
Authors: Cerasti Flavia , Mastrantonio Valentina , Cemmi Alessia , Di Sarcina Ilaria , Cristofaro Massimo , Porretta Daniele 
Published: February 2025

AbstractThe spotted-wing drosophila (Drosophila suzukii), a highly invasive agricultural pest, poses significant challenges to fruit production worldwide. Traditional chemical control methods are costly and raise concerns about resistance and environmental sustainability. The Heterospecific Sterile Insect Technique (h-SIT) has emerged as a promising alternative, using sterile heterospecific males (Drosophila melanogaster) to suppressD. suzukiipopulations through reproductive interference. However, optimizing irradiation doses is critical to balancing male sterility, maintaining biological quality and mating performances. This study aimed to determine the optimal irradiation dose forD. melanogastermales by assessing their sterility, longevity, and courtship behavior following exposure to gamma-ray doses ranging from 80 to 180 Gy. Results showed a significant reduction in fertility across all irradiation doses, with near-complete sterility at 180 Gy. However, longevity decreased with increasing doses, with males irradiated at 160–180 Gy showing a lifespan reduction of up to 50 days compared to controls. Behavioral trials revealed that irradiatedD. melanogastermales retained their courtship ability towardD. suzukiifemales, although males exposed to 160 Gy exhibited reduced courtship activity. These findings highlight that, among the tested doses, 80 Gy emerged as the most effective, preserving male longevity and mating performance while significantly reducing fertility. While 180 Gy achieved the highest sterility, the potential lifespan and courtship behavior trade-offs warrant further evaluation. Future studies should evaluate field performance to refine the balance between sterility, longevity, and mating performances for effectiveD. suzukiipopulation suppression.
Identification ofde novovariants from parent-proband duos via long-read sequencing
Authors: Boukas Leandros , Délot Emmanuèle C. , Pitsava Georgia , Lambert Christine , Fanslow Cairbre , Baybayan Primo , Belhadj Sami , Losic Bojan , Harting John , Bluske Krista , LoTempio Jonathan , Al-Kouatly Huda , Karam Rachid , Rowell William , Xiao Changrui , Vilain Eric , Berger Seth I. 
Published: February 2025

AbstractWhilede novovariants cause many Mendelian disorders, their detection currently requires sequencing of the proband and both biological parents. This is not feasible when only one parent is available, a limitation for millions of families. We developedduoNovo, which identifiesde novovariants from single parent-proband duos using long-read sequencing followed by haplotype reconstruction and detection of identical-by-descent haplotype blocks. We sequenced 40 trios and appliedduoNovoto each of the 80 duos constructed by masking one parent, classifying over 20 million variants. We evaluatedduoNovo’s performance against classifications obtained using the full trios (which included over 1,900de novovariants), demonstrating very high precision and low error rate, and perfect accuracy among variants absent from gnomAD.duoNovois freely available to the community as an R package, and may represent an example where long-read sequencing provides clear diagnostic benefit over short-read sequencing.
Epidemic-Ready Primary Health Care and the Application of the 717 Metrics: A Case Study on a Measles Outbreak in Sierra Leone, January-March 2024
Authors: Eleeza Oliver , Barrera-Cancedda Amy Elizabeth , Mutebi Ronald R. , Njenga Amon , Vandi Mohamed A. , Mearns Stacey , Yakubu AbdulRaheem , Toure Mame , Michaels-Strasser Susan 
Published: February 2025

AbstractThe COVID-19 pandemic exposed vulnerabilities in health systems’ abilities to detect, report, and respond to threats. Inadequate preparedness led to healthcare worker infections (HCW), essential service disruptions, and impacts on communities. Primary health care (PHC) is often overlooked in health security initiatives. Epidemic Ready Primary Health Care (ERPHC) is an initiative that strengthens PHC facilities to prevent, detect and respond to outbreaks, while maintaining essential services.ICAP at Columbia University, the Ministry of Health of Sierra Leone, and Resolve to Save Lives is implementing a multi-year ERPHC project in Sierra Leone. A retrospective data review of 52 confirmed measles cases across four PHC facilities from January – March 2024 was conducted. Data is presented using an adapted 7-1-7 quality improvement approach for detection and notification to evaluate the key tenants of ERPHC: speed, safety, surge.Out of 52 confirmed cases, 98% and 100% met the first “7” and “1” for detection and notification. Immediate case management and safety actions were completed for all 52 cases (100%). Zero facilities were able to implement two readiness parameters for surge: sufficient supplies and referral pathways. Key bottlenecks included late presentation to health facilities, delayed notification via the electronic case-based surveillance system, inadequate PPE, and no updated referral pathways.These results underscore the need to scale and implement ERPHC, using adapted 7-1-7 metrics, in PHC facilities. HCW safety, increased community engagement, national supply chain mechanism strengthening, and established patient referral pathways need to be the foci of further health security investment in Sierra Leone.