bluuebunny/crossref_metadata_2025_split huggingface dataset:
How can you manage an indomethacin-responsive headache in someone who cannot take indomethacin?
Authors: Osiowski Aleksander , Stolarz Kacper , Taterra Dominik 
Published: February 2025

Purpose of review
Paroxysmal hemicrania and hemicrania continua are rare primary headache disorders which are distinguished by an absolute response to indomethacin. As a matter of importance, no guidelines have been proposed for alternative therapeutic options in case of indomethacin intolerance. The purpose of this review is to provide an update on the current findings, especially focusing on the past 18 months, in the treatment of both paroxysmal hemicrania and hemicrania continua and to provide proposed management recommendations based on summarized evidence.

Recent findings
Apart from well recognized gastrolesive effects of indomethacin, a substantial number of patients may suffer from neuropsychiatric adverse reactions. Recent studies demonstrated that melatonin, which has been known for its effectiveness for hemicrania continua, is also useful for paroxysmal hemicrania. Promising nonpharmacological treatment option, which is noninvasive vagus nerve stimulation, has been shown to be beneficial for both indomethacin-responsive headache disorders allowing the reduction of indomethacin dosage. Although the data on substitutive medication choice for indomethacin are currently scarce, the most consistent results have been repeatedly achieved with acemethacin, selective COX-2 inhibitors, and anticonvulsants. However, considering the crucial role of pathophysiology, research investigating the efficacy of drugs targeting the trigemino-vascular system activation, as well as controlled trials assessing the efficacy involving the aforementioned therapeutic options are still vague.

Summary
In spite of numerous reports suggesting reliable alternatives to indomethacin, the consensus on pharmacological therapy guidelines for indomethacin-responsive headache disorders has not yet been reached. Further research and agreement from the experts’ standpoint are needed for an establishment of reliable treatment recommendations.
Scaling in Biological Systems: A Molecular-Ensemble Duality
Authors: Ellsworth Julie A. , Baker Josh E. 
Published: February 2025

AbstractWe have observed in muscle the statistical mechanics of irreversible chemical thermodynamics, revealing the solution to multiple seemingly unrelated paradoxes in science. Analogous to Boltzmann’s H theorem, we observe that chemical reaction energy landscapes (ensemble entropic wells) irreversibly evolve over time, pulling reversible chemical reactions forward in time. Loschmidt’s paradox assumes that reversible molecular reactions scale up to irreversible changes in an ensemble, and many mathematical constructs have been created to satisfy this assumption (Boltzmann’s H-function, chemical activities, the kinetics theory of gases, molecular mechanisms of biological function, etc.). However, using a simple statistical argument, here we show that the irreversible time evolutions of molecular and ensemble states are described by two different non-scalable entropies, creating a molecular-ensemble duality in any system on any scale. This inverts common understandings of mechanistic agency and the arrow of time and disproves all molecular mechanisms of irreversible ensemble processes.Significance StatemenThis statistical analysis inverts common understandings of mechanistic agency, entropy, and the arrow of time; it solves several paradoxes in physics; and it disproves molecular mechanisms of irreversible processes.
Pupillometry reveals autonomic adjustments during diving reflex in face immersion apnea
Authors: Rizzuto V. , Montanari R. , Mesin L. , Bortolozzo-Gleich M. H. , Laurino M. , Bonneh Y. , Yellin D. , Laganovska G. , Vanags J. , Gemignani A 
Published: February 2025

AbstractThe human diving reflex (DR), an innate defensive reflex triggered during periods of apnea, concurrently activates both the sympathetic and parasympathetic branches of the autonomic nervous system to regulate physiology against challenging demands. Despite pupil dilation and constriction being antagonistically controlled by the two autonomic branches, the effect of the diving reflex on pupil diameter fluctuations is still unknown. Thus, we compared participants’ pupil diameter fluctuations while breathing or performing apnea either with (Wet) or without (Dry) face immersion in cold water. We found that pupil diameter fluctuations in both apneic conditions are associated with lower power in the low-frequency band (< 0.25 Hz) while in the Wet condition, a reallocation of power towards higher frequencies (> 0.25 Hz) occurs, together with an increased entropy, contrary to the remaining conditions. This indicates a shift in autonomic balance and an increased complexity of pupil fluctuations during the diving reflex. Our findings present pupil dynamics as a valuable entry point to the exploration of autonomic adjustments for this reflex.
Using artificial intelligence to optimize ecological restoration for climate and biodiversity
Authors: Silvestro Daniele , Goria Stefano , Groom Ben , Sterner Thomas , Antonelli Alexandre 
Published: February 2025

AbstractThe restoration of degraded ecosystems can provide important contributions to help mitigate climate change and bend the curve of biodiversity loss. Depending on the primary objective – such as maximizing carbon storage, protecting threatened species, or reducing overall costs – different spatial priorities have been identified at global and regional levels. Funding mechanisms to support such work comprise public sources, philanthropy, and the private sector, including the sales of carbon and biodiversity credits. However, effectively exploring tradeoffs between restoration objectives and estimating the price of biodiversity and carbon credits to design financially viable projects remain challenging. Here we harness the power of artificial intelligence in our software CAPTAIN, which we further develop to identify spatial priorities for ecological restoration that maximize multiple objectives at once and which allows a robust evaluation of biodiversity and climate outcomes. We find through a series of realistic simulations that even low to moderate consideration of biodiversity in restoration projects leads to the selection of restored areas that substantially improve the conservation of threatened species, while resulting in a relatively small decrease in total carbon captured. We propose a data-driven valuation of biodiversity credits in relation to carbon credits enabling the design of a blended financial model that could support restoration efforts even in areas previously excluded for economic reasons. This study shows how the use of a robust methodological framework can lead to significant improvements in outcomes for climate and nature, while minimizing costs.
Positive associations between growth and thermal tolerance in the reef-building coralMontipora capitata
Authors: Walker Nia S. , Luke Hayley , Miller Spencer , Kealoha Darienne , Caruso Carlo , Johnston Erika C. , Mujica Elena M. , Hancock Joshua R. , Drury Crawford 
Published: February 2025

AbstractRelationships between ecologically important traits are increasingly important for the future of coral reefs, which are declining globally due to a variety of stressors. Corals that resist and recover from bleaching will be selected under future climates, which may negatively or positively impact a range of associated traits important for the structure and function of contemporary and future reefs. Using standardized assays, we investigated growth under ambient conditions, bleaching resistance and recovery after bleaching in a model population of 60Montipora capitatacolonies harboring diverse symbiont communities. We found significantly higher trait variance withinDurusdinium-dominated colonies, highlighting the interaction of host and symbiont. We also show that symbiont community impacted thermal tolerance and survivorship during the thermal stress assay, but not recovery or growth. There was also a positive relationship between thermal tolerance and change in surface area and thermal tolerance and recovery from equivalent amounts of stress. These results demonstrate limited tradeoffs to thermal tolerance and suggest that bleaching tolerant corals in this model system are suited to recover from stress and maintain high growth rates under ambient conditions, providing insight into the adaptive capacity of thermally tolerant corals in the Anthropocene.
In Silico Discovery of Small Molecule Modulators Targeting Ebola Virus VP 35 and VP 40 protein
Authors: Liu Yang , Zhu Chen , chen Mei , Guo Daoyu 
Published: February 2025

AbstractEbola virus (EBoV) proteins VP35 and VP40 are acknowledged as significant pharmacological targets for disrupting viral replication, virion assembly, and the budding process from host cells. We employed molecular docking based throughput virtual screening (HTVS), standard precision (SP), and extra precision (XP) docking to discover candidate compounds. Subsequently, molecular dynamics simulations, and ADMET analyses to identify potential small molecular compounds that could inhibit the Ebola virus. Among 210,590 compounds from the SPECS database, we found the compounds AO-022/43452438, AN-465/43369333, and AN-465/43369198 were optimal candidates for the EBOV-VP35 protein, while AN-465/43369160, AN-465/4341136, and AN-465/43369952 also emerged as optimal compounds for the EBOV-VP40 protein. Furthermore, we employed the energy decomposition technique, MM-GB/SA, to identify the top ten amino acids that significantly contribute to the binding interactions. ADMET result implicated that the six compounds have potential druggability, but special attention should be given to AN-465/43369333 due to potential cardiac toxicity. In conclusions, the six compounds and their key interacting amino acid sites identified in this study may serve as a valuable platform for the future development of novel therapeutics targeting the Ebola virus.
A simple method to classify behaviours of aerial predators using tri-axial high-frequency accelerometers
Authors: García-Silveira D. , Benhamou S. , Lopez-Ricaurte L. , Hernández-Pliego J. , Duriez O. , Bustamante J. 
Published: February 2025

AbstractBackgroundRemote monitoring of animals has opened new avenues in behavioural research. The advent of animal-borne accelerometers makes it possible to derive the body posture and activity level, and thereby to identify fine-scale behaviours with no need for direct observation. This is particularly useful for species that forage or hunt beyond human sight in sometimes hard-to-access or remote areas. However, the complexity of numerous methods developed for this purpose may discourage researchers from effectively using acceleration data.ResultsWe present a simple and straightforward approach to identify and classify behaviours based on tri-axial high-frequency (25 Hz) acceleration data. This method relies on constructing a decision tree to assign predefined behaviours to time series of acceleration data using four accelerometer-based parameters that are biologically relevant and easy to interpret. Initially, we manually labelled sequences of acceleration data with the behaviours using paired high-frequency (i.e. 1 Hz) GPS tracking data as ground-truth. Then, threshold values of the acceleration-based parameters were objectively determined based on receiver operating characteristic (ROC) analysis. Finally, we built the decision tree to automatically classify the behaviours of the whole dataset and tested further improvements. As a case study, we used two falcon species (lesser kestrelFalco naumanniand common kestrelF. tinnunculus). Our simple method achieved an overall accuracy of 97.6% in classifying the following behaviours: perching (99.9%), soaring-gliding (99.3%), flapping (93.1%) and hovering (86.4%). We also showed that kestrels’ prey capture attempts can be identified from the tri-axial high-frequency accelerometers due to diagnostic signatures (the so-called ‘spikes’).ConclusionsOur simple method has broad applicability to free-ranging aerial predators. We show that behavioural categories can be accurately classified from a relatively small subset of manually labelled acceleration data (43,075 seconds). Although quantifying hunting success needs further investigation, the detection of prey capture attempts opens new possibilities for studying the hunting behaviour of aerial predators.
Reconstructing the three-dimensional architecture of extrachro-mosomal DNA with ec3D
Authors: Chowdhury Biswanath , Zhu Kaiyuan , Li Chaohui , Luebeck Jens , Chapman Owen S. , Kraft Katerina , Zhang Shu , Chavez Lukas , Henssen Anton G. , Mischel Paul S. , Chang Howard Y. , Bafna Vineet 
Published: February 2025

AbstractExtrachromosomal DNAs (ecDNAs) are large, acentric, circular DNA molecules that occur pervasively across many human cancers. EcDNA can drive tumor formation and evolution, contribute to drug resistance, and associate with poor patient survival outcomes. Beyond mediating high copy numbers, the circular topology and dynamic conformational changes of ecDNA disrupt topological domains and rewire regulatory networks, thereby conferring an important role in the transcriptional regulation of oncogenes. Here, we develop ec3D, a computational method for reconstructing the three-dimensional structures of ecDNA and analyzing significant interactions from high-throughput chromatin capture (Hi-C) data. Given a candidate ecDNA sequence and the corresponding whole-genome Hi-C as input, ec3D reconstructs the spatial structure of ecDNA by maximizing the Poisson likelihood of observed interactions. Ec3D’s performance was validated using both simulated ecDNA structures with varying conformations, and Hi-C data from previously-characterized cancer cell lines. Our reconstructions reveal that ecDNAs occupy spherical configurations and mediate unique long-range interactions involved in gene regulation. Through algorithmic innovations, ec3D can resolve complex ecDNA structures with duplicated copies of large genomic segments, identify multi-way interactions, distinguish between interactions arising from direct spatial proximity and secondary interactions resulting from alternative folding patterns or intermolecular (trans) contacts of ecDNA molecules. Our findings provide insights into how the spatial organization of ecDNA may influence gene regulation and contribute to increased oncogene expression.Code availabilityhttps://github.com/AmpliconSuite/ec3D
Viral kinetics of H5N1 infections in dairy cattle
Authors: Eales Oliver , McCaw James M. , Shearer Freya M. 
Published: February 2025

AbstractSince early-2024 unprecedented outbreaks of highly pathogenic avian influenza H5N1 clade 2.3.4.4b have been ongoing in dairy cattle in the United States with significant consequences for the dairy industry and public health. Estimation of key epidemiological parameters is required to support outbreak response, including predicting the likely effectiveness of interventions and testing strategies. Here we pool limited publicly available data from three studies of naturally and experimentally infected dairy cattle. We quantify Ct value trajectories of infected dairy cattle and the relationship between Ct value and the log-titre of infectious virus, β2a proxy for infectiousness. We estimate that following infection peak Ct values are rapidly reached within 1–2 days with a population mean Ct value of 16.9 (13.2, 20.5). We identify a critical threshold Ct value of 21.5 (20.1, 23.6), with values of Ct value above this threshold representing little-to-no infectious viral load. Finally, we estimate the distribution of the duration of infectiousness for dairy cattle (i.e. the duration their Ct value remains above the critical threshold) with a population median of 6.2 (2.8, 13.1) days.
Adaptive selection of p53 mutation metaplastic phenotypes in estrogen-independent progression of ER+ tumors: A mechanism for acquired resistance to hormonal therapy
Authors: Moon Hyeongsun , Mori Hidetoshi , Chen Jane , Patino Alejandra , Penzvalto Zsofia , Ramamurthy Kavya , Choi Jaeyong , McPherson John D. , Snyder Joshua C. , Cardiff Robert D. , Borowsky Alexander D. 
Published: February 2025

ABSTRACTEstrogen receptor positive (ER+) subtypes of mammary adenocarcinoma comprise 79% of all breast cancer diagnosis and 67% of all breast cancer mortality. The paucity of models of ER+mammary cancer that mimic human disease and response to treatment has limited critical preclinical study of mechanisms and new therapies for ER+breast cancer. TheStat1knockout, 129S6/SvEvTac-Stat1tm1Rds(Stat1-/-), females develop luminal type FoxA1+, ER+, and PR+mammary carcinomas after prolonged latencies. Initial studies showed that a cell line derived from a Stat1-/- mammary carcinoma was tumorigenic in syngeneic mice, but non-tumorigenic in ovariectomized (Ovx) mice. Here, data shows that Ovx performed after SSM2 tumors establish growth results in ovarian hormone independent growth. The viable post-Ovx tumors were primarily composed of metaplastic CK14+basal type cells with a high percentage p53 immunohistochemistry (IHC) positive “mutation pattern”, rather than the original luminal type tumors with low percent “wild type” pattern p53. Comparing whole exome sequences of ER+Stat1-/-mammary tumors before and after Ovx, revealed basal keratins, mesenchymal (EMT) phenotypes, and unique mutation profiles in genes, includingTrp53andPrlr,in the estrogen-independent tumors. Our experimental findings are consistent with the clinical evidence of tumor heterogeneity of ER+breast cancers in patients in recent whole genome sequencing studies. Similarly, spontaneous Stat1-/- tumors with high percentage p53 “mutation pattern” were more basaloid and grew rapidly after Ovx, while retaining high expression of ER and FoxA1. This study demonstrates that the STAT1-/-, ER+estrogen dependent breast cancers can become resistant to through clonal selection of mammary cells comprised of metaplastic p53+/CK14+basaloid cells.
Vaccine Hesitancy, Coercion and Regret: Post-Pandemic Lessons on COVID-19 Vaccine Policies and Outreach among Newcomer Communities in Alberta, Canada
Authors: Antonio Minnella , Ramirez-Cerino Edna , Sahilie Adanech , Yemane Mussie , Youssef Michael , Nielssen Ingrid , Holdbrook Linda , Essar Mohammad Yasir , Santana Maria , Spitzer Denise , Pottie Kevin , Fabreau Gabriel E. 
Published: February 2025

AbstractBackgroundSince the COVID-19 pandemic routine vaccination rates have dropped in Canada. Many newcomers and refugees experience significant vaccine inequities despite wide vaccine availability and COVID-19 pandemic vaccination campaigns. We aimed to investigate post-pandemic vaccine hesitancy, acceptance, and vaccine outreach strategies among newcomers’ communities.MethodsWe conducted a prospective community-based-participatory research (CBPR) qualitative study with self-identified newcomers in Alberta between October 2022 - January 2023. Community Scholars, leaders representing various ethnocultural communities trained in community-engaged research conducted semi-structured interviews and focus groups in English and first languages. Scholars collected and translated detailed qualitative notes and sociodemographic data with a standardized survey. Qualitative data was thematically analyzed and coded using a consensus-based approach.ResultsWe conducted two focus groups and five semi-structured interviews with 12 participants, 50% who identified as female and originated from the Philippines, Ethiopia, Eritrea, Mexico, Burundi, and Egypt. We identified three main themes, each with two subthemes: (1) vaccine hesitancy due to lack of reliable information and religious and cultural beliefs, (2) access to COVID-19 vaccines and information, and (3) vaccine acceptance as voluntary or coerced. Employer mandated vaccination emerged as a critical issue with potential long-term negative public health implications, leading to vaccine regret and loss of trust of public health authorities and healthcare systems.ConclusionDuring population-wide COVID-19 vaccination campaigns newcomers perceived their communities’ circumstances were overlooked, potentially increasing vaccine hesitancy. Perceived coercive vaccination policies had unintended negative public health consequences. These findings may help inform future emergency and routine public health vaccination policies.
Prognostic Implications of Codon-SpecificKRASMutations in Localized and Advanced Stages of Pancreatic Cancer
Authors: Raji Sara , Zaribafzadeh Hamed , Jones Tyler , Kanu Elishama , Tong Kunling , Fletcher Ashley , Howell T. Clark , McCall Shannon J. , Marks Jeffrey R. , Rogers Bruce , Niedzwiecki Donna , Allen Peter J. , Nussbaum Daniel P. , Kabiri Zahra 
Published: February 2025

AbstractIntroductionWhileKRASmutations represent the primary oncogenic driver in pancreatic ductal adenocarcinoma (PDAC), the association between codon-specific alterations and patient outcomes remains poorly elucidated, largely due to a lack of datasets coupling genomic profiling with rich clinical annotations across disease stages.Patients and MethodsWe utilized AACR’s GENIE Biopharma Consortium Pancreas v1.2 dataset to test the associating of codon-specificKRASmutations with clinicogenomic features and patient outcomes in PDAC patients diagnosed with localized (stages I-III) and advanced disease (stage IV). Overall survival was compared using Kaplan–Meier and multivariable Cox proportional hazards methods.ResultsAmong 1,032 eligible patients, 949 (92%) exhibited mutantKRAS. These mutations were predominantly observed at G12D (n=390, 41%), G12V (n=305, 32%), and G12R (n=149, 16%). In the group of patients who presented with localized disease, those with G12V mutation had notably longer survival compared to G12D mutation (P= 0.002). In contrast, patients with G12V mutation who presented with metastatic disease experienced shorter overall survival compared to those with G12R (P= 0.005), and G12D mutations (P= 0.009). Furthermore, no significant differences were observed in the frequencies of co-altered driver genes, includingTP53,CDKN2A, andSMAD4, across the differentKRASmutations.ConclusionsThese findings demonstrated that codon-specificKRASmutations impact PDAC outcomes differently based on disease stage at diagnosis. As studies testingKRASinhibitors continue to emerge and mature, these data offer important contextual insights regarding survival outcomes associated with codon-specificKRASmutations based on existing therapeutic approaches.
A Binary Prototype for Time-Series Surveillance and Intervention
Authors: Olejarz Jason , Hoffmann Till , Zapf Alex , Mugahid Douaa , Molinaro Ross , Brown Chadwick , Boltyenkov Artem , Dudykevych Taras , Gupta Ankit , Lipsitch Marc , Atun Rifat , Onnela Jukka-Pekka , Fortune Sarah , Sampath Rangarajan , Grad Yonatan H. 
Published: February 2025

AbstractDespite much research on early detection of anomalies from surveillance data, a systematic framework for appropriately acting on these signals is lacking. We addressed this gap by formulating a hidden Markov-style model for time-series surveillance, where the system state, the observed data, and the decision rule are all binary. We incur a delayed cost,c, whenever the system is abnormal and no action is taken, or an immediate cost,k, with action, wherek<c. If action costs are too high, then surveillance is detrimental, and intervention should never occur. If action costs are sufficiently low, then surveillance is detrimental, and intervention should always occur. Only when action costs are intermediate and surveillance costs are sufficiently low is surveillance beneficial. Our equations provide a framework for assessing which approach may apply under a range of scenarios and, if surveillance is warranted, facilitate methodical classification of intervention strategies. Our model thus offers a conceptual basis for designing real-world public health surveillance systems.