bluuebunny/crossref_metadata_2025_split huggingface dataset:
On Livestreaming and the Collaborative Potential of Public Music Theory
Authors: Grasso Julianne 
Published: December 2024

Abstract
This essay considers the livestreaming medium as a site of largely untapped potential for music theory. Using the “Ludomusicology Thursday” Twitch stream series as a basis, I argue that the live, processual, collaborative, and publicly accessible aspects of streaming attune us to the possibilities for music theory’s public presence to be truly reciprocal. I consider three key aspects of this potential in turn: open collaboration, playfulness, and camaraderie.
Varied Ostinato and the Functions of Repetition in Harrison Birtwistle’s “Frieze 2” and “Frieze 3”
Authors: Boyle Antares 
Published: December 2024

Abstract
Harrison Birtwistle has stated that the “Frieze” movements of his Nine Movements for String Quartet are “about repetition.” I show how Birtwistle uses what he terms “varied ostinati” in two movements, “Frieze 2” and “Frieze 3,” to explore a set of contradictions and paradoxes surrounding our perception of repetition. In addition to fundamental ontological mysteries, such as the way in which a repeated element is simultaneously the same and different and the difficulty of defining what “counts” as a repetition, these include paradoxes of textural and temporal perception. Texturally, repeating musical material can either draw attention to a musical object or cause it to recede into the background, whereas temporally, repetition can either draw a listener more intensely into the present moment or seem to remove material from its temporal context for abstract contemplation. Building upon David Lidov’s (1979) typology of repetition types to explore the relationship between the structure of repeated material and its perceived textural and temporal function, I argue that Birtwistle’s varied ostinati, due to features such as rhythmic play, variation and development, and lack of clear unit boundaries, often invite the participatory rhythmic experience of a more typical ostinato while occupying a liminal textural role that hovers between perceptual background and foreground. The layering of such varied ostinati creates a dynamic and multifaceted musical surface. Finally, I demonstrate how hidden global repetition processes in each movement explore these themes at a deeper structural level, creating a linear thread below the ever-changing surface material.
The RodentGPOmics Atlas: a comprehensive database of rodent biology for genomes and pathogens
Authors: Jiang Zhiwen , Yan Ziqing , Hou Yali , Tang Jia , Zheng Mengdi , Lu Meng , Ji Xiang , Gangavarapu Karthik , Li Xinxin , Su Shuo 
Published: December 2024

Abstract
Rodents represent the most abundant order of mammals, exhibiting remarkable diversity in morphology, habitats, behaviors, and hosted pathogens. Significant attention is currently focused on rodents as experimental animals for biomedical research. However, numerous aspects of rodents remain unexplored, such as their potential in unconventional biomedical models, molecular underpinnings of intriguing complex phenotypes, adaptations to environment or climate change, and host-pathogen interactions and arms race evolution. These challenges require a systematic framework to integrate the genomic variations among rodents with information on rodent-borne pathogens. To address this gap, we have established a comprehensive, freely accessible, and user-friendly atlas named Rodent Genome and Pathogen multi-Omics (RodentGPOmics), which provides comparative analysis of rodent genomes and information on zoonotic pathogen sequences in rodents. The RodentGPOmics Atlas provides: (i) basic information on 2706 rodent species; (ii) chromosome-level visualization of genomes, functional annotations, and genomic comparisons across 121 rodent species; (iii) epidemiological profiles based on 21 852 pathogen sequences reported in rodents and (iv) a few genomic tools for in-depth exploration of rodent multi-omics. This resource aims to advance the development of biomedical models for humans for promoting public health, as well as innovate the genetics, genomics, and molecular evolution in rodents, and offer valuable knowledge on rodent-borne emerging/re-emerging zoonotic infectious diseases. The resources are freely available and easy-to-use at http://RodentGPOmics.njau.edu.cn:8888/Rodent/index/homePage.
Single-molecule studies reveal the off-pathway early paused state intermediates as a target of streptolydigin inhibition of RNA polymerase and its dramatic enhancement by Gre factors
Authors: Arseniev Anatolii , Panfilov Mikhail , Pobegalov Georgii , Potyseva Alina , Pavlinova Polina , Yakunina Maria , Lee Jookyung , Borukhov Sergei , Severinov Konstantin , Khodorkovskii Mikhail 
Published: December 2024

Abstract
Antibiotic streptolydigin (Stl) inhibits bacterial transcription by blocking the trigger loop folding in the active center of RNA polymerase (RNAP), which is essential for catalysis. We use acoustic force spectroscopy to characterize the dynamics of transcription elongation in ternary elongation complexes (ECs) of RNAP in the presence of Stl at a single-molecule level. We found that Stl induces long-lived stochastic pauses while the instantaneous velocity of transcription between the pauses is unaffected. Stl enhances the short-lived pauses associated with an off-pathway early paused state intermediates of the RNAP nucleotide addition cycle. Unexpectedly, we found that transcript cleavage factors GreA and GreB, which were thought to be Stl competitors, do not alleviate the Stl-induced pausing; instead, they synergistically increase transcription inhibition by Stl. This is the first known instance of a transcriptional factor enhancing antibiotic activity. We propose a structural model of the EC-Gre-Stl complex that explains the observed Stl activities and provides insight into possible cooperative action of secondary channel factors and other antibiotics binding at the Stl pocket. These results offer a new strategy for high-throughput screening for prospective antibacterial agents.
Comprehensive genome annotation of the model ciliate Tetrahymena thermophila by in-depth epigenetic and transcriptomic profiling
Authors: Ye Fei , Chen Xiao , Li Yuan , Ju Aili , Sheng Yalan , Duan Lili , Zhang Jiachen , Zhang Zhe , Al-Rasheid Khaled A S , Stover Naomi A , Gao Shan 
Published: December 2024

Abstract
The ciliate Tetrahymena thermophila is a well-established unicellular model eukaryote, contributing significantly to foundational biological discoveries. Despite its acknowledged importance, current studies on Tetrahymena biology face challenges due to gene annotation inaccuracy, particularly the notable absence of untranslated regions (UTRs). To comprehensively annotate the Tetrahymena macronuclear genome, we collected extensive transcriptomic data spanning various cell stages. To ascertain transcript orientation and transcription start/end sites, we incorporated data on epigenetic marks displaying enrichment towards the 5′ end of gene bodies, including H3 lysine 4 tri-methylation (H3K4me3), histone variant H2A.Z, nucleosome positioning and N6-methyldeoxyadenine (6mA). Cap-seq data was subsequently applied to validate the accuracy of identified transcription start sites. Additionally, we integrated Nanopore direct RNA sequencing (DRS), strand-specific RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) data. Using a newly developed bioinformatic pipeline, coupled with manual curation and experimental validation, our work yielded substantial improvements to the current gene models, including the addition of 2,481 new genes, updates to 23,936 existing genes, and the incorporation of 8,339 alternatively spliced isoforms. Furthermore, novel UTR information was annotated for 26,687 high-confidence genes. Intriguingly, 20% of protein-coding genes were identified to have natural antisense transcripts characterized by high diversity in alternative splicing, thus offering insights into understanding transcriptional regulation. Our work will enhance the utility of Tetrahymena as a robust genetic toolkit for advancing biological research, and provides a promising framework for genome annotation in other eukaryotes.
Intracranial administration of anti-PD-1 and anti-CTLA-4 immune checkpoint-blocking monoclonal antibodies in patients with recurrent high-grade glioma
Authors: Duerinck Johnny , Lescrauwaet Louise , Dirven Iris , Del’haye Jacomi , Stevens Latoya , Geeraerts Xenia , Vaeyens Freya , Geens Wietse , Brock Stefanie , Vanbinst Anne-Marie , Everaert Hendrik , Caljon Ben , Bruneau Michaël , Lebrun Laetitia , Salmon Isabelle , Kockx Marc , Tuyaerts Sandra , Neyns Bart 
Published: December 2024

Abstract

Background
Recurrent high-grade glioma (rHGG) lacks effective life-prolonging treatments and the efficacy of systemic PD-1 and CTLA-4 immune checkpoint inhibitors is limited. The multi-cohort Glitipni phase I trial investigates the safety and feasibility of intraoperative intracerebral (iCer) and postoperative intracavitary (iCav) nivolumab (NIVO) ± ipilimumab (IPI) treatment following maximal safe resection (MSR) in rHGG.

Materials and methods
Patients received 10 mg IV NIVO within 24 h before surgery, followed by MSR, iCer 5 mg IPI and 10 mg NIVO, and Ommaya catheter placement in the resection cavity. Biweekly postoperative iCav administrations of 1–5–10 mg NIVO (cohort 4) or 10 mg NIVO plus 1–5–10 mg IPI (cohort 7) were combined with 10 mg IV NIVO for 11 cycles.

Results
42 rHGG patients underwent MSR with iCer NIVO + IPI. 16 pts were treated in cohort 4 (postoperative iCav NIVO at escalating doses) while 28 patients were treated in cohort 7 (intra and postoperative iCav NIVO and escalating doses of IPI). The most common TRAE was fatigue; no grade 5 AE occurred. Dose-limiting toxicity was grade 3 neutrophilic pleocytosis (4 pts) receiving iCav NIVO plus 5 or 10 mg IPI. PFS and OS did not significantly differ between cohorts (median OS: 42 [95% CI 26–57] vs. 35 [29–40] weeks; 1-year OS rate: 37% vs. 29%). Baseline B7–H3 expression significantly correlated with worse survival. OS compared favorably to a historical pooled cohort (n = 469) of Belgian rHGG pts treated with anti-VEGF therapies (log-rank P = .015).

Conclusion
Intraoperative iCer IPI + NIVO with postoperative iCav NIVO ± IPI up to biweekly doses of 1 mg IPI + 10 mg NIVO is feasible and safe, showing encouraging OS in rHGG patients. ClinicalTrials.gov registration: NCT03233152
Effect of Saffron (Crocus sativus) Supplementation on Oxidative Stress, Inflammatory Indices, and Renal and Liver Function Parameters in Patients With Type 2 Diabetes Mellitus: A GRADE-Assessed Systematic Review and Meta-analysis of Randomized Clinical Trials
Authors: Mafi Alireza , Mokhtari Zeinab , Hosseini Elham , Alimohammadi Mina , Aarabi Mohammad Hosein , Askari Gholamreza 
Published: December 2024

Abstract

Context
Clinical investigation has shown that the addition of saffron or crocin to standard antidiabetic medications improves a patient's metabolic profile, oxidative stress (OS), and inflammatory response. Despite a large number of studies examining the impact of saffron supplementation on OS, inflammation, and renal and liver function parameters, no systematic review or meta-analysis has been conducted to compile the outcomes in patients with type 2 diabetes mellitus (T2DM).

Objective
The current systematic review and meta-analysis was performed to investigate the effect of saffron or crocin intake on OS, inflammation, and renal and liver function parameters in patients with T2DM.

Data Sources
Online databases including PubMed, Scopus, ISI Web of Science, and Cochrane Library were searched up to December 2023.

Data Extraction
The mean differences and their respective SDs were extracted. Using a random-effects model, the pooled data were calculated as standardized mean difference (SMD) with 95% CI.

Data Analysis
17 eligible randomized controlled trials were included in this meta-analysis. The pooled findings showed that saffron supplementation remarkably decreased the levels of tumor necrosis factor-α (SMD: −0.37; 95% CI: −0.69 to −0.05; I2 = 40.77%, P = .15), interleukin-6 (IL-6) (SMD: −0.38; 95% CI: −0.65 to −0.10; I2 = 0%, P = .68), and malondialdehyde (MDA) (SMD: −0.36; 95% CI: −0.65 to -0.07; I2= 20.51%, P = .02) compared with the control. In addition, based on subgroup analyses, taking ≥100 mg of saffron daily in individuals with T2DM reduced the serum levels of IL-6 (SMD: −0.50; 95% CI: −0.90 to −0.10; I2 = 0%, P = .50) and MDA (SMD: −0.36; 95% CI: −0.68 to -0.03; I2 = 0, P = .97). Furthermore, the level of alanine transaminase was decreased (SMD: -0.43; 95% CI: −0.73 to −0.12; I2 = 0, P = .66) with a treatment period of &lt;60 days of saffron or crocin supplementation.

Conclusion
Larger studies with more follow-up and higher doses of both saffron and crocin are needed in order to understand the efficacy and safety of these herbs for long-term use as routine therapies.

Systematic Review Registration
PROSPERO registration no. CRD42023458119.
Roman Law on the Just Price in Nicolaus Bernoulli’s Mathematics
Authors: Kennefick Ciara 
Published: December 2024

Abstract
It must be rare that discoveries which transform mathematics also undermine legal rules. Yet this is precisely what happened when probability was first developed in the second half of the 17th century and the first decades of the following one. The focus of this article is a doctoral thesis in law written in 1709 by Nicolaus Bernoulli, an important mathematician of the age. He highlighted the dramatic implications of the new mathematics of probability for a rule which was fundamental to contemporary contract law in continental Europe. This article reconstructs a remarkable story about the place of mathematics in the history of contractual justice and the place of contractual justice in the history of mathematics.
Squamous cell carcinoma arising in chronically damaged skin (Marjolin’s Ulcer): still an unmet need in the era of immunotherapy
Authors: Miodovnik Mor , Dolev Yardenna , Buchen Roni , Brezis Miriam Rivka , Nikolaevski-Berlin Alla , Finkel Inbar , Wolf Ido , Ospovat Inna , Gutfeld Orit , Leshem Yasmin 
Published: December 2024

Abstract

Background
Cutaneous squamous cell carcinoma (cSCC) is characterized by a high tumor mutational burden due to solar damage and a favorable response to anti-PD-1 immunotherapy. Yet, we encounter tumors arising in areas with minimal sun exposure, such as cSCC that develops in chronically inflamed skin, also known as Marjolin’s Ulcer (MU). The response of MU-SCC to immunotherapy remains unknown.

Methods
We performed a retrospective analysis of patients diagnosed with cSCC and treated with cemiplimab or pembrolizumab in a single tertiary medical center. Patients lost to follow up were excluded.

Results
Of the 84 eligible patients, 9 (11%) had MU-SCC. Of these, 2 (22%) reached partial response (PR), and none reached complete response (CR). In contrast, of the 75 patients with solar damage-related cSCC, 40 had PR (53%), and 20 had CR (26%). The difference between the two subtypes was significant (P &lt; .001). Interestingly, 3 patients with MU-SCC received a second-line chemo-immunotherapy and experienced a partial response that continued for 5 to 21 months. Patients with MU-SCC had a significantly shorter median time to progression (TTP) (1.6 vs 51.6 months, P &lt; .001) and progression-free survival (PFS) (1.6 vs 15.4 months, P &lt; .001). Overall survival (OS) was not significantly shorter (17.4 vs 36.7 months, P = .096). Multivariate analysis confirmed that MU-SCC is an independent risk factor for shorter TTP (HR 5.5, 95% CI 2.2-14.0, P &lt; .001) and PFS (HR 3.5, 95% CI 1.5-8.1, P = .003).

Conclusions
This study suggests that immunotherapy is less beneficial in SCC-MU. More work is needed to verify our findings and explore other treatment options.
Empowering the people: The evolution and impact of Portugal’s citizens’ legislative initiatives in a comparative perspective
Authors: Serra-Silva Sofia , Gaio e Silva João 
Published: December 2024

Abstract
Citizens’ legislative initiatives (CLIs) are vital instruments of direct democracy that allow citizens to participate in decision-making and influence the legislative agenda. Despite the growing interest globally, there has been limited scholarly attention on Portugal, which implemented this tool in 2003. This study conducts an in-depth case analysis of CLIs in Portugal, examining their legal evolution, institutional design within the European context, and their usage and success. An original dataset characterizes the initiatives, proponents, and subscribers to provide comprehensive insights. While efforts have been made to make CLIs more accessible in Portugal, the existing requirements and procedures remain moderately accessible, with high signature-to-population ratios and lengthy processing times. The study also finds that most CLIs face rejection, expiration, or withdrawal. Successful CLIs, which result in legislation, often lead to laws that are significantly different from the original proposals. This discrepancy arises because parties substantially modify the original texts during the parliamentary discussion and citizens have little influence over the final version of the law. This research highlights the challenges and limitations faced by CLIs emphasizing the need for reforms to enhance citizen influence in the legislative process and the importance of balancing parliamentary control with genuine and meaningful citizen participation.
Modeling with uncertainty quantification reveals the essentials of a non-canonical algal carbon-concentrating mechanism
Authors: Steensma Anne K , Kaste Joshua A M , Heo Junoh , Orr Douglas J , Sung Chih-Li , Shachar-Hill Yair , Walker Berkley J 
Published: December 2024

Abstract
The thermoacidophilic red alga Cyanidioschyzon merolae survives its challenging environment likely in part by operating a carbon-concentrating mechanism (CCM). Here, we demonstrated that C. merolae's cellular affinity for CO2 is stronger than the affinity of its rubisco for CO2. This finding provided additional evidence that C. merolae operates a CCM while lacking the structures and functions characteristic of CCMs in other organisms. To test how such a CCM could function, we created a mathematical compartmental model of a simple CCM, distinct from those we have seen previously described in detail. The results of our modeling supported the feasibility of this proposed minimal and non-canonical CCM in C. merolae. To facilitate the robust modeling of this process, we measured and incorporated physiological and enzymatic parameters into the model. Additionally, we trained a surrogate machine-learning model to emulate the mechanistic model and characterized the effects of model parameters on key outputs. This parameter exploration enabled us to identify model features that influenced whether the model met the experimentally derived criteria for functional carbon concentration and efficient energy usage. Such parameters included cytosolic pH, bicarbonate pumping cost and kinetics, cell radius, carboxylation velocity, number of thylakoid membranes, and CO2 membrane permeability. Our exploration thus suggested that a non-canonical CCM could exist in C. merolae and illuminated the essential features generally necessary for CCMs to function.
Backwards counterfactuals
Authors: Rennick Stephanie , McDonnell Neil 
Published: December 2024

Abstract
This paper offers two novel conceptual tools: one concerning the semantics of counterfactuals and what should be held fixed when assessing them (the modal moat), and the other concerning the pragmatics of counterfactual assertions and how to avoid the potential pitfalls of meaning more than we say (antecedent gluttony). These allow us to address existing issues with the assessment of backwards counterfactuals within a framework that applies equally to forwards cases. In addition to solving a thorny problem from the time travel literature, what we learn teaches us something quite general about our evaluation of counterfactuals.
Spectral data of special orthogonal Higgs bundles and Hecke modification
Authors: KLINGNER T 
Published: December 2024

ABSTRACT
We give a complete, self-contained computation of the spectral data parametrizing Higgs bundles in the generic fibres of $\mathrm{SO}_{2n+1}$-Hitchin fibration where the Higgs fields are L-twisted endomorphisms. Although the spectral data are known in the literature, we develop a new approach, which takes advantage of Hecke modification. Furthermore, we present the computation for $\mathrm{Sp}_{2n}$ and $\mathrm{SO}_{2n}$ cases while clarifying some aspects of the correspondence, which are not well explained in the pre-existing literature. We also compute the number of connected components of the generic fibres and demonstrate Langlands duality in the fibres via the canonical duality in the fibres.
Results of the proficiency test for the Ka CMC of the SSDL-ININ Mexico, for diagnostic radiology IEC 61267:2005 and radiation protection ISO 4037:2019 X-ray beam qualities
Authors: Romero José Trinidad Álvarez , Salas Gonzalo Walwyn , de los Angeles Montes Rodríguez María , Vertti Mario Raymundo Cabrera , Acosta Andy Luis Romero 
Published: December 2024

Abstract
The present work describes the results for the bilateral comparison between the Secondary Standards Dosimetry Laboratories of the Instituto Nacional de Investigaciones Nucleares (SSDL-ININ), Mexico, and the pilot laboratory, the Centro de Protección e Higiene de las Radiaciones (SSDL-CPHR), Cuba, for the realization of the air kerma (${\boldsymbol{K}}_{\boldsymbol{a}}$) quantity to: (i) diagnostic X-ray (DXR) IEC 61267:2005 beam qualities: RQR 5 RQR 9, RQT 8, and RQT 9 and (ii) radiation protection (RP) ISO 4037:2019 X-ray beam qualities: N60, N100, and W60, as well S-Cs for gamma radiation. The matched and characterized reference fields are realized at SSDL-ININ with a Toshiba E7252FX X-ray tube. In all cases, the ${\boldsymbol{K}}_{\boldsymbol{a}}$ measurements are traceable to PTB, except for S-Cs, traceable to ININ. The SSDL-CPHR realizes its reference radiation beam qualities also as matched reference fields with a Pantak HF160C X-ray tube. For the S-Cs beam quality, the CPHR uses a Buchler OB6 irradiator; the ININ, a Siemens Cesagammatron. The transfer ionization chambers calibrated in the RQR and RQT qualities are an Exradin A650/DO70312; for the RQT qualities for CT, a PTW 30009/0655 and RC3CT/9217 were calibrated; and for the RP X-ray qualities, the Exradin A650/DO70312 and a PTW 32002/073 were calibrated. The ratio ${\boldsymbol{R}}_{\boldsymbol{k}}$ of the resulting calibration coefficients ${\boldsymbol{N}}_{{\boldsymbol{K}}_{\boldsymbol{a}}}$ of each SSDL of the RQR qualities are consistent within the $\boldsymbol{U}\left(\boldsymbol{k}=\mathbf{2}\right)\%$ ≤ 2.3%; for the RQT qualities, the differences are less than the $\boldsymbol{U}\left(\boldsymbol{k}=\mathbf{2}\right)\%$ ≤ 3.6%; and for the RP X-ray qualities, within the order of $\boldsymbol{U}\left(\boldsymbol{k}=\mathbf{2}\right)\%$ ≤ 3.5%. For the S-Cs quality, the ${\boldsymbol{R}}_{\boldsymbol{k}}$ is in the order of $\boldsymbol{U}\left(\boldsymbol{k}=\mathbf{2}\right)$ ≤ 3.0%. It should be noted that the ININ U's are generally larger due to the failure of the ${\boldsymbol{k}}_{\boldsymbol{TP}}$ correction factor, a brief discussion is given here. The ${\boldsymbol{E}}_{\boldsymbol{n}}$ score from ISO 17043 provides statistical support to this comparison.