bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spotted Hyena skull size variation across geography favors the energetic equivalence rule over Bergmann’s Rule
Authors: Cavalieri Cybil N , McElhinny Teresa L , Holekamp Kay E , Lundrigan Barbara L 
Published: April 2024

Abstract
Much historic work has focused on establishing geographical and ecological rules that broadly explain patterns in size variation. We examined geographic variation in Spotted Hyena skull size using geometric morphometrics and spatial statistics. We quantified size variation and sexual size dimorphism of the skull, and evaluated the influence of temperature, precipitation, land cover type, and population density on skull size. We found that female spotted hyenas are slightly larger on average than males. Our analysis of regional differences did not indicate geographic variation in sexual size dimorphism. Skull size of Spotted Hyenas varies with geography but does not adhere to Bergmann’s Rule. The smallest individuals of both sexes occur between −5.00° and 10.00° latitude and east of 28.50° longitude, with larger individuals being found elsewhere. Although Spotted Hyena skull size co-varies in some views with such variables as habitat type and climate indicators, skull size in this species most strongly co-varies with population density. The highest population densities are associated with the smallest skull size, possibly reflecting a relationship between high population density and access to resources. These results suggest that geographic variation in Spotted Hyena skull size is better explained by the energetic equivalence rule than Bergmann’s Rule.
Bayesian issues in the 1950s: an episode involving Karl Popper and Jimmie Savage
Authors: Stigler Stephen M 
Published: April 2024

Abstract
In the 1950s, the growing importance of Bayesian inference attracted both supporters and critics. In 1958, the philosopher Karl Popper published what he called a paradox that purported to show the foolishness of subjectivist Bayesian inference. In correspondence, Jimmie Savage pointed out what he considered an error in his reasoning, but Popper was unmoved and did not change his example when he reprinted it. It is argued that Popper did not acknowledge that the new subjectivists reasoned with distributions, not simply expected values. Excerpts from Jimmie Savage’s correspondence at the time with Popper and with Allen Wallis highlight the issues involved at this time when Bayesian statisticians were seeking general acceptance.
Expanding the Leibniz Hierarchy
Authors: Almeida Ugo C M , Pinto Darllan Conceição 
Published: April 2024

Abstract
In this work we present two new classes of logics determined by specific properties of the Leibniz operator that expand the Leibniz hierarchy. By doing so, we present a sufficient condition for the commutativity of the Leibniz operator with inverse substitutions/homomorphisms, which gives us a negative answer to the possibility of establishing a precise connection between Leibniz classes and the behavior of the Leibniz operator.
“Doesn’t Matter if It’s Crack or . . . Pesticides, AIDS, It’s All the Same Shit”: Body-Land Metonymies in Cherríe Moraga’s Heroes and Saints
Authors: Miller M A 
Published: April 2024

Abstract
This article closely examines Mario Valle, the seroconverted Chicano gay male minor protagonist in Cherríe Moraga’s play Heroes and Saints (1992) as a case study of Chicanx environmentalism informed by a materially metonymic body-land relationship. The article addresses Mario Valle’s HIV+ status not as a peripheral aberration but as integral to the play. The play renders legible the entangled impact of environmental toxins—pesticide poisoning and AIDS—as necessary to understanding the soothing metonymic acts of substitution queer care makes possible. AIDS and pesticide poisoning, this article argues, are mutually reinforcing and intra-acting embodied parts of an environmental, soil, and land-based whole. Through Moraga’s recuperative lens of “Queer Aztlán,” AIDS can finally be understood as its own unique environmental issue alongside agrochemical usage rather than as a separately delineated social concern of individualized risky behavior. The poetic potential of metonymy does not solely focus on individual human actors in service of one another. Rather, such a literary device considers the environmental nesting potential of part/whole substitutability: human, non/human, and more-than-human parts continuously generate connection and care beyond the borders of skin and soil. There is no membrane of separation between toxic bodies and toxic lands. Characters in the play often fulfill alternative roles, abilities, and bodily parts—a sister acting as a substitute child, lesbian lover, nourishing/nourished mouth for a sibling—in order to alleviate the suffering caused by acts of environmental degradation. Although truncated by enforced forms of toxicity, such contaminated bodies negate negation, producing canceling forms of negativity that are neither anti-relational nor driven toward death. Rather, these body-land relationships reinscribe the possibility for toxic bodies to perform acts of emotional labor and alleviate suffering in the face of forcibly foreclosed futurity.
New evidence of binarity in young α-rich turn-off and subgiant stars: fast rotation and strong magnetic activity
Authors: Yu Jie , Casagrande Luca , Ciucă Ioana , Ting Yuan-Sen , Murphy Simon J , Chen Boquan 
Published: April 2024

ABSTRACT
Young α-rich (YAR) stars within the old Galactic thick disc exhibit a dual characteristic of relative youth determined with asteroseismology and abundance enhancement in α elements measured from high-resolution spectroscopy. The youth origin of YAR stars has been proposed to be binary evolution via mass transfer or stellar mergers. If that is the case, YAR stars should spin rapidly and thus be magnetically active, because they are mass and angular momentum gainers. In this study, to seek this binary footprint, we select YAR stars on the main-sequence turn-off or the subgiant branch (MSTO-SGB) from APOGEE DR17, whose ages and projected rotation velocities (vsin i) can be precisely measured. With APOGEE vsin i and LAMOST spectra, we find that YAR stars are indeed fast rotators and magnetically active. In addition, we observe low [C/N] ratios and high Gaia RUWE in some YAR stars, suggesting that these MSTO-SGB stars probably have experienced mass transfer from red-giant companions. Our findings underscore that magnetic activity can serve as a valuable tool for probing the binary evolution for other chemically peculiar stars, such as red giants with lithium anomalies and carbon-enhanced metal-poor stars.
MaNGA DynPop – V. The dark-matter fraction versus stellar velocity dispersion relation and stellar initial mass function variations in galaxies: dynamical models and full spectrum fitting of integral-field spectroscopy
Authors: Lu Shengdong , Zhu Kai , Cappellari Michele , Li Ran , Mao Shude , Xu Dandan 
Published: April 2024

ABSTRACT
Using the final Mapping Nearby Galaxies at Apache Point Observatory sample of 10K galaxies, we investigate the dark matter (DM) fraction fDM within one half-light radius Re for about 6K galaxies with good kinematics spanning a wide range of morphologies and stellar velocity dispersion. We employ two techniques to estimate fDM: (i) Jeans anisotropic modelling (JAM), which performs DM decomposition based on stellar kinematics and (ii) comparing the total dynamical mass-to-light ratios (M/L)JAM and (M*/L)SPS from stellar population synthesis (SPS). We find that both methods consistently show a significant trend of increasing fDM with decreasing σe and low fDM at larger σe. For 235 early-type galaxies with the best models, we explore the variation of stellar initial mass function (IMF) by comparing the stellar mass-to-light ratios from JAM and SPS. We confirm that the stellar mass excess factor αIMF increases with σe, consistent with previous studies that reported a transition from Chabrier-like to Salpeter IMF among galaxies. We show that the αIMF trend cannot be driven by M*/L or IMF gradients as it persists when allowing for radial gradients in our model. We find no evidence for the total M/L increasing toward the centre. We detect weak positive correlations between αIMF and age, but no correlations with metallicity. We stack galaxy spectra according to their αIMF to search for differences in IMF-sensitive spectral features (e.g. the $\rm Na_{\rm I}$ doublet). We only find marginal evidence for such differences, which casts doubt on the validity of one or both methods to measure the IMF.
Alteration of mechanical stresses in the murine brain by age and hemorrhagic stroke
Authors: Zheng Siyi , Banerji Rohin , LeBourdais Rob , Zhang Sue , DuBois Eric , O’Shea Timothy , Nia Hadi T 
Published: April 2024

Abstract
Residual mechanical stresses, also known as solid stresses, emerge during rapid differential growth or remodeling of tissues, as observed in morphogenesis and tumor growth. While residual stresses typically dissipate in most healthy adult organs, as the growth rate decreases, high residual stresses have been reported in mature, healthy brains. However, the origins and consequences of residual mechanical stresses in the brain across health, aging, and disease remain poorly understood. Here, we utilized and validated a previously developed method to map residual mechanical stresses in the brains of mice across three age groups: 5–7 days, 8–12 weeks, and 22 months. We found that residual solid stress rapidly increases from 5–7 days to 8–12 weeks and remains high in mature 22 months mice brains. Three-dimensional mapping revealed unevenly distributed residual stresses from the anterior to posterior coronal brain sections. Since the brain is rich in negatively charged hyaluronic acid, we evaluated the contribution of charged extracellular matrix (ECM) constituents in maintaining solid stress levels. We found that lower ionic strength leads to elevated solid stresses, consistent with its unshielding effect and the subsequent expansion of charged ECM components. Lastly, we demonstrated that hemorrhagic stroke, accompanied by loss of cellular density, resulted in decreased residual stress in the murine brain. Our findings contribute to a better understanding of spatiotemporal alterations of residual solid stresses in healthy and diseased brains, a crucial step toward uncovering the biological and immunological consequences of this understudied mechanical phenotype in the brain.
OA29 Epigenetic regulation of IL-4 promoter targeting p300 attenuating intervertebral disc degeneration and pain by inhibiting IL-1β
Authors: Cui Haowen , Zheng Zhaomin 
Published: April 2024

Abstract

Background/Aims
Low back pain (LBP) is a prevalent condition primarily caused by intervertebral disc degeneration (IVDD), which imposes a substantial social and medical burden. Effective targeted treatments to prevent the progression of IVDD and alleviate LBP are still lacking. p300, a critical member of the histone acetyltransferase (HAT) family, is involved in the regulation of inflammation. This study aims to investigate the role of p300/IL-4 in IVDD and pain and elucidate the underlying molecular mechanism.

Methods
Human intervertebral disc samples were collected and graded based on the Pfirrmann grading scheme. A rat model of IVDD was established through posterior disc puncture, and various treatments were administered. Human nucleus pulposus cells (NPCs) were isolated and cultured, followed by assessments including qRT-PCR, Western blotting, immunofluorescence, and histopathological analyses. The mechanical and thermal hyperalgesia were assessed using von Frey hair tests and the plantar test, respectively. Chromatin immunoprecipitation (ChIP) and ChIP-qPCR were performed, and lentivirus transduction was used for p300 knockdown.

Results
We investigated the role of CREB binding protein (CBP)/p300 in IVDD. Degenerated nucleus pulposus (NP) tissues from IVDD patients exhibited a significant downregulation of p300 at both nucleic acid and protein levels, while CBP levels remained unchanged. Manipulating p300 expression in NPCs regulated matrix production, with p300 overexpression enhancing aggrecan and collagen II expression and knockdown leading to increased matrix-degrading proteins. In a rat IVDD model, activating p300 function with CTPB (p300-specific activator) alleviated IVDD and pain, while inhibiting p300 with C646 exacerbated IVDD and pain. Transcriptome analysis implicated IL-4 as a downstream effector of p300, and IL-4 demonstrated protective effects against IVDD and pain. Mechanistically, p300 was found to acetylate H3K27 at the IL-4 promoter, promoting its expression.

Conclusion
The novel findings of this study suggest that the p300/IL-4/IL-1β axis may represent a promising therapeutic target for IVDD and LBP. These results propose a hypothesis that, early in the inflammatory phase, NPCs may initiate a self-protective mechanism through p300, aiding itself in preserving a favourable metabolic microenvironment. This mechanism is primarily mediated by the expression of IL-4, which has the capacity to counteract IL-1β, rather than TNF-α.

Disclosure
H. Cui: None. Z. Zheng: None.
OA30 Primary osteoarthritis chondrocyte map of chromatin conformation reveals novel effector genes
Authors: Bittner Norbert , Shi Chenfu , Zhao Danyun , Ding James , Southam Lorraine , Swift Diane , Kreitmaier Peter , Tutino Mauro , Hankinson Jenny , Wilkinson Mark , Orozco Gisela , Zeggini Eleftheria 
Published: April 2024

Abstract

Background/Aims
Osteoarthritis is a complex disease with a huge public health burden. Genome-wide association studies (GWAS) have identified hundreds of osteoarthritis-associated sequence variants, but the effector genes underpinning these signals remain largely elusive. Understanding chromosome organisation in 3D space is essential for identifying long-range contacts between distant genomic features (e.g., between genes and regulatory elements), in a tissue-specific manner. Here, we generate the first whole genome chromosome conformation analysis (Hi-C) map of primary osteoarthritis chondrocytes and identify novel effector genes for the disease.

Methods
Primary chondrocytes collected from eight knee osteoarthritis patients underwent Hi-C analysis to link chromosomal structure to genomic sequence. The identified loops were then combined with osteoarthritis GWAS results to identify variants involved in gene regulation via enhancer-promoter interactions.

Results
We identified 36 genetic variants residing within chromatin loop anchors that are associated with 13 osteoarthritis GWAS signals. Five of these variants reside directly in enhancer regions of 3 enhancer-promoter loops newly described in chondrocytes, pointing to high-confidence effector genes: PAPPA, NSD2 and NCOA6. PAPPA is directly associated with the turnover of IGF-1 transport proteins, and IGF-1 is an important factor in the repair of damaged chondrocytes.

Conclusion
We have constructed the first Hi-C map of primary human chondrocytes and have made it available as a resource for the scientific community. By integrating 3D-genomics with large-scale genetic association data, we identify high-confidence osteoarthritis effector genes which enhance our understanding of disease and can serve as putative high-value novel targets.

Disclosure
N. Bittner: None. C. Shi: None. D. Zhao: None. J. Ding: None. L. Southam: None. D. Swift: None. P. Kreitmaier: None. M. Tutino: None. J. Hankinson: None. M. Wilkinson: None. G. Orozco: None. E. Zeggini: None.
P001 An audit to assess whether patients who had a delayed or missed denosumab dose during the covid-19 pandemic came to any harm or suffered a subsequent fracture
Authors: Rehman Sumaiya , Sultan Shabina 
Published: April 2024

Abstract

Background/Aims
Denosumab is licensed by NICE for the secondary prevention of osteoporosis in patients who are unable to comply, have an intolerance, or contraindication to bisphosphonates. With the outbreak of Covid-19, denosumab appointments were delayed. A delay of denosumab doses by more than 16 weeks is associated with an increased risk of vertebral fractures. This audit was carried out to see if the Pandemic caused a delayed (&gt;1 month) or missed (&gt;6 months) dose in patients receiving their denosumab injection and whether this delay/missed dose resulted in patients coming to any harm such as a subsequent fracture.

Methods
We included 166 patients of which 95% were female. We stratified data utilising the Oberoi consulting clinical audit services which provided a database of patients who were on six monthly repeat prescriptions for Denosumab. Retrospective data was collected including indications for denosumab, start date, duration, missed or delayed doses, reasons for delayed doses and whether a fracture of a pathological nature was sustained. We later reviewed if the missed or delayed doses occurred during the covid pandemic (2020-22) and subsequently, if the fracture occurred as a result of the pandemic.

Results
34/166(21%) patients did not receive their Denosumab dose on time during Covid-19. 21/166(12.6%) patients had a delayed dose (6 pre-Covid and 15 post-Covid) and 13/166 (7.8%) patients missed a dose entirely (3 pre-Covid and 10 post-Covid) showing more delays/missed doses occurred during the pandemic. Reasons as to why patients did not receive timely doses include, clinical reasons (7/34 20.6%), patient safety decisions made by clinicians in patients’ best interest 12/34(35.3%) and patient choice related factors 15/34 (44.1%). Reasons for delays include not wanting repeat bloods, being on holiday, chest infection low Vitamin D levels, pre dose bloods delayed, patient had covid, and isolating. Whilst on Denosumab, 8/166(4.8%) patients sustained a fracture of which 6/8(75%) also experienced a delayed/missed dose during Covid-19.

Conclusion
Of the 34/166 patients that had a delayed/missed dose, eight suffered a fracture bringing the fracture risk to 23.5% which is an increase from baseline (6.6%) confirming that a missed Denosumab dose does increase fracture risk. We can conclude a greater proportion of patients endured a missed or delayed dose as a consequence of the Covid-19 pandemic. 8/166(4.8%) patients sustained a fracture of which six had a missed/delayed dose as a result of the pandemic. The conclusions drawn are in keeping with the MHRA4 alert, a missed dose of Denosumab does increase the risk of pathological treatment discontinuation fractures. This highlights to clinicians the significance of timely doses and uninterrupted treatment.

Disclosure
S. Rehman: None. S. Sultan: None.
P002 A comparison between radiologically reported osteopenia and the FRAX score as an indication for bone densitometry
Authors: Srinivas Sourabh , Hood Katharine , Sapkota Hem 
Published: April 2024

Abstract

Background/Aims
Osteopenia is defined as a bone mineral density score between -1 and -2.5 standard deviations compared to a young adult reference mean (T-score) based on dual energy x-ray absorptiometry (DXA). Radiologists continue to use the term in a generic and qualitative manner to mean decreased bone mineral density, but they cannot distinguish between osteopenia and osteoporosis which means patients then go on to have a DXA. We would like to see if a FRAX (fracture risk assessment tool) can safely replace osteopenia as an indication for a DXA.

Methods
We retrospectively identified 2276 patients to have had a DXA scan from October 2022 to March 2023 according to the departmental database. Their referral forms were obtained from the Electronic Medical Record (EMR). Out of these, 150 patients were referred with a sole indication being radiologically reported osteopenia. Out of 150 patients, 22 were excluded as they were found to have other indications not reported on their referral from and seven more were excluded as three had bilateral hip replacement, three were below 40 and one was undergoing gender reassignment and was on oestrogen. The remaining 121 patients were included in the study and their post BMD ( bone mineral density) FRAX score was obtained from patient EMR. Pre BMD FRAX was also calculated using clinical information available on patient’s EMR retrospectively. NOGG ( National Osteoporosis Guideline Group) recommendation of treatment based on the fracture risk as per the FRAX were then compared between pre and post BMD retrospectively to see if there would be any change in treatment plan.

Results
Of total 121 patients included, 94 were female. Mean age was 68 years. Retrospective review of the case notes revealed that using a FRAX with BMD, total 34 (28.1%) patients needed treatment for osteoporosis while 87 (71.9%) did not. Of 87 patients not requiring treatment, 55 would not have received DXA scan if FRAX assessment was done without BMD. Of the 34 who did need treatment, 32 would still be recommended for a DXA while only two patients wouldn’t. However, these two patients had other clinical indications for osteoporosis assessment and would still have required a specialist referral such that a decision can be made about DXA.

Conclusion
If radiologically reported osteopenia as an indication for a DXA is replaced by FRAX, DXA would not be needed in nearly half of the patients. This will have potential to save scarce DXA resource without compromising patient safety, treatment plan, and will reduce waiting times.

Disclosure
S. Srinivas: None. K. Hood: None. H. Sapkota: None.
P007 Successful use of patient initiated follow-up in a tertiary paediatric rheumatology service
Authors: Calvert William , Spinty Jean , McCann Liza J , Cleary Gavin 
Published: April 2024

Abstract

Background/Aims
Patient initiated follow-up (PIFU) is a national strategy enabling patients or carers to initiate contact with a service rather than a traditional model of routine scheduled appointments. PIFU enables patient empowerment and elective recovery after the Covid-19 pandemic. NHSE identified Paediatrics as appropriate for PIFU, but specific measures are needed to ensure safeguarding of paediatric patients is maintained.

Methods
With NHSE & I support and extrapolating guidance implementing PIFU in adult rheumatology services, we developed a clinical pathway that included safeguarding/governance structures within Paediatric Rheumatology at Alder Hey Children’s Hospital. Two strategies were developed - PIFU culminating with either a timed return (PEND) or discharge (DISCHARGE) model. A PIFU feasibility study in paediatric rheumatology initially targeted three index conditions (arthritis, mechanical pain and primary Raynaud’s) in March 2022. This was extended within a Plan-Do-Study-Act model of Quality Improvement.

Results
We placed 536 patients within PIFU pathways (PEND = 297, DISCHARGE = 239). The monthly usage of PIFU increased from &lt;10 patients per month in March 2022 to &gt; 40 patients per month in August 2023 with expansion of PIFU conditions. Within this time frame the number of patients put through the DISCHARGE model increased steadily to 60% of the monthly proportion as clinician confidence in PIFU increased. We demonstrate an 11% (total Rheumatology patients) PIFU rate over the study time frame, with a 2.7% (15/536) reactivation rate. Where calculable, timescale for review following activation was &lt;48 hours. In our experience, patients/families are comfortable with PIFU and feel reassured by the safety-net provided. Decision for PIFU PEND/DISCHARGE is made in partnership with patients/families. As well as increased use within Rheumatology, PIFU use has extended to 80% of clinical teams across Alder Hey. The Trust-wide PIFU rate of 10% in September 2023 is double the original NHS England guidance target of 5%.

Conclusion
We advocate safety of PIFU in the correct population and its ability to empower patients. Table 1 shows the significant impact that correct use of PIFU can have on increasing capacity for seeing new patients, decreasing time to review and matching the number of patient reviews to referrals.

Disclosure
W. Calvert: None. J. Spinty: None. L.J. McCann: None. G. Cleary: None.