bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep learning predicts DNA methylation regulatory variants in specific brain cell types and enhances fine mapping for brain disorders
Authors: Zhou Jiyun , Weinberger Daniel R. , Han Shizhong
Published: January 2025

DNA methylation (DNAm) is essential for brain development and function and potentially mediates the effects of genetic risk variants underlying brain disorders. We present INTERACT, a transformer-based deep learning model to predict regulatory variants affecting DNAm levels in specific brain cell types, leveraging existing single-nucleus DNAm data from the human brain. We show that INTERACT accurately predicts cell type–specific DNAm profiles, achieving an average area under the receiver operating characteristic curve of 0.99 across cell types. Furthermore, INTERACT predicts cell type–specific DNAm regulatory variants, which reflect cellular context and enrich the heritability of brain-related traits in relevant cell types. We demonstrate that incorporating predicted variant effects and DNAm levels of CpG sites enhances the fine mapping for three brain disorders—schizophrenia, depression, and Alzheimer’s disease—and facilitates mapping causal genes to particular cell types. Our study highlights the power of deep learning in identifying cell type–specific regulatory variants, which will enhance our understanding of the genetics of complex traits.
Cortical VIP neurons as a critical node for dopamine actions
Authors: Bae Jung Won , Yi Jee Hyun , Choe Seo Yeon , Li Yulong , Jung Min Whan
Published: January 2025

Dopamine modulates a wide range of cognitive processes in the prefrontal cortex, but the underlying mechanisms remain unclear. Here, we examined the roles of prefrontal vasoactive intestinal polypeptide (VIP)–expressing neurons and their D1 receptors (D1Rs) in working memory using a delayed match-to-sample task in mice. VIP neurons conveyed robust working-memory signals, and their inactivation impaired behavioral performance. Moreover, selective knockdown of D1Rs in VIP neurons also resulted in impaired performance, indicating the critical role of VIP neurons and their D1Rs in supporting working memory. Additionally, we found that dopamine release dynamics during the delay period varied depending on the target location. Furthermore, dopaminergic terminal stimulation induced a contralateral response bias and enhanced neuronal target selectivity in a laterality-dependent manner. These results suggest that prefrontal dopamine modulates behavioral responses and delay-period activity based on laterality. Overall, these findings shed light on dopamine-modulated prefrontal neural processes underlying higher-order cognitive functions.
Mesolimbic dopamine neurons drive infradian rhythms in sleep-wake and heightened activity state
Authors: Markam Pratap S. , Bourguignon Clément , Zhu Lei , Ward Bridget , Darvas Martin , Sabatini Paul V. , Kokoeva Maia V. , Giros Bruno , Storch Kai-Florian
Published: January 2025

Infradian mood and sleep-wake rhythms with periods of 48 hours and beyond have been observed in patients with bipolar disorder (BD), which even persist in the absence of exogenous timing cues, indicating an endogenous origin. Here, we show that mice exposed to methamphetamine in drinking water develop infradian locomotor rhythms with periods of 48 hours and beyond which extend to sleep length and manic state–associated behaviors in support of a model for cycling in BD. The cycling capacity is abrogated upon genetic disruption of dopamine (DA) production in DA neurons of the ventral tegmental area (VTA) or ablation of nucleus accumbens projecting DA neurons. Furthermore, chemogenetic activation of
VTA
DA neurons including those that project to the nucleus accumbens led to locomotor period lengthening in circadian clock–deficient mice, which was counteracted by antipsychotic treatment. Together, our findings argue that BD cycling relies on infradian rhythm generation that depends on mesolimbic DA neurons.
Shifting Antarctic Circumpolar Current south of Africa over the past 1.9 million years
Authors: Starr Aidan , Hall Ian R. , Barker Stephen , Nederbragt Alexandra , Owen Lindsey , Hemming Sidney R.
Published: January 2025

The Antarctic Circumpolar Current (ACC) dominates the transfer of heat, salt, and tracers around the Southern Ocean (SO), driving the upwelling of carbon-rich deep waters around Antarctica. Paleoclimate reconstructions reveal marked variability in SO circulation; however, few records exist coupling quantitative reconstructions of ACC flow with tracers of SO upwelling spanning multiple Pleistocene glacial cycles. Here, we reconstruct near-bottom flow speed variability in the SO south of Africa, revealing systematic glacial-interglacial variations in the strength and/or proximity of ACC jets. These are superimposed by warmer-than-present “super-interglacials,” whereby extreme slowdown in the midlatitude ACC (41°S) is opposed by faster flow at higher latitudes (>54°S), implying poleward strengthening of the ACC. Coupled with reconstructions of the subsurface-deep stable carbon isotope gradient, we show that the reorganization of ACC coincides with the upwelling of isotopically light deep waters around Antarctica, likely contributing to the interglacial rise in atmospheric carbon dioxide (CO
2
) levels.
Transcription factor clusters as information transfer agents
Authors: Munshi Rahul , Ling Jia , Ryabichko Sergey , Wieschaus Eric F. , Gregor Thomas
Published: January 2025

Deciphering how genes interpret information from transcription factor (TF) concentrations within the cell nucleus remains a fundamental question in gene regulation. Recent advancements have revealed the heterogeneous distribution of TF molecules, posing challenges to precisely decoding concentration signals. Using high-resolution single-cell imaging of the fluorescently tagged TF Bicoid in living
Drosophila
embryos, we show that Bicoid accumulation in submicrometer clusters preserves the spatial information of the maternal Bicoid gradient. These clusters provide precise spatial cues through intensity, size, and frequency. We further discover that Bicoid target genes colocalize with these clusters in an enhancer-binding affinity-dependent manner. Our modeling suggests that clustering offers a faster sensing mechanism for global nuclear concentrations than freely diffusing TF molecules detected by simple enhancers.
Persistent but weak magnetic field at the Moon’s midstage revealed by Chang’e-5 basalt
Authors: Cai Shuhui , Qin Huafeng , Wang Huapei , Deng Chenglong , Yang Saihong , Xu Ya , Zhang Chi , Tang Xu , Gu Lixin , Li Xiaoguang , Shen Zhongshan , Zhang Min , He Kuang , Qi Kaixian , Fan Yunchang , Dong Liang , Hou Yifei , Shi Pingyuan , Liu Shuangchi , Su Fei , Chen Yi , Li Qiuli , Li Jinhua , Mitchell Ross N. , He Huaiyu , Li Chunlai , Pan Yongxin , Zhu Rixiang
Published: January 2025

The evolution of the lunar magnetic field can reveal the Moon’s interior structure, thermal history, and surface environment. The mid-to-late-stage evolution of the lunar magnetic field is poorly constrained, and thus, the existence of a long-lived lunar dynamo remains controversial. The Chang’e-5 mission returned the heretofore youngest mare basalts from Oceanus Procellarum uniquely positioned at midlatitude. We recovered weak paleointensities of ~2 to 4 microtesla from the Chang’e-5 basalt clasts at 2 billion years ago, attesting to the longevity of the lunar dynamo until at least the Moon’s midstage. This paleomagnetic result implies the existence of thermal convection in the lunar deep interior at the lunar midstage, which may have supplied mantle heat flux for young volcanism.
Spatial transcriptomics in bone mechanomics: Exploring the mechanoregulation of fracture healing in the era of spatial omics
Authors: Mathavan Neashan , Singh Amit , Marques Francisco Correia , Günther Denise , Kuhn Gisela A. , Wehrle Esther , Müller Ralph
Published: January 2025

In recent decades, the field of bone mechanobiology has sought experimental techniques to unravel the molecular mechanisms governing the phenomenon of mechanically regulated fracture healing. Each cell within a fracture site resides within different local microenvironments characterized by different levels of mechanical strain; thus, preserving the spatial location of each cell is critical in relating cellular responses to mechanical stimuli. Our spatial transcriptomics–based “mechanomics” platform facilitates spatially resolved analysis of the molecular profiles of cells with respect to their local in vivo mechanical environment by integrating time-lapsed in vivo micro–computed tomography, spatial transcriptomics, and micro–finite element analysis. We investigate the transcriptomic responses of cells as a function of the local strain magnitude by identifying the differential expression of genes in regions of high and low strain within a fracture site. Our platform thus has the potential to address fundamental open questions within the field and to discover mechano-responsive targets to enhance fracture healing.
Deep learning–enabled filter-free fluorescence microscope
Authors: Dai Bo , You Shaojie , Wang Kan , Long Yan , Chen Junyi , Upreti Neil , Peng Jing , Zheng Lulu , Chang Chenliang , Huang Tony Jun , Guan Yangtai , Zhuang Songlin , Zhang Dawei
Published: January 2025

Optical filtering is an indispensable part of fluorescence microscopy for selectively highlighting molecules labeled with a specific fluorophore and suppressing background noise. However, the utilization of optical filtering sets increases the complexity, size, and cost of microscopic systems, making them less suitable for multifluorescence channel, high-speed imaging. Here, we present filter-free fluorescence microscopic imaging enabled with deep learning–based digital spectral filtering. This approach allows for automatic fluorescence channel selection after image acquisition and accurate prediction of fluorescence by computing color changes due to spectral shifts with the presence of excitation scattering. Fluorescence prediction for cells and tissues labeled with various fluorophores was demonstrated under different magnification powers. The technique offers accurate identification of labeling with robust sensitivity and specificity, achieving consistent results with the reference standard. Beyond fluorescence microscopy, the deep learning–enabled spectral filtering strategy has the potential to drive the development of other biomedical applications, including cytometry and endoscopy.
Atomic-scale structure of ZrO
2
: Formation of metastable polymorphs
Authors: Solomon Alexandre P. , O’Quinn Eric C. , Liu Juejing , Gussev Igor M. , Guo Xiaofeng , Neuefeind Joerg , Trautmann Christina , Ewing Rodney C. , Baldinozzi Gianguido , Lang Maik K.
Published: January 2025

Metastable phases can exist within local minima in the potential energy landscape when they are kinetically “trapped” by various processing routes, such as thermal treatment, grain size reduction, chemical doping, interfacial stress, or irradiation. Despite the importance of metastable materials for many technological applications, little is known about the underlying structural mechanisms of the stabilization process and atomic-scale nature of the resulting defective metastable phase. Investigating ion-irradiated and nanocrystalline zirconia with neutron total scattering experiments, we show that metastable tetragonal ZrO
2
consists of an underlying structure of ferroelastic, orthorhombic nanoscale domains stabilized by a network of domain walls. The apparent long-range tetragonal structure that can be recovered to ambient conditions is only the configurational ensemble average of the underlying orthorhombic domains. This structural heterogeneity with a distinct short-range order is more broadly applicable to other nonequilibrium materials and provides insight into the synthesis and recovery of functional metastable phases with unique physical and chemical properties.
Self-healing and hyperelastic magneto-iono-elastomers through molecular confinement of magnetic anions
Authors: Zhang Xuan , Zhang Lishu , Liu Meilin , Chng Chin Boon , Ler Eddy Pang Yi , Zhou Jinrun , Matsuhisa Naoji , Tan Yu Jun
Published: January 2025

Magneto-responsiveness in living organisms, exemplified by migratory birds navigating vast distances, offers inspiration for soft robots and human-computer interfaces. However, achieving both high magneto-responsiveness and resilient mechanical properties in synthetic materials has been challenging. Here, we develop magneto-iono-elastomers (MINEs), combining exceptional magnetization [2.6 emu (electromagnetic units)/g] with hyperelasticity and self-healability. Such a MINE consists of a magnetic ionic liquid (MIL; [Emim][FeCl
4
]) and a urethane group–based polymer that can distinctively confine magnetic anions through strong intermolecular interactions, including potential hydrogen bonds and metal-coordination bonds. This confinement enables high MIL loading (80 wt %) while maintaining structure integrity, resulting in a high ionic conductivity exceeding 10
−3
S/cm. Furthermore, the synergistic interplay of these reversible bonds in MINEs contributes to an outstanding elastic recovery that surpasses 99%, alongside good self-healing capabilities. The unique combination of these attributes positions MINE as a promising candidate for diverse magnetoelectronic applications, encompassing wearable strain sensors, contactless magneto-responsive electronics, see-through touch panels, and soft magnetic carriers.
Large language models for human-machine collaborative particle accelerator tuning through natural language
Authors: Kaiser Jan , Lauscher Anne , Eichler Annika
Published: January 2025

Autonomous tuning of particle accelerators is an active and challenging research field with the goal of enabling advanced accelerator technologies and cutting-edge high-impact applications, such as physics discovery, cancer research, and material sciences. A challenge with autonomous accelerator tuning remains that the most capable algorithms require experts in optimization and machine learning to implement them for every new tuning task. Here, we propose the use of large language models (LLMs) to tune particle accelerators. We demonstrate on a proof-of-principle example the ability of LLMs to tune an accelerator subsystem based on only a natural language prompt from the operator, and compare their performance to state-of-the-art optimization algorithms, such as Bayesian optimization and reinforcement learning–trained optimization. In doing so, we also show how LLMs can perform numerical optimization of a nonlinear real-world objective. Ultimately, this work represents another complex task that LLMs can solve and promises to help accelerate the deployment of autonomous tuning algorithms to day-to-day particle accelerator operations.
Extracellular fluid viscosity regulates human mesenchymal stem cell lineage and function
Authors: Amitrano Alice , Yuan Qinling , Agarwal Bhawana , Sen Anindya , Dance Yoseph W. , Zuo Yi , Phillip Jude M. , Gu Luo , Konstantopoulos Konstantinos
Published: January 2025

Human mesenchymal stem cells (hMSCs) respond to mechanical stimuli, including stiffness and viscoelasticity. To date, it is unknown how extracellular fluid viscosity affects hMSC function on substrates of different stiffness and viscoelasticity. While hMSCs assume an adipogenic phenotype on gels of low stiffness and prescribed stress relaxation times, elevated fluid viscosity is sufficient to bias hMSCs toward an osteogenic phenotype. Elevated viscosity induces Arp2/3-dependent actin remodeling, enhances NHE1 activity, and promotes hMSC spreading via up-regulation of integrin-linked kinase. The resulting increase in membrane tension triggers the activation of transient receptor potential cation vanilloid 4 to facilitate calcium influx, thereby stimulating RhoA/ROCK and driving YAP-dependent RUNX2 translocation to the nucleus, leading to osteogenic differentiation. hMSCs on soft gels at elevated relative to basal viscosity favor an M2 macrophage phenotype. This study establishes fluid viscosity as a key physical cue that imprints osteogenic memory in hMSCs and promotes an immunosuppressive phenotype.
Determinants of increased muscle insulin sensitivity of exercise-trained versus sedentary normal weight and overweight individuals
Authors: Pesta Dominik , Anadol-Schmitz Evrim , Sarabhai Theresia , Op den Kamp Yvo , Gancheva Sofiya , Trinks Nina , Zaharia Oana-Patricia , Mastrototaro Lucia , Lyu Kun , Habets Ivo , Op den Kamp-Bruls Yvonne M. H. , Dewidar Bedair , Weiss Jürgen , Schrauwen-Hinderling Vera , Zhang Dongyan , Gaspar Rafael Calais , Strassburger Klaus , Kupriyanova Yuliya , Al-Hasani Hadi , Szendroedi Julia , Schrauwen Patrick , Phielix Esther , Shulman Gerald I. , Roden Michael
Published: January 2025

The athlete’s paradox states that intramyocellular triglyceride accumulation associates with insulin resistance in sedentary but not in endurance-trained humans. Underlying mechanisms and the role of muscle lipid distribution and composition on glucose metabolism remain unclear. We compared highly trained athletes (ATHL) with sedentary normal weight (LEAN) and overweight-to-obese (OVWE) male and female individuals. This observational study found that ATHL show higher insulin sensitivity, muscle mitochondrial content, and capacity, but lower activation of novel protein kinase C (nPKC) isoforms, despite higher diacylglycerol concentrations. Notably, sedentary but insulin sensitive OVWE feature lower plasma membrane-to-mitochondria
sn
-1,2-diacylglycerol ratios. In ATHL, calpain-2, which cleaves nPKC, negatively associates with PKCε activation and positively with insulin sensitivity along with higher GLUT4 and hexokinase II content. These findings contribute to explaining the athletes’ paradox by demonstrating lower nPKC activation, increased calpain, and mitochondrial partitioning of bioactive diacylglycerols, the latter further identifying an obesity subtype with increased insulin sensitivity (NCT03314714).
G6PC2 controls glucagon secretion by defining the set point for glucose in pancreatic α cells
Authors: Bahl Varun , Rifkind Reut , Waite Eric , Hamdan Zenab , May Catherine Lee , Manduchi Elisabetta , Voight Benjamin F. , Lee Michelle Y. Y. , Tigue Mark , Manuto Nicholas , Glaser Benjamin , Avrahami Dana , Kaestner Klaus H.
Published: January 2025

Elevated glucagon concentrations have been reported in patients with type 2 diabetes (T2D). A critical role for α cell–intrinsic mechanisms in regulating glucagon secretion was previously established through genetic manipulation of the glycolytic enzyme glucokinase (GCK) in mice. Genetic variation at the glucose-6-phosphatase catalytic subunit 2 (
G6PC2
) locus, encoding an enzyme that opposes GCK, has been reproducibly associated with fasting blood glucose and hemoglobin A1c. Here, we found that trait-associated variants in the
G6PC2
promoter are located in open chromatin not just in β but also in α cells and documented allele-specific
G6PC2
expression of linked variants in human α cells. Using α cell–specific gene ablation of
G6pc2
in mice, we showed that this gene plays a critical role in controlling glucose suppression of amino acid–stimulated glucagon secretion independent of alterations in insulin output, islet hormone content, or islet morphology, findings that we confirmed in primary human α cells. Collectively, our data demonstrate that
G6PC2
affects glycemic control via its action in α cells and possibly suggest that G6PC2 inhibitors might help control blood glucose through a bihormonal mechanism.
Vaccination with different group 2 influenza subtypes alters epitope targeting and breadth of hemagglutinin stem–specific human B cells
Authors: Mantus Grace E. , Chopde Ankita J. , Gorman Jason , Cominsky Lauren Y. , Ourahmane Amine , Creanga Adrian , Shimberg Geoffrey D. , Gillespie Rebecca A. , Van Wazer David J. , Zhou Tongqing , Gajjala Suprabhath R. , Williams Connor , Maestle Emma , Reed Douglas S. , Serebryannyy Leonid , Costner Pamela , Holman Lasonji , Casazza Joseph P. , Koup Richard A. , Dropulic Lesia K. , Kwong Peter D. , McDermott Adrian B. , Kanekiyo Masaru , Andrews Sarah F.
Published: January 2025

The conserved influenza hemagglutinin stem, which is a target of cross-neutralizing antibodies, is now used in vaccine strategies focused on protecting against influenza pandemics. Antibody responses to group 1 stem have been extensively characterized, but little is known about group 2. Here, we characterized the stem-specific repertoire of individuals vaccinated with one of three group 2 influenza subtypes (H3, H7, or H10). Epitope mapping revealed two epitope supersites on the group 2 stem. Antibodies targeting the central epitope were broadly cross-reactive, whereas antibodies targeting the lower epitope had narrower breadth but higher potency against H3 subtypes. The ratio of B cells targeting each of the supersites varied with the vaccine subtype, leading to differences in the cross-reactivity of the B cell response. Our findings suggest that vaccine strategies targeting both group 2 stem epitopes would be complementary, eliciting broader and more potent protection against both seasonal and pandemic influenza strains.
Respiratory health outcomes of children with Down Syndrome following dysphagia management: a service evaluation
Authors: de Silva Himali , Shah Neekita , Mathura Narad , Smith Christina
Published: January 2025

Children living with Down syndrome are at a high risk of eating and drinking difficulties (dysphagia) and are more susceptible to respiratory infections. In an urban National Health Service community Trust, a retrospective service evaluation was carried out for referrals received during 2012–2017. The study examined the respiratory health outcomes 3 years after dysphagia intervention. Children whose dysphagia was identified early (<12 months) using cervical auscultation with subsequent intervention did not develop lower respiratory tract infections (LRTI) post intervention. Children whose dysphagia management was commenced after 12 months of age and those who had no intervention developed LRTI.
Comparison of the performance of myopia control in European children and adolescents with defocus incorporated multiple segments (DIMS) and highly aspherical lenslets (HAL) spectacles
Authors: Lembo Andrea , Schiavetti Irene , Serafino Massimiliano , Caputo Roberto , Nucci Paolo
Published: January 2025

Purpose

A performance comparison of two myopia control spectacle lens designs, defocus incorporated multiple segments (DIMS) and highly aspherical lenslets (HAL), at slowing myopia progression in a European child/adolescent population. Previous research directly comparing these designs has been limited to Chinese participants and 1-year follow-up. The prevalence of myopia in European child/adolescent has been estimated at 22.60%.

Methods

Retrospective cohort study of individuals (6–17 years) with myopia progression. Participants wore DIMS (Hoya MiyoSmart) or HAL (Essilor Stellest) spectacles for a minimum of 2 years. Axial length (AL) and cycloplegic autorefraction (spherical equivalent refraction (SER)) were measured at baseline and 1 and 2 years.

Results

Mean 1-year SER changes for DIMS were −0.34D (±0.46 SD) and HAL −0.30D (±0.30); 2-year changes for DIMS were −0.50D (±0.64 SD) and HAL −0.63D (±0.56). Mean 1-year AL increases for DIMS were 0.19 mm (±0.56) and HAL 0.15 mm (±0.47); 2-year increases for DIMS were 0.29 mm (±0.63) and HAL 0.32 mm (±0.72). For equivalence margins of 0.25D and 0.50D for SER at 1 and 2 years, respectively, and similarly 0.20 mm and 0.30 mm margins for AL, DIMS and HAL lenses were equivalent apart from AL at 1 year where the 0.21 mm 95% CI upper limit just exceeded 0.20 mm. At both 1 and 2 years, none of the differences in mean SERs or ALs between DIMS and HAL were clinically or statistically significant (p≥0.05 Mann–Whitney U test). Using linear mixed model analysis, the interaction between lens type and time did not significantly affect SER or AL at 1- or 2-year follow-up (p≥0.05). 38.4% of children/adolescents with DIMS had no SER progression at 2 years, compared with 21.9% with HAL (p=0.047).

Conclusion

In a European population, DIMS and HAL lenses are essentially equivalent in their ability to reduce myopia progression and AL elongation over a 2-year follow-up period.
Gut-kidney interaction reinforces dapagliflozin-mediated alleviation in diabetic nephropathy
Authors: Ni Yinhua , Du Haimei , Ke Lehui , Zheng Liujie , Nan Sujie , Ni Liyang , Pan Yuxiang , Fu Zhengwei , He Qiang , Jin Juan
Published: January 2025

We demonstrated that dapagliflozin administration alleviated renal inflammation and fibrosis in vivo and in vitro, along with reshaping the gut microbiota composition and altering levels of key microbial metabolites, including argininosuccinic acid (ASA) and palmitic acid (PA), while increasing S-allylcysteine (SAC). Importantly, the genera Muribaculaceae and Desulfovibrionaceae emerged as pivotal microbial genera mediating the protective effects of dapagliflozin against diabetic nephropathy.
Stakeholder prioritization preferences for individuals awaiting hip and knee arthroplasty
Authors: Farrow Luke , Clement Nick D. , Smith Diane , Dominic Meek R. M. , Ryan Mandy , Gillies Katie , Anderson Lesley
Published: January 2025

Aims

Prolonged waits for hip and knee arthroplasty have raised questions about the equity of current approaches to waiting list prioritization for those awaiting surgery. We therefore set out to understand key stakeholder (patient and surgeon) preferences for the prioritization of patients awaiting such surgery, in order to guide future waiting list redesign.

Methods

A combined qualitative/quantitative approach was used. This comprised a Delphi study to first inform which factors patients and surgeons designate as important for prioritization of patients on hip and knee arthroplasty waiting lists, followed by a discrete choice experiment (DCE) to determine how the factors should be weighed against each other. Coefficient values for each included DCE attribute were used to construct a ‘priority score’ (weighted benefit score) that could be used to rank individual patients waiting for surgery based on their respective characteristics.

Results

In total, 43 people participated in the initial round of the Delphi study (16 patients and 27 surgeons), with a 91% completion rate across all three rounds. Overall, 73 surgeons completed the DCE. Following the final consensus meeting of the Delphi component, the seven final factors designated for inclusion were Pain, Mobility/Function, Activities of Daily Living, Inability to Work/Care, Length of Time Waited, Radiological Severity, and Mental Wellbeing. Output from the adjusted multinomial regression revealed radiological severity to be the most significant factor (coefficient 2.27 (SD 0.31); p < 0.001), followed by pain (coefficient 1.08 (SD 0.13); p < 0.001) and time waited (coefficient for one month additional wait 0.12 (SD 0.02); p < 0.001).

Conclusion

These results present a new robust method for determining comparative priority for those on primary hip and knee hip arthroplasty waiting lists. Evaluation of potential implementation in clinical practice is now required.

Cite this article: Bone Joint J 2025;107-B(1):89–96.
Robotic arm-assisted medial compartment knee arthroplasty is a cost-effective intervention at ten-year follow-up
Authors: Blyth Mark J. G. , Clement Nick D. , Choo Xin Y. , Doonan James , MacLean Angus , Jones Bryn G.
Published: January 2025

Aims

The aim of this study was to perform an incremental cost-utility analysis and assess the impact of differential costs and case volume on the cost-effectiveness of robotic arm-assisted medial unicompartmental knee arthroplasty (rUKA) compared to manual (mUKA).

Methods

Ten-year follow-up of patients who were randomized to rUKA (n = 64) or mUKA (n = 65) was performed. Patients completed the EuroQol five-dimension health questionnaire preoperatively, at three months, and one, two, five, and ten years postoperatively, which was used to calculate quality-adjusted life years (QALY) gained and the incremental cost-effectiveness ratio (ICER). Costs for the index and additional surgery and healthcare costs were calculated.

Results

mUKA had a lower survival for reintervention (84.8% (95% CI 76.2 to 93.4); p = 0.001), all-cause revision (88.9% (95% CI 81.3 to 96.5); p = 0.007) and aseptic revision (91.9% (95% CI 85.1 to 98.7); p = 0.023) when compared to the rUKA group at ten years, which was 100%. The rUKA group had a greater QALY gain per patient (mean difference 0.186; p = 0.651). Overall rUKA was the dominant intervention, being cost-saving and more effective with a greater health-related quality of life gain. On removal of infected reinterventions (n = 2), the ICER was £757 (not discounted) and £481 (discounted). When including all reintervention costs, rUKA was cost-saving when more than 100 robotic cases were performed per year. When removing the infected cases, rUKA was cost-saving when undertaking more than 800 robotic cases per year.

Conclusion

rUKA had lower reintervention and revision risks at ten years, which was cost-saving and associated with a greater QALY gain, and was the dominant procedure. When removing the cost of infection, which could be a random event, rUKA was a cost-effective intervention with an ICER (£757) which was lower than the willingness-to-pay threshold (£20,000).

Cite this article: Bone Joint J 2025;107-B(1):72–80.
A systematic review of short- compared with standard-length Exeter stems in primary total hip arthroplasty
Authors: Mc Donald Stephen , Yoong Andrel , Evans Jonathan T. , Farrow Luke
Published: January 2025

Aims

The Exeter femoral stem has a cemented, polished taper-slip design, and an excellent track record. The current range includes short-length options for various offsets, but less is known about the performance of these stems. The aim of this study was to compare the survival of short-length stems with standard-length Exeter stems.

Methods

A systematic review of all studies reporting the use of short-length Exeter stems in primary total hip arthroplasty (THA) was undertaken. Survival data, the indication for revision, and patient-reported outcomes were gathered from observational and randomized studies. Studies based on registry data were analyzed separately.

Results

The review included nine studies which covered a total of 2,190 short stems. The mean follow-up was 6.4 years (2 to 12) with an all-cause survival of 95.4%. When revisions due to aseptic acetabular loosening were excluded, the survival was 97.7%. Four stems fractured (0.18%). The mean Oxford Hip Score improved from 18.29 (1.33 to 21.6) preoperatively to 41.59 (32.9 to 43.4) at final follow-up. Three studies used data from national registries. A total of 25,895 short stems (offset ≤ 35.5 mm) were used compared with 336,218 standard-length stems. In these studies, short stems had a hazard ratio (HR) for all-cause survival of 1.19 (95% CI 0.96 to 1.43) with a rate of revision per 1,000 component-years of 0.037 compared with 0.035 for standard-length stems. One study from the New Zealand Joint Registry divided short stems into standard and small offset groups. Standard offset short stems (≥ 37.5 mm) had a 0.84 HR (95% CI 0.38 to 1.88) while small offset short stems (≤ 35.5 mm) had a 1.6 HR compared with standard stems (95% CI 1.3 to 1.98).

Conclusion

Short Exeter stems perform well and are a safe femoral component in primary THA, according to the current literature. There does not appear to be an increased risk of implant fracture associated with these stems.

Cite this article: Bone Joint J 2025;107-B(1):27–33.
Supportive bandage, removable splint, or walking casts for low-risk ankle fractures in children: a feasibility randomized controlled trial
Authors: Marson Ben A. , Gurney Matilda , Manning Joseph C. , James Marilyn , Ogollah Reuben , Durand Charlotte , Ollivere Benjamin J.
Published: January 2025

Aims

It is unclear if a supportive bandage, removable splint, or walking cast offers the best outcome following low-risk ankle fractures in children. The aim of this study was to evaluate the feasibility of a randomized controlled trial to compare these treatments.

Methods

Children aged five to 15 years with low-risk ankle fractures were recruited to this feasibility trial from 1 February 2020 to 30 March 2023. Children were randomized to supportive bandage, removable splint, or walking cast for two weeks. Follow-up at two, six, and 12 weeks was undertaken to determine feasibility for a definitive trial. Outcomes collected included complications, the Patient-Reported Outcomes Measurement Information System (PROMIS) mobility score, Paediatric Quality of Life Inventory, youth version of the EuroQol five-dimension health questionnaire, and Activities Scale for Kids - Performance.

Results

A total of 87 children from six hospitals were randomized at a rate of 0.9 participants per site per month. Two children in the supportive bandage group crossed over to an alternative device. Complications were reported in six children. One child in the cast group developed skin blisters. One child in cast and one in bandage sustained a reinjury during the 12-week follow-up, and two children (one splint and one cast) required additional immobilization after the two-week treatment for persistent pain. Of the 84 participants who remained in the study at six weeks, 43 (51.2%) returned follow-up questionnaires at six weeks. Of the patient-reported outcome measures (PROMs), proxy-reported PROMIS mobility showed good responsiveness, low ceiling effects, and low missing item rates. In an exploratory analysis, small differences were observed between groups, with no evidence that any of the treatments were superior.

Conclusion

This feasibility study showed acceptable recruitment and retention rates. There remains equipoise regarding the best treatment of these injuries. All three treatments appear well tolerated with similar complication rates. A primary outcome of complications or treatment failure would provide the highest study retention with secondary PROMs and economic analysis.

Cite this article: Bone Joint J 2025;107-B(1):108–117.
Hip-lumbar mobility loss affects quality of life in patients undergoing both lumbar fusion and total hip arthroplasty
Authors: Tokuyasu Hiroyuki , Kim Youngwoo , Vergari Claudio , Tada Hiroshi , Tanaka Chiaki , Takemoto Mitsuru
Published: January 2025

Aims

Overall sagittal flexion is restricted in patients who have undergone both lumbar fusion and total hip arthroplasty (THA). However, it is not evident to what extent this movement is restricted in these patients and how this influences quality of life (QoL). The purpose of this study was to determine the extent to which hip-lumbar mobility is decreased in these patients, and how this affects their QoL score.

Methods

Patients who underwent primary THA at our hospital between January 2010 and March 2021 were considered (n = 976). Among them, 44 patients who underwent lumbar fusion were included as cases, and 44 THA patients without lumbar disease matched by age, sex, and BMI as Control T. Among those who underwent lumbar fusion, 44 patients without hip abnormalities matched by age, sex, and BMI to the cases were considered as Control F. Outcome and spinopelvic parameters were measured radiologically in extension and flexed-seated positions. Hip, lumbar, and hip-lumbar mobility were calculated as parameter changes between positions.

Results

There were 20 male and 112 female patients in the case and control groups, with a mean age of 77 years (5 to 94) and a mean BMI of 24 kg/m2 (15 to 34). QoL score and hip-lumbar mobility were reduced in cases compared to Control T and F, and were further reduced as the number of fused levels increased. Hip-lumbar mobility was associated with reduction in activity-related QoL, mostly for those activities requiring sagittal flexion.

Conclusion

This study confirmed that hip-lumbar mobility is a factor that influences activity, most of all those requiring overall sagittal flexion. Clinicians should focus on hip-lumbar mobility and counteract disability by suggesting appropriate assistive devices.

Cite this article: Bone Joint J 2025;107-B(1):34–41.
Implant survival at four years for hemiarthroplasty and total shoulder arthroplasty in the treatment of atraumatic avascular necrosis of the humeral head
Authors: Smeitink Nick , Schröder Femke F. , Dorrestijn Oscar , Spekenbrink-Spooren Anneke , Govaert Louise H. M. , Veen Egbert J. D.
Published: January 2025

Aims

Hemiarthroplasty (HA) and total shoulder arthroplasty (TSA) are often the preferred forms of treatment for patients with atraumatic avascular necrosis of the humeral head when conservative treatment fails. Little has been reported about the survival of HA and TSA for this indication. The aim of this study was to investigate the differences in revision rates between HA and TSA in these patients, to determine whether one of these implants has a superior survival and may be a better choice in the treatment of this condition.

Methods

Data from 280 shoulders with 159 primary HAs and 121 TSAs, which were undertaken in patients with atraumatic avascular necrosis of the humeral head between January 2014 and January 2023 from the Dutch Arthroplasty Register (LROI), were included. Kaplan-Meier survival analysis and Cox regression analysis were undertaken.

Results

Within four years of follow-up, a total of 15 revisions were required, involving seven HAs (4%) and eight TSAs (7%). This difference was not statistically significant (p = 0.523). Two HAs were revised because of progressive glenoid erosion, and three TSAs were revised for loosening of the glenoid component. The cumulative percentages of revision of HA and TSA were 6% and 8%, respectively (HR 1.1 (95% CI 0.5 to 2.7)).

Conclusion

We found no significant difference in short- to mid-term implant survival between the use of a HA and a TSA in the treatment of atraumatic avascular necrosis of the humeral head, without significant glenoid wear.

Cite this article: Bone Joint J 2025;107-B(1):97–102.
Haemodynamic measurements during hip hemiarthroplasty surgery for hip fracture
Authors: Fernandez Miguel A. , Henshaw Freddie , Carlos William J. , Kelly Andrew , Griffin Xavier L. , Costa Matt L.
Published: January 2025

Aims

There is compelling evidence for the use of cemented hip hemiarthroplasty for displaced intracapsular hip fractures; however, the risks of cement are well reported and in rare cases may be associated with haemodynamic collapse. It is therefore important to improve our understanding of haemodynamic instability, intraoperative monitoring, and strategies to reduce the risk to patients.

Methods

We measured arterial blood pressure using the LiDCOrapid Continuous Non-invasive Arterial Pressure (CNAP) finger cuff during surgery in patients enrolled in the WHiTE 5 trial randomized to cemented or modern uncemented hip hemiarthroplasty at a single recruiting site. We observed the incidence, timing, and magnitude of haemodynamic instability at key stages of the surgical procedure.

Results

We obtained measurements from 56 patients, of whom 46 had complete recordings and were used in the analysis. Modest falls in systolic blood pressure (20% to 30%) occurred in four patients (15%) who received a cemented hemiarthroplasty and one patient (5%) in the uncemented group. The fall in blood pressure occurred either within five minutes of cementing or at final hip reduction. We observed concurrent drops in cardiac output (CO) and stroke volume (SV).

Conclusion

We observed the presence of two potential periods for haemodynamic instability during hip hemiarthroplasty surgery: the first was within five minutes of cementing the femoral canal and the second after final reduction of the prosthesis (observed in both cemented and uncemented hemiarthroplasty). The falls in blood pressure appeared to be driven by reduced CO and SV.

Cite this article: Bone Joint J 2025;107-B(1):103–107.
Automating radiological measurements of the hip in children with cerebral palsy
Authors: Thompson Peter , Khattak Mohammed , Joseph P. J. , Perry Daniel C. , Cootes Timothy F. , Lindner Claudia
Published: January 2025

Aims

The aims of this study were to develop an automatic system capable of calculating four radiological measurements used in the diagnosis and monitoring of cerebral palsy (CP)-related hip disease, and to demonstrate that these measurements are sufficiently accurate to be used in clinical practice.

Methods

We developed a machine-learning system to automatically measure Reimer’s migration percentage (RMP), acetabular index (ACI), head shaft angle (HSA), and neck shaft angle (NSA). The system automatically locates points around the femoral head and acetabulum on pelvic radiographs, and uses these to calculate measurements. The system was evaluated on 1,650 pelvic radiographs of children with CP (682 females and 968 males, mean age 8.3 years (SD 4.5)). Each radiograph was manually measured by five clinical experts. Agreement between the manual clinical measurements and the automatic system was assessed by mean absolute deviation (MAD) from the mean manual measurement, type 1 and type 2 intraclass correlation coefficients (ICCs), and a linear mixed-effects model (LMM) for assessing bias.

Results

The MAD scores were 5.7% (SD 8.5%) for RMP, 4.3° (SD 5.4°) for ACI, 5.0° (SD 5.2°) for NSA, and 5.7° (SD 6.1°) for HSA. Overall ICCs quantifying the agreement between the mean manual measurement and the automatic results were 0.91 for RMP, 0.66 for ACI, 0.85 for NSA, and 0.73 for HSA. The LMM showed no statistically significant bias.

Conclusion

The results showed excellent agreement between the manual and automatic measurements for RMP, good agreement for NSA, and moderate agreement for HSA and ACI. The performance of the system is sufficient for application in clinical practice to support the assessment of hip migration based on RMP. The system has the potential to save clinicians time and to improve patient care by enabling more comprehensive, consistent, and reliable monitoring of hip migration in children with CP.

Cite this article: Bone Joint J 2025;107-B(1):124–132.
Chronicles from a Walled-Up Ward: The Black Hole of Public Housing Policies and Its Consequences in a Medium-Sized Italian City
Authors: Perini Lorenza
Published: January 2025

The research aims to shed light on the case of a medium-sized town in the northeast part of Italy, where a semi-central neighbourhood, encompassing a triangle of streets and hundreds of apartments, has recently acquired the reputation of being an ‘urban social problem’, and is described by the local media as a ‘drug-dealing suburb’. Specifically, since 2021, most of the state- and company-owned buildings have been completely bricked up, families evicted, and apartments and gardens left in a state of complete abandonment, without giving residents any explanation, and without a plan for the future, except demolition. Using ethnographic and qualitative methodologies, this study seeks to investigate the reasons why such negative narratives have quickly become established in common discourse and are then immediately amplified by the media until they remain the only description of the neighbourhood, and to examine how residents have strived and worked to restore the centrality of their ‘sense of place’. In the conclusions, an attempt will be made to sketch out an answer to the classic question of whether a turnaround can be more easily brought about by large urban renewal plans, or whether community involvement in a network of ‘small plans’ might be more effective.
Caminos de inclusión: ayuda mutua y reconstrucción de identidades juveniles
Authors: Martín García Xus
Published: January 2025

La situación de los chicos y chicas que viven en riesgo de exclusión social se complica cuando abandonan las instituciones socioeducativas de las que han formado parte durante su infancia y adolescencia. La mayoría no cuenta con el soporte emocional ni económico de sus progenitores, y se encuentra en una situación marcada por la soledad y la sensación de desamparo. Reconociendo esta realidad, la investigación cualitativa que se presenta en este artículo se ha orientado a diseñar una propuesta que permita reconstruir y afianzar la relación de estas y estos jóvenes atendiendo a tres dimensiones: la relación con uno mismo, la relación con los iguales, y la relación con los adultos.
Se parte de la hipótesis que la puesta en práctica y activación de tres dinamismos pedagógicos –ayuda mutua, estrategias de autoconocimiento y procesos de acompañamiento por parte de un adulto– favorece en los jóvenes, la inclusión en la comunidad, la reconstrucción de la identidad y el diseño de proyectos vitales normalizados alejados de la marginación.
Durante veinte meses se ha realizado un trabajo de campo en un grupo formado por nueve chicos y dos chicas de edades comprendidas entre los diecisiete y los veintiún años. Se han llevado a cabo cuarenta y tres sesiones y ocho tutorías individuales. El análisis de la información ha permitido poner de manifiesto el impacto formativo de la experiencia. Los resultados apuntan a progresos en la aparición de conductas cooperativas, la reconciliación con el pasado, la creación de proyectos de futuro alejados de la marginalidad, el interés por la formación académica y el desarrollo de la conciencia social.
Questioning the Challenge to Screen Use Guidelines
Authors: L'ecuyer Catherine , Oron Semper José Víctor , Montiel Irene , Osorio Alfonso , López-Fidalgo Jesús , Salmerón Ruiz M. Angustias
Published: January 2025

In September 2023, “An umbrella review of the benefits and risks associated with youths’ interactions with electronic screens” was published in Nature. This review aimed at understanding the influence of electronic screens on the health and educational outcome of children and adolescents from 0-18 years old. The authors concluded that current screen use guidelines may be too simplistic, that they mischaracterize the strength of the evidence or do not acknowledge the important nuances of the issue. As a result, they supported the trend of moving away from recommendations to reduce screen use and instead focus on the type of screen use. Our contribution focuses on answering the question of whether the results of this review are sufficient to challenge current screen use guidelines. To do so, we explain the current literature on screen use guidelines that the review generically referred to as well as the rationale behind them, and then we proceed to explain why the review’s findings are insufficient to challenge these guidelines. We demonstrate that some of the review's main conclusions are not consistent with its own findings and that they fail to explain the relationship between their findings and the discreditation of current guidelines. Absence of evidence is not evidence of absence and investigators should be careful in questioning public health recommendations based on incomplete evidence.