bluuebunny/crossref_metadata_2025_split huggingface dataset:
The EstroGene2.0 database for endocrine therapy response and resistance in breast cancer
Authors: Li Zheqi , Chen Fangyuan , Chen Li , Liu Jiebin , Tseng Danielle , Hadi Fazal , Omarjee Soleilmane , Kishore Kamal , Kent Joshua , Kirkpatrick Joanna , D’Santos Clive , Lawson Mandy , Gertz Jason , Sikora Matthew J. , McDonnell Donald P. , Carroll Jason S. , Polyak Kornelia , Oesterreich Steffi , Lee Adrian V. 
Published: December 2024

AbstractEndocrine therapies targeting the estrogen receptor (ER/ESR1) are the cornerstone to treat ER-positive breast cancers patients, but resistance often limits their effectiveness. Notable progress has been made although the fragmented way data is reported has reduced their potential impact. Here, we introduce EstroGene2.0, an expanded database of its precursor 1.0 version. EstroGene2.0 focusses on response and resistance to endocrine therapies in breast cancer models. Incorporating multi-omic profiling of 361 experiments from 212 studies across 28 cell lines, a user-friendly browser offers comprehensive data visualization and metadata mining capabilities (https://estrogeneii.web.app/). Taking advantage of the harmonized data collection, our follow-up meta-analysis revealed transcriptomic landscape and substantial diversity in response to different classes of ER modulators. Endocrine-resistant models exhibit a spectrum of transcriptomic alterations including a contra-directional shift in ER and interferon signalings, which is recapitulated clinically. Dissecting multiple ESR1-mutant cell models revealed the different clinical relevance of cell model engineering and identified high-confidence mutant-ER targets, such as NPY1R. These examples demonstrate how EstroGene2.0 helps investigate breast cancer’s response to endocrine therapies and explore resistance mechanisms.
Chiral Floquet engineering on topological fermions in chiral crystals
Authors: Fan Benshu , Duan Wenhui , Rubio Angel , Tang Peizhe 
Published: December 2024

AbstractThe interplay of chiralities in light and quantum matter provides an opportunity to design and manipulate chirality-dependent properties in quantum materials. Herein we report the chirality-dependent Floquet engineering on topological fermions with the high Chern number in chiral crystal CoSi via circularly polarized light (CPL) pumping. Intense light pumping does not compromise the gapless nature of topological fermions in CoSi, but displaces the crossing points in momentum space along the direction of light propagation. The Floquet chirality index is proposed to signify the interplay between the chiralities of topological fermion, crystal, and incident light, which determines the amplitudes and directions of light-induced momentum shifts. Regarding the time-reversal symmetry breaking induced by the CPL pumping, momentum shifts of topological fermions result in the birth of transient anomalous Hall signals in non-magnetic CoSi within an ultrafast time scale, which Mid-infrared (IR) pumping and terahertz (THz) Kerr or Faraday probe spectroscopy could experimentally detect. Our findings provide insights into exploring novel applications in optoelectronic devices by leveraging the degree of freedom of chirality in the non-equilibrium regime.
Artificial intelligence in risk prediction and diagnosis of vertebral fractures
Authors: Namireddy Srikar R. , Gill Saran S. , Peerbhai Amaan , Kamath Abith G. , Ramsay Daniele S. C. , Ponniah Hariharan Subbiah , Salih Ahmed , Jankovic Dragan , Kalasauskas Darius , Neuhoff Jonathan , Kramer Andreas , Russo Salvatore , Thavarajasingam Santhosh G. 
Published: December 2024

AbstractWith the increasing prevalence of vertebral fractures, accurate diagnosis and prognostication are essential. This study assesses the effectiveness of AI in diagnosing and predicting vertebral fractures through a systematic review and meta-analysis. A comprehensive search across major databases selected studies utilizing AI for vertebral fracture diagnosis or prognosis. Out of 14,161 studies initially identified, 79 were included, with 40 undergoing meta-analysis. Diagnostic models were stratified by pathology: non-pathological vertebral fractures, osteoporotic vertebral fractures, and vertebral compression fractures. The primary outcome measure was AUROC. AI showed high accuracy in diagnosing and predicting vertebral fractures: predictive AUROC = 0.82, osteoporotic vertebral fracture diagnosis AUROC = 0.92, non-pathological vertebral fracture diagnosis AUROC = 0.85, and vertebral compression fracture diagnosis AUROC = 0.87, all significant (p < 0.001). Traditional models had the highest median AUROC (0.90) for fracture prediction, while deep learning models excelled in diagnosing all fracture types. High heterogeneity (I² > 99%, p < 0.001) indicated significant variation in model design and performance. AI technologies show considerable promise in improving the diagnosis and prognostication of vertebral fractures, with high accuracy. However, observed heterogeneity and study biases necessitate further research. Future efforts should focus on standardizing AI models and validating them across diverse datasets to ensure clinical utility.
Testing perioperative meloxicam analgesia to enhance welfare while preserving model validity in an inflammation-induced seizure model
Authors: Weiß Edna , Pauletti Alberto , Egilmez Asya , Bröer Sonja 
Published: December 2024

AbstractDespite the international effort to improve laboratory animal welfare through the 3R principles (Reduce, Refine, Replace), many scientists still fail to implement and report their assessment of pain and well-being, likely due to concerns regarding the potential effects of analgesics on experimental outcomes. This study aimed to determine whether refining our viral encephalitis model with perioperative analgesia could enhance well-being and recovery after intracerebral virus infection without impacting disease outcomes. We routinely use the Theiler’s Murine Encephalomyelitis Virus (TMEV) model to study virus-induced epilepsy. Given the crucial role of immune cell activation in acute seizure development, we evaluated the effects of the non-steroidal anti-inflammatory drug (NSAID) meloxicam on inflammation, neurodegeneration, and neuronal cell proliferation at 7 days post-infection (dpi). Overall, the impact of virus infection on well-being was less severe than anticipated, and meloxicam treatment did not affect well-being or nest building behavior in TMEV-infected mice. Furthermore, meloxicam treatment did not influence key experimental readouts such as seizure burden, central inflammatory response, neurodegeneration, or neuronal proliferation within the hippocampus. Notably, animals experiencing seizures displayed heightened inflammatory responses and neurodegeneration, which were not influenced by meloxicam treatment. In summary, perioperative analgesia did not compromise key outcome measures such as seizure frequency, inflammation, and neurodegeneration or -regeneration in the TMEV model. However, it also did not add any significant benefits to well-being in the first week after intracranial injections.
Histone variant H3.5 in testicular cell differentiation and its interactions with histone chaperones
Authors: Weil Patrick Philipp , Pembaur Anton , Wirth Beatrice , Oetjen Eda , Büsscher Hannes , Zirngibl Klemens , Czarnetzki Malte , Braun Stella , Cremers Jann-Frederik , Gödde Daniel , Degener Stephan , Postberg Jan 
Published: December 2024

AbstractTesticular cell differentiation is a highly regulated process, essential for male reproductive health. The histone variant H3.5 is apparently a critical player in this intricate orchestra of cell types, but its regulation and function remains poorly understood. To elucidate its role, we fractionized testicular cells using c-Kit/CD117 as a separation marker and analyzed H3.5 expression. Further, we investigated the regulation of H3.5 expression using public data repositories. We explored DNA methylation patterns in specific regions of the H3-5 gene and assessed H3-5 copy number gain in seminoma specimens. Additionally, we examined the testicular localization of H3.5 and its histone chaperone interactions to understand its regulation at the protein level. We used qRT-PCR, MeDIP, and qPCR to study H3.5 expression and DNA methylation in various cell types. H3-5 copy number gain was analyzed using qPCR. Protein interactions were investigated through fluorescence-2-hybrid assays in baby hamster kidney cells. H3.5 is primarily enriched in spermatocytes. DNA methylation of a CpG island overlapping the H3-5 promoter appeared to be involved in the tissue-specific regulation of H3.5 expression. Elevated H3.5 expression was observed in seminoma specimens, suggesting a potential link to testicular tumors. H3-5 copy number gain was associated with elevated H3.5 expression in seminoma specimens. Furthermore, we identified physical interactions between H3.5 and histone chaperones Asf1a and Asf1b, HIRA, CAF p150 and DAXX, shedding light on the protein-level regulation of H3.5. These findings provide valuable insights into the molecular mechanisms governing testicular cell differentiation and the potential role of H3.5 in testicular pathologies.
Geometric deep learning improves generalizability of MHC-bound peptide predictions
Authors: Marzella Dario F. , Crocioni Giulia , Radusinović Tadija , Lepikhov Daniil , Severin Heleen , Bodor Dani L. , Rademaker Daniel T. , Lin ChiaYu , Georgievska Sonja , Renaud Nicolas , Kessler Amy L. , Lopez-Tarifa Pablo , Buschow Sonja I. , Bekkers Erik , Xue Li C. 
Published: December 2024

AbstractThe interaction between peptides and major histocompatibility complex (MHC) molecules is pivotal in autoimmunity, pathogen recognition and tumor immunity. Recent advances in cancer immunotherapies demand for more accurate computational prediction of MHC-bound peptides. We address the generalizability challenge of MHC-bound peptide predictions, revealing limitations in current sequence-based approaches. Our structure-based methods leveraging geometric deep learning (GDL) demonstrate promising improvement in generalizability across unseen MHC alleles. Further, we tackle data efficiency by introducing a self-supervised learning approach on structures (3D-SSL). Without being exposed to any binding affinity data, our 3D-SSL outperforms sequence-based methods trained on ~90 times more data points. Finally, we demonstrate the resilience of structure-based GDL methods to biases in binding data on an Hepatitis B virus vaccine immunopeptidomics case study. This proof-of-concept study highlights structure-based methods’ potential to enhance generalizability and data efficiency, with possible implications for data-intensive fields like T-cell receptor specificity predictions.
Proteomic and metabolomic analyses of the human adult myocardium reveal ventricle-specific regulation in end-stage cardiomyopathies
Authors: Hunter Benjamin , Li Mengbo , Parker Benjamin L. , Koay Yen Chin , Harney Dylan J. , Pearson Evangeline , Cao Jacob , Chen Gavin T. , Guneratne Oneka , Smyth Gordon K. , Larance Mark , O’Sullivan John F. , Lal Sean 
Published: December 2024

AbstractThe left and right ventricles of the human heart are functionally and developmentally distinct such that genetic or acquired insults can cause dysfunction in one or both ventricles resulting in heart failure. To better understand ventricle-specific molecular changes influencing heart failure development, we first performed unbiased quantitative mass spectrometry on pre-mortem non-diseased human myocardium to compare the metabolome and proteome between the normal left and right ventricles. Constituents of gluconeogenesis, glycolysis, lipogenesis, lipolysis, fatty acid catabolism, the citrate cycle and oxidative phosphorylation were down-regulated in the left ventricle, while glycogenesis, pyruvate and ketone metabolism were up-regulated. Inter-ventricular significance of these metabolic pathways was then found to be diminished within end-stage dilated cardiomyopathy and ischaemic cardiomyopathy, while heart failure-associated pathways were increased in the left ventricle relative to the right within ischaemic cardiomyopathy, such as fluid sheer-stress, increased glutamine-glutamate ratio, and down-regulation of contractile proteins, indicating a left ventricular pathological bias.
Structural insights into the enzymatic breakdown of azomycin-derived antibiotics by 2-nitroimdazole hydrolase (NnhA)
Authors: Ahmed F. Hafna , Liu Jian-Wei , Royan Santana , Warden Andrew C. , Esquirol Lygie , Pandey Gunjan , Newman Janet , Scott Colin , Peat Thomas S. 
Published: December 2024

AbstractThe antibiotic 2-nitroimidazole (2NI) or azomycin, used for treating drug-resistant tuberculosis and imaging tumor hypoxia, requires activation by bacterial nitroreductases for its antibiotic and cytotoxic effect. Mycobacterium sp. JS330 produces 2-nitroimidazole nitrohydrolase (NnhA) that circumvents 2NI activation, conferring 2NI resistance by hydrolysing it to nitrite and imidazol-2-one (IM2O) instead. This study elucidates NnhA’s structure, catalytic mechanism, and evolutionary background within the guanidino-group modifying enzyme (GME) superfamily, aided by a more soluble protein variant engineered through directed evolution. Despite low sequence similarity and limited occurrence in a few soil-dwelling mycobacteria and Actinomycetota, NnhA maintains the α/β propeller fold characteristic of GME superfamily enzymes and forms an unusual hexameric ring structure formed by a trimer of domain-swapped dimers. The similarity of its active site to arginine deiminases (ADIs) and human dimethylarginine dimethylaminohydrolases (DDAHs), along with molecular dynamics simulations, suggests NnhA’s catalytic mechanism resembles the hydrolysis reactions of these related enzymes.
Flexibility of intrinsic neural timescales during distinct behavioral states
Authors: Çatal Yasir , Keskin Kaan , Wolman Angelika , Klar Philipp , Smith David , Northoff Georg 
Published: December 2024

AbstractRecent neuroimaging studies demonstrate a heterogeneity of timescales prevalent in the brain’s ongoing spontaneous activity, labeled intrinsic neural timescales (INT). At the same time, neural timescales also reflect stimulus- or task-related activity. The relationship of the INT during the brain’s spontaneous activity with their involvement in task states including behavior remains unclear. To address this question, we combined calcium imaging data of spontaneously behaving mice and human electroencephalography (EEG) during rest and task states with computational modeling. We obtained four primary findings: (i) the distinct behavioral states can be accurately predicted from INT, (ii) INT become longer during behavioral states compared to rest, (iii) INT change from rest to task is correlated negatively with the variability of INT during rest, (iv) neural mass modeling shows a key role of recurrent connections in mediating the rest-task change of INT. Extending current findings, our results show the dynamic nature of the brain’s INT in reflecting continuous behavior through their flexible rest-task modulation possibly mediated by recurrent connections.
Enhanced Weyl semimetal signature in Co3Sn2S2 Kagome ferromagnet by chlorine doping
Authors: He Bin , Yao Mengyu , Pan Yu , Arpino Kathryn E. , Chen Dong , Serrano-Sanchez Federico M. , Ju Sailong , Shi Ming , Sun Yan , Felser Claudia 
Published: December 2024

AbstractWeyl fermions are chiral massless fermions with exotic properties. In the first established magnetic Weyl semimetal, Co3Sn2S2, a giant anomalous Hall effect has been observed, while its Fermi energy remaining 60 meV from the Weyl points. Shifting the Fermi energy closer to the Weyl points may assist in the identification of Weyl Fermion related transport signatures. Here we show that effective chlorine doping has resulted in a shift of the Fermi energy by 15 meV towards the Weyl points, which is confirmed by a combination of the systematic angular-resolved photoemission spectroscopy measurements and density function theory calculations. A five-fold reduction in resistivity is observed in the ferromagnetic phase, accompanied by a pronounced magnetoresistance of over 150%. The anomalous Hall conductivity shows a peak of 1680 Scm−1 at 40 K, which is 30% higher than the undoped sample due to a stronger Weyl point contribution. This work demonstrates the essential role of doping in Co3Sn2S2 for an enhanced Weyl semimetal signature.
Cu-MOF-based targeted nanomedicine utilizing biorthogonally catalyzed chemotherapy and chemodynamic therapy with spatiotemporal orchestration to treat hepatocellular carcinoma
Authors: Wan Xiuyan , Zhang Yu , Zhang Huiwen , Pan Wei , Qiao Xincheng , Li Na , Tang Bo 
Published: December 2024

A targeted nanomedicine based on a Cu-MOF was developed to treat hepatocellular carcinoma utilizing biorthogonally catalyzed chemotherapy and chemodynamic therapy, which significantly suppresses tumor growth with minimum toxicity.
Inelastic H + H3+ collision rates and their impact on the determination of the excitation temperature of H3+
Authors: Félix-González Daniel , del Mazo-Sevillano Pablo , Aguado Alfredo , Roncero Octavio , Le Bourlot Jacques , Roueff Evelyne , Le Petit Franck , Bron Emeric 
Published: December 2024

Context. In diffuse interstellar clouds, the excitation temperature derived from the lowest levels of H3+ is systematically lower than that derived from H2. The differences may be attributed to the lack of state-specific formation and destruction rates of H3+, which are needed to thermalize the two species.
Aims. In this work, we aim to investigate the possible influence of rotational excitation collisions of H3+ with atomic hydrogen on its excitation temperature.
Methods. We used a time-independent close-coupling method to calculate the state-to-state rate coefficients, incorporating a very accurate and full-dimensional potential energy surface recently developed for H4+. We take a symmetric top approach to describe a frozen H3+ as an equilateral triangle.
Results. We derive rotational excitation collision rate coefficients of H3+ with atomic hydrogen in a temperature range corresponding to diffuse interstellar conditions up to (J, K, ±) = (7, 6, +) and (J, K, ±) = (6, 4, +) for its ortho and para forms. This allows us to obtain a consistent set of collisional excitation rate coefficients and to improve on a previous study that included speculations regarding these contributions.
Conclusions. The new state-specific inelastic H3+ + H rate coefficients yield differences of up to 20% in the excitation temperature, and their impact increases with decreasing molecular fraction. We also confirm the impact of chemical state-to-state destruction reactions on the excitation balance of H3+, and that reactive H + H3+ collisions are also needed to account for possible further ortho to para transitions.
Evaluation of irritable bowel syndrome in patients with systemic
sclerosis based on Rome IV criteria
Authors: Tuncel Elif Tugba , Sahinoglu Irem , Uslu Sadettin 
Published: December 2024

Abstract
Objectives The gastrointestinal system is the second most frequently
affected organ system in patients with systemic sclerosis (SSc). Patients with
SSc experience gastrointestinal dysmotility due to pathophysiological changes,
including alterations in intestinal microbiota, inflammation, fibrosis, vascular
ischaemia, and muscle atrophy. The aim of this study was to determine the
prevalence of functional gastrointestinal disorders in patients with SSc.
Material and Methods This study included 66 patients with SSc. Demographic
data, including age, gender, and clinical findings, were recorded. The Rome IV
criteria were used to assess gastrointestinal complaints.
Results A total of 66 (F=61, M=5) patients (limited cutaneous SSc
(lcSSc=31), diffuse cutaneous SSc (dcSSc=35)) were included in this study. In
lcSSs patients, the prevalence of functional dyspepsia, irritable bowel syndrome
(IBS), constipation, and diarrhoea was 29.0%, 12.9%, 6.5% and 3.2%,
respectively, whereas in dcSSc, the prevalence of these disorders was 37.1%,
8.6%, 8.6%, and 0.0%, respectively. There was no statistically significant
difference regarding the presence of functional gastrointestinal disorders
between lcSSc and dcSSc patients. When patients with SSc were compared based on
functional gastrointestinal disorders, no significant differences were observed
between the groups in terms of mean age, disease duration, smoking, lung
involvement, and presence of body mass index≥25.
Conclusion Alterations in gut microbiota and inflammatory changes have
been proposed as contributing factors in IBS. Chronic inflammatory diseases,
such as SSc, may therefore predispose individuals to its development. In our
study, IBS was found in 10.7% of the SSc patients. To identify patients at high
risk of IBS, further studies are required.
Utility of Urine Dipstick Testing in Pediatric Appendicitis: Assessing its Role in Identifying Complicated Cases and Retrocecal Appendicitis
Authors: Biehl Clara Månsson , Elliver Matilda , Gudjonsdottir Johanna , Salö Martin 
Published: December 2024

Abstract
Background Diagnosing appendicitis in children remains a challenge, and the role of urine dipstick is controversial. This study aimed to evaluate the association between abnormal urine dipstick results and appendicitis, particularly appendicitis severity and appendix position.
Methods A prospective cohort study was conducted from 2017 to 2021 at a tertiary hospital in Sweden. Children aged ≤ 15 years with suspected appendicitis were included. Logistic regression was used to assess associations between abnormal urine dipstick results and sex, age, peritonitis, body temperature, C-reactive protein, complicated appendicitis, and appendix position.
Results A total of 311 children with suspected appendicitis were included, with 193 (62%) diagnosed with appendicitis. Among these, 80 (41%) had complicated appendicitis. There was no difference in appendicitis rate between children with positive and normal urine dipstick results. Among children with appendicitis, 119 (62%) had positive urine dipstick results: 49% ketones, 29% erythrocytes, 23% protein, 19% leukocytes, and 2% nitrite. Multivariable analysis revealed that female sex (adjusted odds ratio: 2.41 [95% confidence interval, CI: 1.21–4.80], p = 0.013), retrocecal appendicitis (aOR: 2.39 [95% CI: 1.18–4.84], p = 0.015), and complicated appendicitis (aOR: 2.27 [1.01–5.13], p = 0.015) were significantly associated with abnormal urine dipstick results. Sensitivity and specificity of positive urine dipstick for complicated appendicitis was 56% (95% CI: 45–67%) and 64% (95% CI: 54–73%), respectively, with an area under the curve of 0.62 (95% CI: 0.54–0.70). Limitations in this study include potential unmeasured confounders such as hydration status and urinary tract infections.
Conclusion Abnormal urine dipstick results are common in children with appendicitis. Urine dipstick might help identify cases of complicated and retrocecal appendicitis.