bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum soluble isoform of receptor for advanced glycation end product is a predictive biomarker for acute exacerbation of idiopathic pulmonary fibrosis: a German and Japanese cohort study
Authors: Kitadai Erika , Yamaguchi Kakuhiro , Ohshimo Shinichiro , Iwamoto Hiroshi , Sakamoto Shinjiro , Horimasu Yasushi , Masuda Takeshi , Nakashima Taku , Hamada Hironobu , Bonella Francesco , Guzman Josune , Costabel Ulrich , Hattori Noboru 
Published: November 2024

Abstract
Background
The receptor for advanced glycation end product (RAGE) is a transmembrane receptor accelerating a pro-inflammatory signal. RAGE signalling is promoted by decreased soluble isoform of RAGE (sRAGE), which is a decoy receptor for RAGE ligands, and RAGE SNP rs2070600 minor allele. In Caucasian and Japanese cohorts, low circulatory sRAGE levels and presence of the minor allele are associated with poor survival of idiopathic pulmonary fibrosis (IPF) and increased disease susceptibility to interstitial lung disease, respectively. However, whether sRAGE and RAGE SNP rs2070600 are associated with acute exacerbation of IPF (AE-IPF) is unclear.

Methods
This retrospective cohort study evaluated the association between the onset of AE-IPF and serum sRAGE levels in 69 German and 102 Japanese patients with IPF. The association of AE-IPF with RAGE SNP rs2070600 in 51 German and 84 Japanese patients, whose DNA samples were stored, was also investigated.

Results
In each cohort, the incidence of AE-IPF was significantly and reproducibly higher in the patients with sRAGE < 467.1 pg/mL. In a pooled exploratory analysis, the incidence of AE-IPF was lowest in the patients with higher sRAGE levels and rs2070600 minor allele, although no significant difference in the incidence was observed between the patients with and without the rs2070600 minor allele.

Conclusions
Low sRAGE levels were associated with increased incidence of AE-IPF in two independent cohorts of different ethnicities. The combination of rs2070600 and sRAGE levels may stratify patients with IPF for the risk of AE.
Harm reduction techniques among cisgender gay, bisexual, and queer men using anabolic androgenic steroids: a qualitative study
Authors: Kutscher Eric , Arshed Arslaan , Greene Richard E. , Kladney Mat 
Published: November 2024

Abstract
Background
Anabolic androgenic steroids (AAS) are synthetic forms of testosterone frequently used as performance enhancing drugs among gay, bisexual, and queer (GBQ) men. Despite widespread use, associated harms, and the likely existence of an AAS use disorder, there is no medical consensus on standards of care for people who use AAS, with most medical providers focusing exclusively on abstinence. Individuals using AAS have developed community-based harm reduction strategies to mitigate these harms.

Methods
This paper is a sub-analysis of qualitative data obtained through semi-structured interviews with GBQ men using AAS for 8 or more weeks recruited through convenience and snowball sampling from clinical sites and LGBTQ + venues in New York City as well as through social media. Interviews were coded with themes developed using reflexive thematic analysis. Data related to harm reduction techniques were then re-analyzed through a prevention strategies framework lens of primary, secondary, and tertiary harm prevention.

Results
Thematic saturation was reached at twelve interviews in the primary analysis, with men reporting frequent use of multiple harm reduction techniques. For primary prevention, men avoided oral steroids and simultaneous substance use, tried to obtain AAS from reputable sources, used “cycling” to dose steroids, and practiced sterile injection techniques. Secondary prevention methods included patient-directed lab testing for hematocrit, liver and kidney function, cholesterol, prostate specific antigen, testosterone, and self-performed blood pressure checks. Tertiary prevention included donating blood and the use of medications without a prescription, including aromatase inhibitors, selective estrogen receptor blockers, aspirin, statins, angiotensin receptor blockers, clomiphene, and human chorionic gonadotropin.

Conclusions
Despite many GBQ men experiencing harms from anabolic androgenic steroids, community members have often sought harm reduction techniques in lieu of abstinence. Though many of these techniques embrace clinical reasoning and may be more broadly applicable, additional research is needed to understand the impact of each intervention on the overall health of individuals using AAS.
The impact of androgen-induced translation in modulating androgen receptor activity
Authors: Israel Justus S. , Marcelin Laura-Maria , Mehralivand Sherif , Scholze Jana , Hofmann Jörg , Stope Matthias B. , Puhr Martin , Thomas Christian , Erb Holger H. H. 
Published: November 2024

Abstract
Introduction
Dysregulated androgen receptor (AR) activity is central to various diseases, particularly prostate cancer (PCa), in which it drives tumour initiation and progression. Consequently, antagonising AR activity via anti-androgens is an indispensable treatment option for metastatic PCa. However, despite initial tumour remission, drug resistance occurs. Therefore, the AR signalling pathway has been intensively investigated. However, the role of AR protein stability in AR signalling and therapy resistance has not yet been deciphered. Therefore, this study aimed to investigate the role of AR protein changes in transactivity and assess its mechanism as a possible target in PCa.

Methods
LNCaP, C4-2, and 22Rv1 cells were treated with R1881, enzalutamide, cycloheximide, and Rocaglamide. Mass spectrometry analyses were performed on LNCaP cells to identify the pathways enriched by the treatments. Western blotting was performed to investigate AR protein levels and localisation changes. Changes in AR transactivity were determined by qPCR.

Results
Mass spectrometry analyses were performed on LNCaP cells to decipher the molecular mechanisms underlying androgen- and antiandrogen-induced alterations in the AR protein. Pathway analysis revealed the enrichment of proteins involved in different pathways that regulate translation. Translational and proteasome inhibitor experiments revealed that these AR protein changes were attributable to modifications in translational activity. Interestingly, the effects on AR protein levels in castration-resistant PCa (CRPC) cells C4-2 or enzalutamide-resistant cells 22Rv1 were less prominent and non-existent. This outcome was similarly observed in the alteration of AR transactivation, which was suppressed in hormone-sensitive prostate cancer (HSPC) LNCaP cells by translational inhibition, akin to the effect of enzalutamide. In contrast, treatment-resistant cell lines showed only a slight change in AR transcription.

Conclusion
This study suggests that in HSPC, AR activation triggers a signalling cascade that increases AR protein levels by enhancing its translation rate, thereby amplifying AR activity. However, this mechanism appears to be dysregulated in castration-resistant PCa cells.
Distinct neutrophil effector functions in response to different isolates of Leishmania aethiopica
Authors: Adem E. , Cruz Cervera E. , Yizengaw E. , Takele Y. , Shorter S. , Cotton J. A. , Getti G. , Kropf P. 
Published: November 2024

Abstract
Background
In Ethiopia, cutaneous leishmaniasis is mainly caused by Leishmania (L.) aethiopica parasites and presents in three main clinical forms. It is still not clear if the host immune response plays a role in the development of these different presentations. Since neutrophils are likely to be one of the first immune cells present at the site of the sand fly bite, we set up an in vitro model of infection of neutrophils with L. aethiopica and assessed some of the main neutrophil effector functions: association with and internalisation of parasites, apoptosis and ROS production. We used three freshly isolated clinical isolates and one isolate that has been kept in culture for decades.

Results
Our results showed by flow cytometry that all four L. aethiopica isolates had the ability to associate with neutrophils. The three clinical isolates of L. aethiopica associated more efficiently with neutrophils than the long-term cultured L. aethiopica. At 18 h, two distinct populations of neutrophils were identified that associated with L. aethiopica, CD15high and CD15low neutrophils. Confocal microscopy demonstrated that all isolates can be internalised. Our results also showed that all parasites induced apoptosis in L. aethiopica-associated neutrophils. Moreover, our results showed that after 2 h, L. aethiopica-associated neutrophils upregulated their production of ROS, but to a greater extent with the long-term cultured L. aethiopica. After 18 h of incubation, CD15lowparasite+ showed an impaired ability to produce ROS compared to CD15highparasite+.

Conclusions
Using this in vitro model, our results show that different L. aethiopica parasite isolates, most notably long-term cultured parasites, had differential effects on neutrophil effector functions.

Graphical Abstract
Neutrophil and mononuclear leukocyte pathways and upstream regulators revealed by serum proteomics of adult and juvenile dermatomyositis
Authors: Sparling A. Clare , Ward James M. , Sarkar Kakali , Schiffenbauer Adam , Farhadi Payam Noroozi , Smith Michael A. , Rahman Saifur , Zerrouki Kamelia , Miller Frederick W. , Li Jian-Liang , Casey Kerry A. , Rider Lisa G. 
Published: November 2024

Abstract
Objectives
Serum protein abundance was assessed in adult and juvenile dermatomyositis (DM and JDM) patients to determine differentially regulated proteins, altered pathways, and candidate disease activity biomarkers.

Methods
Serum protein expression from 17 active adult DM and JDM patients each was compared to matched, healthy control subjects by a multiplex immunoassay. Pathway analysis and protein clustering of the differentially regulated proteins were examined to assess underlying mechanisms. Candidate disease activity biomarkers were identified by correlating protein expression with disease activity measures.

Results
Seventy-eight of 172 proteins were differentially expressed in the sera of DM and JDM patients compared to healthy controls. Forty-eight proteins were differentially expressed in DM, 32 proteins in JDM, and 14 proteins in both DM and JDM. Twelve additional differentially expressed proteins were identified after combining the DM and JDM cohorts. C-X-C motif chemokine ligand 10 (CXCL10) was the most strongly upregulated protein in both DM and JDM sera. Other highly upregulated proteins in DM included S100 calcium binding protein A12 (S100A12), CXCL9, and nicotinamide phosphoribosyltransferase (NAMPT), while highly upregulated proteins in JDM included matrix metallopeptidase 3 (MMP3), growth differentiation factor 15 (GDF15), and von Willebrand factor (vWF). Pathway analysis indicated that phosphoinositide 3-kinase (PI3K), p38 mitogen-activated protein kinase (MAPK), and toll-like receptor 7 (TLR7) signaling were activated in DM and JDM. Additional pathways specific to DM or JDM were identified. A protein cluster associated with neutrophils and mononuclear leukocytes and a cluster of interferon-associated proteins were observed in both DM and JDM. Twenty-two proteins in DM and 24 proteins in JDM sera correlated with global, muscle, and/or skin disease activity. Seven proteins correlated with disease activity measures in both DM and JDM sera. IL-1 receptor like 1 (IL1RL1) emerged as a candidate global disease activity biomarker in DM and JDM.

Conclusion
Coordinate analysis of protein expression in DM and JDM patient sera by a multiplex immunoassay validated previous gene expression studies and identified novel dysregulated proteins, altered signaling pathways, and candidate disease activity biomarkers. These findings may further inform the assessment of DM and JDM patients and aid in the identification of potential therapeutic targets.
Glucose chemical exchange saturation transfer MRI for predicting the histological grade of rectal cancer: a comparative study with amide proton transfer-weighted and diffusion-weighted imaging
Authors: Meng Nan , Huang Zhun , Jiang Han , Dai Bo , Shen Lei , Liu Xue , Wu Yaping , Yu Xuan , Fu Fangfang , Li Zheng , Shen Zhiwei , Jiang Baiyan , Wang Meiyun 
Published: November 2024

Abstract
Background
To evaluate the utility of glucose chemical exchange saturation transfer (glucoCEST) MRI with non-contrast injection in predicting the histological grade of rectal cancer.

Methods
This prospective analysis included 60 patients with preoperative rectal cancer who underwent pelvic glucoCEST, amide proton transfer-weighted imaging (APTWI), and diffusion-weighted imaging (DWI). In total, 21 low-grade and 39 high-grade cases were confirmed by postoperative pathology. The MTRasym (1.2 ppm), MTRasym (3.5 ppm), and apparent diffusion coefficient (ADC) values of lesions between the low-grade and high-grade groups were compared. The area under the receiver operating characteristic curve (AUC) was generated to evaluate the diagnostic performance of each technique. Logistic regression (LR) analysis was applied to determine independent predictors and for multi-parameter combined diagnosis.

Results
Elevated MTRasym (1.2 ppm), MTRasym (3.5 ppm) values and lower ADC values were observed in the high-grade group compared with low-grade cases (all p < 0.01). The AUCs of MTRasym (1.2 ppm), MTRasym (3.5 ppm), and ADC for differentiating between low- and high-grade rectal cancer cases were 0.792, 0.839, and 0.855, respectively. The diagnostic performance of the combination of the three indexes was improved (AUC, 0.969; sensitivity, 95.24%; specificity, 87.18%). The good consistency and reliability of the combination of independent predictors were demonstrated by calibration curve analysis and DCA.

Conclusion
The glucoCEST MRI without contrast injection, APTWI, and DWI all facilitate the assessment of histological grade in rectal cancer, and the combination of the three can effectively discriminate between high- and low-grade rectal cancer, which is expected to be a promising imaging marker.

Critical relevance statement
The glucose chemical exchange saturation transfer MRI method facilitates the assessment of histological grade in rectal cancer and offers additional information to improve the diagnostic performance of amide proton transfer-weighted imaging, and diffusion-weighted imaging.

Key Points

Glucose chemical exchange saturation transfer imaging could differentiate histological grade.

Amide proton transfer-weighted and diffusion-weighted were associated with histological grade.

The combination of different parameters showed the best diagnostic performance.

Graphical Abstract
Comparative evaluation of methods for the prediction of protein–ligand binding sites
Authors: Utgés Javier S. , Barton Geoffrey J. 
Published: November 2024

AbstractThe accurate identification of protein–ligand binding sites is of critical importance in understanding and modulating protein function. Accordingly, ligand binding site prediction has remained a research focus for over three decades with over 50 methods developed and a change of paradigm from geometry-based to machine learning. In this work, we collate 13 ligand binding site predictors, spanning 30 years, focusing on the latest machine learning-based methods such as VN-EGNN, IF-SitePred, GrASP, PUResNet, and DeepPocket and compare them to the established P2Rank, PRANK and fpocket and earlier methods like PocketFinder, Ligsite and Surfnet. We benchmark the methods against the human subset of our new curated reference dataset, LIGYSIS. LIGYSIS is a comprehensive protein–ligand complex dataset comprising 30,000 proteins with bound ligands which aggregates biologically relevant unique protein–ligand interfaces across biological units of multiple structures from the same protein. LIGYSIS is an improvement for testing methods over earlier datasets like sc-PDB, PDBbind, binding MOAD, COACH420 and HOLO4K which either include 1:1 protein–ligand complexes or consider asymmetric units. Re-scoring of fpocket predictions by PRANK and DeepPocket display the highest recall (60%) whilst IF-SitePred presents the lowest recall (39%). We demonstrate the detrimental effect that redundant prediction of binding sites has on performance as well as the beneficial impact of stronger pocket scoring schemes, with improvements up to 14% in recall (IF-SitePred) and 30% in precision (Surfnet). Finally, we propose top-N+2 recall as the universal benchmark metric for ligand binding site prediction and urge authors to share not only the source code of their methods, but also of their benchmark.Scientific contributionsThis study conducts the largest benchmark of ligand binding site prediction methods to date, comparing 13 original methods and 15 variants using 10 informative metrics. The LIGYSIS dataset is introduced, which aggregates biologically relevant protein–ligand interfaces across multiple structures of the same protein. The study highlights the detrimental effect of redundant binding site prediction and demonstrates significant improvement in recall and precision through stronger scoring schemes. Finally, top-N+2 recall is proposed as a universal benchmark metric for ligand binding site prediction, with a recommendation for open-source sharing of both methods and benchmarks.
Promoting real-time electricity tariffs for more demand response from German households: a review of four policy options
Authors: Häseler Sönke , Wulf Alexander J. 
Published: November 2024

Abstract
Background
Demand response is an important option for accommodating growing shares of renewable electricity, and therefore, crucial for the success of the energy transition in Germany and elsewhere. In conjunction with smart meters, real-time (or ‘dynamic’) electricity tariffs can facilitate the flexibilization of power consumption and reduce energy bills. Whilst such tariffs are already quite common in several EU member states, Germany lags behind in this respect. The country makes for an interesting case study because of the sheer volume of additional flexibility that its energy transition necessitates.

Main text
This paper discusses how German policymakers can make real-time tariffs more attractive for households and thus entice them to better adapt their consumption to current market conditions. Following an analysis of the current impediments to the adoption of such tariffs, we discuss four policy options: (1) a more ambitious legal definition of real-time tariffs that can promote market transparency and leverage potential savings for consumers, (2) a shift in energy taxation that encourages the uptake of renewable power and increases price spreads, (3) a new model of dynamic network charges which combines grid-serving and market-serving incentives, and (4) a subsidy for users of real-time tariffs that helps internalise the benefits they provide to all electricity consumers. Given the similar regulatory framework, our suggestions should generally also apply to other countries in Europe and beyond.

Conclusions
Overall, we argue that there is considerable scope for policymakers to better exploit market forces to ensure security of electricity supply at lower social cost. Our call for stricter regulation in order to allow the markets to better guide consumer behaviour may seem like a paradox—but it is one well worth embracing.
Temporal patterns and individual characteristics of compulsory treatment orders for mental disorders in Scotland from 2007 to 2020
Authors: Schölin Lisa , Borschmann Rohan , Chopra Arun 
Published: November 2024

Background
Compulsory mental health treatment has increased globally. In Scotland, compulsory treatment for >28 days is permitted under hospital- and community-based compulsory treatment orders. Community-based compulsory treatment has not been shown to lead to improved outcomes, and scrutiny of their use is needed.

Aims
To describe the trend, duration and demographic characteristics of compulsory treatment orders in Scotland over a 14-year period.

Method
We conducted a retrospective analysis of order use in Scotland from 1 January 2007 to 31 December 2020, focusing on the (a) number and demographic characteristics of those treated, (b) duration, (c) extensions beyond the 6-month review point and (d) characteristics of new versus continued orders.

Results
The number of individuals on a community-based order increased by 118% (571 v. 1243) from 2007 to 2020, compared with a 16% increase (1316 v. 1532) for hospital-based orders. Of orders starting in 2007, 57.3% were extended, compared with 43.7% in 2020. The median duration was 6 months for first-time orders and 9 months for subsequent orders, which were longest for males (median 11 months); those of African, Caribbean or Black (median 11 months), Asian (median 11 months) and mixed ethnicity (median 10 months); and individuals from the most deprived communities (median 10 months).

Conclusions
There has been a marked rise of community-based compulsory treatment orders in Scotland. If existing trends continue, there will be more people receiving care under community-based orders than hospital-based orders, fundamentally changing the nature of involuntary treatment. Further work needs to explore associations between demographic and diagnostic characteristics on order duration.
Brain Abscess Causes Brain Damage With Long-Lasting Focal Cerebral Hypoactivity that Correlates With Abscess Size: A Cross-Sectional 18F-Fluoro-Deoxyglucose Positron Emission Tomography Study
Authors: Müller Ebba Gløersen , Dahlberg Daniel , Hassel Bjørnar , Revheim Mona-Elisabeth , Connelly James Patrick 
Published: November 2024

BACKGROUND AND OBJECTIVES:
Bacterial brain abscesses may have long-term clinical consequences, eg, mental fatigue or epilepsy, but long-term structural consequences to the brain remain underexplored. We asked if brain abscesses damage brain activity long term, if the extent of such damage depends on the size of the abscess, and if the abscess capsule, which is often left in place during neurosurgery, remains a site of inflammation, which could explain long-lasting symptoms in patients with brain abscess.

METHODS:
2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT), electroencephalography, and MRI were performed 2 days to 9 years after neurosurgery for bacterial brain abscess.

RESULTS:
FDG-PET/CT revealed hypometabolism in the neocortex or cerebellum overlying the previous bacterial abscess in 38 of 40 patients. The larger the abscess, the greater was the extent of the subsequent hypometabolism (r = 0.63; p = 3 × 10−5). In 9 patients, the extent of subsequent hypometabolism seemed to coincide with the extent of peri-abscess edema in the acute phase. Follow-up MRI after ≥1 year in 9 patients showed focal tissue loss and gliosis. In 13 patients with abnormal electroencephalography recordings, abnormalities extended beyond the cerebral lobe affected by the abscess, indicating damage to wider brain networks. The abscess capsule had an FDG signal indicating inflammation only during the first week after neurosurgical pus drainage.

CONCLUSION:
The bigger a brain abscess is allowed to grow, the more extensive is the long-term focal reduction in brain activity. This finding emphasizes the need for rapid neurosurgical intervention. The abscess capsule does not display long-lasting inflammation and probably does not explain long-term symptoms after brain abscess.