bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nanoarchitectonics of copper sulfide nanoplating for improvement of computed tomography efficacy of bismuth oxide constructs toward drugless theranostics
Authors: Meng Ruo-Yin , Xia Hong-Ying , Zhao Ying , Ye Ying-Tong , Wang Shi-Bin , Chen Ai-Zheng , Kankala Ranjith Kumar 
Published: October 2024

Abstract
Triple-negative breast cancer (TNBC) has emerged as one of the dreadful metastatic tumors in women due to complexity, specificity and high recurrence, resulting in poor therapeutic outcomes and requiring real-time monitoring for improved theranostics. Despite the success as efficient radiosensitizers and computed tomography (CT)-based contrast agents, bismuth (Bi)-based composites suffer from poor colloidal stability, dose-dependent toxicity and pharmacokinetic shortcomings, leading to poor therapeutic monitoring. In addition, several small molecule-based therapeutics, including nanoparticle-based delivery systems, suffer from several limitations of poor therapeutic delivery and acquired multidrug resistance by cancer cells, depriving the therapeutic needs. To overcome this aspect, this study demonstrates the fabrication of drug-like/drugless nanoarchitectures based on copper sulfide-nanoplated bismuth oxide (Bi2O3@CuS, shortly BC) composites for improved theranostic efficacy against TNBC. These systematically characterized BC nanocomposites exhibited pH-/near-infrared (NIR, 808 nm) light-responsive degradability toward dual modal therapies. Due to the band transition of Cu species, the designed BC composites displayed exceptional photothermal (PTT) conversion efficiency toward localized PTT effects. In addition to pH-/NIR-responsiveness, the internally overexpressed glutathione (GSH)-responsiveness facilitated the release of Cu2+ species for chemodynamic therapy (CDT)-based effects. To this end, the Bi3+ species in the core could be fully hydrated in the acidic tumor microenvironment, resulting in GSH depletion and reducing CDT-induced reactive oxygen species clearance, thereby ablating tumors. The acid-responsive degradability of CuS resulted in the intratumoral enrichment of BC, demonstrating remarkable CT imaging efficacy in vivo. Together, these pH-/NIR-/GSH-responsive biodegradable BC composites could realize the integrated PTT/CDT/CT theranostics against breast carcinoma.
Revisiting R&I policy assessment in the EU: a semantic analysis of ERAWATCH and RIO reports
Authors: Zacharewicz Thomas , García-Flores Victor , González-Vázquez Ignacio , Palma-Martos Luis-Antonio 
Published: October 2024

Abstract
The monitoring and evaluation of R&I policies relies on quantitative and qualitative methods with important methodological shortcomings. Quantitative assessments rely on standardized indicators that do not capture context-specific challenges, while qualitative approaches lack comparability. Both approaches are complementary but not always analyzed in combination, thereby considerably limiting their validity. In this study, we propose an alternative approach by using semantic analysis to analyze the large body of evidence available in the 189 annual country-specific qualitative assessments developed between 2011 and 2019 for all EU Member States in the European Commission’s ERAWATCH and RIO reports. We show that the semantic analysis of recurrent qualitative reviews of R&I policies can overcome the limitations of both quantitative scoreboards and ad hoc qualitative reviews, by taking into account country-specific challenges while allowing comparisons across countries. In our analysis, we first identify the main R&I challenges highlighted in all EU countries. Secondly, we focus on a set of four EU Member States to identify structural commonalities and contextual differences across countries. Finally, we focus on the case of Spain to compare the findings from the ERAWATCH and RIO reports with the European Innovation Scoreboard as the main quantitative assessment instrument used in the EU to assess Member States’ R&I performance. By showing that semantic analysis of recurrent and cross-country qualitative assessments of EU R&I policies provide a clear added value to the understanding of the main challenges faced in this field, we recommend the creation of a renewed EU research and innovation observatory.
Predictors of irreversible renal dysfunction in patients with idiopathic retroperitoneal fibrosis
Authors: Ji Zongfei , Sun Ying , Zhang Lijuan , Kong Xiufang , Jiang Lindi 
Published: October 2024

Abstract

Objectives
Idiopathic retroperitoneal fibrosis (iRPF) can lead to irreversible kidney damage. This study aimed to investigate predictors of irreversible renal dysfunction in patients with iRPF.

Methods
Eighty-three patients with newly diagnosed iRPF were enrolled between January 2010 and September 2022 at Zhongshan Hospital of Fudan University, including 60 in the training set and 23 in the validation set. They were regularly contacted or followed up via outpatient examinations by specialist doctors, who documented their condition and treatment progress. Predictors of irreversible renal dysfunction were identified using univariate and multivariate regression, logistic model, and receiver operating curve analyses.

Results
In the training set, over a median follow-up of 29 months, 16.7% of patients had an estimated glomerular filtration rate (eGFR) of &lt;60 ml/min/1.73 m2 at the last follow-up, and 25% had hydronephrosis or required prolonged double-J stents. A prognostic score was developed by assigning 1, 1, and 2 points for peripheral CD19+ B cells &lt;9.3%, serum creatinine (sCr) ≥120 µmol/L, and no response at 6 months, respectively. A score of ≥2 for predicting irreversible renal dysfunction had sensitivity and specificity of 100% and 92%, respectively. In the validation set, 21.7% of patients suffered from irreversible renal dysfunction. The sensitivity and specificity for predicting irreversible renal dysfunction were 100% and 94.4%, respectively.

Conclusions
A prognostic score based on factors including CD19+ B cells &lt;9.3% and sCr ≥120 µmol/L at baseline, and no response at 6 months, is suitable for predicting irreversible renal dysfunction in iRPF.
Contributors to organ damage in childhood lupus: corticosteroid use and disease activity
Authors: Hanif Maria , Sarker Chandni , Al-Abadi Eslam , Armon Kate , Bailey Kathryn , Bohm Marek , Brennan Mary , Ciurtin Coziana , Gardner-Medwin Janet , Hawley Daniel P , Kinder Alison , Leahy Alice , Malik Gulshan , McLaren Zoe , Moraitis Elena , Mosley Ellen , Ramanan Athimalaipet V , Rangaraj Satyapal , Ratcliffe Annie , Riley Philip , Rostron Heather , Sen Ethan , Beresford Michael W , Smith Eve M D 
Published: October 2024

Abstract

Objectives
Awareness of paediatric-specific predictors of damage in childhood lupus is needed to inform mitigation measures. The objective of this study was to ascertain how clinical and demographic variables correlate with damage accrual and identify predictors of damage.

Methods
This analysis included UK JSLE Cohort Study participants. Univariable and multivariable Prentice-Williams-Peterson models investigated how demographic and clinical factors influenced the hazards of new damage. Analyses were performed across the entire cohort, in patients with minimal disease activity marked by a time-adjusted average SLEDAI-2K score (AMS) of ≤2, in patients with low activity (AMS of ≤4), patients with moderate-to-high activity (AMS of &gt;4) and patients with no CS use.

Results
Within the entire cohort (n = 430), factors associated with damage included: any methylprednisolone [hazard ratio, HR 2.20 (CI 1.33–3.62)], time-adjusted mean Physician’s Global Assessment (PGA) [HR 2.87 (CI 1.48–5.56)] and AMS score [HR 1.13 (CI 1.03–1.24), all P &lt; 0.05]. Within the low activity subgroup, any methylprednisolone [HR 2.61 (CI 1.04–6.53)] and time-adjusted mean PGA [HR 3.41 (CI 1.52–7.76)] were associated with damage (both P &lt; 0.05). Within the moderate-to-high activity subgroup, any methylprednisolone [HR 2.29 (CI 1.31–4.00)], time-adjusted mean PGA [HR 2.66, (CI 1.20–5.87)] and AMS score [HR 1.15 (CI 1.03–1.29)] were predictive of damage (all P &lt; 0.05). Baseline organ damage was predictive of subsequent damage accrual in the minimal disease activity subgroup [HR 1.33 (CI 1.78–8.08)] and the no CSs subgroup [HR 3.64 (CI 1.83–7.24), both P &lt; 0.005].

Conclusion
Disease activity levels (AMS/PGA) and proxy indicators (methylprednisolone exposure, baseline damage) were found to be key predictors of damage accrual. This highlights the importance of practical strategies, such as treat-to-target, for reducing disease activity and long-term treatment toxicity.
A de novo missense mutation in PPP2R5D alters dopamine pathways and morphology of iPSC-derived midbrain neurons
Authors: Carter Jasmine L , Halmai Julian A N M , Waldo Jennifer J , Vij Paula A , Anguiano Maribel , Villegas Isaac J , Du Yu Xin , Nolta Jan , Fink Kyle D 
Published: October 2024

Abstract
Induced pluripotent stem cell (iPSC) models of neurodevelopmental disorders (NDDs) have promoted an understanding of commonalities and differences within or across patient populations by revealing the underlying molecular and cellular mechanisms contributing to disease pathology. Here, we focus on developing a human model for PPP2R5D-related NDD, called Jordan syndrome, which has been linked to Early-Onset Parkinson’s Disease (EOPD). Here we sought to understand the underlying molecular and cellular phenotypes across multiple cell states and neuronal subtypes in order to gain insight into Jordan syndrome pathology. Our work revealed that iPSC-derived midbrain neurons from Jordan syndrome patients display significant differences in dopamine-associated pathways and neuronal architecture. We then evaluated a CRISPR-based approach for editing heterozygous dominant G-to-A mutations at the transcript level in patient-derived neural stem cells. Our findings show that site-directed RNA editing is influenced by sgRNA length and cell type. These studies support the potential for a CRISPR RNA editor system to selectively edit mutant transcripts harboring G-to-A mutations in neural stem cells while providing an alternative editing technology for those suffering from NDDs.
A comprehensive summary of eponymous awards and scholarships in sexual medicine
Authors: Alvermann Thomas A , Robertson Christopher C , Jones James M , Gross Martin S 
Published: October 2024

Abstract

Introduction
Numerous eponymous awards and scholarships exist within sexual medicine. This comprehensive review is intended to summarize these awards and highlight the esteemed sexual medicine experts for whom these awards are named.

Objectives
To provide historical background and context for the various eponymous awards in sexual medicine.

Methods
The websites of the International Society for Sexual Medicine (ISSM) and the regional affiliate societies, including the Sexual Medicine Society of North America (SMSNA), International Society for the Study of Women’s Sexual Health (ISSWSH), and various regional societies were identified, and all awards associated with a member of note were documented. In cases where no awards were identified within a regional society and a contact person was available, inquiries were made regarding the existence of awards. Several documents on the history of the ISSM were utilized for background on awards.

Results
A comprehensive list of current awards and their history was compiled.

Conclusion
This is the first comprehensive history of eponymous awards and scholarships available in sexual medicine.
The impact of neonicotinoid pesticides on reproductive health
Authors: Oladosu Jadesola I , Flaws Jodi A 
Published: October 2024

Abstract
Neonicotinoids are some of the most widely used insecticides in the world because they broadly target chewing and sucking insects. Neonicotinoids are used in commercial agricultural systems, sold for use in home gardens, and found in veterinary pharmaceuticals in the form of flea and tick preventatives for companion animals. They are also used as crop seed treatments and spread throughout crops as they mature. As a result, humans, wildlife, livestock, and pets are routinely exposed to neonicotinoids through the consumption of contaminated food and water as well as through the use of some veterinary pharmaceuticals. Although several studies indicate that neonicotinoid exposure causes genotoxicity, neurotoxicity, hepatotoxicity, and immunotoxicity in some non-target species, the impact of neonicotinoid pesticides on the male and female reproductive systems in mammals is largely understudied. This review summarizes current insights on the impact of common neonicotinoid pesticides such as acetamiprid, clothianidin, imidacloprid, and thiacloprid on male and female reproductive health in mammals. The review also summarizes the impacts of exposure to mixtures of neonicotinoids on reproductive endpoints. In addition, this review highlights where gaps in research on neonicotinoid pesticides and reproductive health exist so that future studies can be designed to fill current gaps in knowledge.
Choroidal Infiltration in Erdheim-Chester Disease: A Case Series
Authors: Fatam El Fakih , Stéphane Abramowicz , Adélaïde Toutée , Valérie Touitou , Bahram Bodaghi 
Published: October 2024

Purpose:
We describe two cases of choroidal involvement in patients with Erdheim-Chester disease (ECD), a rare non-Langerhans cell histiocytosis.

Methods:
Short case series.

Results:
The first patient was a 25-year-old man with asymptomatic ECD at the level of bones, lung, and central nervous system. Fundus examination revealed bilateral yellowish choroidal infiltration in the superior macula and nasal mid-periphery. After initial mild enlargement of the choroidal lesions, treatment with weekly subcutaneous pegylated interferon α2a (PEG-IFN) was started inducing partial regression of the lesions. The second patient was a 45-year-old man with ECD involving the left orbit, maxillary sinus, heart, blood vessels, kidney, retroperitoneum, bones and testes. Fundus examination of the left eye showed choroidal folds. Macular spectral-domain optical coherence tomography confirmed the folds and revealed underlying choroidal infiltration. Final ocular diagnosis was left choroidal, scleral, and orbital involvement. The patient was initially treated with PEG-IFN, and later with cobimetinib, a MEK inhibitor, with favorable results. Neither patient developed choroidal neovascularization (CNV) during the follow-up.

Conclusions:
ECD is a rare multisystem disorder that can present with ocular involvement, including orbital masses, xanthelasma-like lesions, and occasionally, choroidal infiltrates. Early recognition and prompt treatment can lead to improvement of ophthalmic and systemic symptoms and prevent further complications. We recommend treating patients with choroidal ECD, regardless of the presence of symptoms, considering these patients are at increased risk of developing CNV.
Changes in Clinical Competence of Novice Physical Therapists During Their First Year of Employment: A Single Center Retrospective Observational Study in Japan
Authors: Motoya Ikuo , Tanabe Shigeo , Koyama Soichiro , Hirakawa Yuichi , Iwai Masanobu , Takeda Kazuya , Kanada Yoshikiyo , Kawamura Nobutoshi , Kawamura Mami , Sakurai Hiroaki 
Published: October 2024

Background and Objectives:
This study aimed to examine the development of clinical competence of novice physical therapists (PTs) during their first year of employment, following the implementation of an original in-house educational program. The educational program was designed to offer diverse training opportunities at an early stage, during the first year of employment.

Methods:
Thirty-eight novice PTs (21 males and 17 females, mean age 23.4 ± 3.2 years) participated in this study. All participants underwent educational programs and a self-assessment using the Clinical Competence Evaluation Scale in Physical Therapy (CEPT) on the first day of employment (entry-level) and after 1, 3, 6, and 12 months of employment. The total score and CEPT component-wise scores—“knowledge,” “clinical reasoning,” “skill,” “communication,” “attitude,” “self-education,” and “self-management”—at the 4 assessment points (1, 3, 6, and 12 months) were compared with values on the first day.

Results:
The total scores at 3, 6, and 12 months of employment were significantly higher than those on the first day of employment (P < .05). Among the total scores on the 7 components, those for “knowledge,” “clinical reasoning,” “skill,” and “communication” at 3, 6, and 12 months after employment were also significantly higher than those on the first day of employment (P < .05). The scores for “attitude” and “self-education” 12 months after employment were significantly higher than those on the first day of employment. However, the “self-management” scores at 1, 3, 6, and 12 months after employment did not significantly change compared with those on the first day of employment.

Conclusions:
The total score was significantly higher after 3 months. The participant’s clinical competence may have improved because they participated in an educational program related to “knowledge,” “clinical reasoning,” “skills,” and “communication” at an earlier stage in the first year. However, their progress was comparatively slower in other areas, suggesting that the content might not have been sufficient. This study revealed the effectiveness of the educational program on novice PTs’ clinical competence at a single institution in Japan. Positive outcomes were obtained for several parameters. Furthermore, the results reveal the need for content modifications within the educational program to improve PTs’ performance across all evaluated items.
Paternal genome elimination, monogenic reproduction, and the evolutionary genetics of atypical sex chromosome systems
Authors: Hitchcock Thomas J. , Baird Robert B. , Gardner Andy , Ross Laura 
Published: October 2024

AbstractSex chromosomes differ from autosomes in both their ploidy and transmission genetics. Consequently, selection, mutation, and drift may act differently upon them, driving distinct patterns in genetic divergence, diversity, and gene content. Recently, researchers have begun to consider a wider set of organisms with non-standard inheritance and sex-determination systems, however in many cases we lack theory which extends to such cases. One such example is paternal genome elimination (PGE), an unusual reproductive system which has independently evolved in two fly families, the fungus gnats (Sciaridae) and gall midges (Cecidomyiidae), and one order of springtails (Symphypleona). Under PGE, males receive but do not transmit a paternal genome, such that the autosomes and X chromosomes exhibit the same transmission genetics, but with different somatic ploidy. This makes them uniquely suited to test hypotheses about the role of haploid selection in males. Additionally, repeatedly throughout these groups a novel sex determination system – monogeny – has evolved, whereby females produce broods of exclusively one sex. The genetic basis of monogeny partitions the X chromosome into three segments, all displaying distinct inheritance patterns. Here we develop a series of theoretical models adapted to the genetics of these groups, generating testable predictions as to the relative genetic diversity within populations, and divergence between populations. Our results suggest that these species are excellent systems with which to test many fundamental principles in evolutionary genetics.
Trapped ion mobility spectrometry-guided molecular discrimination between plasmalogens and other ether lipids in lipidomics experiments
Authors: Koch Jakob , Neumann Lukas , Lackner Katharina , Fernández-Quintero Monica L. , Watschinger Katrin , Keller Markus A. 
Published: October 2024

AbstractTrapped Ion Mobility Spectrometry (TIMS) has demonstrated promissing potential as a powerful discriminating method when coupled with mass spectrometry, enhancing the precision of feature annotation. Such a technique is particularly valuable for lipids, where a large number of isobaric but structurally distinct molecular species often coexist within the same sample matrix. In this study we explored the potential of ion mobility for ether lipid isomer differentiation. Mammalian ether phospholipids are characterized by a fatty alcohol residue at thesn-1 position of their glycerol backbone. Ether lipids can make up to 20% of the total phospholipid mass. They are present in a broad range of tissues where they are for example crucial for nervous system function, membrane homeostasis and inter-as well as intracellular signaling.Molecular ether lipid species are difficult to distinguish analytically, as they occur as 1-O-alkyl and 1-O-alkenyl subclasses, with the latter being also known as plasmalogens. Isomeric ether lipid pairs can be separated with reversed-phase chromatography. However, their precise identification remains challenging due to the lack of clear internal reference points, inherent to the nature of lipid profiles and the lack of sufficient commercially available standard substances.Here, we demonstrate - with focus on phosphatidylethanolamines - that ion mobility measurements allow to discriminate between the ether lipid subclasses through distinct differences in their gas phase geometries. This approach offers significant advantages as it does not depend on the variability of chromatography. However, the current resolution in the ion mobility dimension is not sufficient to baseline separate 1-O-alkyl and 1-O-alkenyl isobars, and the observed differences are not yet accurately represented in existing collision cross section databases.Despite these challenges, the predictable properties of the ion mobility behavior of ether lipid species can significantly support their accurate annotation and hold promise for future advancements in lipid research.
Mutagenic ligation of polβ mismatch insertion products during 8-oxoG bypass by LIG1 and LIG3α at the downstream steps of base excision repair pathway
Authors: Lee Kar Men , Castro Erick , Ratcliffe Jacob E. , Çağlayan Melike 
Published: October 2024

AbstractBase excision repair (BER) maintains genome integrity by fixing oxidized bases that could be formed when reactive oxygen species attack directly on the DNA. We previously reported the importance of a proper coordination at the downstream steps involving gap filling by DNA polymerase (pol) β and subsequent nick sealing by DNA ligase (LIG) 1 or 3α. Yet, how the fidelity of 8-oxoG bypass by polβ affects the efficiency of ligation remains unclear. Here, we show that LIG1 can seal nick products of polβ after both dATP and dCTP insertions during 8- oxoG bypass, while ribonucleotide insertions completely diminish the repair coordination with both ligases, highlighting a critical role for nucleotide selectivity in maintaining BER accuracy. Furthermore, our results demonstrate that LIG3α exhibits an inability to ligate nicks of polβ dCTP:8-oxoG insertion or with preinserted 3’-dC:8-oxoG. Finally, AP-Endonuclease 1 (APE1) proofreads nick repair intermediates containing 3’-dA/rA and 3’-dC/rC mismatches templating 8-oxoG. Overall, our findings provide a mechanistic insight into how the dual coding potential of the oxidative lesion and identity of BER ligase govern mutagenicversuserror-free repair outcomes at the final steps and how the ribonucleotide challenge compromises the BER coordination leading to the formation of deleterious repair intermediates.