bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of the new hazard classes in the CLP regulation on EU chemicals legislation
Authors: Kättström Diana , Beronius Anna , Boije af Gennäs Urban , Rudén Christina , Ågerstrand Marlene 
Published: January 2025

Abstract
The EU recently introduced four new hazard classes to the Classification, Labelling and Packaging Regulation (CLP) (EC) 1272/2008. The classes are endocrine disruption for human health (ED HH) and the environment (ED ENV), persistent, bioaccumulative and toxic (PBT) or very persistent and very bioaccumulative (vPvB), and persistent, mobile and toxic (PMT) or very persistent and very mobile (vPvM). This action was a direct consequence of the EU’s Chemicals Strategy for Sustainability, which aims at strengthening the protection of human health and the environment, as well as reinforcing the CLP Regulation as the central piece of the chemicals legislation. This study examined the regulatory obligations triggered by these new hazard classes, as well as the existing obligations for endocrine disrupters and PBT/vPvB substances identified in other EU regulations. In addition, we compared the CLP criteria for endocrine disruption and PBT/vPvB to criteria existing in other EU regulations and investigated how these criteria are used in the EU chemicals legislation. We found that the implementation of the new hazard classes under the CLP into existing EU chemicals legislation will require the revision of all regulations that rely on the CLP hazard criteria for risk management. Without revision, the immediate impact of the new hazard classes will only extend to six regulations and the regulatory obligations they contain, all of which apply to substances classified under any of the CLP hazard classes. Meanwhile, substances with endocrine disrupting and PBT/vPvB properties are already being identified and regulated using criteria from regulations other than the CLP. When comparing the criteria for identification of endocrine disrupters and PBT/vPvB substances across the chemicals legislation, we found that the criteria differed between regulations. The findings aim to support the efficient implementation of the new CLP hazard classes and harmonization of criteria across regulations, in line with the Chemicals Strategy for Sustainability.
Sustainable utilization of bovine adipose tissue derivatives as robust antimicrobial agents against Methicillin-resistant Staphylococcus aureus
Authors: Alcici Muhammed Abdelhameed Ismael , Abdelhaleem Salma Waheed , Fahim Karima Mogahed , Saleh Neveen Mohamed , Farag Heba Saeed 
Published: January 2025

Abstract

Background
The excessive use of antibiotics is a major contributor to the global issue of antimicrobial resistance (AMR), a significant threat to human and animal health. Hence, assessing new strategies for managing Multi-Drug Resistant (MDR) microorganisms is vital. In this study, the use of mechanically isolated mature adipose cells (MIMACs) and their lysate (Adipolysate) as a new sustainable antimicrobial agent was assessed against Methicillin-resistant Staphylococcus aureus (MRSA).

Conclusions
The minimum volume of MIMACs achieved complete bacterial inhibition (Minimum Lethal volume) was 75 µl and 100 µl for bacterial concentration of 1010 and 1012 cfu/ml, respectively. Direct bacterial membrane attachment and intracellular capture was visualized under light and electron microscopy. Adipolysate was characterized via GC–MS, the fatty acid profile demonstrated several components with known antimicrobial properties. The tested Adipolysate revealed inhibition zone of diameter 25.33 ± 0.88 mm against the tested S. aureus strain, compared with the inhibition zone of Vancomycin (24.0 ± 0.00 mm) and Erythromycin (30.0 ± 0.00). The study revealed the potential effects of MIMACs and Adipolysate as sustainable, natural, and robust antimicrobial agents. However, these preliminary results will be further investigated to understand the mechanism of action and explore possible applications in various fields.
The implementation and side effect management of immune checkpoint inhibitors in gynecologic oncology: a JAGO/NOGGO survey
Authors: Riedel Maximilian , Herrmann Helene , Bartl Thomas , Rossner Anna-Maria , Tatzber Anna , Flethe Chiara , Zocholl Dario , Schmalfeldt Barbara , Sehouli Jalid , Pietzner Klaus 
Published: January 2025

Abstract

Background
The integration of immune checkpoint inhibitors (ICIs) into routine gynecologic cancer treatment requires a thorough understanding of how to manage immune-related adverse events (irAEs) to ensure patient safety. However, reports on real-world clinical experience in the management of ICIs in gynecologic oncology are very limited. The aim of this survey was to provide a real-world overview of the experiences and the current state of irAE management of ICIs in Germany, Switzerland, and Austria.

Methods
We designed a questionnaire consisting of 34 items focused on physicans’ clinical experiences with ICIs and their management of irAEs. The survey was distributed between October 2022 and May 2023 to medical professionals with experience in the field of gynecologic oncology.

Results
A total of 221 gynecologists participated in the study. Most respondents (n = 130, 59.1%) were primarily engaged in gynecologic oncology at the time of the survey, with an average of ten years of clinical experience. Individual experiences with regard to irAEs varied significantly. When asked which irAEs they had observed “frequently” or “very frequently”, respondents most commonly reported thyroiditis (37.2%), followed by skin reactions (23.6%), and pneumonitis (10.6%). A total of n = 16 (7.4%) reported at least one death of a patient due to irAEs. Feeling “unconfident” or “very unconfident” about managing irAEs was reported by 35.6% (n = 78). With regard to clinical management of adverse events after discontinuation of treatment, 32.4% (n = 68) ceased to inquire about irAEs after six months.

Conclusion
The results of this survey provide valuable insights into physicians’ real-world experiences with irAEs associated with ICI treatment. Dealing with serious immune-related and potentially life-threatening side effects has become a routine aspect of clinical practice. Many physicians, however, express a lack of sufficient familiarity with irAEs and their management. Therefore, it is essential to improve medical education, specialized oncological training, and close interdisciplinary collaboration to improve patient care.
Knights in shining armour and (M)others in life jackets: Women’s experiences of advocating for care alone when suffering recurrent early pregnancy loss during the SARS-CoV-2 pandemic
Authors: Kent-Nye Flora E. , Sheen Kayleigh S. , Burgess Karen , Oza Munira , Magee Laura A. , Jurković Davor , Silverio Sergio A. 
Published: January 2025

Abstract

Background
Recurrent early pregnancy loss [rEPL] is a traumatic experience, marked by feelings such as grief and depression, and often anxiety. Despite this, the psychological consequences of rEPL are often overlooked, particularly when considering future reproductive health or approaching subsequent pregnancies. The SARS-CoV-2 pandemic led to significant reconfiguration of maternity care and a negative impact on the perinatal experience, but the specific impact on women’s experience of rEPL has yet to be explored. This study aimed to examine the impact of changes to early pregnancy loss care and social restrictions during the pandemic on women’s experience of rEPL.

Methods
A qualitative interview study design was employed, with semi-structured interviews conducted virtually. A total of 16 women who had suffered two or more early pregnancy losses (≤ 14 weeks gestation) during the SARS-CoV-2 pandemic in the United Kingdom participated. Data were recorded, transcribed, and analysed by hand, following a Classical Grounded Theory Analysis, appropriate for cross-disciplinary health research.

Results
Iterative and inductive analysis generated the theory ‘Knights in Shining Armour and (M)others in Life Jackets’, which describes women’s experience of advocating for care alone, when suffering rEPL during the pandemic. This theory was derived from the way in which three emergent themes inter-related: (1) Dismantling Validation; (2) Preserving an Identity of Motherhood; and (3) Support Waning.

Conclusions
This study affirms recent findings of devalued maternity care during the pandemic, and magnification of pre-pandemic issues with EPL care, such as a lack of support or perceived empathy.
Oral health in patients with cleft lip and palate: a systematic literature review and meta-analysis of periodontal and dental disease and oral microbiota (part 1)
Authors: Pardo A. , Vanti V. , Lonardi F. , Signoriello A. , Lobbia G. , Lombardo G. , Trevisiol L. , D’Agostino A. 
Published: January 2025

Abstract

Introduction
Orofacial cleft impacts jawbone and dental development and function, often with consequences for oral health. The first in this two-part systematic review of the literature on oral health in persons with cleft lip and/or palate focuses on periodontal parameters and composition of oral bacterial flora, while the second analyzes data on dental caries.

Materials and Methods
Four databases (PubMed, Cochrane, Scopus, Web of Science) were searched for studies that compared periodontal parameters, caries index, and microbiota composition between persons with cleft lip and/or palate and healthy controls. The Newcastle–Ottawa scale and the Joanna Briggs Institute checklist were applied to evaluate study quality.

Results
A total of 24 studies underwent systematic review, 18 of which entered meta-analysis. Twenty studies included a control group, while four included only persons with orofacial cleft. The first part (18 studies) compared periodontal parameters and oral microbiota.

Conclusions
Meta-analysis of periodontal parameters (plaque index, gingival index, bleeding index, probing pocket depth, clinical attachment level) revealed an association between orofacial cleft and greater risk for poor oral health and periodontal disease. Good oral health relies on correct home oral hygiene and regular visits to the dentist starting at an early age.
Medical Student Musculoskeletal Knowledge: Examining the Impact and Value of an Orthopaedic Surgery Clerkship Using the Freedman and Bernstein Examination
Authors: Nishime Nicole , Seibel Mary , Lindskog Dieter , Wiznia Daniel 
Published: January 2025

Abstract

Purpose
Given the importance of musculoskeletal knowledge but the limited orthopaedic instruction offered in medical school, our Orthopaedic Surgery Department developed a three-week clerkship for interested students. This study assesses the clerkship’s impact on medical student musculoskeletal knowledge through administration of the Freedman and Bernstein Basic Cognitive Musculoskeletal Examination.

Methods
Medical students enrolled in the orthopaedic surgery clerkship between February 2019 and May 2024 were asked to participate in pre- and post-clerkship surveys using the Freedman and Bernstein Basic Cognitive Musculoskeletal Examination. Raw and weighted scores were computed according to the guidelines provided by Freedman and Bernstein. Averaged scores were used to compute mean pre- and post-test scores.

Results
There were 64 responses to the pre-test and 33 responses to the post-test. The mean pre-test weighted score was 54% with 12 students (18.8%) passing. The mean post-test score was 70% with 17 students (51.5%) passing. Raw scores showed that musculoskeletal knowledge improved from pre-test (M = 55.13, SD = 19.90) to post-test (M = 70.22, SD = 14.70; p < .001). The results comparing weighted scores showed that the participants’ musculoskeletal knowledge also improved from pre-test (M = 52.86, SD = 21.12) to post-test (M = 67.11, SD = 19.02; p < .001).

Conclusion
While students demonstrated improved musculoskeletal knowledge after completing our institution’s orthopaedic surgery clerkship, almost half of the students did not pass the post-test. Most of the students who did not pass the post-test expressed definite or possible interest in pursuing an orthopaedic surgery residency.
Pharmacological pain management in patients with rheumatoid arthritis: a narrative literature review
Authors: Cox Natasha , Mallen Christian D. , Scott Ian C. 
Published: January 2025

Abstract

Background
Pain is a major challenge for patients with rheumatoid arthritis (RA), with many people suffering chronic pain. Current RA management guidelines focus on assessing and reducing disease activity using disease-modifying anti-rheumatic drugs (DMARDs). Consequently, pain care is often suboptimal, with growing evidence that analgesics are widely prescribed to patients with RA, despite potential toxicities and limited evidence for efficacy. Our review provides an overview of pharmacological treatments for pain in patients with RA, summarising their efficacy and use.

Findings
Thirteen systematic reviews of drug efficacy for pain in patients with RA were included in this review. These showed moderate- to high-quality evidence from clinical trials in more contemporary time-periods (mainly 1990s/2000s for synthetic DMARDs and post-2000 for biological/targeted synthetic DMARDs) that, in patients with active RA, short-term glucocorticoids and synthetic, biologic, and targeted synthetic DMARDs have efficacy at reducing pain intensity relative to placebo. In contrast, they showed low-quality evidence from trials in more historical time-periods (mainly in the 1960s–1990s for opioids and paracetamol) that (aside from naproxen) analgesics/neuromodulators provide any improvements in pain relative to placebo, and no supportive evidence for gabapentinoids, or long-term opioids. Despite this evidence base, 21 studies of analgesic prescribing in patients with RA consistently showed substantial and sustained prescribing of analgesics, particularly opioids, with approximately one quarter and > 40% of patients receiving chronic opioid prescriptions in each year in England and North America, respectively. Whilst NSAID prescribing had fallen over time across countries, gabapentinoid prescribing in England had risen from < 1% of patients in 2004 to approximately 10% in 2020. Prescribing levels varied substantially between individual clinicians and groups of patients.

Conclusions
In patients with active RA, DMARDs have efficacy at reducing pain, supporting the role of treat-to-target strategies. Despite limited evidence that analgesics improve pain in patients with RA, these medicines are widely prescribed. The reasons for this are unclear. We consider that closing this evidence-to-practice gap requires qualitative research exploring the drivers of this practice, high-quality trials of analgesic efficacy in contemporary RA populations, alongside an increased focus on pain management (including pharmacological and non-pharmacological options) within RA guidelines.
Diagnostic utility of LEF1 and β-catenin in WNT pathway tumors with CTNNB1 mutation
Authors: Li Can , Dong Lingdan , Zhu Li , Guan Wenbin 
Published: January 2025

Abstract

Objective
This study aimed to compare the expression of lymphoid enhancer factor 1 (LEF1) and β-catenin in basal cell adenoma (BA), desmoid-type fibromatosis (DF), and pancreatic solid pseudopapillary neoplasm (SPN) to evaluate their diagnostic utility in tumors associated with the WNT/β-catenin signaling pathway harboring the mutation of CTNNB1 gene 3 exon.

Methods
Eighty tumor patients, including 26 BAs, 30 DFs, and 24 SPNs, were analyzed. Immunohistochemical staining was identified positive (nuclear staining of LEF1 and β-catenin in > 50% of tumor cells). The diagnostic rate of LEF1 alone, β-catenin alone, and their combination were compared for each tumor type and all patients.

Results
Compared to β-catenin, when LEF1 alone was used for diagnosis, the diagnostic rate increased by 46.16% for BA, 16.67% for SPN, and 11.25% for all patients, but decreased by 23.34% for DF. The combined use of β-catenin and LEF1 significantly increased the diagnostic ratio in BA (46.16%), SPN (16.67%), and all patients (21.25%), but only marginally in DF (3.33%). In terms of all WNT pathway tumors with CTNNB1 gene mutation encompassed by our study, statistical analysis revealed no significant difference between LEF1 alone and β-catenin alone. However, their combined application was highly significant (P = 0.001) .

Conclusion
While β-catenin is commonly used as a marker for WNT pathway tumors, its variable expression and localization can be challenging for diagnosis. Our study emphasizes the importance of LEF1 as a complementary marker to β-catenin in diagnosing BA, DF, SPN, and other WNT pathway tumors activated by exon 3 CTNNB1 gene mutation. The combined use of LEF1 and β-catenin enhances diagnostic accuracy and may help the identification of these tumor types.
Neurocognitive impact of different irradiation modalities for patients with grade I-II skull base meningioma: a prospective multi-arm cohort study (CANCER COG)
Authors: Lesueur Paul , Joly Florence , Clarisse Benedicte , Lequesne Justine , Stefan Dinu , Balosso Jacques , Lange Marie , Thureau Sebastien , Capel Aurelie , Castera Marie , Legrand Berenice , Goliot Nicolas , Grellard Jean Michel , Tessonier Thomas , Castel Helene , Valable Samuel 
Published: January 2025

Abstract

Background
Radiotherapy as a complement or an alternative to neurosurgery has a central role in the treatment of skull base grade I-II meningiomas. Radiotherapy techniques have improved considerably over the last two decades, becoming more effective and sparing more and more the healthy tissue surrounding the tumour. Currently, hypo-fractionated stereotactic radiotherapy (SRT) for small tumours and normo-fractionated intensity-modulated radiotherapy (IMRT) or proton-therapy (PT) for larger tumours are the most widely used techniques. It is expected a decrease of the risk of cognitive impairment with these modern techniques. However prospective data about cognitive long-term consequences of partial brain irradiation with SRT, PT, or IMRT remain very scarce to date.

Methods
CANCER COG is one of the first multicentric study in the world to prospectively assess the cognitive performances of patients following different modalities of cerebral radiotherapy (stereotactic radiotherapy, proton therapy, intensity modulated radiotherapy) for the treatment of grade I-II skull base meningioma, up to at least 10 years after the end of radiotherapy. This longitudinal study includes the follow-up of 3 cohorts, including: patients treated with PRT, IMRT, and SRT. An additionally control group will be formed. The primary objective is to report long-term cognitive deterioration in each cohort until 10 years after the end of irradiation. The rate of clinical symptomatology improvement over time after irradiation, the evolution of health-related quality-of-life, anxiety/depression, fatigue, over time after irradiation, the tumoral local control after irradiation, the progression-free survival (PFS), the professional reintegration for working-age patients will also be assessed. CANCER COG aims to help clinicians to choose the best irradiation techniques with the best benefit/risk ratio. Inclusions started on september 2023.

Trial registration
The study was registered on clinicaltrials.gov with the following number: NCT 06036706.
The psychometric properties of the child anxiety and depression life interference scale (CADLIS)
Authors: O’Gradey-Lee Maddison , Jones Alana , Gandhi Esther , Lyneham Heidi , M. Rapee Ronald , Hudson Jennifer L. 
Published: January 2025

Abstract

Objective
Life interference is a key diagnostic feature for anxiety and depressive disorders. Measures focusing on life interference caused by anxiety and depressive disorders in children and adolescents have received minimal attention. This study evaluated the psychometric properties of the Child Anxiety and Depression Life Interference Scale (CADLIS), a brief child (CADLIS-C) and parent-report (CADLIS-P) measure designed to assess life interference from anxiety and depressive disorders in both the child and parent’s life.

Method
A total of 672 parents of children aged 4–18 years completed the CADLIS-P, and 627 children aged 7–18 years completed the CADLIS-C.

Results
The proposed two-factor CADLIS-C model was not supported, instead, due to high inter-factor covariance a one-factor model of life interference was proposed. The one-factor model demonstrated better model fit. The proposed three-factor model for the CADLIS-P was not supported, instead, an exploratory factor analysis found a two-factor model differentiating life interference into child and parent life interference a better model fit. The CADLIS demonstrated excellent internal consistency, good convergent and divergent validity, interrater correlations and was able to differentiate between children with and without clinical levels of anxiety and depressive symptoms.

Limitations
Limitations of the study included the sample population which consisted of a small clinical sample, an over-representation of high-income families and the use of a panel provider.

Conclusions
Overall, the CADLIS demonstrated sound psychometric properties. The CADLIS is a reliable measure that demonstrates evidence of convergent validity for the assessment of life interference associated with anxiety and depressive symptoms in children.
3D-AttenNet model can predict clinically significant prostate cancer in PI-RADS category 3 patients: a retrospective multicenter study
Authors: Bao Jie , Zhao Litao , Qiao Xiaomeng , Li Zhenkai , Ji Yanting , Su Yueting , Ji Libiao , Shen Junkang , Liu Jiangang , Tian Jie , Wang Ximing , Shen Hailin , Hu Chunhong 
Published: January 2025

Abstract

Purposes
The presence of clinically significant prostate cancer (csPCa) is equivocal for patients with prostate imaging reporting and data system (PI-RADS) category 3. We aim to develop deep learning models for re-stratify risks in PI-RADS category 3 patients.

Methods
This retrospective study included a bi-parametric MRI of 1567 consecutive male patients from six centers (Centers 1–6) between Jan 2015 and Dec 2020. Deep learning models with double channel attention modules based on MRI (AttenNet) for predicting PCa and csPCa were constructed separately. Each model was first pretrained using 1144 PI-RADS 1–2 and 4–5 images and then retrained using 238 PI-RADS 3 images from three training centers (centers 1–3), and tested using 185 PI-RADS 3 images from the other three testing centers (centers 4–6).

Results
Our AttenNet models achieved excellent prediction performances in testing cohort of center 4–6 with the area under the receiver operating characteristic curves (AUC) of 0.795 (95% CI: [0.700, 0.891]), 0.963 (95% CI: [0.915, 1]) and 0.922 (95% CI: [0.810, 1]) in predicting PCa, and the corresponding AUCs were 0.827 (95% CI: [0.703, 0.952]) and 0.926 (95% CI: [0.846, 1]) in predicting csPCa in testing cohort of center 4 and center 5. In particular, 71.1% to 92.2% of non-csPCa patients were identified by our model in three testing cohorts, who can spare from invasive biopsy or RP procedure.

Conclusions
Our model offers a noninvasive screening clinical tool to re-stratify risks in PI-RADS 3 patients, thereby reducing unnecessary invasive biopsies and improving the effectiveness of biopsies.

Critical relevance statement
The deep learning model with MRI can help to screen out csPCa in PI-RADS category 3.

Key Points

AttenNet models included channel attention and soft attention modules.

71.1–92.2% of non-csPCa patients were identified by the AttenNet model.

The AttenNet models can be a screen clinical tool to re-stratify risks in PI-RADS 3 patients.

Graphical Abstract